{
	"type": "force",
	"categories": [
		{
			"name": "reference",
			"keyword": {},
			"base": "reference"
		},
		{
			"name": "query",
			"keyword": {},
			"base": "query"
		},
		{
			"name": "citation",
			"keyword": {},
			"base": "citation"
		}
	],
	"nodes": [
		{
			"PMID": 26698910,
			"title": "Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F.",
			"journal": "The New England journal of medicine",
			"authorList": [
				"Shaw Alice T",
				"Friboulet Luc",
				"Leshchiner Ignaty",
				"Gainor Justin F",
				"Bergqvist Simon",
				"Brooun Alexei",
				"Burke Benjamin J",
				"Deng Ya-Li",
				"Liu Wei",
				"Dardaei Leila",
				"Frias Rosa L",
				"Schultz Kate R",
				"Logan Jennifer",
				"James Leonard P",
				"Smeal Tod",
				"Timofeevski Sergei",
				"Katayama Ryohei",
				"Iafrate A John",
				"Le Long",
				"McTigue Michele",
				"Getz Gad",
				"Johnson Ted W",
				"Engelman Jeffrey A"
			],
			"DOI": "10.1056/NEJMoa1508887",
			"date": "2016-01-19",
			"PMC": "",
			"citation": "",
			"abstract": "In a patient who had metastatic anaplastic lymphoma kinase (ALK)-rearranged lung cancer, resistance to crizotinib developed because of a mutation in the ALK kinase domain. This mutation is predicted to result in a substitution of cysteine by tyrosine at amino acid residue 1156 (C1156Y). Her tumor did not respond to a second-generation ALK inhibitor, but it did respond to lorlatinib (PF-06463922), a third-generation inhibitor. When her tumor relapsed, sequencing of the resistant tumor revealed an ALK L1198F mutation in addition to the C1156Y mutation. The L1198F substitution confers resistance to lorlatinib through steric interference with drug binding. However, L1198F paradoxically enhances binding to crizotinib, negating the effect of C1156Y and resensitizing resistant cancers to crizotinib. The patient received crizotinib again, and her cancer-related symptoms and liver failure resolved. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT01970865.).",
			"category": 1,
			"name": "Shaw Alice T,2016"
		},
		{
			"PMID": 23044827,
			"title": "Evolution of the cancer genome.",
			"journal": "Nature reviews. Genetics",
			"authorList": [
				"Yates Lucy R",
				"Campbell Peter J"
			],
			"DOI": "10.1038/nrg3317",
			"date": "2013-01-04",
			"PMC": "",
			"citation": "",
			"abstract": "The advent of massively parallel sequencing technologies has allowed the characterization of cancer genomes at an unprecedented resolution. Investigation of the mutational landscape of tumours is providing new insights into cancer genome evolution, laying bare the interplay of somatic mutation, adaptation of clones to their environment and natural selection. These studies have demonstrated the extent of the heterogeneity of cancer genomes, have allowed inferences to be made about the forces that act on nascent cancer clones as they evolve and have shown insight into the mutational processes that generate genetic variation. Here we review our emerging understanding of the dynamic evolution of the cancer genome and of the implications for basic cancer biology and the development of antitumour therapy.",
			"category": 1,
			"name": "Yates Lucy R,2013"
		},
		{
			"PMID": 32025013,
			"title": "The evolutionary history of 2,658 cancers.",
			"journal": "Nature",
			"authorList": [
				"Gerstung Moritz",
				"Jolly Clemency",
				"Leshchiner Ignaty",
				"Dentro Stefan C",
				"Gonzalez Santiago",
				"Rosebrock Daniel",
				"Mitchell Thomas J",
				"Rubanova Yulia",
				"Anur Pavana",
				"Yu Kaixian",
				"Tarabichi Maxime",
				"Deshwar Amit",
				"Wintersinger Jeff",
				"Kleinheinz Kortine",
				"V\u00e1zquez-Garc\u00eda Ignacio",
				"Haase Kerstin",
				"Jerman Lara",
				"Sengupta Subhajit",
				"Macintyre Geoff",
				"Malikic Salem",
				"Donmez Nilgun",
				"Livitz Dimitri G",
				"Cmero Marek",
				"Demeulemeester Jonas",
				"Schumacher Steven",
				"Fan Yu",
				"Yao Xiaotong",
				"Lee Juhee",
				"Schlesner Matthias",
				"Boutros Paul C",
				"Bowtell David D",
				"Zhu Hongtu",
				"Getz Gad",
				"Imielinski Marcin",
				"Beroukhim Rameen",
				"Sahinalp S Cenk",
				"Ji Yuan",
				"Peifer Martin",
				"Markowetz Florian",
				"Mustonen Ville",
				"Yuan Ke",
				"Wang Wenyi",
				"Morris Quaid D",
				"PCAWG Evolution & Heterogeneity Working Group",
				"Spellman Paul T",
				"Wedge David C",
				"Van Loo Peter",
				"PCAWG Consortium"
			],
			"DOI": "10.1038/s41586-019-1907-7",
			"date": "2020-04-13",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer develops through a process of somatic evolution",
			"category": 1,
			"name": "Gerstung Moritz,2020"
		},
		{
			"PMID": 19360079,
			"title": "The cancer genome.",
			"journal": "Nature",
			"authorList": [
				"Stratton Michael R",
				"Campbell Peter J",
				"Futreal P Andrew"
			],
			"DOI": "10.1038/nature07943",
			"date": "2009-04-20",
			"PMC": "",
			"citation": "",
			"abstract": "All cancers arise as a result of changes that have occurred in the DNA sequence of the genomes of cancer cells. Over the past quarter of a century much has been learnt about these mutations and the abnormal genes that operate in human cancers. We are now, however, moving into an era in which it will be possible to obtain the complete DNA sequence of large numbers of cancer genomes. These studies will provide us with a detailed and comprehensive perspective on how individual cancers have developed.",
			"category": 1,
			"name": "Stratton Michael R,2009"
		},
		{
			"PMID": 38448512,
			"title": "New pan-ALK inhibitor-resistant EML4::ALK mutations detected by liquid biopsy in lung cancer patients.",
			"journal": "NPJ precision oncology",
			"authorList": [
				"Villa Matteo",
				"Malighetti Federica",
				"Sala Elisa",
				"Sharma Geeta G",
				"Arosio Giulia",
				"Gemelli Maria",
				"Manfroni Chiara",
				"Fontana Diletta",
				"Cordani Nicoletta",
				"Meneveri Raffaella",
				"Zambon Alfonso",
				"Piazza Rocco",
				"Pagni Fabio",
				"Cortinovis Diego",
				"Mologni Luca"
			],
			"DOI": "10.1038/s41698-024-00498-w",
			"date": "2024-03-09",
			"PMC": "",
			"citation": "",
			"abstract": "ALK and ROS1 fusions are effectively targeted by tyrosine kinase inhibitors (TKIs), however patients inevitably relapse after an initial response, often due to kinase domain mutations. We investigated circulating DNA from TKI-relapsed NSCLC patients by deep-sequencing. New EML4::ALK substitutions, L1198R, C1237Y and L1196P, were identified in the plasma of NSCLC ALK patients and characterized in a Ba/F3 cell model. Variants C1237Y and L1196P demonstrated pan-inhibitor resistance across 5 clinical and 2 investigational TKIs.",
			"category": 2,
			"name": "Villa Matteo,2024"
		},
		{
			"PMID": 38421881,
			"title": "Updated overall survival and circulating tumor DNA analysis of ensartinib for crizotinib-refractory ALK-positive NSCLC from a phase II study.",
			"journal": "Cancer communications (London, England)",
			"authorList": [
				"Zheng Jing",
				"Wang Tao",
				"Yang Yunpeng",
				"Huang Jie",
				"Feng Jifeng",
				"Zhuang Wu",
				"Chen Jianhua",
				"Zhao Jun",
				"Zhong Wei",
				"Zhao Yanqiu",
				"Zhang Yiping",
				"Song Yong",
				"Hu Yi",
				"Yu Zhuang",
				"Gong Youling",
				"Chen Yuan",
				"Ye Feng",
				"Zhang Shucai",
				"Cao Lejie",
				"Fan Yun",
				"Wu Gang",
				"Guo Yubiao",
				"Zhou Chengzhi",
				"Ma Kewei",
				"Fang Jian",
				"Feng Weineng",
				"Liu Yunpeng",
				"Zheng Zhendong",
				"Li Gaofeng",
				"Wang Huijie",
				"Cang Shundong",
				"Wu Ning",
				"Song Wei",
				"Liu Xiaoqing",
				"Zhao Shijun",
				"Ding Lieming",
				"Selvaggi Giovanni",
				"Wang Yang",
				"Xiao Shanshan",
				"Wang Qian",
				"Shen Zhilin",
				"Zhou Jianya",
				"Zhou Jianying",
				"Zhang Li"
			],
			"DOI": "10.1002/cac2.12524",
			"date": "2024-04-19",
			"PMC": "",
			"citation": "",
			"abstract": "The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib-refractory, anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study.",
			"category": 2,
			"name": "Zheng Jing,2024"
		},
		{
			"PMID": 38408285,
			"title": "KIT ATP-Binding Pocket/Activation Loop Mutations in GI Stromal Tumor: Emerging Mechanisms of Kinase Inhibitor Escape.",
			"journal": "Journal of clinical oncology : official journal of the American Society of Clinical Oncology",
			"authorList": [
				"M\u00fchlenberg Thomas",
				"Falkenhorst Johanna",
				"Schulz Tom",
				"Fletcher Benjamin S",
				"Teuber Alina",
				"Krzeciesa Dawid",
				"Klooster Isabella",
				"Lundberg Meijun",
				"Wilson Lydia",
				"Lategahn Jonas",
				"von Mehren Margaret",
				"Grunewald Susanne",
				"T\u00fcns Alicia Isabell",
				"Wardelmann Eva",
				"Sicklick Jason K",
				"Brahmi Mehdi",
				"Serrano C\u00e9sar",
				"Schildhaus Hans-Ulrich",
				"Sievers Sonja",
				"Treckmann J\u00fcrgen",
				"Heinrich Michael C",
				"Raut Chandrajit P",
				"Ou Wen-Bin",
				"Marino-Enriquez Adrian",
				"George Suzanne",
				"Rauh Daniel",
				"Fletcher Jonathan A",
				"Bauer Sebastian"
			],
			"DOI": "10.1200/JCO.23.01197",
			"date": "2024-04-19",
			"PMC": "",
			"citation": "",
			"abstract": "Imatinib resistance in GI stromal tumors (GISTs) is primarily caused by secondary ",
			"category": 2,
			"name": "M\u00fchlenberg Thomas,2024"
		},
		{
			"PMID": 38397899,
			"title": "Unraveling the Potential of ALK-Targeted Therapies in Non-Small Cell Lung Cancer: Comprehensive Insights and Future Directions.",
			"journal": "Biomedicines",
			"authorList": [
				"Parvaresh Hannaneh",
				"Roozitalab Ghazaal",
				"Golandam Fatemeh",
				"Behzadi Payam",
				"Jabbarzadeh Kaboli Parham"
			],
			"DOI": "10.3390/biomedicines12020297",
			"date": "2024-02-27",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "Parvaresh Hannaneh,2024"
		},
		{
			"PMID": 38201357,
			"title": "From Development to Place in Therapy of Lorlatinib for the Treatment of ALK and ROS1 Rearranged Non-Small Cell Lung Cancer (NSCLC).",
			"journal": "Diagnostics (Basel, Switzerland)",
			"authorList": [
				"Fabbri Laura",
				"Di Federico Alessandro",
				"Astore Martina",
				"Marchiori Virginia",
				"Rejtano Agnese",
				"Seminerio Renata",
				"Gelsomino Francesco",
				"De Giglio Andrea"
			],
			"DOI": "10.3390/diagnostics14010048",
			"date": "2024-01-27",
			"PMC": "",
			"citation": "",
			"abstract": "Following the results of the CROWN phase III trial, the third-generation macrocyclic ALK inhibitor lorlatinib has been introduced as a salvage option after the failure of a first-line TKI in ALK-rearranged NSCLC, while its precise role in the therapeutic algorithm of ROS1 positive disease is still to be completely defined. The ability to overcome acquired resistance to prior generation TKIs (alectinib, brigatinib, ceritinib, and crizotinib) and the high intracranial activity in brain metastatic disease thanks to increased blood-brain barrier penetration are the reasons for the growing popularity and interest in this molecule. Nevertheless, the major vulnerability of this drug resides in a peculiar profile of related collateral events, with neurological impairment being the most conflicting and debated clinical issue. The cognitive safety concern, the susceptibility to heterogeneous resistance pathways, and the absence of a valid alternative in the second line are strongly jeopardizing a potential paradigm shift in this oncogene-addicted disease. So, when prescribing lorlatinib, clinicians must face two diametrically opposed characteristics: a great therapeutic potential without the intrinsic limitations of its precursor TKIs, a cytotoxic activity threatened by suboptimal tolerability, and the unavoidable onset of resistance mechanisms we cannot properly manage yet. In this paper, we give a critical point of view on the stepwise introduction of this promising drug into clinical practice, starting from its innovative molecular and biochemical properties to intriguing future developments, without forgetting its weaknesses.",
			"category": 2,
			"name": "Fabbri Laura,2024"
		},
		{
			"PMID": 38042915,
			"title": "Clonal heterogeneity in ER+ breast cancer reveals the proteasome and PKC as potential therapeutic targets.",
			"journal": "NPJ breast cancer",
			"authorList": [
				"Beumers Lukas",
				"Vlachavas Efstathios-Iason",
				"Borgoni Simone",
				"Schwarzm\u00fcller Luisa",
				"Penso-Dolfin Luca",
				"Michels Birgitta E",
				"Sofyali Emre",
				"Burmester Sara",
				"Heiss Daniela",
				"Wilhelm Heike",
				"Yarden Yosef",
				"Helm Dominic",
				"Will Rainer",
				"Goncalves Angela",
				"Wiemann Stefan"
			],
			"DOI": "10.1038/s41523-023-00604-4",
			"date": "2023-12-05",
			"PMC": "",
			"citation": "",
			"abstract": "Intratumoral heterogeneity impacts the success or failure of anti-cancer therapies. Here, we investigated the evolution and mechanistic heterogeneity in clonal populations of cell models for estrogen receptor positive breast cancer. To this end, we established barcoded models of luminal breast cancer and rendered them resistant to commonly applied first line endocrine therapies. By isolating single clones from the resistant cell pools and characterizing replicates of individual clones we observed inter- (between cell lines) and intra-tumor (between different clones from the same cell line) heterogeneity. Molecular characterization at RNA and phospho-proteomic levels revealed private clonal activation of the unfolded protein response and respective sensitivity to inhibition of the proteasome, and potentially shared sensitivities for repression of protein kinase C. Our in vitro findings are consistent with tumor-heterogeneity that is observed in breast cancer patients thus highlighting the need to uncover heterogeneity at an individual patient level and to adjust therapies accordingly.",
			"category": 2,
			"name": "Beumers Lukas,2023"
		},
		{
			"PMID": 37999149,
			"title": "Sharing Experience with Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitors in Lung Cancer: An Italian Expert Panel Discussion.",
			"journal": "Current oncology (Toronto, Ont.)",
			"authorList": [
				"Gridelli Cesare",
				"Tiseo Marcello",
				"Cortinovis Diego Luigi",
				"Migliorino Maria Rita",
				"Barbieri Vito",
				"Bironzo Paolo",
				"Bearz Alessandra",
				"Attili Ilaria",
				"de Marinis Filippo"
			],
			"DOI": "10.3390/curroncol30110729",
			"date": "2023-11-27",
			"PMC": "",
			"citation": "",
			"abstract": "ALK tyrosine kinase inhibitors (TKIs) have revolutionized the treatment and largely improved the survival outcomes of patients with NSCLC harboring ",
			"category": 2,
			"name": "Gridelli Cesare,2023"
		},
		{
			"PMID": 37954850,
			"title": "Anaplastic lymphoma kinase inhibitors-a review of anticancer properties, clinical efficacy, and resistance mechanisms.",
			"journal": "Frontiers in pharmacology",
			"authorList": [
				"Kie\u0142bowski Kajetan",
				"\u017bychowska Justyna",
				"Becht Rafa\u0142"
			],
			"DOI": "10.3389/fphar.2023.1285374",
			"date": "2023-11-14",
			"PMC": "",
			"citation": "",
			"abstract": "Fusions and mutations of anaplastic lymphoma kinase (ALK), a tyrosine kinase receptor, have been identified in several neoplastic diseases. Rearranged ALK is a driver of tumorigenesis, which activates various signaling pathway associated with proliferation and survival. To date, several agents that target and inhibit ALK have been developed. The most studied ALK-positive disease is non-small cell lung cancer, and three generations of ALK tyrosine kinase inhibitors (TKIs) have been approved for the treatment of metastatic disease. Nevertheless, the use of ALK-TKIs is associated with acquired resistance (resistance mutations, bypass signaling), which leads to disease progression and may require a substitution or introduction of other treatment agents. Understanding of the complex nature and network of resistance mutations may allow to introduce sequential and targeted therapies. In this review, we aim to summarize the efficacy and safety profile of ALK inhibitors, describe off-target anticancer effects, and discuss resistance mechanisms in the context of personalized oncology.",
			"category": 2,
			"name": "Kie\u0142bowski Kajetan,2023"
		},
		{
			"PMID": 37917191,
			"title": "MIG6 loss confers resistance to ALK/ROS1 inhibitors in NSCLC through EGFR activation by low-dose EGF.",
			"journal": "JCI insight",
			"authorList": [
				"Kondo Nobuyuki",
				"Utsumi Takahiro",
				"Shimizu Yuki",
				"Takemoto Ai",
				"Oh-Hara Tomoko",
				"Uchibori Ken",
				"Subat-Motoshi Sophia",
				"Ninomiya Hironori",
				"Takeuchi Kengo",
				"Nishio Makoto",
				"Miyazaki Yasunari",
				"Katayama Ryohei"
			],
			"DOI": "10.1172/jci.insight.173688",
			"date": "2024-01-03",
			"PMC": "",
			"citation": "",
			"abstract": "Although tyrosine kinase inhibitor (TKI) therapy shows marked clinical efficacy in patients with anaplastic lymphoma kinase-positive (ALK+) and ROS proto-oncogene 1-positive (ROS1+) non-small cell lung cancer (NSCLC), most of these patients eventually relapse with acquired resistance. Therefore, genome-wide CRISPR/Cas9 knockout screening was performed using an ALK+ NSCLC cell line established from pleural effusion without ALK-TKI treatment. After 9 days of ALK-TKI therapy, sequencing analysis was performed, which identified several tumor suppressor genes, such as NF2 or MED12, and multiple candidate genes. Among them, this study focused on ERRFI1, which is known as MIG6 and negatively regulates EGFR signaling. Interestingly, MIG6 loss induced resistance to ALK-TKIs by treatment with quite a low dose of EGF, which is equivalent to plasma concentration, through the upregulation of MAPK and PI3K/AKT/mTOR pathways. Combination therapy with ALK-TKIs and anti-EGFR antibodies could overcome the acquired resistance in both in vivo and in vitro models. In addition, this verified that MIG6 loss induces resistance to ROS1-TKIs in ROS1+ cell lines. This study found a potentially novel factor that plays a role in ALK and ROS1-TKI resistance by activating the EGFR pathway with low-dose ligands.",
			"category": 2,
			"name": "Kondo Nobuyuki,2024"
		},
		{
			"PMID": 37894445,
			"title": "New Generations of Tyrosine Kinase Inhibitors in Treating NSCLC with Oncogene Addiction: Strengths and Limitations.",
			"journal": "Cancers",
			"authorList": [
				"Attili Ilaria",
				"Corvaja Carla",
				"Spitaleri Gianluca",
				"Del Signore Ester",
				"Trillo Aliaga Pamela",
				"Passaro Antonio",
				"de Marinis Filippo"
			],
			"DOI": "10.3390/cancers15205079",
			"date": "2023-10-30",
			"PMC": "",
			"citation": "",
			"abstract": "Tyrosine kinase inhibitors (TKIs) revolutionized the treatment of patients with advanced or metastatic non-small cell lung cancer (NSCLC) harboring most driver gene alterations. Starting from the first generation, research rapidly moved to the development of newer, more selective generations of TKIs, obtaining improved results in terms of disease control and survival. However, the use of novel generations of TKIs is not without limitations. We reviewed the main results obtained, as well as the ongoing clinical trials with TKIs in oncogene-addicted NSCLC, together with the biology underlying their potential strengths and limitations. Across driver gene alterations, novel generations of TKIs allowed delayed resistance, prolonged survival, and improved brain penetration compared to previous generations, although with different toxicity profiles, that generally moved their use from further lines to the front-line treatment. However, the anticipated positioning of novel generation TKIs leads to abolishing the possibility of TKI treatment sequencing and any role of previous generations. In addition, under the selective pressure of such more potent drugs, resistant clones emerge harboring more complex and hard-to-target resistance mechanisms. Deeper knowledge of tumor biology and drug properties will help identify new strategies, including combinatorial treatments, to continue improving results in patients with oncogene-addicted NSCLC.",
			"category": 2,
			"name": "Attili Ilaria,2023"
		},
		{
			"PMID": 37787868,
			"title": "Diagnosis and Treatment of Advanced ALK Rearrangement-Positive Non-Small-Cell Lung Cancer in Portugal: Results of a National Questionnaire.",
			"journal": "Drugs - real world outcomes",
			"authorList": [
				"Figueiredo Ana",
				"Rodrigues Ana",
				"Gaspar Carina",
				"Felizardo Margarida"
			],
			"DOI": "10.1007/s40801-023-00393-z",
			"date": "2024-04-06",
			"PMC": "",
			"citation": "",
			"abstract": "Rearrangements in the anaplastic lymphoma kinase (ALK) gene define a molecular subgroup of non-small-cell lung carcinoma (NSCLC) that should be treated with ALK-targeting tyrosine kinase inhibitors (TKIs).",
			"category": 2,
			"name": "Figueiredo Ana,2024"
		},
		{
			"PMID": 37773318,
			"title": "ALK fusions in the pan-cancer setting: another tumor-agnostic target?",
			"journal": "NPJ precision oncology",
			"authorList": [
				"Shreenivas Aditya",
				"Janku Filip",
				"Gouda Mohamed A",
				"Chen Hui-Zi",
				"George Ben",
				"Kato Shumei",
				"Kurzrock Razelle"
			],
			"DOI": "10.1038/s41698-023-00449-x",
			"date": "2023-11-23",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) alterations (activating mutations, amplifications, and fusions/rearrangements) occur in ~3.3% of cancers. ALK fusions/rearrangements are discerned in >50% of inflammatory myofibroblastic tumors (IMTs) and anaplastic large cell lymphomas (ALCLs), but only in ~0.2% of other cancers outside of non-small cell lung cancer (NSCLC), a rate that may be below the viability threshold of even large-scale treatment trials. Five ALK inhibitors -alectinib, brigatinib, ceritinb, crizotinib, and lorlatinib-are FDA approved for ALK-aberrant NSCLCs, and crizotinib is also approved for ALK-aberrant IMTs and ALCL, including in children. Herein, we review the pharmacologic tractability of ALK alterations, focusing beyond NSCLC. Importantly, the hallmark of approved indications is the presence of ALK fusions/rearrangements, and response rates of ~50-85%. Moreover, there are numerous reports of ALK inhibitor activity in multiple solid and hematologic tumors (e.g., histiocytosis, leiomyosarcoma, lymphoma, myeloma, and colorectal, neuroendocrine, ovarian, pancreatic, renal, and thyroid cancer) bearing ALK fusions/rearrangements. Many reports used crizotinib or alectinib, but each of the approved ALK inhibitors have shown activity. ALK inhibitor activity is also seen in neuroblastoma, which bear ALK mutations (rather than fusions/rearrangements), but response rates are lower (~10-20%). Current data suggests that ALK inhibitors have tissue-agnostic activity in neoplasms bearing ALK fusions/rearrangements.",
			"category": 2,
			"name": "Shreenivas Aditya,2023"
		},
		{
			"PMID": 37748191,
			"title": "MIG6 Mediates Adaptive and Acquired Resistance to ALK/ROS1 Fusion Kinase Inhibition through EGFR Bypass Signaling.",
			"journal": "Molecular cancer therapeutics",
			"authorList": [
				"Chen Nan",
				"Tyler Logan C",
				"Le Anh T",
				"Welsh Eric A",
				"Fang Bin",
				"Elliott Andrew",
				"Davies Kurtis D",
				"Danhorn Thomas",
				"Riely Gregory J",
				"Ladanyi Marc",
				"Haura Eric B",
				"Doebele Robert C"
			],
			"DOI": "10.1158/1535-7163.MCT-23-0218",
			"date": "2024-01-04",
			"PMC": "",
			"citation": "",
			"abstract": "Despite the initial benefit from tyrosine kinase inhibitors (TKI) targeting oncogenic ALK and ROS1 gene fusions in non-small cell lung cancer, complete responses are rare and resistance ultimately emerges from residual tumor cells. Although several acquired resistance mechanisms have been reported at the time of disease progression, adaptative resistance mechanisms that contribute to residual diseases before the outgrowth of tumor cells with acquired resistance are less clear. For the patients who have progressed after TKI treatments, but do not demonstrate ALK/ROS1 kinase mutations, there is a lack of biomarkers to guide effective treatments. Herein, we found that phosphorylation of MIG6, encoded by the ERRFI1 gene, was downregulated by ALK/ROS1 inhibitors as were mRNA levels, thus potentiating EGFR activity to support cell survival as an adaptive resistance mechanism. MIG6 downregulation was sustained following chronic exposure to ALK/ROS1 inhibitors to support the establishment of acquired resistance. A higher ratio of EGFR to MIG6 expression was found in ALK TKI-treated and ALK TKI-resistant tumors and correlated with the poor responsiveness to ALK/ROS1 inhibition in patient-derived cell lines. Furthermore, we identified and validated a MIG6 EGFR-binding domain truncation mutation in mediating resistance to ROS1 inhibitors but sensitivity to EGFR inhibitors. A MIG6 deletion was also found in a patient after progressing to ROS1 inhibition. Collectively, this study identifies MIG6 as a novel regulator for EGFR-mediated adaptive and acquired resistance to ALK/ROS1 inhibitors and suggests EGFR to MIG6 ratios and MIG6-damaging alterations as biomarkers to predict responsiveness to ALK/ROS1 and EGFR inhibitors.",
			"category": 2,
			"name": "Chen Nan,2024"
		},
		{
			"PMID": 37407818,
			"title": "Therapy-induced APOBEC3A drives evolution of persistent cancer cells.",
			"journal": "Nature",
			"authorList": [
				"Isozaki Hideko",
				"Sakhtemani Ramin",
				"Abbasi Ammal",
				"Nikpour Naveed",
				"Stanzione Marcello",
				"Oh Sunwoo",
				"Langenbucher Adam",
				"Monroe Susanna",
				"Su Wenjia",
				"Cabanos Heidie Frisco",
				"Siddiqui Faria M",
				"Phan Nicole",
				"Jalili P\u00e9gah",
				"Timonina Daria",
				"Bilton Samantha",
				"Gomez-Caraballo Maria",
				"Archibald Hannah L",
				"Nangia Varuna",
				"Dionne Kristin",
				"Riley Amanda",
				"Lawlor Matthew",
				"Banwait Mandeep Kaur",
				"Cobb Rosemary G",
				"Zou Lee",
				"Dyson Nicholas J",
				"Ott Christopher J",
				"Benes Cyril",
				"Getz Gad",
				"Chan Chang S",
				"Shaw Alice T",
				"Gainor Justin F",
				"Lin Jessica J",
				"Sequist Lecia V",
				"Piotrowska Zofia",
				"Yeap Beow Y",
				"Engelman Jeffrey A",
				"Lee Jake June-Koo",
				"Maruvka Yosef E",
				"Buisson R\u00e9mi",
				"Lawrence Michael S",
				"Hata Aaron N"
			],
			"DOI": "10.1038/s41586-023-06303-1",
			"date": "2023-08-14",
			"PMC": "",
			"citation": "",
			"abstract": "Acquired drug resistance to anticancer targeted therapies remains an unsolved clinical problem. Although many drivers of acquired drug resistance have been identified",
			"category": 2,
			"name": "Isozaki Hideko,2023"
		},
		{
			"PMID": 37339995,
			"title": "Mechanisms of synergistic suppression of ALK-positive lung cancer cell growth by the combination of ALK and SHP2 inhibitors.",
			"journal": "Scientific reports",
			"authorList": [
				"Berry M A",
				"Bland A R",
				"Ashton J C"
			],
			"DOI": "10.1038/s41598-023-37006-2",
			"date": "2023-06-22",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer is a major cause of cancer-related deaths. Alectinib is the first line of treatment for patients with ALK-positive lung cancer, but the survival rate beyond 2-3\u00a0years is low. Co-targeting secondary oncogenic drivers such as SHP2 is a potential strategy for improving drug efficacy. This is because SHP2 is expressed ubiquitously, but ALK expression is largely restricted to cancer cells. Thus, the combination of ALK and SHP2 inhibitors may provide a way to restrict synergistic cytotoxicity to cancer cells only, by reducing the dose of SHP2 inhibitors required for anticancer action and minimising SHP2-dependent systemic toxicity. The objective of this study was to investigate whether the combination of a SHP2 inhibitor (SHP099) with alectinib would synergistically suppress the growth of ALK-positive lung cancer cells. Our results demonstrated that the drug combination significantly and synergistically decreased cell viability at relatively low concentrations in ALK-positive H3122 and H2228 cells, due to G1 cell cycle arrest and increased apoptosis because of suppressed downstream RAS/MAPK signalling. The drug combination also induced the expression of mediators of the intrinsic apoptotic pathway, Bim and cleaved caspase-3, and modulated the expression of cell cycle mediators cyclin D1, cyclin B1, and phosphorylated CDK1.",
			"category": 2,
			"name": "Berry M A,2023"
		},
		{
			"PMID": 37212960,
			"title": "The PD-1 single-nucleotide polymorphism rs11568821 and rs2227981 as a novel prognosis model\u00a0in a triple-negative breast cancer patient.",
			"journal": "Molecular biology reports",
			"authorList": [
				"Boguszewska-Byczkiewicz Katarzyna",
				"Wow Thomas",
				"Szyma\u0144ska Bo\u017cena",
				"Kosny Micha\u0142",
				"Kolacinska-Wow Agnieszka"
			],
			"DOI": "10.1007/s11033-023-08423-3",
			"date": "2023-10-20",
			"PMC": "",
			"citation": "",
			"abstract": "The aim of the study is to determine the relationship between polymorphisms rs11568821 C/T and at rs2227981 G/A in the programmed cell death 1 gene (PDCD1) and the clinicopathologic characteristics of triple negative breast cancer patient (TNBC).",
			"category": 2,
			"name": "Boguszewska-Byczkiewicz Katarzyna,2023"
		},
		{
			"PMID": 37197622,
			"title": "Biology and impact of lineage plasticity in ALK-positive NSCLC: a narrative review.",
			"journal": "Translational lung cancer research",
			"authorList": [
				"Meador Catherine B",
				"Piotrowska Zofia"
			],
			"DOI": "10.21037/tlcr-22-867",
			"date": "2023-05-19",
			"PMC": "",
			"citation": "",
			"abstract": "Lineage transformation is a known mechanism of acquired resistance to targeted therapies in non-small cell lung cancer (NSCLC). Transformation to small cell and squamous carcinoma and epithelial-to-mesenchymal transition (EMT) have all been identified as recurrent but rare events in ALK-positive NSCLC. However, centralized data informing our understanding of the biology and clinical implications of lineage transformation in ALK-positive NSCLC are lacking.",
			"category": 2,
			"name": "Meador Catherine B,2023"
		},
		{
			"PMID": 37149843,
			"title": "EML4-ALK biology and drug resistance in non-small cell lung cancer: a new phase of discoveries.",
			"journal": "Molecular oncology",
			"authorList": [
				"Elshatlawy Mariam",
				"Sampson Josephina",
				"Clarke Katy",
				"Bayliss Richard"
			],
			"DOI": "10.1002/1878-0261.13446",
			"date": "2023-06-15",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) can be driven to oncogenic activity by different types of mutational events such as point-mutations, for example F1174L in neuroblastoma, and gene fusions, for example with echinoderm microtubule-associated protein-like 4 (EML4) in non-small cell lung cancer (NSCLC). EML4-ALK variants result from different breakpoints, generating fusions of different sizes and properties. The most common variants (Variant 1 and Variant 3) form cellular compartments with distinct physical properties. The presence of a partial, probably misfolded beta-propeller domain in variant 1 confers solid-like properties to the compartments it forms, greater dependence on Hsp90 for protein stability and higher cell sensitivity to ALK tyrosine kinase inhibitors (TKIs). These differences translate to the clinic because variant 3, on average, worsens patient prognosis and increases metastatic risk. Latest generation ALK-TKIs are beneficial for most patients with EML4-ALK fusions. However, resistance to ALK inhibitors can occur via point-mutations within the kinase domain of the EML4-ALK fusion, for example G1202R, reducing inhibitor effectiveness. Here, we discuss the biology of EML4-ALK variants, their impact on treatment response, ALK-TKI drug resistance mechanisms and potential combination therapies.",
			"category": 2,
			"name": "Elshatlawy Mariam,2023"
		},
		{
			"PMID": 37149665,
			"title": "New perspectives for targeting therapy in ALK-positive human cancers.",
			"journal": "Oncogene",
			"authorList": [
				"Zhao Simin",
				"Li Jian",
				"Xia Qingxin",
				"Liu Kangdong",
				"Dong Zigang"
			],
			"DOI": "10.1038/s41388-023-02712-8",
			"date": "2023-06-12",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) is a member of the insulin receptor protein-tyrosine kinase superfamily and was first discovered in anaplastic large-cell lymphoma (ALCL). ALK alterations, including fusions, over-expression and mutations, are highly associated with cancer initiation and progression. This kinase plays an important role in different cancers, from very rare to the more prevalent non-small cell lung cancers. Several ALK inhibitors have been developed and received Food and Drug Administration (FDA) approval. However, like other drugs used in targeted therapies, ALK inhibitors inevitably encounter cancer cell resistance. Therefore, monoclonal antibody screening based on extracellular domain or combination therapies may provide viable alternatives for treating ALK-positive tumors. In this review, we discuss the current understanding of wild-type ALK and fusion protein structures, the pathological functions of ALK, ALK target therapy, drug resistance and future therapeutic directions.",
			"category": 2,
			"name": "Zhao Simin,2023"
		},
		{
			"PMID": 37077199,
			"title": "LOREALAUS: LOrlatinib REAL-World AUStralian Experience in Advanced ALK-Rearranged NSCLC.",
			"journal": "JTO clinical and research reports",
			"authorList": [
				"Alexander Marliese",
				"Wei Joe",
				"Parakh Sagun",
				"John Thomas",
				"Kao Steven",
				"Nagrial Adnan",
				"Bowyer Samantha",
				"Warburton Lydia",
				"Moore Melissa",
				"Hughes Brett G M",
				"Clay Timothy D",
				"Pavlakis Nick",
				"Solomon Benjamin J",
				"Itchins Malinda"
			],
			"DOI": "10.1016/j.jtocrr.2023.100490",
			"date": "2023-04-21",
			"PMC": "",
			"citation": "",
			"abstract": "Over the past decade, ALK tyrosine kinase inhibitors have delivered unprecedented survival for individuals with ",
			"category": 2,
			"name": "Alexander Marliese,2023"
		},
		{
			"PMID": 36982897,
			"title": "Molecular Anatomy of the EML4-ALK Fusion Protein for the Development of Novel Anticancer Drugs.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Cheon So Yeong",
				"Kwon Sunghark"
			],
			"DOI": "10.3390/ijms24065821",
			"date": "2023-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "The ",
			"category": 2,
			"name": "Cheon So Yeong,2023"
		},
		{
			"PMID": 36931677,
			"title": "Trends in antineoplastic drug use, cost and prescribing patterns among patients with lung cancer in nine major cities of China, 2016-2020: a retrospective observational study based on inpatient and outpatient hospital data.",
			"journal": "BMJ open",
			"authorList": [
				"Shang Jingyuan",
				"Zhou Lixin",
				"Huang Lin",
				"Yang Feng",
				"Liu Yanguo",
				"Zhang Chunyan",
				"Zu Li'an",
				"Fan Rongrong",
				"Zhang Xiaohong",
				"Liu Yi",
				"Feng Yufei"
			],
			"DOI": "10.1136/bmjopen-2022-069645",
			"date": "2023-03-21",
			"PMC": "",
			"citation": "",
			"abstract": "It is unclear whether the use of antineoplastic drugs for patients with lung cancer in China has changed after the implementation of the national drug price negotiation in 2016 and continual update of clinical guidelines. This study aims to evaluate the trends in antineoplastic drug use, cost and prescribing patterns among patients with lung cancer in major cities of China.",
			"category": 2,
			"name": "Shang Jingyuan,2023"
		},
		{
			"PMID": 36797503,
			"title": "ALK-positive lung cancer: a moving target.",
			"journal": "Nature cancer",
			"authorList": [
				"Schneider Jaime L",
				"Lin Jessica J",
				"Shaw Alice T"
			],
			"DOI": "10.1038/s43018-023-00515-0",
			"date": "2023-03-29",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) is a potent oncogenic driver in lung cancer. ALK tyrosine kinase inhibitors yield significant benefit in patients with ALK fusion-positive (ALK",
			"category": 2,
			"name": "Schneider Jaime L,2023"
		},
		{
			"PMID": 36702855,
			"title": "Adaptive resistance to lorlatinib via EGFR signaling in ALK-rearranged lung cancer.",
			"journal": "NPJ precision oncology",
			"authorList": [
				"Katayama Yuki",
				"Yamada Tadaaki",
				"Tanimura Keiko",
				"Tokuda Shinsaku",
				"Morimoto Kenji",
				"Hirai Soichi",
				"Matsui Yohei",
				"Nakamura Ryota",
				"Ishida Masaki",
				"Kawachi Hayato",
				"Yoneda Kazue",
				"Hosoya Kazutaka",
				"Tsuji Takahiro",
				"Ozasa Hiroaki",
				"Yoshimura Akihiro",
				"Iwasaku Masahiro",
				"Kim Young Hak",
				"Horinaka Mano",
				"Sakai Toshiyuki",
				"Utsumi Takahiro",
				"Shiotsu Shinsuke",
				"Takeda Takayuki",
				"Katayama Ryohei",
				"Takayama Koichi"
			],
			"DOI": "10.1038/s41698-023-00350-7",
			"date": "2023-02-02",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors rarely elicit complete responses in patients with advanced ALK-rearranged non-small cell lung cancer (NSCLC), as a small population of tumor cells survives due to adaptive resistance. Therefore, we focused on the mechanisms underlying adaptive resistance to lorlatinib and therapeutic strategies required to overcome them. We found that epidermal growth factor receptor (EGFR) signaling was involved in the adaptive resistance to lorlatinib in ALK-rearranged NSCLC, activation of which was induced by heparin-binding EGF-like growth factor production via c-Jun activation. EGFR inhibition halted ALK-rearranged lung cancer cell proliferation by enhancing ALK inhibition-induced apoptosis via suppression of Bcl-xL. Xenograft models showed that the combination of EGFR inhibitor and lorlatinib considerably suppressed tumor regrowth following cessation of these treatments. This study provides new insights regarding tumor evolution due to EGFR signaling after lorlatinib treatment and the development of combined therapeutic strategies for ALK-rearranged lung cancer.",
			"category": 2,
			"name": "Katayama Yuki,2023"
		},
		{
			"PMID": 36647478,
			"title": "Ensartinib in advanced ALK-positive non-small cell lung cancer: a multicenter, open-label, two-staged, phase 1 trial.",
			"journal": "Journal of thoracic disease",
			"authorList": [
				"Ma Yuxiang",
				"Pan Hui",
				"Liu Yu",
				"Zhang Yang",
				"Hong Shaodong",
				"Huang Jianjin",
				"Weng Shanshan",
				"Yang Yunpeng",
				"Fang Wenfeng",
				"Huang Yan",
				"Xiao Shanshan",
				"Wang Tao",
				"Ding Lieming",
				"Cui Lingling",
				"Zhang Li",
				"Zhao Hongyun"
			],
			"DOI": "10.21037/jtd-22-1606",
			"date": "2023-01-18",
			"PMC": "",
			"citation": "",
			"abstract": "Ensartinib, a potent second-generation tyrosine kinase inhibitor (TKI) that targets anaplastic lymphoma kinase (ALK), MET and ROS1, was evaluated in a phase I clinical trial in patients with advanced, ALK-rearranged non-small cell lung cancer (NSCLC).",
			"category": 2,
			"name": "Ma Yuxiang,2023"
		},
		{
			"PMID": 36508072,
			"title": "Molecular pathways, resistance mechanisms and targeted interventions in non-small-cell lung cancer.",
			"journal": "Molecular biomedicine",
			"authorList": [
				"Wang Zixi",
				"Xing Yurou",
				"Li Bingjie",
				"Li Xiaoyu",
				"Liu Bin",
				"Wang Yongsheng"
			],
			"DOI": "10.1186/s43556-022-00107-x",
			"date": "2022-12-22",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer is the leading cause of cancer-related mortality worldwide. The discovery of tyrosine kinase inhibitors effectively targeting EGFR mutations in lung cancer patients in 2004 represented the beginning of the precision medicine era for this refractory disease. This great progress benefits from the identification of driver gene mutations, and after that, conventional and new technologies such as NGS further illustrated part of the complex molecular pathways of NSCLC. More targetable driver gene mutation identification in NSCLC patients greatly promoted the development of targeted therapy and provided great help for patient outcomes including significantly improved survival time and quality of life. Herein, we review the literature and ongoing clinical trials of NSCLC targeted therapy to address the molecular pathways and targeted intervention progress in NSCLC. In addition, the mutations in EGFR gene, ALK rearrangements, and KRAS mutations in the main sections, and the less common molecular alterations in MET, HER2, BRAF, ROS1, RET, and NTRK are discussed. The main resistance mechanisms of each targeted oncogene are highlighted to demonstrate the current dilemma of targeted therapy in NSCLC. Moreover, we discuss potential\u00a0therapies to overcome the challenges of drug resistance. In this review, we manage to display the current landscape of targetable therapeutic patterns in NSCLC in this era of precision medicine.",
			"category": 2,
			"name": "Wang Zixi,2022"
		},
		{
			"PMID": 36506539,
			"title": "Primary resistance to first- and second-generation ALK inhibitors in a non-small cell lung cancer patient with coexisting ALK rearrangement and an ALK F1174L-cis-S1189C ",
			"journal": "Frontiers in pharmacology",
			"authorList": [
				"Zhao Jiuzhou",
				"Li Xiang",
				"Fan Ruizhe",
				"Qin Yaping",
				"Wang Zhizhong",
				"Wang Bo",
				"Li Shaomei",
				"Fan Jianfeng",
				"Wu Xinxin",
				"Liu Hongxia",
				"Guan Yuping",
				"Liang Yinfeng",
				"Zhang Xiao",
				"Guo Yongjun"
			],
			"DOI": "10.3389/fphar.2022.1060460",
			"date": "2022-12-22",
			"PMC": "",
			"citation": "",
			"abstract": "The effectiveness of the tyrosine kinase inhibitor ALK (TKI) for non-small cell lung cancer has been confirmed. However, resistance to ALK-TKIs seems inevitable. Mutations in the ALK kinase domain have been reported as an important mechanism of acquired resistance to ALK therapy. However, patients with ",
			"category": 2,
			"name": "Zhao Jiuzhou,2022"
		},
		{
			"PMID": 36439976,
			"title": "Pyrazole-containing pharmaceuticals: target, pharmacological activity, and their SAR studies.",
			"journal": "RSC medicinal chemistry",
			"authorList": [
				"Li Guangchen",
				"Cheng Yifu",
				"Han Chi",
				"Song Chun",
				"Huang Niu",
				"Du Yunfei"
			],
			"DOI": "10.1039/d2md00206j",
			"date": "2023-11-02",
			"PMC": "",
			"citation": "",
			"abstract": "Pyrazole is a five-membered heterocycle bearing two adjacent nitrogen atoms. Both pharmaceutical agents and natural products with pyrazole as a nucleus have exhibited a broad spectrum of biological activities. In the last few decades, more than 40 pyrazole-containing drugs have been approved by the FDA for the treatment of a broad range of clinical conditions including celecoxib (anti-inflammatory), CDPPB (antipsychotic), difenamizole (analgesic), ",
			"category": 2,
			"name": "Li Guangchen,2023"
		},
		{
			"PMID": 36358595,
			"title": "Molecular Targeting of the Most Functionally Complex Gene in Precision Oncology: p53.",
			"journal": "Cancers",
			"authorList": [
				"Brown Douglas W",
				"Beatty Perrin H",
				"Lewis John D"
			],
			"DOI": "10.3390/cancers14215176",
			"date": "2022-11-17",
			"PMC": "",
			"citation": "",
			"abstract": "While chemotherapy is a key treatment strategy for many solid tumors, it is rarely curative, and most tumor cells eventually become resistant. Because of this, there is an unmet need to develop systemic treatments that capitalize on the unique mutational landscape of each patient's tumor. The most frequently mutated protein in cancer, p53, has a role in nearly all cancer subtypes and tumorigenesis stages and therefore is one of the most promising molecular targets for cancer treatment. Unfortunately, drugs targeting p53 have seen little clinical success despite promising preclinical data. Most of these drug compounds target specific aspects of p53 inactivation, such as through inhibiting negative regulation by the mouse double minute (MDM) family of proteins. These treatment strategies fail to address cancer cells' adaptation mechanisms and ignore the impact that p53 loss has on the entire p53 network. However, recent gene therapy successes show that targeting the p53 network and cellular dysfunction caused by p53 inactivation is now possible and may soon translate into successful clinical responses. In this review, we discuss p53 signaling complexities in cancer that have hindered the development and use of p53-targeted drugs. We also describe several current therapeutics reporting promising preclinical and clinical results.",
			"category": 2,
			"name": "Brown Douglas W,2022"
		},
		{
			"PMID": 36303600,
			"title": "Non-small-cell lung cancer: how to manage ",
			"journal": "Drugs in context",
			"authorList": [
				"Marinelli Daniele",
				"Siringo Marco",
				"Metro Giulio",
				"Ricciuti Biagio",
				"Gelibter Alain J"
			],
			"DOI": "10.7573/dic.2022-3-1",
			"date": "2022-10-29",
			"PMC": "",
			"citation": "",
			"abstract": "Oncogene addiction in non-small-cell lung cancer (NSCLC) has profound diagnostic and therapeutic implications. ",
			"category": 2,
			"name": "Marinelli Daniele,2022"
		},
		{
			"PMID": 36291069,
			"title": "Biomarker-Targeted Therapies in Non-Small Cell Lung Cancer: Current Status and Perspectives.",
			"journal": "Cells",
			"authorList": [
				"Guo Haiyang",
				"Zhang Jun",
				"Qin Chao",
				"Yan Hang",
				"Liu Tao",
				"Hu Haiyang",
				"Tang Shengjie",
				"Tang Shoujun",
				"Zhou Haining"
			],
			"DOI": "10.3390/cells11203200",
			"date": "2022-10-28",
			"PMC": "",
			"citation": "",
			"abstract": "Non-small-cell lung cancer (NSCLC) is one of the most common malignancies and the leading causes of cancer-related death worldwide. Despite many therapeutic advances in the past decade, NSCLC remains an incurable disease for the majority of patients. Molecular targeted therapies and immunotherapies have significantly improved the prognosis of NSCLC. However, the vast majority of advanced NSCLC develop resistance to current therapies and eventually progress. In this review, we discuss current and potential therapies for NSCLC, focusing on targeted therapies and immunotherapies. We highlight the future role of metabolic therapies and combination therapies in NSCLC.",
			"category": 2,
			"name": "Guo Haiyang,2022"
		},
		{
			"PMID": 36209184,
			"title": "Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021.",
			"journal": "Journal of hematology & oncology",
			"authorList": [
				"Wu Qing",
				"Qian Wei",
				"Sun Xiaoli",
				"Jiang Shaojie"
			],
			"DOI": "10.1186/s13045-022-01362-9",
			"date": "2022-10-11",
			"PMC": "",
			"citation": "",
			"abstract": "The United States Food and Drug Administration (US FDA) has always been a forerunner in drug evaluation and supervision. Over the past 31\u00a0years, 1050 drugs (excluding vaccines, cell-based therapies, and gene therapy products) have been approved as new molecular entities (NMEs) or biologics license applications (BLAs). A total of 228 of these 1050 drugs were identified as cancer therapeutics or cancer-related drugs, and 120 of them were classified as therapeutic drugs for solid tumors according to their initial indications. These drugs have evolved from small molecules with broad-spectrum antitumor properties in the early stage to monoclonal antibodies (mAbs) and antibody\u2012drug conjugates (ADCs) with a more precise targeting effect during the most recent decade. These drugs have extended indications for other malignancies, constituting a cancer treatment system for monotherapy or combined therapy. However, the available targets are still mainly limited to receptor tyrosine kinases (RTKs), restricting the development of antitumor drugs. In this review, these 120 drugs are summarized and classified according to the initial indications, characteristics, or functions. Additionally, RTK-targeted therapies and immune checkpoint-based immunotherapies are also discussed. Our analysis of existing challenges and potential opportunities in drug development may advance solid tumor treatment in the future.",
			"category": 2,
			"name": "Wu Qing,2022"
		},
		{
			"PMID": 36203454,
			"title": "Case report: Durable response to alectinib in ",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Rao Chuangzhou",
				"Nie Liangqin",
				"Wu Xiaokang",
				"Miao Xiaobo",
				"Chen Ting",
				"Chen Liuxi",
				"Zhang Dongqing",
				"Lin Quan"
			],
			"DOI": "10.3389/fonc.2022.915502",
			"date": "2022-10-09",
			"PMC": "",
			"citation": "",
			"abstract": "Treatment of ",
			"category": 2,
			"name": "Rao Chuangzhou,2022"
		},
		{
			"PMID": 36201110,
			"title": "Prediction of Resistance Mutations Against Upcoming Anaplastic Lymphoma Kinase Inhibitors.",
			"journal": "Targeted oncology",
			"authorList": [
				"Doi Yuta",
				"Tagaya Hiroaki",
				"Noge Ayaka",
				"Semba Kentaro"
			],
			"DOI": "10.1007/s11523-022-00919-5",
			"date": "2022-11-25",
			"PMC": "",
			"citation": "",
			"abstract": "Chromosomal aberrations involving the anaplastic lymphoma kinase (ALK) gene have been observed in approximately 4% of patients with non-small cell lung cancer (NSCLC). Although these patients clinically benefit from treatment with various ALK tyrosine kinase inhibitors (ALK-TKIs), none of these can inhibit the development of resistance mutations. Considering inevitable drug resistance and the variety of available ALK-TKIs, it is necessary to predict the pattern of drug-resistance mutations to determine the optimal treatment strategy.",
			"category": 2,
			"name": "Doi Yuta,2022"
		},
		{
			"PMID": 36086904,
			"title": "Pan-HER inhibitors overcome lorlatinib resistance caused by NRG1/HER3 activation in ALK-rearranged lung cancer.",
			"journal": "Cancer science",
			"authorList": [
				"Taniguchi Hirokazu",
				"Akagi Kazumasa",
				"Dotsu Yosuke",
				"Yamada Tadaaki",
				"Ono Sawana",
				"Imamura Erika",
				"Gyotoku Hiroshi",
				"Takemoto Shinnosuke",
				"Yamaguchi Hiroyuki",
				"Sen Triparna",
				"Yano Seiji",
				"Mukae Hiroshi"
			],
			"DOI": "10.1111/cas.15579",
			"date": "2023-01-05",
			"PMC": "",
			"citation": "",
			"abstract": "Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor (TKI) with a broad coverage against ALK mutations, has demonstrated dramatic effects in patients with ALK-rearranged lung cancer. The mechanisms of acquired resistance to lorlatinib by secondary ALK compound mutations have recently been reported; however, resistance mechanisms other than secondary mutations remain unclear. Here, we investigated the molecular mechanisms of the acquired resistance in ALK-rearranged lung cancer cells in vitro. We established two different lorlatinib-resistant ALK-rearranged lung cancer cell lines (H3122LR and A925LLR) via long-term administration of lorlatinib. These resistant cells did not harbor the secondary ALK mutations and showed cross-resistance to the other kinds of ALK-TKIs (crizotinib or alectinib) compared with the parental cells; however, these resistant cells overexpressed the phosphorylated human epidermal growth factor receptor 3 (HER3) protein and the ligand of HER3 (neuregulin 1; NRG1). Pharmacological inhibition of HER3 with pan-HER inhibitors or genetic knockdown of HER3 with siRNA resensitized H3122LR and A925LLR cells to lorlatinib in vitro, indicating that H3122LR and A925LLR acquired resistance by NRG1/HER3 activation. These findings demonstrated that targeting NRG1/HER3 is a potential novel therapeutic option for lorlatinib-resistant ALK-rearranged lung cancer.",
			"category": 2,
			"name": "Taniguchi Hirokazu,2023"
		},
		{
			"PMID": 36051879,
			"title": "Allosteric regulation of autoinhibition and activation of c-Abl.",
			"journal": "Computational and structural biotechnology journal",
			"authorList": [
				"Liu Yonglan",
				"Zhang Mingzhen",
				"Tsai Chung-Jung",
				"Jang Hyunbum",
				"Nussinov Ruth"
			],
			"DOI": "10.1016/j.csbj.2022.08.014",
			"date": "2022-09-07",
			"PMC": "",
			"citation": "",
			"abstract": "c-Abl, a non-receptor tyrosine kinase, regulates cell growth and survival in healthy cells and causes chronic myeloid leukemia (CML) when fused by Bcr. Its activity is blocked in the assembled inactive state, where the SH3 and SH2 domains dock into the kinase domain, reducing its conformational flexibility, resulting in the autoinhibited state. It is active in an extended 'open' conformation. Allostery governs the transitions between the autoinhibited and active states. Even though experiments revealed the structural hallmarks of the two states, a detailed grasp of the determinants of c-Abl autoinhibition and activation at the atomic level, which may help innovative drug discovery, is still lacking. Here, using extensive molecular dynamics simulations, we decipher exactly how these determinants regulate it. Our simulations confirm and extend experimental data that the myristoyl group serves as the switch for c-Abl inhibition/activation. Its dissociation from the kinase domain promotes the SH2-SH3 release, initiating c-Abl activation. We show that the precise SH2/",
			"category": 2,
			"name": "Liu Yonglan,2022"
		},
		{
			"PMID": 36003760,
			"title": "The quantum leap in therapeutics for advanced ",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Itchins Malinda",
				"Pavlakis Nick"
			],
			"DOI": "10.3389/fonc.2022.959637",
			"date": "2022-08-26",
			"PMC": "",
			"citation": "",
			"abstract": "Since the discovery 15 years ago, we have seen a quantum leap in the treatment and survival for individuals diagnosed with ALK+ lung cancers. Unfortunately however, for most, the diagnosis is made in an incurable circumstance given the late presentation of symptoms. Through a revolutionary wave of therapeutics, individuals may remarkably live over a decade, however many fall short of this milestone, as the molecular profile of this disease is very heterogeneous, reflected in variable survival outcomes. Despite a significant improval in survival and quality of life with ALK-inhibitor monotherapies, now available across multiple-generations, drug resistance and disease relapse remains inevitable, and treatment is offered in an empiric, stepwise, non personalised biomarker informed fashion. A proposed future focus to treating ALK to improve the chronicity of this disease and even promote cure, is to deliver a personalised dynamic approach to care, with rational combinations of drugs in conjunction with local ablative therapies to prevent and constantly proactively alter clonal selection. Such an approach would be informed by precision imaging with MRI-brain and FDG-PETs sequentially, and by regular plasma sampling including for circulating tumour DNA sequencing with personalised therapeutic switches occurring prior to the emergence of radiological and clinical relapse. Such an approach to care will require a complete paradigm shift in the way we approach the treatment of advanced cancer, however evidence to date in ALK+ lung cancers, support this new frontier of investigation.",
			"category": 2,
			"name": "Itchins Malinda,2022"
		},
		{
			"PMID": 35950895,
			"title": "Fibroblast growth factor receptor 3 overexpression mediates ALK inhibitor resistance in ALK-rearranged non-small cell lung cancer.",
			"journal": "Cancer science",
			"authorList": [
				"Sakashita Takuya",
				"Yanagitani Noriko",
				"Koike Sumie",
				"Low Siew-Kee",
				"Takagi Satoshi",
				"Baba Satoko",
				"Takeuchi Kengo",
				"Nishio Makoto",
				"Fujita Naoya",
				"Katayama Ryohei"
			],
			"DOI": "10.1111/cas.15529",
			"date": "2022-11-08",
			"PMC": "",
			"citation": "",
			"abstract": "The rearrangement of anaplastic lymphoma kinase (ALK) occurs in 3%-5% of patients with non-small cell lung cancer (NSCLC) and confers sensitivity to ALK-tyrosine kinase inhibitors (TKIs). For the treatment of patients with ALK-rearranged NSCLC, various additional ALK-TKIs have been developed. Ceritinib is a second-generation ALK-TKI and has shown great efficacy in the treatment of patients with both newly diagnosed and crizotinib (a first-generation ALK-TKI)-refractory ALK-rearranged NSCLC. However, tumors can also develop ceritinib resistance. This may result from secondary ALK mutations, but other mechanisms responsible for this have not been fully elucidated. In this study, we explored the mechanisms of ceritinib resistance by establishing ceritinib-resistant, echinoderm microtubule-associated protein-like 4 (EML4)-ALK-positive H3122 cells and ceritinib-resistant patient-derived cells. We identified a mechanism of ceritinib resistance induced by bypass signals that is mediated by the overexpression and activation of fibroblast growth factor receptor 3 (FGFR3). FGFR3 knockdown by small hairpin RNA or treatment with FGFR inhibitors was found to resensitize the resistant cells to ceritinib in vitro and in vivo. FGFR ligands from either human serum or fetal bovine serum were able to activate FGFR3 and induce ceritinib resistance. A detailed analysis of ceritinib-resistant patient-derived specimens confirmed that tyrosine-protein kinase Met (cMET) amplification induces ceritinib resistance. Amplified cMET counteractivated EGFR and/or Her3 and induced ceritinib resistance. These results reveal multiple ceritinib resistance mechanisms and suggest that ceritinib resistance might be overcome by identifying precise resistance mechanisms.",
			"category": 2,
			"name": "Sakashita Takuya,2022"
		},
		{
			"PMID": 35941871,
			"title": "Case report: Two novel ",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Liao Shan",
				"Sun Huiying",
				"Wu Jianhua",
				"Lu Hao",
				"Fang Yisheng",
				"Wang Yuanyuan",
				"Liao Wangjun"
			],
			"DOI": "10.3389/fonc.2022.916315",
			"date": "2022-08-10",
			"PMC": "",
			"citation": "",
			"abstract": "The anaplastic lymphoma kinase (",
			"category": 2,
			"name": "Liao Shan,2022"
		},
		{
			"PMID": 35941190,
			"title": "Fragment size and dynamics of EGFR-mutated tumor-derived DNA provide prognostic information regarding EGFR-TKI efficacy in patients with EGFR-mutated NSCLC.",
			"journal": "Scientific reports",
			"authorList": [
				"Kunimasa Kei",
				"Nishino Kazumi",
				"Sato Yoshiharu",
				"Mori Masahide",
				"Ihara Shoichi",
				"Suzuki Hidekazu",
				"Nagatomo Izumi",
				"Kumagai Toru",
				"Morishima Toshitaka",
				"Imamura Fumio"
			],
			"DOI": "10.1038/s41598-022-17848-y",
			"date": "2022-08-10",
			"PMC": "",
			"citation": "",
			"abstract": "Circulating tumor DNA (ctDNA)-based next-generation sequencing (NGS) is a complementary and alternative test to tissue-based NGS. We performed NGS analysis of ctDNA samples collected from patients with EGFR-mutated non-small cell lung cancer (NSCLC) who received osimertinib; the samples were collected after second-line treatment, before osimertinib treatment, one week and one month after osimertinib treatment, and at the time of resistance formation. We examinedthe correlation with osimertinib efficacy. From January to December 2018, 34 patients with EGFR-mutated NSCLC harboring EGFR T790M mutations were enrolled, and a total of 132 peripheral blood samples were collected. The fragment sizes of EGFR-mutated ctDNAs were significantly shorter than that of their corresponding normal fragments. Osimertinib treatment of patients with shorter EGFR-mutated ctDNA fragments resulted in shorter progression-free survival (PFS). The disappearance time of EGFR-mutated fragment fractions and clonal evolution patterns (new driver mutation group, additional mutation group vs. attenuation group) were each associated with the PFS achieved with osimertinib treatment; however,multivariate analysis revealed that only shorter EGFR-mutated ctDNA fragments were associated with the PFS resulting from osimertinib treatment. EGFR-mutated ctDNA fragment size, time of disappearance of these fragments, and clonal evolution pattern were related to the effects of osimertinib. In particular, short EGFR-mutated ctDNA fragmentation may be closely related to osimertinib efficacy prediction.",
			"category": 2,
			"name": "Kunimasa Kei,2022"
		},
		{
			"PMID": 35898298,
			"title": "Racial and Ethnic Trends and Disparities in NSCLC.",
			"journal": "JTO clinical and research reports",
			"authorList": [
				"Primm Kristin M",
				"Zhao Hui",
				"Hernandez Daphne C",
				"Chang Shine"
			],
			"DOI": "10.1016/j.jtocrr.2022.100374",
			"date": "2022-07-29",
			"PMC": "",
			"citation": "",
			"abstract": "Detailed evaluations of racial and ethnic trends and disparities in NSCLC outcomes are lacking, and it remains unclear whether recent advances in screening and targeted therapies for NSCLC have benefited all population groups equally.",
			"category": 2,
			"name": "Primm Kristin M,2022"
		},
		{
			"PMID": 35892510,
			"title": "Applications of Liquid Biopsies in Non-Small-Cell Lung Cancer.",
			"journal": "Diagnostics (Basel, Switzerland)",
			"authorList": [
				"Pesta Martin",
				"Shetti Dattatrya",
				"Kulda Vlastimil",
				"Knizkova Tereza",
				"Houfkova Katerina",
				"Bagheri Mahyar Sharif",
				"Svaton Martin",
				"Polivka Jiri"
			],
			"DOI": "10.3390/diagnostics12081799",
			"date": "2022-07-31",
			"PMC": "",
			"citation": "",
			"abstract": "The concept of liquid biopsy as an analysis tool for non-solid tissue carried out for the purpose of providing information about solid tumors was introduced approximately 20 years ago. Additional to the detection of circulating tumor cells (CTCs), the liquid biopsy approach quickly included the analysis of circulating tumor DNA (ctDNA) and other tumor-derived markers such as circulating cell-free RNA or extracellular vesicles. Liquid biopsy is a non-invasive technique for detecting multiple cancer-associated biomarkers that is easy to obtain and can reflect the characteristics of the entire tumor mass. Currently, ctDNA is the key component of the liquid biopsy approach from the point of view of the prognosis assessment, prediction, and monitoring of the treatment of non-small-cell lung cancer (NSCLC) patients. ctDNA in NSCLC patients carries variants or rearrangements that drive carcinogenesis, such as those in ",
			"category": 2,
			"name": "Pesta Martin,2022"
		},
		{
			"PMID": 35726063,
			"title": "Analysis of lorlatinib analogs reveals a roadmap for targeting diverse compound resistance mutations in ALK-positive lung cancer.",
			"journal": "Nature cancer",
			"authorList": [
				"Shiba-Ishii Aya",
				"Johnson Ted W",
				"Dagogo-Jack Ibiayi",
				"Mino-Kenudson Mari",
				"Johnson Theodore R",
				"Wei Ping",
				"Weinrich Scott L",
				"McTigue Michele A",
				"Walcott Makeba A",
				"Nguyen-Phuong Linh",
				"Dionne Kristin",
				"Acker Adam",
				"Kiedrowski Lesli A",
				"Do Andrew",
				"Peterson Jennifer L",
				"Barth Jaimie L",
				"Yeap Beow Y",
				"Gainor Justin F",
				"Lin Jessica J",
				"Yoda Satoshi",
				"Hata Aaron N"
			],
			"DOI": "10.1038/s43018-022-00399-6",
			"date": "2022-06-29",
			"PMC": "",
			"citation": "",
			"abstract": "Lorlatinib is currently the most advanced, potent and selective anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor for the treatment of ALK-positive non-small cell lung cancer in the clinic; however, diverse compound ALK mutations driving therapy resistance emerge. Here, we determine the spectrum of lorlatinib-resistant compound ALK mutations in patients, following treatment with lorlatinib, the majority of which involve ALK G1202R or I1171N/S/T. We further identify structurally diverse lorlatinib analogs that harbor differential selective profiles against G1202R versus I1171N/S/T compound ALK mutations. Structural analysis revealed increased potency against compound mutations through improved inhibition of either G1202R or I1171N/S/T mutant kinases. Overall, we propose a classification of heterogenous ALK compound mutations enabling the development of distinct therapeutic strategies for precision targeting following sequential tyrosine kinase inhibitors.",
			"category": 2,
			"name": "Shiba-Ishii Aya,2022"
		},
		{
			"PMID": 35603167,
			"title": "Functionalized Lineage Tracing Can Enable the Development of Homogenization-Based Therapeutic Strategies in Cancer.",
			"journal": "Frontiers in immunology",
			"authorList": [
				"Gutierrez Catherine",
				"Vilas Caroline K",
				"Wu Catherine J",
				"Al'Khafaji Aziz M"
			],
			"DOI": "10.3389/fimmu.2022.859032",
			"date": "2022-05-24",
			"PMC": "",
			"citation": "",
			"abstract": "The therapeutic landscape across many cancers has dramatically improved since the introduction of potent targeted agents and immunotherapy. Nonetheless, success of these approaches is too often challenged by the emergence of therapeutic resistance, fueled by intratumoral heterogeneity and the immense evolutionary capacity inherent to cancers. To date, therapeutic strategies have attempted to outpace the evolutionary tempo of cancer but frequently fail, resulting in lack of tumor response and/or relapse. This realization motivates the development of novel therapeutic approaches which constrain evolutionary capacity by reducing the degree of intratumoral heterogeneity prior to treatment. Systematic development of such approaches first requires the ability to comprehensively characterize heterogeneous populations over the course of a perturbation, such as cancer treatment. Within this context, recent advances in functionalized lineage tracing approaches now afford the opportunity to efficiently measure multimodal features of clones within a tumor at single cell resolution, enabling the linkage of these features to clonal fitness over the course of tumor progression and treatment. Collectively, these measurements provide insights into the dynamic and heterogeneous nature of tumors and can thus guide the design of homogenization strategies which aim to funnel heterogeneous cancer cells into known, targetable phenotypic states. We anticipate the development of homogenization therapeutic strategies to better allow for cancer eradication and improved clinical outcomes.",
			"category": 2,
			"name": "Gutierrez Catherine,2022"
		},
		{
			"PMID": 35582571,
			"title": "Targeting MYCN and ALK in resistant and relapsing neuroblastoma.",
			"journal": "Cancer drug resistance (Alhambra, Calif.)",
			"authorList": [
				"Tucker Elizabeth R",
				"Poon Evon",
				"Chesler Louis"
			],
			"DOI": "10.20517/cdr.2019.009",
			"date": "2022-05-19",
			"PMC": "",
			"citation": "",
			"abstract": "Neuroblastoma, a tumor of peripheral nerve, is the most common solid tumor of young children. In high-risk disease, which comprises approximately half of patients, death from chemotherapy-resistant, metastatic relapse is very frequent. Children who relapse exhibit clonal enrichment of two genomic alterations: high-level amplification of the ",
			"category": 2,
			"name": "Tucker Elizabeth R,2022"
		},
		{
			"PMID": 35534623,
			"title": "Third-generation EGFR and ALK inhibitors: mechanisms of resistance and management.",
			"journal": "Nature reviews. Clinical oncology",
			"authorList": [
				"Cooper Alissa J",
				"Sequist Lecia V",
				"Lin Jessica J"
			],
			"DOI": "10.1038/s41571-022-00639-9",
			"date": "2022-07-25",
			"PMC": "",
			"citation": "",
			"abstract": "The discoveries of EGFR mutations and ALK rearrangements as actionable oncogenic drivers in non-small-cell lung cancer (NSCLC) has propelled a biomarker-directed treatment paradigm for patients with advanced-stage disease. Numerous EGFR and ALK tyrosine kinase inhibitors (TKIs) with demonstrated efficacy in patients with EGFR-mutant and ALK-rearranged NSCLCs have been developed, culminating in the availability of the highly effective third-generation TKIs osimertinib and lorlatinib, respectively. Despite their marked efficacy, resistance to these agents remains an unsolved fundamental challenge. Both 'on-target' mechanisms (largely mediated by acquired resistance mutations in the kinase domains of EGFR or ALK) and 'off-target' mechanisms of resistance (mediated by non-target kinase alterations such as bypass signalling activation or phenotypic transformation) have been identified in patients with disease progression on osimertinib or lorlatinib. A growing understanding of the biology and spectrum of these mechanisms of resistance has already begun to inform the development of more effective therapeutic strategies. In this Review, we discuss the development of third-generation EGFR and ALK inhibitors, predominant mechanisms of resistance, and approaches to tackling resistance in the clinic, ranging from novel fourth-generation TKIs to combination regimens and other investigational therapies.",
			"category": 2,
			"name": "Cooper Alissa J,2022"
		},
		{
			"PMID": 35527776,
			"title": "Role of ",
			"journal": "Oncology letters",
			"authorList": [
				"Zhou Wen",
				"Yan Lu-Da",
				"Yu Zhi-Qiong",
				"Li Na",
				"Yang Yong-Hua",
				"Wang Meng",
				"Chen Yuan-Yuan",
				"Mao Meng-Xia",
				"Peng Xiao-Chun",
				"Cai Jun"
			],
			"DOI": "10.3892/ol.2022.13301",
			"date": "2022-05-10",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase ",
			"category": 2,
			"name": "Zhou Wen,2022"
		},
		{
			"PMID": 35463328,
			"title": "Targeting ALK Rearrangements in NSCLC: Current State of the Art.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Peng Ling",
				"Zhu Liping",
				"Sun Yilan",
				"Stebbing Justin",
				"Selvaggi Giovanni",
				"Zhang Yongchang",
				"Yu Zhentao"
			],
			"DOI": "10.3389/fonc.2022.863461",
			"date": "2022-07-16",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) alterations in non-small cell lung cancer (NSCLC) can be effectively treated with a variety of ALK-targeted drugs. After the approval of the first-generation ALK inhibitor crizotinib which achieved better results in prolonging the progression-free survival (PFS) compared with chemotherapy, a number of next-generation ALK inhibitors have been developed including ceritinib, alectinib, brigatinib, and ensartinib. Recently, a potent, third-generation ALK inhibitor, lorlatinib, has been approved by the Food and Drug Administration (FDA) for the first-line treatment of ALK-positive (ALK+) NSCLC. These drugs have manageable toxicity profiles. Responses to ALK inhibitors are however often not durable, and acquired resistance can occur as on-target or off-target alterations. Studies are underway to explore the mechanisms of resistance and optimal treatment options beyond progression. Efforts have also been undertaken to develop further generations of ALK inhibitors. This review will summarize the current situation of targeting the ALK signaling pathway.",
			"category": 2,
			"name": "Peng Ling,2022"
		},
		{
			"PMID": 35459209,
			"title": "Protective autophagy decreases lorlatinib cytotoxicity through Foxo3a-dependent inhibition of apoptosis in NSCLC.",
			"journal": "Cell death discovery",
			"authorList": [
				"Lu Conghua",
				"Yu Rui",
				"Zhang Chong",
				"Lin Caiyu",
				"Dou Yuanyao",
				"Wu Di",
				"Pan Yonghong",
				"Peng Tao",
				"Tang Huan",
				"Han Rui",
				"He Yong"
			],
			"DOI": "10.1038/s41420-022-01027-z",
			"date": "2022-07-16",
			"PMC": "",
			"citation": "",
			"abstract": "Lorlatinib is a promising third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) that has been approved for treating ALK-positive non-small-cell lung cancer (NSCLC) patients with previous ALK-TKI treatment failures. However, the inevitable emergence of acquired resistance limits its long-term efficacy. A more comprehensive understanding of the acquired resistance mechanisms to lorlatinib will enable the development of more efficacious therapeutic strategies. The efficacy of chloroquine (CQ) in combination with lorlatinib in ALK-positive NSCLC cells in vitro and in vivo was assessed using CCK-8, colony formation, immunofluorescence staining, flow cytometry analysis, western blot analysis, and xenograft implantation. Here, we show that lorlatinib induced apoptosis and protective autophagy in ALK-positive NSCLC cells. However, the protective autophagy can gradually lead to decreased cytotoxicity of loratinib in ALK-positive NSCLC cells. Meanwhile, we found that the combination of lorlatinib and CQ, an inhibitor of autophagy, inhibited autophagy and promoted apoptosis both in vitro and in vivo, which sensitized cells to lorlatinib through the dephosphorylation of Foxo3a and promoted nuclear translocation, then activation of Foxo3a/Bim axis. Taken together, our results suggest that inhibition of protective autophagy might be a therapeutic target for delaying the occurrence of acquired resistance to lorlatinib in ALK-positive NSCLC patients.",
			"category": 2,
			"name": "Lu Conghua,2022"
		},
		{
			"PMID": 35328235,
			"title": "Multiple Genetic Alterations as Resistance Mechanism during Second-Line Lorlatinib for Advanced ALK-Rearranged Lung Adenocarcinoma: A Case Report.",
			"journal": "Diagnostics (Basel, Switzerland)",
			"authorList": [
				"Catino Annamaria",
				"Lacalamita Rosanna",
				"De Summa Simona",
				"Pesola Francesco",
				"Tommasi Stefania",
				"Galetta Domenico"
			],
			"DOI": "10.3390/diagnostics12030682",
			"date": "2022-03-28",
			"PMC": "",
			"citation": "",
			"abstract": "Second and third-generation ALK-TKI inhibitors have showed better activity and have replaced crizotinib in most of cases of advanced ALK-rearranged lung adenocarcinoma. The emergence of resistance adversely affects also the activity of these newer drugs; in particular, lorlatinib often shows multiple and complex resistance mechanisms. The case reported here highlights the importance of reassessing the biomolecular profile during the disease course, both by tissutal and liquid biopsy, with the aim of improving the knowledge of these resistance mechanisms, and so identifying new drugs or sequences able to optimize the management of these patients.",
			"category": 2,
			"name": "Catino Annamaria,2022"
		},
		{
			"PMID": 35301419,
			"title": "GSK3 inhibition circumvents and overcomes acquired lorlatinib resistance in ALK-rearranged non-small-cell lung cancer.",
			"journal": "NPJ precision oncology",
			"authorList": [
				"Shimizu Yuki",
				"Okada Koutaroh",
				"Adachi Jun",
				"Abe Yuichi",
				"Narumi Ryohei",
				"Uchibori Ken",
				"Yanagitani Noriko",
				"Koike Sumie",
				"Takagi Satoshi",
				"Nishio Makoto",
				"Fujita Naoya",
				"Katayama Ryohei"
			],
			"DOI": "10.1038/s41698-022-00260-0",
			"date": "2022-11-12",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) fusion is found in ~3%-5% of patients with non-small-cell lung cancers (NSCLCs). Although the third-generation ALK tyrosine kinase inhibitor (TKI) lorlatinib shows high clinical efficacy in ALK-positive NSCLC, most of the patients eventually relapse with acquired resistance. Recently, drug-tolerant persister (DTP) cells have been considered an important seed of acquired resistance cells. In this study, we established lorlatinib intermediate resistant cells from a patient-derived cell model. Glycogen synthase kinase 3 (GSK3) inhibitions significantly suppressed lorlatinib intermediate resistant cell growth. GSK3 inhibition also sensitized acquired resistance cells derived from alectinib-treated patients with or without secondary mutations to lorlatinib. Therefore, GSK3 plays a crucial role in developing acquired resistance against lorlatinib in ALK-positive NSCLC mediated by lorlatinib intermediate resistant cells and could be a potential molecular target to prevent acquired lorlatinib resistance and overcome ALK-TKI resistance.",
			"category": 2,
			"name": "Shimizu Yuki,2022"
		},
		{
			"PMID": 35250311,
			"title": "Update on Lorlatinib: Role in Reducing the Risk of Disease Progression in ALK-Positive NSCLC.",
			"journal": "Cancer management and research",
			"authorList": [
				"Yun Karen M",
				"Bazhenova Lyudmila A"
			],
			"DOI": "10.2147/CMAR.S283199",
			"date": "2022-03-08",
			"PMC": "",
			"citation": "",
			"abstract": "Lorlatinib is an oral third-generation inhibitor of anaplastic lymphoma kinase (ALK) with activity in advanced ALK-positive non-small cell lung cancer (NSCLC) in both the first and subsequent line setting. Superior systemic and intracranial efficacy of lorlatinib over crizotinib, a first-generation ALK tyrosine kinase inhibitor (TKI), in treatment-na\u00efve patients with advanced ALK-positive NSCLC was demonstrated by the phase 3 CROWN trial. Lorlatinib retains anti-tumor effect against single and some compound ALK resistance mutations after disease progression on first- and second-generation ALK TKIs. Currently, alectinib, brigatinib, ceritinib, crizotinib and lorlatinib are approved for treatment of advanced ALK-positive NSCLC. However, no head-to-head studies have directly compared lorlatinib to second-generation ALK inhibitors. Herein, we aim to provide an overview of the efficacy and safety of lorlatinib and discuss where lorlatinib stands in the therapeutic approach to advanced ALK-positive NSCLC.",
			"category": 2,
			"name": "Yun Karen M,2022"
		},
		{
			"PMID": 35236940,
			"title": "Cancer proteogenomics: current impact and future prospects.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Mani D R",
				"Krug Karsten",
				"Zhang Bing",
				"Satpathy Shankha",
				"Clauser Karl R",
				"Ding Li",
				"Ellis Matthew",
				"Gillette Michael A",
				"Carr Steven A"
			],
			"DOI": "10.1038/s41568-022-00446-5",
			"date": "2022-05-02",
			"PMC": "",
			"citation": "",
			"abstract": "Genomic analyses in cancer have been enormously impactful, leading to the identification of driver mutations and development of targeted therapies. But the functions of the vast majority of somatic mutations and copy number variants in tumours remain unknown, and the causes of resistance to targeted therapies and methods to overcome them are poorly defined. Recent improvements in mass spectrometry-based proteomics now enable direct examination of the consequences of genomic aberrations, providing deep and quantitative characterization of tumour tissues. Integration of proteins and their post-translational modifications with genomic, epigenomic and transcriptomic data constitutes the new field of proteogenomics, and is already leading to new biological and diagnostic knowledge with the potential to improve our understanding of malignant transformation and therapeutic outcomes. In this Review we describe recent developments in proteogenomics and key findings from the proteogenomic analysis of a wide range of cancers. Considerations relevant to the selection and use of samples for proteogenomics and the current technologies used to generate, analyse and integrate proteomic with genomic data are described. Applications of proteogenomics in translational studies and immuno-oncology are rapidly emerging, and the prospect for their full integration into therapeutic trials and clinical care seems bright.",
			"category": 2,
			"name": "Mani D R,2022"
		},
		{
			"PMID": 35230691,
			"title": "Patient-Derived In Vitro and In Vivo Models of Cancer.",
			"journal": "Advances in experimental medicine and biology",
			"authorList": [
				"Claridge Sally E",
				"Cavallo Julie-Ann",
				"Hopkins Benjamin D"
			],
			"DOI": "10.1007/978-3-030-91836-1_12",
			"date": "2022-03-03",
			"PMC": "",
			"citation": "",
			"abstract": "Over the last two decades, cancer researchers have taken the promise offered by the Human Genome Project and have expanded its capacity to use sequencing to identify the genomic alterations that give rise to and sustain individual tumors. This expansion has allowed researchers to identify and target highly recurrent alterations in specific cancer contexts, such as EGFR mutations in non-small cell lung cancer (Lynch et al, N Engl J Med 350:2129-2139, 2004; Sharifnia et al., Proc Natl Acad Sci U S A 111:18661-18666, 2014), BCR-ABL translocations in chronic myeloid leukemia (Deininger, Pharmacol Rev 55:401-423. https://doi.org/10.1124/pr.55.3.4 , 2003; Druker et al, N Engl J Med 344. 1038-1042, 2001; Druker et al, N Engl J Med 344:1031-1037. https://doi.org/10.1056/NEJM200104053441401 , 2001), or HER2 amplifications in breast cancer (Slamon et al, N Engl J Med 344:783-792. https://doi.org/10.1056/NEJM200103153441101 , 2001; Solca et al, Beyond trastuzumab: second-generation targeted therapies for HER-2-positive breast cancer. In: Sibilia M, Zielinski CC, Bartsch R, Grunt TW (eds) Drugs for HER-2-positive breast cancer. Springer, Basel, pp 91-107, 2011). Despite these advances in our capacity to identify the genetic alterations that drive tumor initiation, survival, and proliferation, our ability to target these alterations to provide effective treatment options for patients in need, particularly those with rare or advanced cancers, remains limited (Gould et al, Nat Med 21:431-439. https://doi.org/10.1038/nm.3853 , 2015). Patient-derived models of cancer offer one potential mechanism to overcome this barrier between the bench and bedside. Through the development and testing of patient-derived models of cancer, functional genomics efforts can identify tumor-specific drug sensitivities and thereby provide a connection between tumor genetics and effective therapeutics for patients in need of treatment options.Recognizing that cancer is a multifaceted set of disease states, the development of personalized models of cancer that can be used to compare treatment options, identify tumor-specific vulnerabilities, and guide clinical decision-making has tremendous potential for improving patient outcomes. This chapter will describe a representative set of patient-derived models of cancer, reviewing each of their strengths and weaknesses and highlighting how selecting a model to suit a specific question or context is critical. Each model comes with a unique set of pros and cons, making them more or less appropriate for each specific research or clinical question. As each model can be leveraged to gain new insights into cancer biology, the key to their deployment is to identify the most appropriate model for a specific context, while carefully considering the strengths and limitations of the selected model. When used appropriately, patient-derived models may prove to be the missing link needed to bring the promise of personalized oncology to fruition in the clinic.",
			"category": 2,
			"name": "Claridge Sally E,2022"
		},
		{
			"PMID": 35211406,
			"title": "Holistic View of ALK TKI Resistance in ALK-Positive Anaplastic Large Cell Lymphoma.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Wang Yuan",
				"He Jing",
				"Xu Manyu",
				"Xue Qingfeng",
				"Zhu Cindy",
				"Liu Juan",
				"Zhang Yaping",
				"Shi Wenyu"
			],
			"DOI": "10.3389/fonc.2022.815654",
			"date": "2022-02-26",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase expressed at early stages of normal development and in various cancers including ALK-positive anaplastic large cell lymphoma (ALK+ ALCL), in which it is the main therapeutic target. ALK tyrosine kinase inhibitors (ALK TKIs) have greatly improved the prognosis of ALK+ALCL patients, but the emergence of drug resistance is inevitable and limits the applicability of these drugs. Although various mechanisms of resistance have been elucidated, the problem persists and there have been relatively few relevant clinical studies. This review describes research progress on ALK+ ALCL including the application and development of new therapies, especially in relation to drug resistance. We also propose potential treatment strategies based on current knowledge to inform the design of future clinical trials.",
			"category": 2,
			"name": "Wang Yuan,2022"
		},
		{
			"PMID": 35117060,
			"title": "Prospective analysis of liquid biopsies of advanced non-small cell lung cancer patients after progression to targeted therapies using GeneReader NGS platform.",
			"journal": "Translational cancer research",
			"authorList": [
				"Mayo de Las Casas Clara",
				"Garz\u00f3n-Iba\u00f1ez M\u00f3nica",
				"Jordana-Ariza N\u00faria",
				"Viteri-Ram\u00edrez Santiago",
				"Moya-Horno Irene",
				"Karachaliou Niki",
				"Yeste Zaira",
				"Campos Raquel",
				"Villatoro Sergi",
				"Balada-Bel Ariadna",
				"Garc\u00eda-Pel\u00e1ez Beatriz",
				"Reguart Noem\u00ed",
				"Teixid\u00f3 Cristina",
				"Jant\u00fas Eloisa",
				"Calabuig Silvia",
				"Aguado Cristina",
				"Gim\u00e9nez-Capit\u00e1n Ana",
				"Rom\u00e1n-Llad\u00f3 Ruth",
				"P\u00e9rez-Rosado Ana",
				"Catal\u00e1n Maria Jos\u00e9",
				"Bertr\u00e1n-Alamillo Jordi",
				"Garc\u00eda-Rom\u00e1n Silvia",
				"Rodriguez Sonia",
				"Alonso Lidia",
				"Aldeguer Erika",
				"Mart\u00ednez-Bueno Alejandro",
				"Gonz\u00e1lez-Cao Maria",
				"Aguilar Hernandez Andr\u00e9s",
				"Garcia-Mosquera Juan",
				"de Los Llanos Gil Maria",
				"Fernandez Manuel",
				"Rosell Rafael",
				"Molina-Vila Miguel \u00c1ngel"
			],
			"DOI": "10.21037/tcr.2018.10.12",
			"date": "2022-05-01",
			"PMC": "",
			"citation": "",
			"abstract": "In a significant percentage of advanced non-small cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses at time to progression. We prospectively analyzed the appearance of genetic alterations associated with resistance in liquid biopsies of advanced NSCLC patients progressing to targeted therapies using the NGS platform.",
			"category": 2,
			"name": "Mayo de Las Casas Clara,2022"
		},
		{
			"PMID": 34997674,
			"title": "Utility of the Ba/F3 cell system for exploring on-target mechanisms of resistance to targeted therapies for lung cancer.",
			"journal": "Cancer science",
			"authorList": [
				"Koga Takamasa",
				"Suda Kenichi",
				"Mitsudomi Tetsuya"
			],
			"DOI": "10.1111/cas.15263",
			"date": "2022-03-10",
			"PMC": "",
			"citation": "",
			"abstract": "Molecular targeted therapies are the standard of care for front-line treatment of metastatic non-small-cell lung cancers (NSCLCs) harboring driver gene mutations. However, despite the initial dramatic responses, the emergence of acquired resistance is inevitable. Acquisition of secondary mutations in the target gene (on-target resistance) is one of the major mechanisms of resistance. The mouse pro-B cell line Ba/F3 is dependent on interleukin-3 for survival and proliferation. Upon transduction of a driver gene, Ba/F3 cells become independent of interleukin-3 but dependent on the transduced driver gene. Therefore, the Ba/F3 cell line has been a popular system to generate models with oncogene dependence and vulnerability to specific targeted therapies. These models have been used to estimate oncogenicity of driver mutations or efficacies of molecularly targeted drugs. In addition, Ba/F3 models, together with N-ethyl-N-nitrosourea mutagenesis, have been used to derive acquired resistant cells to investigate on-target resistance mechanisms. Here, we reviewed studies that used Ba/F3 models with EGFR mutations, ALK/ROS1/NTRK/RET fusions, MET exon 14 skipping mutations, or KRAS G12C mutations to investigate secondary/tertiary drug resistant mutations. We determined that 68% of resistance mutations reproducibly detected in clinical cases were also found in Ba/F3 models. In addition, sensitivity data generated with Ba/F3 models correlated well with clinical responses to each drug. Ba/F3 models are useful to comprehensively identify potential mutations that induce resistance to molecularly targeted drugs and to explore drugs to overcome the resistance.",
			"category": 2,
			"name": "Koga Takamasa,2022"
		},
		{
			"PMID": 34977873,
			"title": "Therapeutic advances in non-small cell lung cancer: Focus on clinical development of targeted therapy and immunotherapy.",
			"journal": "MedComm",
			"authorList": [
				"Cheng Yuan",
				"Zhang Tao",
				"Xu Qing"
			],
			"DOI": "10.1002/mco2.105",
			"date": "2023-11-08",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer still contributes to nearly one-quarter cancer-related deaths in the past decades, despite the rapid development of targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC). The development and availability of comprehensive genomic profiling make the classification of NSCLC more precise and personalized. Most treatment decisions of advanced-stage NSCLC have been made based on the genetic features and PD-L1 expression of patients. For the past 2 years, more than 10 therapeutic strategies have been approved as first-line treatment for certain subgroups of NSCLC. However, some major challenges remain, including drug resistance and low rate of overall survival. Therefore, we discuss and review the therapeutic strategies of NSCLC, and focus on the development of targeted therapy and immunotherapy in advanced-stage NSCLC. Based on the latest guidelines, we provide an updated summary on the standard treatment for NSCLC. At last, we discussed several potential therapies for NSCLC. The development of new drugs and combination therapies both provide promising therapeutic effects on NSCLC.",
			"category": 2,
			"name": "Cheng Yuan,2023"
		},
		{
			"PMID": 34919136,
			"title": "Association of Stage Shift and Population Mortality Among Patients With Non-Small Cell Lung Cancer.",
			"journal": "JAMA network open",
			"authorList": [
				"Flores Raja",
				"Patel Parth",
				"Alpert Naomi",
				"Pyenson Bruce",
				"Taioli Emanuela"
			],
			"DOI": "10.1001/jamanetworkopen.2021.37508",
			"date": "2022-01-13",
			"PMC": "",
			"citation": "",
			"abstract": "Early detection by computed tomography and a more attention-oriented approach to incidentally identified pulmonary nodules in the last decade has led to population stage shift for non-small cell lung cancer (NSCLC). This stage shift could substantially confound the evaluation of newer therapeutics and mortality outcomes.",
			"category": 2,
			"name": "Flores Raja,2022"
		},
		{
			"PMID": 34824841,
			"title": "Liquid biopsy: Novel perspectives on the importance and spectrum of ",
			"journal": "Molecular and clinical oncology",
			"authorList": [
				"Sahin Ibrahim",
				"Saat Hanife",
				"Aksoy Sercan",
				"Dizdar Omer",
				"Erdem Haktan Bagis",
				"Bahsi Taha"
			],
			"DOI": "10.3892/mco.2021.2434",
			"date": "2021-11-27",
			"PMC": "",
			"citation": "",
			"abstract": "Many people die from lung and breast cancer. Consequently, both physicians and researchers strive to provide reliable monitoring for disease, diagnosis and prognosis as well as resistance prediction. In the present study, a comprehensive liquid biopsy panel was performed on 474 patients to examine the importance and spectrum of recurrent somatic cancer mutations. Most patients visited the clinic with a diagnosis of advanced resistant cancer. The patients underwent a comprehensive liquid biopsy panel. Patients were divided into four groups based on cancer type as follows: Lung (n=379, 79.9%), breast (n=72, 15.2%), gastrointestinal (n=11, 2.3%) and other (n=12, 2.5%). Tier I-II-III classified variants were included in the study. The mean age was 60 years, with a range of 20-86 years. There were notably more male (n=272, 57.4%) than female patients (n=202, 42.6%). The most commonly mutated genes were ",
			"category": 2,
			"name": "Sahin Ibrahim,2021"
		},
		{
			"PMID": 34766150,
			"title": "Two novel strategies to overcome the resistance to ALK tyrosine kinase inhibitor drugs: Macrocyclic inhibitors and proteolysis-targeting chimeras.",
			"journal": "MedComm",
			"authorList": [
				"Song Xiaoling",
				"Zhong Hui",
				"Qu Xiaojuan",
				"Yang Linsong",
				"Jiang Biao"
			],
			"DOI": "10.1002/mco2.42",
			"date": "2021-12-04",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer is the most malignant tumor in the worldwide. About 3%-5% non-small cell lung cancer (NSCLC) patients carry anaplastic lymphoma kinase (ALK) gene fusions and receive great benefits from ALK-targeted therapy. However, drug resistance inevitably occurs even with the most potent inhibitor drug lorlatinib. About half of the resistance are caused by alteration in ALK proteins for earlier ALK TKI drugs and near one-third of loratinib resistant cases are caused by compound mutations without current effective treatment strategy in clinic. Novel strategies are in great need to overcome drug resistance. Lately, two novel strategies have been developed and attracted great attentions for their potentials to overcome drug resistance problems: (1) developed small compact macrocyclic ALK kinase inhibitors and (2) developed ALK targeted proteolysis-targeting chimera (PROTAC) drugs. The macrocyclic molecules are small and compact in size, brain barrier permeable, and highly potent against lorlatinib-resistant compound mutations. Developed ALK targeted PROTAC molecules could degrade oncogenic ALK driver proteins. Some showed superiority in killing ALK positive cancer cells and inhibiting the growth of cells expressing G1202R resistant ALK proteins comparing to inhibitor drugs. The update on these two treatment strategies was reviewed.",
			"category": 2,
			"name": "Song Xiaoling,2021"
		},
		{
			"PMID": 34660278,
			"title": "The Resistance Mechanisms and Treatment Strategies for ALK-Rearranged Non-Small Cell Lung Cancer.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Pan Yue",
				"Deng Chao",
				"Qiu Zhenhua",
				"Cao Chenghui",
				"Wu Fang"
			],
			"DOI": "10.3389/fonc.2021.713530",
			"date": "2021-10-22",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) is a validated molecular target for non-small-cell lung cancer (NSCLC). The use of tyrosine kinase inhibitors (TKIs) has led to significantly improved survival benefits. However, the clinical benefits of targeting ALK using TKIs are limited due to the emergence of drug resistance. The landscape of resistance mechanisms and treatment decisions has become increasingly complex. Therefore, continued research into new drugs and combinatorial therapies is required to improve outcomes in NSCLC. In this review, we explore the resistance mechanisms of ALK TKIs in advanced NSCLC in order to provide a theoretical basis and research ideas for solving the problem of ALK drug resistance.",
			"category": 2,
			"name": "Pan Yue,2021"
		},
		{
			"PMID": 34589977,
			"title": "A Novel Sequentially Evolved ",
			"journal": "JTO clinical and research reports",
			"authorList": [
				"Zhu Viola W",
				"Nagasaka Misako",
				"Madison Russell",
				"Schrock Alexa B",
				"Cui Jean",
				"Ou Sai-Hong Ignatius"
			],
			"DOI": "10.1016/j.jtocrr.2020.100116",
			"date": "2021-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "Lorlatinib is a third-generation ALK inhibitor that can overcome the largest number of acquired ",
			"category": 2,
			"name": "Zhu Viola W,2021"
		},
		{
			"PMID": 34572931,
			"title": "Current Landscape of Non-Small Cell Lung Cancer: Epidemiology, Histological Classification, Targeted Therapies, and Immunotherapy.",
			"journal": "Cancers",
			"authorList": [
				"Rodak Olga",
				"Peris-D\u00edaz Manuel David",
				"Olbromski Mateusz",
				"Podhorska-Oko\u0142\u00f3w Marzenna",
				"Dzi\u0119giel Piotr"
			],
			"DOI": "10.3390/cancers13184705",
			"date": "2023-09-21",
			"PMC": "",
			"citation": "",
			"abstract": "Non-small cell lung cancer (NSCLC) is a subtype of the most frequently diagnosed cancer in the world. Its epidemiology depends not only on tobacco exposition but also air quality. While the global trends in NSCLC incidence have started to decline, we can observe region-dependent differences related to the education and the economic level of the patients. Due to an increasing understanding of NSCLC biology, new diagnostic and therapeutic strategies have been developed, such as the reorganization of histopathological classification or tumor genotyping. Precision medicine is focused on the recognition of a genetic mutation in lung cancer cells called \"driver mutation\" to provide a variety of specific inhibitors of improperly functioning proteins. A rapidly growing group of approved drugs for targeted therapy in NSCLC currently allows the following mutated proteins to be treated: EGFR family (ERBB-1, ERBB-2), ALK, ROS1, MET, RET, NTRK, and RAF. Nevertheless, one of the most frequent NSCLC molecular sub-types remains without successful treatment: the K-Ras protein. In this review, we discuss the current NSCLC landscape treatment focusing on targeted therapy and immunotherapy, including first- and second-line monotherapies, immune checkpoint inhibitors with chemotherapy treatment, and approved predictive biomarkers.",
			"category": 2,
			"name": "Rodak Olga,2023"
		},
		{
			"PMID": 34531319,
			"title": "Epigenetic Alterations and Mechanisms That Drive Resistance to Targeted Cancer Therapies.",
			"journal": "Cancer research",
			"authorList": [
				"Wajapeyee Narendra",
				"Gupta Romi"
			],
			"DOI": "10.1158/0008-5472.CAN-21-1606",
			"date": "2022-01-10",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a complex disease and cancer cells typically harbor multiple genetic and epigenetic alterations. Large-scale sequencing of patient-derived cancer samples has identified several druggable driver oncogenes. Many of these oncogenes can be pharmacologically targeted to provide effective therapies for breast cancer, leukemia, lung cancer, melanoma, lymphoma, and other cancer types. Initial responses to these agents can be robust in many cancer types and some patients with cancer experience sustained tumor inhibition. However, resistance to these targeted therapeutics frequently emerges, either from intrinsic or acquired mechanisms, posing a major clinical hurdle for effective treatment. Several resistance mechanisms, both cell autonomous and cell nonautonomous, have been identified in different cancer types. Here we describe how alterations of the transcriptome, transcription factors, DNA, and chromatin regulatory proteins confer resistance to targeted therapeutic agents. We also elaborate on how these studies have identified underlying epigenetic factors that drive drug resistance and oncogenic pathways, with direct implications for the prevention and treatment of drug-resistant cancer.",
			"category": 2,
			"name": "Wajapeyee Narendra,2022"
		},
		{
			"PMID": 34378333,
			"title": "Treatment of advanced lung cancer based on genomic profiling using liquid biopsy (plasma): A review of three cases.",
			"journal": "Thoracic cancer",
			"authorList": [
				"Mitsumura Takahiro",
				"Kumaki Yuichi",
				"Takahashi Kenta",
				"Matsudera Shotaro",
				"Sakakibara Rie",
				"Honda Takayuki",
				"Ishizuka Masahiro",
				"Iijima Yuki",
				"Shirai Tsuyoshi",
				"Okamoto Tsukasa",
				"Tateishi Tomoya",
				"Sakashita Hiroyuki",
				"Miyake Satoshi",
				"Ikeda Sadakatsu",
				"Miyazaki Yasunari"
			],
			"DOI": "10.1111/1759-7714.14098",
			"date": "2022-01-28",
			"PMC": "",
			"citation": "",
			"abstract": "Of the 80 solid tumor cases in which liquid biopsy (LB) was performed using Guardant360 in the PROFILE study, nine were lung cancer cases. Here, we review three cases in which LB was useful in diagnosing ALK fusion-positive lung cancer, selecting sequential ALK-tyrosine kinase inhibitors, confirming uncommon EGFR mutations, and receiving biomarker-compatible therapy.",
			"category": 2,
			"name": "Mitsumura Takahiro,2022"
		},
		{
			"PMID": 34210658,
			"title": "Exceptional response to the ALK and ROS1 inhibitor lorlatinib and subsequent mechanism of resistance in relapsed ",
			"journal": "Cold Spring Harbor molecular case studies",
			"authorList": [
				"Liu Tingting",
				"Merguerian Matthew D",
				"Rowe Steven P",
				"Pratilas Christine A",
				"Chen Allen R",
				"Ladle Brian H"
			],
			"DOI": "10.1101/mcs.a006064",
			"date": "2022-01-04",
			"PMC": "",
			"citation": "",
			"abstract": "Treatment of high-risk neuroblastoma typically incorporates multiagent chemotherapy, surgery, radiation therapy, autologous stem cell transplantation, immunotherapy, and differentiation therapy. The discovery of activating mutations in ALK receptor tyrosine kinase (",
			"category": 2,
			"name": "Liu Tingting,2022"
		},
		{
			"PMID": 34198738,
			"title": "Precision Medicine in Oncology: A Review of Multi-Tumor Actionable Molecular Targets with an Emphasis on Non-Small Cell Lung Cancer.",
			"journal": "Journal of personalized medicine",
			"authorList": [
				"Stein Matthew K",
				"Oluoha Oluchukwu",
				"Patel Kruti",
				"VanderWalde Ari"
			],
			"DOI": "10.3390/jpm11060518",
			"date": "2024-04-02",
			"PMC": "",
			"citation": "",
			"abstract": "Precision medicine is essential for the modern care of a patient with cancer. Comprehensive molecular profiling of the tumor itself is necessary to determine the presence or absence of certain targetable abnormalities or biomarkers. In particular, lung cancer is a disease for which targetable genomic alterations will soon guide therapy in the majority of cases. In this comprehensive review of solid tumor-based biomarkers, we describe the genomic alterations for which targeted agents have been approved by the United States Food and Drug Administration (FDA). While focusing on alterations leading to approvals in a tumor-agnostic fashion (MSI-h, TMB-h, ",
			"category": 2,
			"name": "Stein Matthew K,2024"
		},
		{
			"PMID": 34159737,
			"title": "A patient with ALK-positive lung adenocarcinoma who survived alectinib-refractory postoperative recurrence for 4\u2009years by switching to ceritinib.",
			"journal": "Thoracic cancer",
			"authorList": [
				"Matsumura Yuki",
				"Inomata Sho",
				"Yamaguchi Hikaru",
				"Mine Hayato",
				"Takagi Hironori",
				"Watanabe Masayuki",
				"Ozaki Yuki",
				"Yamaura Takumi",
				"Fukuhara Mitsuro",
				"Muto Satoshi",
				"Okabe Naoyuki",
				"Hasegawa Takeo",
				"Shio Yutaka",
				"Suzuki Hiroyuki"
			],
			"DOI": "10.1111/1759-7714.14058",
			"date": "2021-12-21",
			"PMC": "",
			"citation": "",
			"abstract": "Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangements are found in ~\u20095% of patients with non-small cell lung cancer (NSCLC). Several tyrosine kinase inhibitors (TKIs) have been developed for treatment of so-called ALK-positive NSCLC. In cases of tumor progression during treatment with second-generation ALK-TKIs, such as alectinib, brigatinib, or ceritinib, National Comprehensive Cancer Network guidelines propose a switch to lorlatinib, a third-generation ALK-TKI, or to cytotoxic chemotherapy. However, they do not mention switching to other second-generation ALK-TKIs. Here, we present a rare case of a 53-year-old Japanese woman, who had never smoked, with ALK-positive lung adenocarcinoma who survived alectinib-resistant postoperative recurrence for 4\u2009years by switching to ceritinib. She underwent curative resection for lung adenocarcinoma, but the cancer recurred at the bronchial stump and mediastinal lymph nodes. After platinum-doublet chemotherapy, the patient still had a single growing liver metastasis, but the tumor was found to harbor EML4-ALK rearrangement. Therefore, the patient started to take ALK-TKIs. Alectinib was the second ALK-TKI used to treat this patient. Alectinib shrank the liver metastasis, which was surgically resected. The tumor relapsed again during continued treatment with alectinib, which was switched to ceritinib. Ceritinib was effective for the relapsed tumor and treatment continued well for 4\u2009years. This case report suggests that, in case of tumor progression during treatment with a second-generation ALK-TKI, switching to another second-generation ALK-TKI may be one of the treatment options. Further analyses are warranted to find robust markers to determine which ALK-TKI is best for each patient.",
			"category": 2,
			"name": "Matsumura Yuki,2021"
		},
		{
			"PMID": 34082691,
			"title": "An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance.",
			"journal": "Bosnian journal of basic medical sciences",
			"authorList": [
				"Patcas Adela",
				"Chis Ana Florica",
				"Militaru Claudia Florentina",
				"Bordea Ioana Roxana",
				"Rajnoveanu Ruxandra",
				"Coza Ovidiu Florin",
				"Hanna Reem",
				"Tiberiu Tamas",
				"Todea Doina Adina"
			],
			"DOI": "10.17305/bjbms.2021.5859",
			"date": "2022-02-22",
			"PMC": "",
			"citation": "",
			"abstract": "Implementation of precision medicine in lung cancer has benefited from intense research in the past years, developing subsequently an improved quality of life and increased overall survival of the patients. Targeted therapy has become one of the most important therapeutic innovations for the non-small cell lung cancer (NSCLC) category with anaplastic lymphoma kinase (ALK) gene rearrangement. The aim of this review is to provide a through overview of the main molecules of ALK tyrosine kinase inhibitors (TKI) with their general and particular mechanisms of resistance, the main methods of ALK gene detection, each with advantages and limits and the future perspectives currently under research which try to overcome the mechanisms of resistance. We have used two of the most reliable medical databases EMBASE and PubMed to properly select the latest and the most relevant articles for this topic. Encouraged by the promising results, the clinical practice was enriched by the approval of tyrosine kinase inhibitor molecules, three generations being developed, each one with more powerful agents than the previous ones. Unfortunately, the resistance to TKI eventually occurs and it may be induced by several mechanisms, either known or unknown. Crizotinib was the most intensely studied TKI , becoming the first molecule approved into clinical practice and although four other drugs have been broadly used (alectinib, ceritinib, brigatinib and lorlatinib) it seems that even the most recently developed one remains imperfect due to the resistance mutations that developed. There are two types of resistance generally described for the entire class and for the particular drugs, but half of them remain unknown.",
			"category": 2,
			"name": "Patcas Adela,2022"
		},
		{
			"PMID": 34054126,
			"title": "Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.",
			"journal": "Signal transduction and targeted therapy",
			"authorList": [
				"Zhong Lei",
				"Li Yueshan",
				"Xiong Liang",
				"Wang Wenjing",
				"Wu Ming",
				"Yuan Ting",
				"Yang Wei",
				"Tian Chenyu",
				"Miao Zhuang",
				"Wang Tianqi",
				"Yang Shengyong"
			],
			"DOI": "10.1038/s41392-021-00572-w",
			"date": "2022-03-07",
			"PMC": "",
			"citation": "",
			"abstract": "Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Despite great progress, small-molecule targeted anti-cancer drugs still face many challenges, such as a low response rate and drug resistance. To better promote the development of targeted anti-cancer drugs, we conducted a comprehensive review of small-molecule targeted anti-cancer drugs according to the target classification. We present all the approved drugs as well as important drug candidates in clinical trials for each target, discuss the current challenges, and provide insights and perspectives for the research and development of anti-cancer drugs.",
			"category": 2,
			"name": "Zhong Lei,2022"
		},
		{
			"PMID": 34040000,
			"title": "Treatment scheduling effects on the evolution of drug resistance in heterogeneous cancer cell populations.",
			"journal": "NPJ breast cancer",
			"authorList": [
				"Patwardhan Gauri A",
				"Marczyk Michal",
				"Wali Vikram B",
				"Stern David F",
				"Pusztai Lajos",
				"Hatzis Christos"
			],
			"DOI": "10.1038/s41523-021-00270-4",
			"date": "2024-04-02",
			"PMC": "",
			"citation": "",
			"abstract": "The effect of scheduling of targeted therapy combinations on drug resistance is underexplored in triple-negative breast cancer (TNBC). TNBC constitutes heterogeneous cancer cell populations the composition of which can change dynamically during treatment resulting in the selection of resistant clones with a fitness advantage. We evaluated crizotinib (ALK/MET inhibitor) and navitoclax (ABT-263; Bcl-2/Bcl-xL inhibitor) combinations in a large design consisting of 696 two-cycle sequential and concomitant treatment regimens with varying treatment dose, duration, and drug holiday length over a 26-day period in MDA-MB-231 TNBC cells and found that patterns of resistance depend on the schedule and sequence in which the drugs are given. Further, we tracked the clonal dynamics and mechanisms of resistance using DNA-integrated barcodes and single-cell RNA sequencing. Our study suggests that longer formats of treatment schedules in vitro screening assays are required to understand the effects of resistance and guide more realistically in vivo and clinical studies.",
			"category": 2,
			"name": "Patwardhan Gauri A,2024"
		},
		{
			"PMID": 33893983,
			"title": "Intratumor heterogeneity, microenvironment, and mechanisms of drug resistance in glioma recurrence and evolution.",
			"journal": "Frontiers of medicine",
			"authorList": [
				"Bao Zhaoshi",
				"Wang Yongzhi",
				"Wang Qiangwei",
				"Fang Shengyu",
				"Shan Xia",
				"Wang Jiguang",
				"Jiang Tao"
			],
			"DOI": "10.1007/s11684-020-0760-2",
			"date": "2021-08-20",
			"PMC": "",
			"citation": "",
			"abstract": "Glioma is the most common lethal tumor of the human brain. The median survival of patients with primary World Health Organization grade IV glioma is only 14.6 months. The World Health Organization classification of tumors of the central nervous system categorized gliomas into lower-grade gliomas and glioblastomas. Unlike primary glioblastoma that usually develop de novo in the elderly, secondary glioblastoma enriched with an isocitrate dehydrogenase mutant typically progresses from lower-grade glioma within 5-10 years from the time of diagnosis. Based on various evolutional trajectories brought on by clonal and subclonal alterations, the evolution patterns of glioma vary according to different theories. Some important features distinguish the normal brain from other tissues, e.g., the composition of the microenvironment around the tumor cells, the presence of the blood-brain barrier, and others. The underlying mechanism of glioma recurrence and evolution patterns of glioma are different from those of other types of cancer. Several studies correlated tumor recurrence with tumor heterogeneity and the immune microenvironment. However, the detailed reasons for the progression and recurrence of glioma remain controversial. In this review, we introduce the different mechanisms involved in glioma progression, including tumor heterogeneity, the tumor microenvironment and drug resistance, and their pre-clinical implements in clinical trials. This review aimed to provide new insights into further clinical strategies for the treatment of patients with recurrent and secondary glioma.",
			"category": 2,
			"name": "Bao Zhaoshi,2021"
		},
		{
			"PMID": 33831375,
			"title": "Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes.",
			"journal": "Cell",
			"authorList": [
				"Dentro Stefan C",
				"Leshchiner Ignaty",
				"Haase Kerstin",
				"Tarabichi Maxime",
				"Wintersinger Jeff",
				"Deshwar Amit G",
				"Yu Kaixian",
				"Rubanova Yulia",
				"Macintyre Geoff",
				"Demeulemeester Jonas",
				"V\u00e1zquez-Garc\u00eda Ignacio",
				"Kleinheinz Kortine",
				"Livitz Dimitri G",
				"Malikic Salem",
				"Donmez Nilgun",
				"Sengupta Subhajit",
				"Anur Pavana",
				"Jolly Clemency",
				"Cmero Marek",
				"Rosebrock Daniel",
				"Schumacher Steven E",
				"Fan Yu",
				"Fittall Matthew",
				"Drews Ruben M",
				"Yao Xiaotong",
				"Watkins Thomas B K",
				"Lee Juhee",
				"Schlesner Matthias",
				"Zhu Hongtu",
				"Adams David J",
				"McGranahan Nicholas",
				"Swanton Charles",
				"Getz Gad",
				"Boutros Paul C",
				"Imielinski Marcin",
				"Beroukhim Rameen",
				"Sahinalp S Cenk",
				"Ji Yuan",
				"Peifer Martin",
				"Martincorena Inigo",
				"Markowetz Florian",
				"Mustonen Ville",
				"Yuan Ke",
				"Gerstung Moritz",
				"Spellman Paul T",
				"Wang Wenyi",
				"Morris Quaid D",
				"Wedge David C",
				"Van Loo Peter",
				"PCAWG Evolution and Heterogeneity Working Group and the PCAWG Consortium"
			],
			"DOI": "10.1016/j.cell.2021.03.009",
			"date": "2021-10-20",
			"PMC": "",
			"citation": "",
			"abstract": "Intra-tumor heterogeneity (ITH) is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the extent, origin, and drivers of ITH across cancer types are poorly understood. To address this, we extensively characterize ITH across whole-genome sequences of 2,658 cancer samples spanning 38 cancer types. Nearly all informative samples (95.1%) contain evidence of distinct subclonal expansions with frequent branching relationships between subclones. We observe positive selection of subclonal driver mutations across most cancer types and identify cancer type-specific subclonal patterns of driver gene mutations, fusions, structural variants, and copy number alterations as well as dynamic changes in mutational processes between subclonal expansions. Our results underline the importance of ITH and its drivers in tumor evolution and provide a pan-cancer resource of comprehensively annotated subclonal events from whole-genome sequencing data.",
			"category": 2,
			"name": "Dentro Stefan C,2021"
		},
		{
			"PMID": 33790576,
			"title": "Identification of Novel Alectinib-Resistant ",
			"journal": "OncoTargets and therapy",
			"authorList": [
				"Yang Ping",
				"Cao Ran",
				"Bao Hua",
				"Wu Xue",
				"Yang Lingling",
				"Zhu Dongqin",
				"Zhang Lu",
				"Peng Liming",
				"Cai Yuefei",
				"Zhang Weijun",
				"Shao Yang"
			],
			"DOI": "10.2147/OTT.S293901",
			"date": "2022-04-21",
			"PMC": "",
			"citation": "",
			"abstract": "Drug resistance caused by G1202R/G1202del mutation in anaplastic lymphoma kinase (",
			"category": 2,
			"name": "Yang Ping,2022"
		},
		{
			"PMID": 33692962,
			"title": "Case Report: ",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Wen Zhengqi",
				"Xiong Dun",
				"Zhang Shurong",
				"Liu Jiankun",
				"Li Bitao",
				"Li Raomei",
				"Zhang Hushan"
			],
			"DOI": "10.3389/fonc.2021.645370",
			"date": "2024-03-31",
			"PMC": "",
			"citation": "",
			"abstract": "Gastric cancer is one of the most common cancers, while the current treatment options for gastric cancer are relatively scarce due to insufficient understanding of molecular characteristics and subtypes of gastric cancer. Different gene rearrangements of anaplastic lymphocyte kinase (",
			"category": 2,
			"name": "Wen Zhengqi,2024"
		},
		{
			"PMID": 33627640,
			"title": "Gilteritinib overcomes lorlatinib resistance in ALK-rearranged cancer.",
			"journal": "Nature communications",
			"authorList": [
				"Mizuta Hayato",
				"Okada Koutaroh",
				"Araki Mitsugu",
				"Adachi Jun",
				"Takemoto Ai",
				"Kutkowska Justyna",
				"Maruyama Kohei",
				"Yanagitani Noriko",
				"Oh-Hara Tomoko",
				"Watanabe Kana",
				"Tamai Keiichi",
				"Friboulet Luc",
				"Katayama Kazuhiro",
				"Ma Biao",
				"Sasakura Yoko",
				"Sagae Yukari",
				"Kukimoto-Niino Mutsuko",
				"Shirouzu Mikako",
				"Takagi Satoshi",
				"Simizu Siro",
				"Nishio Makoto",
				"Okuno Yasushi",
				"Fujita Naoya",
				"Katayama Ryohei"
			],
			"DOI": "10.1038/s41467-021-21396-w",
			"date": "2021-03-03",
			"PMC": "",
			"citation": "",
			"abstract": "ALK gene rearrangement was observed in 3%-5% of non-small cell lung cancer patients, and multiple ALK-tyrosine kinase inhibitors (TKIs) have been sequentially used. Multiple ALK-TKI resistance mutations have been identified from the patients, and several compound mutations, such as I1171N\u2009+\u2009F1174I or I1171N\u2009+\u2009L1198H are resistant to all the approved ALK-TKIs. In this study, we found that gilteritinib has an inhibitory effect on ALK-TKI-resistant single mutants and I1171N compound mutants in vitro and in vivo. Surprisingly, EML4-ALK I1171N\u2009+\u2009F1174I compound mutant-expressing tumors were not completely shrunk but regrew within a\u00a0short period of time after alectinib or lorlatinib treatment. However, the relapsed tumor was markedly shrunk after switching to the gilteritinib in vivo model. In addition, gilteritinib was effective against NTRK-rearranged cancers including entrectinib-resistant NTRK1 G667C-mutant and ROS1 fusion-positive cancer.",
			"category": 2,
			"name": "Mizuta Hayato,2021"
		},
		{
			"PMID": 33613692,
			"title": "Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations: results from the German early access program.",
			"journal": "Therapeutic advances in medical oncology",
			"authorList": [
				"Frost Nikolaj",
				"Christopoulos Petros",
				"Kauffmann-Guerrero Diego",
				"Stratmann Jan",
				"Riedel Richard",
				"Schaefer Monica",
				"Alt J\u00fcrgen",
				"G\u00fctz Sylvia",
				"Christoph Daniel C",
				"Laack Eckart",
				"Faehling Martin",
				"Fischer Richard",
				"Fenchel Klaus",
				"Haen Sebastian",
				"Heukamp Lukas",
				"Schulz Christian",
				"Griesinger Frank"
			],
			"DOI": "10.1177/1758835920980558",
			"date": "2022-04-20",
			"PMC": "",
			"citation": "",
			"abstract": "We report on the results of the German early access program (EAP) with the third-generation ALK- and ROS1-inhibitor lorlatinib.",
			"category": 2,
			"name": "Frost Nikolaj,2022"
		},
		{
			"PMID": 33572278,
			"title": "Current Knowledge about Mechanisms of Drug Resistance against ALK Inhibitors in Non-Small Cell Lung Cancer.",
			"journal": "Cancers",
			"authorList": [
				"Smolle Elisabeth",
				"Taucher Valentin",
				"Lindenmann Joerg",
				"Jost Philipp J",
				"Pichler Martin"
			],
			"DOI": "10.3390/cancers13040699",
			"date": "2021-03-03",
			"PMC": "",
			"citation": "",
			"abstract": "Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer subtypes. Two to seven percent of NSCLC patients harbor gene rearrangements of the anaplastic lymphoma kinase (ALK) gene or, alternatively, harbor chromosomal fusions of ALK with echinoderm microtubule-associated protein-like 4 (EML4). The availability of tyrosine kinase inhibitors targeting ALK (ALK-TKIs) has significantly improved the progression-free and overall survival of NSCLC patients carrying the respective genetic aberrations. Yet, increasing evidence shows that primary or secondary resistance to ALK-inhibitors during the course of treatment represents a relevant clinical problem. This necessitates a switch to second- or third-generation ALK-TKIs and a close observation of NSCLC patients on ALK-TKIs during the course of treatment by repetitive molecular testing. With this review of the literature, we aim at providing an overview of current knowledge about resistance mechanisms to ALK-TKIs in NSCLC.",
			"category": 2,
			"name": "Smolle Elisabeth,2021"
		},
		{
			"PMID": 33492612,
			"title": "Immune profiling of pituitary tumors reveals variations in immune infiltration and checkpoint molecule expression.",
			"journal": "Pituitary",
			"authorList": [
				"Mei Yu",
				"Bi Wenya Linda",
				"Agolia James",
				"Hu Changchen",
				"Giantini Larsen Alexandra M",
				"Meredith David M",
				"Al Abdulmohsen Sally",
				"Bale Tejus",
				"Dunn Gavin P",
				"Abedalthagafi Malak",
				"Dunn Ian F"
			],
			"DOI": "10.1007/s11102-020-01114-3",
			"date": "2021-12-03",
			"PMC": "",
			"citation": "",
			"abstract": "Pituitary tumors are the second most common primary brain tumors. Functional tumors demonstrate increased PD-L1 expression, but expression of other checkpoint regulators has not been characterized. We sought to characterize the immune microenvironment of human pituitary tumors to identify new treatment opportunities.",
			"category": 2,
			"name": "Mei Yu,2021"
		},
		{
			"PMID": 33489820,
			"title": "Overcoming TKI resistance in fusion-driven NSCLC: new generation inhibitors and rationale for combination strategies.",
			"journal": "Translational lung cancer research",
			"authorList": [
				"Russo Alessandro",
				"Cardona Andr\u00e9s F",
				"Caglevic Christian",
				"Manca Paolo",
				"Ruiz-Pati\u00f1o Alejandro",
				"Arrieta Oscar",
				"Rolfo Christian"
			],
			"DOI": "10.21037/tlcr-2019-cnsclc-06",
			"date": "2022-09-10",
			"PMC": "",
			"citation": "",
			"abstract": "During the last several years, multiple gene rearrangements with oncogenic potential have been described in NSCLC, identifying specific clinic-pathological subgroups of patients that benefit from a targeted therapeutic approach, including ",
			"category": 2,
			"name": "Russo Alessandro,2022"
		},
		{
			"PMID": 33489817,
			"title": "Resistance to anaplastic lymphoma kinase inhibitors: knowing the enemy is half the battle won.",
			"journal": "Translational lung cancer research",
			"authorList": [
				"Tabb\u00f2 Fabrizio",
				"Reale Maria Lucia",
				"Bironzo Paolo",
				"Scagliotti Giorgio V"
			],
			"DOI": "10.21037/tlcr-20-372",
			"date": "2021-01-26",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (",
			"category": 2,
			"name": "Tabb\u00f2 Fabrizio,2021"
		},
		{
			"PMID": 33489815,
			"title": "How to select the best upfront therapy for metastatic disease? Focus on ",
			"journal": "Translational lung cancer research",
			"authorList": [
				"Xia Bing",
				"Nagasaka Misako",
				"Zhu Viola W",
				"Ou Sai-Hong Ignatius",
				"Soo Ross A"
			],
			"DOI": "10.21037/tlcr-20-331",
			"date": "2022-09-10",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) inhibitors have demonstrated robust clinical activity in patients with ",
			"category": 2,
			"name": "Xia Bing,2022"
		},
		{
			"PMID": 33467720,
			"title": "Detecting Resistance to Therapeutic ALK Inhibitors in Tumor Tissue and Liquid Biopsy Markers: An Update to a Clinical Routine Practice.",
			"journal": "Cells",
			"authorList": [
				"Hofman Paul"
			],
			"DOI": "10.3390/cells10010168",
			"date": "2021-07-08",
			"PMC": "",
			"citation": "",
			"abstract": "The survival of most patients with advanced stage non-small cell lung cancer is prolonged by several months when they are treated with first- and next-generation inhibitors targeting ",
			"category": 2,
			"name": "Hofman Paul,2021"
		},
		{
			"PMID": 33288731,
			"title": "Phosphorylation and Driver Mutations in PI3K\u03b1 and PTEN Autoinhibition.",
			"journal": "Molecular cancer research : MCR",
			"authorList": [
				"Nussinov Ruth",
				"Zhang Mingzhen",
				"Tsai Chung-Jung",
				"Jang Hyunbum"
			],
			"DOI": "10.1158/1541-7786.MCR-20-0818",
			"date": "2022-01-12",
			"PMC": "",
			"citation": "",
			"abstract": "PI3K and PTEN are the second and third most highly mutated proteins in cancer following only p53. Their actions oppose each other. PI3K phosphorylates signaling lipid PIP",
			"category": 2,
			"name": "Nussinov Ruth,2022"
		},
		{
			"PMID": 33226527,
			"title": "Treatment Sequencing for Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer.",
			"journal": "Drugs",
			"authorList": [
				"Kauffmann-Guerrero Diego",
				"Kahnert Kathrin",
				"Huber Rudolf M"
			],
			"DOI": "10.1007/s40265-020-01445-2",
			"date": "2021-10-25",
			"PMC": "",
			"citation": "",
			"abstract": "Non-small-cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases and is the leading cause of cancer-related deaths. Most NSCLC patients are diagnosed with advanced disease and require systemic treatment. Despite emerging advances in chemotherapy and immunotherapy, the prognosis of stage IV patients remains poor. However, the discovery of oncogenic driver mutations including mutations in the epidermal growth factor receptor (EGFR), the anaplastic lymphoma kinase (ALK) and others, characterize a subset of patients with the opportunity of targeted therapies. Fusions between the ALK and echinoderm microtubule-associated protein-like 4 (EML4) are present in \u223c 3-5% of patients with NSCLC. Several first-, second-, and third-generation ALK tyrosine kinase inhibitors (TKIs) have been developed in the last decade and have tremendously changed treatment options and outcomes of ALK-positive NSCLC patients. With increasing treatment options, treatment sequence decisions have become more and more complex. ALK-mutations, fusion variants, or activation of by-pass pathways result in treatment resistance during the course of treatment in nearly all patients. Mutation-guided treatment sequencing can lead to better outcomes, and re-biopsy or liquid-biopsy should be performed whenever possible in case of disease progression in ALK-rearranged patients. In the future, combinational treatment of ALK TKIs with other pathway-inhibitors might further improve patients' treatment options and outcomes. Here, we review the data for currently available ALK TKIs, discuss approaches of treatment sequencing, and give an outlook on emerging developments.",
			"category": 2,
			"name": "Kauffmann-Guerrero Diego,2021"
		},
		{
			"PMID": 33203201,
			"title": "[Advances in Drug Resistance Mechanisms and Prognostic Markers of Targeted Therapy in ALK-positive Non-small Cell Lung Cancer].",
			"journal": "Zhongguo fei ai za zhi = Chinese journal of lung cancer",
			"authorList": [
				"Wang Shasha",
				"Shi Yuankai",
				"Han Xiaohong"
			],
			"DOI": "10.3779/j.issn.1009-3419.2020.101.44",
			"date": "2021-08-02",
			"PMC": "",
			"citation": "",
			"abstract": "Echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion accounts for 3%-5% of non-small cell lung cancer (NSCLC) patients. With the in-depth study of the EML4-ALK driver gene, ALK inhibitors represented by crizotinib have been gradually developed and applied in the clinic. However, the response to ALK-targeted therapy is heterogeneous among different patients. Most patients with ALK-targeted therapy will inevitably develop drug resistance, leading to tumor progression. Monitoring the efficacy of patients with prognostic markers to change the treatment in time, and selecting individualized follow-up treatment according to the mechanism of drug resistance, can effectively improve the prognosis of patients. This article will review the mechanism of ALK tyrosine kinase inhibitor (ALK-TKI) resistance and related prognostic markers to discuss the prediction for ALK-targeted therapy and the choice of subsequent treatment for drug-resistant patients.\u2029.",
			"category": 2,
			"name": "Wang Shasha,2021"
		},
		{
			"PMID": 33172113,
			"title": "Focus on ROS1-Positive Non-Small Cell Lung Cancer (NSCLC): Crizotinib, Resistance Mechanisms and the Newer Generation of Targeted Therapies.",
			"journal": "Cancers",
			"authorList": [
				"D'Angelo Alberto",
				"Sobhani Navid",
				"Chapman Robert",
				"Bagby Stefan",
				"Bortoletti Carlotta",
				"Traversini Mirko",
				"Ferrari Katia",
				"Voltolini Luca",
				"Darlow Jacob",
				"Roviello Giandomenico"
			],
			"DOI": "10.3390/cancers12113293",
			"date": "2020-11-28",
			"PMC": "",
			"citation": "",
			"abstract": "The treatment of patients affected by non-small cell lung cancer (NSCLC) has been revolutionised by the discovery of druggable mutations. ROS1 (c-ros oncogene) is one gene with druggable mutations in NSCLC. ROS1 is currently targeted by several specific tyrosine kinase inhibitors (TKIs), but only two of these, crizotinib and entrectinib, have received Food and Drug Administration (FDA) approval. Crizotinib is a low molecular weight, orally available TKI that inhibits ROS1, MET and ALK and is considered the gold standard first-line treatment with demonstrated significant activity for lung cancers harbouring ROS1 gene rearrangements. However, crizotinib resistance often occurs, making the treatment of ROS1-positive lung cancers more challenging. A great effort has been undertaken to identify a new generation or ROS1 inhibitors. In this review, we briefly introduce the biology and role of ROS1 in lung cancer and discuss the underlying acquired mechanisms of resistance to crizotinib and the promising new agents able to overcome resistance mechanisms and offer alternative efficient therapies.",
			"category": 2,
			"name": "D'Angelo Alberto,2020"
		},
		{
			"PMID": 32953006,
			"title": "PI3K inhibitors: review and new strategies.",
			"journal": "Chemical science",
			"authorList": [
				"Zhang Mingzhen",
				"Jang Hyunbum",
				"Nussinov Ruth"
			],
			"DOI": "10.1039/d0sc01676d",
			"date": "2023-11-04",
			"PMC": "",
			"citation": "",
			"abstract": "The search is on for effective specific inhibitors for PI3K\u03b1 mutants. PI3K\u03b1, a critical lipid kinase, has two subunits, catalytic and inhibitory. PIK3CA, the gene that encodes the p110\u03b1 catalytic subunit is a highly mutated protein in cancer. Dysregulation of PI3K\u03b1 signalling is commonly associated with tumorigenesis and drug resistance. Despite its vast importance, only recently the FDA approved the first drug (alpelisib by Novartis) for breast cancer. A second (GDC0077), classified as PI3K\u03b1 isoform-specific, is undergoing clinical trials. Not surprisingly, these ATP-competitive drugs commonly elicit severe concentration-dependent side effects. Here we briefly review PI3K\u03b1 mutations, focus on PI3K drug repertoire and propose new, to-date unexplored PI3K\u03b1 therapeutic strategies. These include (1) an allosteric and orthosteric inhibitor combination and (2) taking advantage of allosteric rescue mutations to guide drug discovery.",
			"category": 2,
			"name": "Zhang Mingzhen,2023"
		},
		{
			"PMID": 32883458,
			"title": "Emerging Therapies in Thoracic Malignancies-Immunotherapy, Targeted Therapy, and T-Cell Therapy in Non-Small Cell Lung Cancer.",
			"journal": "Surgical oncology clinics of North America",
			"authorList": [
				"Sepesi Boris",
				"Cascone Tina",
				"Chun Stephen G",
				"Altan Mehmet",
				"Le Xiuning"
			],
			"DOI": "10.1016/j.soc.2020.06.009",
			"date": "2021-08-12",
			"PMC": "",
			"citation": "",
			"abstract": "Immunotherapy, targeted therapy, and adoptive T-cell therapy have been revolutionary advancements in cancer research. Some of these therapies have become the standard of care for lung cancer and replaced older treatment algorithms; some continue to be studied in clinical trials. This article discusses the current state of novel treatment options for non-small cell lung cancer patients with metastatic and locoregional disease, with focus on immunotherapy, targeted therapy, and adoptive T-cell therapy.",
			"category": 2,
			"name": "Sepesi Boris,2021"
		},
		{
			"PMID": 32802958,
			"title": "Small cell transformation of ",
			"journal": "NPJ precision oncology",
			"authorList": [
				"Lin Jessica J",
				"Langenbucher Adam",
				"Gupta Pranav",
				"Yoda Satoshi",
				"Fetter Isobel J",
				"Rooney Marguerite",
				"Do Andrew",
				"Kem Marina",
				"Chang Kylie Prutisto",
				"Oh Audris Y",
				"Chin Emily",
				"Juric Dejan",
				"Corcoran Ryan B",
				"Dagogo-Jack Ibiayi",
				"Gainor Justin F",
				"Stone James R",
				"Lennerz Jochen K",
				"Lawrence Michael S",
				"Hata Aaron N",
				"Mino-Kenudson Mari",
				"Shaw Alice T"
			],
			"DOI": "10.1038/s41698-020-0127-9",
			"date": "2024-04-28",
			"PMC": "",
			"citation": "",
			"abstract": "Histologic transformation from non-small cell to small cell lung cancer has been reported as a resistance mechanism to targeted therapy in ",
			"category": 2,
			"name": "Lin Jessica J,2024"
		},
		{
			"PMID": 32786189,
			"title": "The Effect of Advances in Lung-Cancer Treatment on Population Mortality.",
			"journal": "The New England journal of medicine",
			"authorList": [
				"Howlader Nadia",
				"Forjaz Gon\u00e7alo",
				"Mooradian Meghan J",
				"Meza Rafael",
				"Kong Chung Yin",
				"Cronin Kathleen A",
				"Mariotto Angela B",
				"Lowy Douglas R",
				"Feuer Eric J"
			],
			"DOI": "10.1056/NEJMoa1916623",
			"date": "2020-08-25",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer is made up of distinct subtypes, including non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Although overall mortality from lung cancer has been declining in the United States, little is known about mortality trends according to cancer subtype at the population level because death certificates do not record subtype information.",
			"category": 2,
			"name": "Howlader Nadia,2020"
		},
		{
			"PMID": 32694636,
			"title": "Chemical strategies to overcome resistance against targeted anticancer therapeutics.",
			"journal": "Nature chemical biology",
			"authorList": [
				"Pisa Rudolf",
				"Kapoor Tarun M"
			],
			"DOI": "10.1038/s41589-020-0596-8",
			"date": "2020-11-23",
			"PMC": "",
			"citation": "",
			"abstract": "Emergence of resistance is a major factor limiting the efficacy of molecularly targeted anticancer drugs. Understanding the specific mutations, or other genetic or cellular changes, that confer drug resistance can help in the development of therapeutic strategies with improved efficacies. Here, we outline recent progress in understanding chemotype-specific mechanisms of resistance and present chemical strategies, such as designing drugs with distinct binding modes or using proteolysis targeting chimeras, to overcome resistance. We also discuss how targeting multiple binding sites with bifunctional inhibitors or identifying collateral sensitivity profiles can be exploited to limit the emergence of resistance. Finally, we highlight how incorporating analyses of resistance early in drug development can help with the design and evaluation of therapeutics that can have long-term benefits for patients.",
			"category": 2,
			"name": "Pisa Rudolf,2020"
		},
		{
			"PMID": 32674491,
			"title": "Inconsistent Intersample ALK FISH Results in Patients with Lung Cancer: Analysis of Potential Causes.",
			"journal": "Cancers",
			"authorList": [
				"Tang Zhenya",
				"Chen Hui",
				"Hong Lingzhi",
				"Tang Guilin",
				"Toruner Gokce A",
				"Wang Wei",
				"Roy Chowdhuri Sinchita",
				"Yin Wei",
				"Jung Hai Suk",
				"Gu Jun",
				"Routbort Mark J",
				"Zhang Jianjun",
				"Khoury Joseph D",
				"Medeiros L Jeffrey"
			],
			"DOI": "10.3390/cancers12071903",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "ALK FISH analyses of multiple specimens occasionally yield inconsistent intersample results in lung cancer patients, posing clinical challenges requiring intensive analysis of all potential causative pre- and post- analytic factors. In this study, 19 patients (8M/11F) with inconsistent intersample ALK FISH results were analyzed, representing 4.9% of patients assessed \u2265 twice in our institution. Fifteen patients received ALK tyrosine kinase inhibitor(s) (TKIs). Nine patients died, and ten were alive for 8 to 74-month follow-ups (median, 40 months). Through strict and stringent laboratory and case-review policies, all postanalytic factors were excluded. Correlating clinical information, ALK results obtained by RNA sequencing (RNA-seq) and other concurrent tests, several pre-analytic factors were determined. A suboptimal specimen was likely the cause in three patients, supported by the failure of one or more concurrent tests or discrepant results between FISH and RNA-seq. ALK inhibition by TKIs might have been responsible for the change of ",
			"category": 2,
			"name": "Tang Zhenya,2020"
		},
		{
			"PMID": 32558067,
			"title": "ALK-Rearranged Non-Small Cell Lung Cancer in 2020: Real-World Triumphs in an Era of Multigeneration ALK-Inhibitor Sequencing Informed by Drug Resistance Profiling.",
			"journal": "The oncologist",
			"authorList": [
				"Itchins Malinda",
				"Lau Brandon",
				"Hudson Amanda L",
				"Westman Helen",
				"Xia Cathy Yi",
				"Hayes Sarah A",
				"Howell Viive M",
				"Rodriguez Michael",
				"Cooper Wendy A",
				"Wei Heng",
				"Buckland Michael",
				"Li Bob T",
				"Li Mark",
				"Rathi Vivek",
				"Fox Stephen B",
				"Gill Anthony J",
				"Clarke Stephen J",
				"Boyer Michael J",
				"Pavlakis Nick"
			],
			"DOI": "10.1634/theoncologist.2020-0075",
			"date": "2021-06-18",
			"PMC": "",
			"citation": "",
			"abstract": "Since its discovery in 2007, we have seen the lives of patients diagnosed with advanced anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancers (NSCLC) transform with the advent of molecular therapies with first-, second-, and third-generation ALK inhibitors now available in the clinic. Despite great gains in patient survival now measured in years and preserved quality of life with targeted therapies, drug resistance is unfortunately inevitably encountered in this rare and unique molecular subset of lung cancer, and patients will eventually succumb to the disease. As these patients are often young, fit, and never smokers, the clinical and scientific communities have aligned to expedite drug development and access. Drug resistance profiling and further strategies are being explored through clinical trials, including the evaluation of specific drug sequencing and combinations to overcome such resistance and promote patient longevity. The cases of this report focus on precision medicine and aim to portray the pertinent aspects to consider when treating ALK-rearranged NSCLC in 2020, an ever-shifting space. By way of case examples, this report offers valuable information to the treating clinician, including the evolution of systemic treatments and the management of oligo-progression and multisite drug resistance. With the maturation of real-world data, we are fortunate to be experiencing quality and length of life for patients with this disease surpassing prior expectations in advanced lung cancer. KEY POINTS: This report focuses on the importance of genetic analysis of serial biopsies to capture the dynamic therapeutic vulnerabilities of a patient's tumor, providing a perspective on the complexity of ALK tyrosine kinase inhibitor (ALKi) treatment sequencing. These case examples contribute to the literature on ALK-rearranged and oncogene addicted non-small cell lung cancer (NSCLC), providing a framework for care in the clinic. In oligo-progressive disease, local ablative therapy and continuation of ALKi postprogression should be considered with potential for sustained disease control. ALK G1202R kinase domain mutations (KDM), highly prevalent at resistance to second-generation ALKi resistances, may emerge in non-EML4-ALK variant 3 cases and is sensitive to third-generation lorlatinib. When in compound with one or more ALK KDMs, resistance to lorlatinib is expected. In the case of rampantly progressive disease, rebiopsy and redefining biology in a timely manner may be informative.",
			"category": 2,
			"name": "Itchins Malinda,2021"
		},
		{
			"PMID": 32272741,
			"title": "Development of a Model for Chemical Screening Based on Collateral Sensitivity to Target BTK C481S Mutant.",
			"journal": "Cancers",
			"authorList": [
				"Libre Camille",
				"Moro-Sibilot Ludovic",
				"Giraud St\u00e9phane",
				"Martin Laetitia",
				"Verhoeyen Els",
				"Costa Caroline",
				"Chebel Amel",
				"Bissay Nathalie",
				"Salles Gilles",
				"Genestier Laurent",
				"Sujobert Pierre"
			],
			"DOI": "10.3390/cancers12040901",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Targeted therapies have improved the outcome of cancer, but their efficacy is intrinsically limited by the emergence of subclones with a mutation in the gene encoding the target protein. A few examples of collateral sensitivity have demonstrated that the conformational changes induced by these mutations can create unexpected sensitivity to other kinase inhibitors, but whether this concept can be generalized is unknown. Here is described the development of a model to screen a library of kinase inhibitors for collateral sensitivity drugs active on the Bruton Tyrosine Kinase (BTK) protein with the ibrutinib resistance mutation C481S. First, we demonstrate that overexpression of the constitutively active mutant of BTK harboring the E41K mutation in Ba/F3 cells creates an oncogenic addiction to BTK. Then, we have exploited this phenotype to perform a screen of a kinase inhibitor library on cells with or without the ibrutinib resistance mutation. The BTK inhibitors showed the expected sensitivity profile, but none of the drugs tested had a specific activity against the C481S mutant of BTK, suggesting that extending the collateral sensitivity paradigm to all kinases targeted by cancer therapy might not be trivial.",
			"category": 2,
			"name": "Libre Camille,2020"
		},
		{
			"PMID": 32207263,
			"title": "Recent Improvements in Genomic and Transcriptomic Understanding of Anaplastic and Poorly Differentiated Thyroid Cancers.",
			"journal": "Endocrinology and metabolism (Seoul, Korea)",
			"authorList": [
				"Yoo Seong Keun",
				"Song Young Shin",
				"Park Young Joo",
				"Seo Jeong Sun"
			],
			"DOI": "10.3803/EnM.2020.35.1.44",
			"date": "2021-06-14",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic thyroid cancer (ATC) is a lethal human cancer with a 5-year survival rate of less than 10%. Recently, its genomic and transcriptomic characteristics have been extensively elucidated over 5 years owing to advance in high throughput sequencing. These efforts have extended molecular understandings into the progression mechanisms and therapeutic vulnerabilities of aggressive thyroid cancers. In this review, we provide an overview of genomic and transcriptomic alterations in ATC and poorly-differentiated thyroid cancer, which are distinguished from differentiated thyroid cancers. Clinically relevant genomic alterations and deregulated signaling pathways will be able to shed light on more effective prevention and stratified therapeutic interventions for affected patients.",
			"category": 2,
			"name": "Yoo Seong Keun,2021"
		},
		{
			"PMID": 32130705,
			"title": "Exploiting Cancer Cells Metabolic Adaptability to Enhance Therapy Response in Cancer.",
			"journal": "Advances in experimental medicine and biology",
			"authorList": [
				"Nunes Sofia C"
			],
			"DOI": "10.1007/978-3-030-34025-4_15",
			"date": "2020-04-07",
			"PMC": "",
			"citation": "",
			"abstract": "Despite all the progresses developed in prevention and new treatment approaches, cancer is the second leading cause of death worldwide, being chemoresistance a pivotal barrier in cancer management. Cancer cells present several mechanisms of drug resistance/tolerance and recently, growing evidence have\u00a0been supporting a role of metabolism reprograming per se as a driver of chemoresistance. In fact, cancer cells display several adaptive mechanisms that allow the emergency of chemoresistance, revealing cancer as a disease that adapts and evolve along with the treatment. Therefore, clinical protocols that take into account the adaptive potential of cancer cells should be more effective than the current traditional standard protocols on the fighting against cancer.In here, some of the recent findings on the role of metabolism reprograming in cancer chemoresistance emergence will be discussed, as the potential evolutionary strategies that could unable these adaptations, hence allowing to prevent the emergency of treatment resistance, changing cancer outcome.",
			"category": 2,
			"name": "Nunes Sofia C,2020"
		},
		{
			"PMID": 31961053,
			"title": "Drug resistance mechanisms in Japanese anaplastic lymphoma kinase-positive non-small cell lung cancer and the clinical responses based on the resistant mechanisms.",
			"journal": "Cancer science",
			"authorList": [
				"Yanagitani Noriko",
				"Uchibori Ken",
				"Koike Sumie",
				"Tsukahara Mika",
				"Kitazono Satoru",
				"Yoshizawa Takahiro",
				"Horiike Atsushi",
				"Ohyanagi Fumiyoshi",
				"Tambo Yuichi",
				"Nishikawa Shingo",
				"Fujita Naoya",
				"Katayama Ryohei",
				"Nishio Makoto"
			],
			"DOI": "10.1111/cas.14314",
			"date": "2020-03-16",
			"PMC": "",
			"citation": "",
			"abstract": "The treatment for anaplastic lymphoma kinase (ALK)-positive lung cancer has been rapidly evolving since the introduction of several ALK tyrosine kinase inhibitors (ALK-TKI) in clinical practice. However, the acquired resistance to these drugs has become an important issue. In this study, we collected a total of 112 serial biopsy samples from 32 patients with ALK-positive lung cancer during multiple ALK-TKI treatments to reveal the resistance mechanisms to ALK-TKI. Among 32 patients, 24\u00a0patients received more than two ALK-TKI. Secondary mutations were observed in 8 of 12 specimens after crizotinib failure (G1202R, G1269A, I1171T, L1196M, C1156Y and F1245V). After alectinib failure, G1202R and I1171N mutations were detected in 7 of 15 specimens. G1202R, F1174V and G1202R, and P-gp overexpression were observed in 3 of 7 samples after ceritinib treatment. L1196M\u00a0+\u00a0G1202R, a compound mutation, was detected in 1 specimen after lorlatinib treatment. ALK-TKI treatment duration was longer in the on-target treatment group than that in the off-target group (13.0 vs 1.2\u00a0months). In conclusion, resistance to ALK-TKI based on secondary mutation in this study was similar to that in previous reports, except for crizotinib resistance. Understanding the appropriate treatment matching resistance mechanisms contributes to the efficacy of multiple ALK-TKI treatment strategies.",
			"category": 2,
			"name": "Yanagitani Noriko,2020"
		},
		{
			"PMID": 31943796,
			"title": "Overcoming resistance by ALK compound mutation (I1171S + G1269A) after sequential treatment of multiple ALK inhibitors in non-small cell lung cancer.",
			"journal": "Thoracic cancer",
			"authorList": [
				"Takahashi Ken",
				"Seto Yosuke",
				"Okada Koutaroh",
				"Uematsu Shinya",
				"Uchibori Ken",
				"Tsukahara Mika",
				"Oh-Hara Tomoko",
				"Fujita Naoya",
				"Yanagitani Noriko",
				"Nishio Makoto",
				"Okubo Kenichi",
				"Katayama Ryohei"
			],
			"DOI": "10.1111/1759-7714.13299",
			"date": "2021-03-08",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) fusion genes are found in 3%-5% of non-small cell lung cancers (NSCLCs). ALK inhibitors show a very high response rate to ALK-positive NSCLCs. However, the emergence of acquired resistance is inevitable. In this study, we investigated the drugs for overcoming resistance especially compound mutations after sequential treatment with crizotinib, alectinib, and lorlatinib.",
			"category": 2,
			"name": "Takahashi Ken,2021"
		},
		{
			"PMID": 31900393,
			"title": "YAP1 mediates survival of ALK-rearranged lung cancer cells treated with alectinib via pro-apoptotic protein regulation.",
			"journal": "Nature communications",
			"authorList": [
				"Tsuji Takahiro",
				"Ozasa Hiroaki",
				"Aoki Wataru",
				"Aburaya Shunsuke",
				"Yamamoto Funazo Tomoko",
				"Furugaki Koh",
				"Yoshimura Yasushi",
				"Yamazoe Masatoshi",
				"Ajimizu Hitomi",
				"Yasuda Yuto",
				"Nomizo Takashi",
				"Yoshida Hironori",
				"Sakamori Yuichi",
				"Wake Hiroaki",
				"Ueda Mitsuyoshi",
				"Kim Young Hak",
				"Hirai Toyohiro"
			],
			"DOI": "10.1038/s41467-019-13771-5",
			"date": "2020-03-24",
			"PMC": "",
			"citation": "",
			"abstract": "Despite the promising clinical efficacy of the second-generation anaplastic lymphoma kinase (ALK) inhibitor alectinib in patients with ALK-rearranged lung cancer, some tumor cells survive and eventually relapse, which may be an obstacle to achieving a\u00a0cure. Limited information is currently available on the mechanisms underlying the initial survival of tumor cells against alectinib. Using patient-derived cell line models, we herein demonstrate that cancer cells survive a treatment with alectinib by activating Yes-associated protein 1 (YAP1), which mediates the expression of the anti-apoptosis factors Mcl-1 and Bcl-xL, and combinatorial inhibition against both YAP1 and ALK provides a longer tumor remission in ALK-rearranged xenografts when compared with alectinib monotherapy. These results suggest that the inhibition of YAP1 is a candidate for combinatorial therapy with ALK inhibitors to achieve complete remission in patients with ALK-rearranged lung cancer.",
			"category": 2,
			"name": "Tsuji Takahiro,2020"
		},
		{
			"PMID": 31891108,
			"title": "Conformation of the Macrocyclic Drug Lorlatinib in Polar and Nonpolar Environments: A MD Simulation and NMR Study.",
			"journal": "ACS omega",
			"authorList": [
				"Peng Cheng",
				"Atilaw Yoseph",
				"Wang Jinan",
				"Xu Zhijian",
				"Poongavanam Vasanthanathan",
				"Shi Jiye",
				"Kihlberg Jan",
				"Zhu Weiliang",
				"Erd\u00e9lyi M\u00e1t\u00e9"
			],
			"DOI": "10.1021/acsomega.9b03797",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "The replica exchange molecular dynamics (REMD) simulation is demonstrated to readily predict the conformations of the macrocyclic drug lorlatinib, as validated by solution NMR studies. In aqueous solution, lorlatinib adopts a conformer identical to its target bound structure. This conformer is stabilized by an extensive hydrogen bond network to the solvents. In chloroform, lorlatinib populates two conformers with the second one being less polar, which may contribute to lorlatinib's ability to cross cell membranes.",
			"category": 2,
			"name": "Peng Cheng,2020"
		},
		{
			"PMID": 31815659,
			"title": "Emerging insights of tumor heterogeneity and drug resistance mechanisms in lung cancer targeted therapy.",
			"journal": "Journal of hematology & oncology",
			"authorList": [
				"Lim Zuan-Fu",
				"Ma Patrick C"
			],
			"DOI": "10.1186/s13045-019-0818-2",
			"date": "2020-07-06",
			"PMC": "",
			"citation": "",
			"abstract": "The biggest hurdle to targeted cancer therapy is the inevitable emergence of drug resistance. Tumor cells employ different mechanisms to resist the targeting agent. Most commonly in EGFR-mutant non-small cell lung cancer, secondary resistance mutations on the target kinase domain emerge to diminish the binding affinity of first- and second-generation inhibitors. Other alternative resistance mechanisms include activating complementary bypass pathways and phenotypic transformation. Sequential monotherapies promise to temporarily address the problem of acquired drug resistance, but evidently are limited by the tumor cells' ability to adapt and evolve new resistance mechanisms to persist in the drug environment. Recent studies have nominated a model of drug resistance and tumor progression under targeted therapy as a result of a small subpopulation of cells being able to endure the drug (minimal residual disease cells) and eventually develop further mutations that allow them to regrow and become the dominant population in the therapy-resistant tumor. This subpopulation of cells appears to have developed through a subclonal event, resulting in driver mutations different from the driver mutation that is tumor-initiating in the most common ancestor. As such, an understanding of intratumoral heterogeneity-the driving force behind minimal residual disease-is vital for the identification of resistance drivers that results from branching evolution. Currently available methods allow for a more comprehensive and holistic analysis of tumor heterogeneity in that issues associated with spatial and temporal heterogeneity can now be properly addressed. This review provides some background regarding intratumoral heterogeneity and how it leads to incomplete molecular response to targeted therapies, and proposes the use of single-cell methods, sequential liquid biopsy, and multiregion sequencing to discover the link between intratumoral heterogeneity and early adaptive drug resistance. In summary, minimal residual disease as a result of intratumoral heterogeneity is the earliest form of acquired drug resistance. Emerging technologies such as liquid biopsy and single-cell methods allow for studying targetable drivers of minimal residual disease and contribute to preemptive combinatorial targeting of both drivers of the tumor and its minimal residual disease cells.",
			"category": 2,
			"name": "Lim Zuan-Fu,2020"
		},
		{
			"PMID": 31776900,
			"title": "cMyc and ERK activity are associated with resistance to ALK inhibitory treatment in glioblastoma.",
			"journal": "Journal of neuro-oncology",
			"authorList": [
				"Berberich Anne",
				"Schmitt Lara-Marie",
				"Pusch Stefan",
				"Hielscher Thomas",
				"R\u00fcbmann Petra",
				"Hucke Nanina",
				"Latzer Pauline",
				"He\u00dfling Bernd",
				"Lemke Dieter",
				"Kessler Tobias",
				"Platten Michael",
				"Wick Wolfgang"
			],
			"DOI": "10.1007/s11060-019-03348-z",
			"date": "2020-06-09",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) is expressed in\u2009~\u200960% of glioblastomas and conveys tumorigenic functions. Therefore, ALK inhibitory strategies with alectinib are conceivable for patients with glioblastoma. The aims of this preclinical study were to investigate efficacy as well as to understand and potentially overcome primary and acquired resistance mechanisms of alectinib in glioblastoma.",
			"category": 2,
			"name": "Berberich Anne,2020"
		},
		{
			"PMID": 31658946,
			"title": "Evolutionary stability of collateral sensitivity to antibiotics in the model pathogen ",
			"journal": "eLife",
			"authorList": [
				"Barbosa Camilo",
				"R\u00f6mhild Roderich",
				"Rosenstiel Philip",
				"Schulenburg Hinrich"
			],
			"DOI": "10.7554/eLife.51481",
			"date": "2020-05-11",
			"PMC": "",
			"citation": "",
			"abstract": "Evolution is at the core of the impending antibiotic crisis. Sustainable therapy must thus account for the adaptive potential of pathogens. One option is to exploit evolutionary trade-offs, like collateral sensitivity, where evolved resistance to one antibiotic causes hypersensitivity to another one. To date, the evolutionary stability and thus clinical utility of this trade-off is unclear. We performed a critical experimental test on this key requirement, using evolution experiments with ",
			"category": 2,
			"name": "Barbosa Camilo,2020"
		},
		{
			"PMID": 31559892,
			"title": "A case of primary pulmonary atypical carcinoid with EML4-ALK rearrangement.",
			"journal": "Cancer biology & therapy",
			"authorList": [
				"Liu Na",
				"Wang Jingjing",
				"Fu Xiao",
				"Zheng Xiaoqiang",
				"Gao Huan",
				"Tian Tao",
				"Ruan Zhiping",
				"Yao Yu"
			],
			"DOI": "10.1080/15384047.2019.1665957",
			"date": "2021-03-29",
			"PMC": "",
			"citation": "",
			"abstract": "Targeted therapy has revolutionized the treatment pattern of advanced drive gene mutation positive non-small cell lung cancer (NSCLC). Advanced testing techniques enable physicians to detect these gene alterations in the clinic, thereby offering targeted therapies as treatment options to their patients. In this article, we reported a 52-year-old Chinese female with a pulmonary nodule in her left lower lung. After thoracoscopic lobectomy, a histopathological diagnosis of moderately differentiated atypical carcinoid (AC) was made. Anaplastic lymphoma kinase (ALK) rearrangement was detected, which is a rare phenomenon in AC. After the failure of chemotherapy and radiotherapy, the patient started taking crizotinib, subsequently with ceritinib, and then alectinib. This sequential therapy approach has significant clinical benefits for the patient. This article reviewed the clinical significance and drug resistance mechanism of ALK rearrangement in lung cancer. We also discussed recent and ongoing researches and applications of ALK-tyrosine kinase inhibitors (ALK-TKIs).",
			"category": 2,
			"name": "Liu Na,2021"
		},
		{
			"PMID": 31555485,
			"title": "From crizotinib to lorlatinib: continuous improvement in precision treatment of ALK-positive non-small cell lung cancer.",
			"journal": "ESMO open",
			"authorList": [
				"Pirker Robert",
				"Filipits Martin"
			],
			"DOI": "10.1136/esmoopen-2019-000548",
			"date": "2021-01-26",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Pirker Robert,2021"
		},
		{
			"PMID": 31425908,
			"title": "Novel derivatives of anaplastic lymphoma kinase inhibitors: Synthesis, radiolabeling, and preliminary biological studies of fluoroethyl analogues of crizotinib, alectinib, and ceritinib.",
			"journal": "European journal of medicinal chemistry",
			"authorList": [
				"Radaram Bhasker",
				"Pisaneschi Federica",
				"Rao Yi",
				"Yang Ping",
				"Piwnica-Worms David",
				"Alauddin Mian M"
			],
			"DOI": "10.1016/j.ejmech.2019.111571",
			"date": "2019-11-21",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK), an oncogenic receptor tyrosine kinase, is a therapeutic target in various cancers, including non-small cell lung cancer. Although several ALK inhibitors, including crizotinib, ceritinib, and alectinib, are approved for cancer treatment, their long-term benefit is often limited by the cancer's acquisition of resistance owing to secondary point mutations in ALK. Importantly, some ALK inhibitors cannot cross the blood-brain barrier (BBB) and thus have little or no efficacy against brain metastases. The introduction of a lipophilic moiety, such as a fluoroethyl group may improve the drug's BBB penetration. Herein, we report the synthesis of fluoroethyl analogues of crizotinib 1, alectinib 4, and ceritinib 9, and their radiolabeling with ",
			"category": 2,
			"name": "Radaram Bhasker,2019"
		},
		{
			"PMID": 31388026,
			"title": "Molecular Modeling of ALK L1198F and/or G1202R Mutations to Determine Differential Crizotinib Sensitivity.",
			"journal": "Scientific reports",
			"authorList": [
				"Chuang Yu-Chung",
				"Huang Bo-Yen",
				"Chang Hsin-Wen",
				"Yang Chia-Ning"
			],
			"DOI": "10.1038/s41598-019-46825-1",
			"date": "2020-10-27",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that has been recognized as a therapeutic target for EML4-ALK fusion-positive nonsmall cell lung cancer (NSCLC) treatment using type I kinase inhibitors such as crizotinib to take over the ATP binding site. According to Shaw's measurements, ALK carrying G1202R mutation shows reduced response to crizotinib (IC",
			"category": 2,
			"name": "Chuang Yu-Chung,2020"
		},
		{
			"PMID": 31358542,
			"title": "Treatment with Next-Generation ALK Inhibitors Fuels Plasma ",
			"journal": "Clinical cancer research : an official journal of the American Association for Cancer Research",
			"authorList": [
				"Dagogo-Jack Ibiayi",
				"Rooney Marguerite",
				"Lin Jessica J",
				"Nagy Rebecca J",
				"Yeap Beow Y",
				"Hubbeling Harper",
				"Chin Emily",
				"Ackil Jennifer",
				"Farago Anna F",
				"Hata Aaron N",
				"Lennerz Jochen K",
				"Gainor Justin F",
				"Lanman Richard B",
				"Shaw Alice T"
			],
			"DOI": "10.1158/1078-0432.CCR-19-1436",
			"date": "2020-09-10",
			"PMC": "",
			"citation": "",
			"abstract": "Acquired resistance to next-generation ALK tyrosine kinase inhibitors (TKIs) is often driven by secondary ",
			"category": 2,
			"name": "Dagogo-Jack Ibiayi,2020"
		},
		{
			"PMID": 31354290,
			"title": "Profile of alectinib for the treatment of ALK-positive non-small cell lung cancer (NSCLC): patient selection and perspectives.",
			"journal": "OncoTargets and therapy",
			"authorList": [
				"Karachaliou Niki",
				"Fernandez Bruno Manuel",
				"Bracht Jillian Wilhelmina Paulina",
				"Rosell Rafael"
			],
			"DOI": "10.2147/OTT.S174548",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "Discovered in 2007, anaplastic lymphoma kinase (ALK) gene rearrangements positive (ALK+) lung cancers compose a small subset of non-small cell lung cancer (NSCLC), with rapidly expanded treatments. There are currently several ALK inhibitors, including crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib which have been licensed by the US Food and Drug Administration or the European Medicines Agency for the treatment of ALK+ NSCLC patients. Along with the multiple therapies, the survival of this subtype of NSCLC has been significantly expanded, even for patients whose disease has spread in the brain. Alectinib (Alecensa), a specific ALK and rearranged during transfection tyrosine kinase inhibitor is approved as first-line therapy for metastatic ALK+ NSCLC patients. It is additionally approved for ALK+ NSCLC previously treated with crizotinib. The main aim of this review is to assemble on the efficacy of alectinib for the treatment of ALK+ NSCLC, to elaborate the activity of the drug in the central nervous system, and to debate on which is the position of this compound in the treatment course of ALK+ lung cancer patients.",
			"category": 2,
			"name": "Karachaliou Niki,2020"
		},
		{
			"PMID": 31338990,
			"title": "Short progression-free survival of ALK inhibitors sensitive to secondary mutations in ALK-positive NSCLC patients.",
			"journal": "Thoracic cancer",
			"authorList": [
				"Haratake Naoki",
				"Seto Takashi",
				"Takamori Shinkichi",
				"Toyozawa Ryo",
				"Nosaki Kaname",
				"Miura Naoko",
				"Ohba Taro",
				"Toyokawa Gouji",
				"Taguchi Kenichi",
				"Yamaguchi Masafumi",
				"Shimokawa Mototsugu",
				"Takenoyama Mitsuhiro"
			],
			"DOI": "10.1111/1759-7714.13143",
			"date": "2020-08-04",
			"PMC": "",
			"citation": "",
			"abstract": "Most non-small cell lung cancer (NSCLC) patients relapse on anaplastic lymphoma kinase-tyrosine kinase inhibitor (ALK-TKI) therapy because of acquired resistance. Rebiopsy is recommended to provide optimal therapy after relapse for some ALK-TKI therapies; however, little clinical data exists on the clinical efficacy of ALK-TKI tailored to secondary mutation.",
			"category": 2,
			"name": "Haratake Naoki,2020"
		},
		{
			"PMID": 31113818,
			"title": "Patient-Specific Tumor Growth Trajectories Determine Persistent and Resistant Cancer Cell Populations during Treatment with Targeted Therapies.",
			"journal": "Cancer research",
			"authorList": [
				"Grassberger Clemens",
				"McClatchy David",
				"Geng Changran",
				"Kamran Sophia C",
				"Fintelmann Florian",
				"Maruvka Yosef E",
				"Piotrowska Zofia",
				"Willers Henning",
				"Sequist Lecia V",
				"Hata Aaron N",
				"Paganetti Harald"
			],
			"DOI": "10.1158/0008-5472.CAN-18-3652",
			"date": "2020-04-08",
			"PMC": "",
			"citation": "",
			"abstract": "The importance of preexisting versus acquired drug resistance in patients with cancer treated with small-molecule tyrosine kinase inhibitors (TKI) remains controversial. The goal of this study is to provide a general estimate of the size and dynamics of a preexisting, drug-resistant tumor cell population versus a slow-growing persister population that is the precursor of acquired TKI resistance. We describe a general model of resistance development, including persister evolution and preexisting resistance, solely based on the macroscopic trajectory of tumor burden during treatment. We applied the model to 20 tumor volume trajectories of EGFR-mutant lung cancer patients treated with the TKI erlotinib. Under the assumption of only preexisting resistant cells or only persister evolution, it is not possible to explain the observed tumor trajectories with realistic parameter values. Assuming only persister evolution would require very high mutation induction rates, while only preexisting resistance would lead to very large preexisting populations of resistant cells at the initiation of treatment. However, combining preexisting resistance with persister populations can explain the observed tumor volume trajectories and yields an estimated preexisting resistant fraction varying from 10",
			"category": 2,
			"name": "Grassberger Clemens,2020"
		},
		{
			"PMID": 31058077,
			"title": "Identification of Genetic Mutations in Cancer: Challenge and Opportunity in the New Era of Targeted Therapy.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Jin Jing",
				"Wu Xu",
				"Yin Jianhua",
				"Li Mingxing",
				"Shen Jing",
				"Li Jing",
				"Zhao Yueshui",
				"Zhao Qijie",
				"Wu Jingbo",
				"Wen Qinglian",
				"Cho Chi Hin",
				"Yi Tao",
				"Xiao Zhangang",
				"Qu Liping"
			],
			"DOI": "10.3389/fonc.2019.00263",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "The introduction of targeted therapy is the biggest success in the treatment of cancer in the past few decades. However, heterogeneous cancer is characterized by diverse molecular alterations as well as multiple clinical profiles. Specific genetic mutations in cancer therapy targets may increase drug sensitivity, or more frequently result in therapeutic resistance. In the past 3 years, several novel targeted therapies have been approved for cancer treatment, including drugs with new targets (i.e., anti-PD1/PDL1 therapies and CDK4/6 inhibitors), mutation targeting drugs (i.e., the EGFR T790M targeting osimertinib), drugs with multiple targets (i.e., the EGFR/HER2 dual inhibitor neratinib) and drug combinations (i.e., encorafenib/binimetinib and dabrafenib/trametinib). In this perspective, we focus on the most up-to-date knowledge of targeted therapy and describe how genetic mutations influence the sensitivity of targeted therapy, highlighting the challenges faced within this era of precision medicine. Moreover, the strategies that deal with mutation-driven resistance are further discussed. Advances in these areas would allow for more targeted and effective therapeutic options for cancer patients.",
			"category": 2,
			"name": "Jin Jing,2020"
		},
		{
			"PMID": 30875928,
			"title": "Newer-Generation EGFR Inhibitors in Lung Cancer: How Are They Best Used?",
			"journal": "Cancers",
			"authorList": [
				"Le Tri",
				"Gerber David E"
			],
			"DOI": "10.3390/cancers11030366",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "The FLAURA trial established osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), as a viable first-line therapy in non-small cell lung cancer (NSCLC) with sensitizing ",
			"category": 2,
			"name": "Le Tri,2020"
		},
		{
			"PMID": 30804663,
			"title": "Brigatinib for ",
			"journal": "Drug design, development and therapy",
			"authorList": [
				"Ali Robert",
				"Arshad Junaid",
				"Palacio Sofia",
				"Mudad Raja"
			],
			"DOI": "10.2147/DDDT.S147499",
			"date": "2019-07-31",
			"PMC": "",
			"citation": "",
			"abstract": "Despite the benefits of first and second generation anaplastic lymphoma kinase (",
			"category": 2,
			"name": "Ali Robert,2019"
		},
		{
			"PMID": 30803032,
			"title": "Targeting anaplastic lymphoma kinase in neuroblastoma.",
			"journal": "APMIS : acta pathologica, microbiologica, et immunologica Scandinavica",
			"authorList": [
				"Umapathy Ganesh",
				"Mendoza-Garcia Patricia",
				"Hallberg Bengt",
				"Palmer Ruth H"
			],
			"DOI": "10.1111/apm.12940",
			"date": "2019-05-31",
			"PMC": "",
			"citation": "",
			"abstract": "Over the last decade, anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase (RTK), has been identified as a fusion partner in a diverse variety of translocation events resulting in oncogenic signaling in many different cancer types. In tumors where the full-length ALK RTK itself is mutated, such as neuroblastoma, the picture regarding the role of ALK as an oncogenic driver is less clear. Neuroblastoma is a complex and heterogeneous tumor that arises from the neural crest derived peripheral nervous system. Although high-risk neuroblastoma is rare, it often relapses and becomes refractory to treatment. Thus, neuroblastoma accounts for 10-15% of all childhood cancer deaths. Since most cases are in children under the age of 2, understanding the role and regulation of ALK during neural crest development is an important goal in addressing neuroblastoma tumorigenesis. An impressive array of tyrosine kinase inhibitors (TKIs) that act to inhibit ALK have been FDA approved for use in ALK-driven cancers. ALK TKIs bind differently within the ATP-binding pocket of the ALK kinase domain and have been associated with different resistance mutations within ALK itself that arise in response to therapeutic use, particularly in ALK-fusion positive non-small cell lung cancer (NSCLC). This patient population has highlighted the importance of considering the relevant ALK TKI to be used for a given ALK mutant variant. In this review, we discuss ALK in neuroblastoma, as well as the use of ALK TKIs and other strategies to inhibit tumor growth. Current efforts combining novel approaches and increasing our understanding of the oncogenic role of ALK in neuroblastoma are aimed at improving the efficacy of ALK TKIs as precision medicine options in the clinic.",
			"category": 2,
			"name": "Umapathy Ganesh,2019"
		},
		{
			"PMID": 30775027,
			"title": "Circulating tumor cells (CTCs) for the noninvasive monitoring and personalization of non-small cell lung cancer (NSCLC) therapies.",
			"journal": "Journal of thoracic disease",
			"authorList": [
				"Pawlikowska Patrycja",
				"Faugeroux Vincent",
				"Oulhen Marianne",
				"Aberlenc Agathe",
				"Tayoun Tala",
				"Pailler Emma",
				"Farace Fran\u00e7oise"
			],
			"DOI": "10.21037/jtd.2018.12.80",
			"date": "2020-09-29",
			"PMC": "",
			"citation": "",
			"abstract": "Growing evidences for tumor heterogeneity confirm that single-tumor biopsies frequently fail to reveal the widespread mutagenic profile of tumor. Repeated biopsies are in most cases unfeasible, especially in advanced cancers. We describe here how circulating tumor cells (CTCs) isolated from minimally invasive blood sample might inform us about intratumor heterogeneity, tumor evolution and treatment resistance. We also discuss the advances of CTCs research, most notably in molecularly selected non-small cell lung cancer (NSCLC) patients, highlighting challenges and opportunities related to personalized therapy.",
			"category": 2,
			"name": "Pawlikowska Patrycja,2020"
		},
		{
			"PMID": 30737082,
			"title": "Refining precision cancer therapy in ALK-positive NSCLC.",
			"journal": "EBioMedicine",
			"authorList": [
				"Lin Jessica J",
				"Shaw Alice T"
			],
			"DOI": "10.1016/j.ebiom.2019.01.059",
			"date": "2019-07-22",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Lin Jessica J,2019"
		},
		{
			"PMID": 30719203,
			"title": "We shall overcome (drug resistance) some day.",
			"journal": "Oncotarget",
			"authorList": [
				"Sharma Geeta G",
				"Mologni Luca"
			],
			"DOI": "10.18632/oncotarget.26550",
			"date": "2020-02-25",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Sharma Geeta G,2020"
		},
		{
			"PMID": 30675517,
			"title": "Utility of the JAX Clinical Knowledgebase in capture and assessment of complex genomic cancer data.",
			"journal": "NPJ precision oncology",
			"authorList": [
				"Patterson Sara E",
				"Statz Cara M",
				"Yin Taofei",
				"Mockus Susan M"
			],
			"DOI": "10.1038/s41698-018-0073-y",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer genomic data is continually growing in complexity, necessitating improved methods for data capture and analysis. Tumors often contain multiple therapeutically relevant alterations, and co-occurring alterations may have a different influence on therapeutic response compared to if those alterations were present alone. One clinically important example of this is the existence of a resistance conferring alteration in combination with a therapeutic sensitizing mutation. The JAX Clinical Knowledgebase (JAX-CKB) (https://ckb.jax.org/) has incorporated the concept of the complex molecular profile, which enables association of therapeutic efficacy data with multiple genomic alterations simultaneously. This provides a mechanism for rapid and accurate assessment of complex cancer-related data, potentially aiding in streamlined clinical decision making. Using the JAX-CKB, we demonstrate the utility of associating data with complex profiles comprising ALK fusions with another variant, which have differing impacts on sensitivity to various ALK inhibitors depending on context.",
			"category": 2,
			"name": "Patterson Sara E,2020"
		},
		{
			"PMID": 30662002,
			"title": "Prediction of ALK mutations mediating ALK-TKIs resistance and drug re-purposing to overcome the resistance.",
			"journal": "EBioMedicine",
			"authorList": [
				"Okada Koutaroh",
				"Araki Mitsugu",
				"Sakashita Takuya",
				"Ma Biao",
				"Kanada Ryo",
				"Yanagitani Noriko",
				"Horiike Atsushi",
				"Koike Sumie",
				"Oh-Hara Tomoko",
				"Watanabe Kana",
				"Tamai Keiichi",
				"Maemondo Makoto",
				"Nishio Makoto",
				"Ishikawa Takeshi",
				"Okuno Yasushi",
				"Fujita Naoya",
				"Katayama Ryohei"
			],
			"DOI": "10.1016/j.ebiom.2019.01.019",
			"date": "2019-07-22",
			"PMC": "",
			"citation": "",
			"abstract": "Alectinib has shown a greater efficacy to ALK-rearranged non-small-cell lung cancers in first-line setting; however, most patients relapse due to acquired resistance, such as secondary mutations in ALK including I1171N and G1202R. Although ceritinib or lorlatinib was shown to be effective to these resistant mutants, further resistance often emerges due to ALK-compound mutations in relapse patients following the use of ceritinib or lorlatinib. However, the drug for overcoming resistance has not been established yet.",
			"category": 2,
			"name": "Okada Koutaroh,2019"
		},
		{
			"PMID": 30643578,
			"title": "Spotlight on the treatment of ",
			"journal": "Lung cancer management",
			"authorList": [
				"Mamdani Hirva",
				"Jalal Shadia I"
			],
			"DOI": "10.2217/lmt-2018-0004",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Mamdani Hirva,2020"
		},
		{
			"PMID": 30604291,
			"title": "Lorlatinib: First Global Approval.",
			"journal": "Drugs",
			"authorList": [
				"Syed Yahiya Y"
			],
			"DOI": "10.1007/s40265-018-1041-0",
			"date": "2019-09-24",
			"PMC": "",
			"citation": "",
			"abstract": "Lorlatinib is an oral small molecule inhibitor of anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (ROS1) kinase developed by Pfizer for the treatment of ALK-positive non-small cell lung cancer (NSCLC). Based on results from a phase I/II trial, lorlatinib received approval in Japan in September 2018 and in the USA in November 2018 for the treatment of ALK-positive NSCLC. This article summarizes the milestones in the development of lorlatinib leading to the first global approval for this indication.",
			"category": 2,
			"name": "Syed Yahiya Y,2019"
		},
		{
			"PMID": 30565433,
			"title": "Detecting EGFR mutations and ALK/ROS1 rearrangements in non-small cell lung cancer using malignant pleural effusion samples.",
			"journal": "Thoracic cancer",
			"authorList": [
				"Yao Yi",
				"Peng Min",
				"Shen Qinglin",
				"Hu Qinyong",
				"Gong Hongyun",
				"Li Qingqing",
				"Zheng Zhongliang",
				"Xu Bin",
				"Li Yingge",
				"Dong Yi"
			],
			"DOI": "10.1111/1759-7714.12932",
			"date": "2020-02-07",
			"PMC": "",
			"citation": "",
			"abstract": "The study was conducted to evaluate the feasibility of using malignant pleural effusion (MPE) as a substitute specimen for genetic testing and to determine the significance of genetic profiling of MPE tumor cells to monitor non-small cell lung cancer (NSCLC) progression and therapeutic response.",
			"category": 2,
			"name": "Yao Yi,2020"
		},
		{
			"PMID": 30555260,
			"title": "Efficacy and safety of crizotinib in patients with anaplastic lymphoma kinase-positive advanced-stage non-small-cell lung cancer.",
			"journal": "Cancer management and research",
			"authorList": [
				"Mohieldin Ahmed",
				"Rasmy Ayman",
				"Ashour Mohamed",
				"Al-Nassar Muath",
				"Ali Rola H",
				"El-Enezi Fahad G"
			],
			"DOI": "10.2147/CMAR.S173084",
			"date": "2022-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer is the leading cause of cancer mortality worldwide, despite advances in management, especially with targeted agents and immunotherapy. Numerous oncogenes have been identified that control the growth of these malignancies. Anaplastic lymphoma kinase (ALK) is a tyrosine kinase that develops distorted functioning as a result of chromosomal rearrangement. Crizotinib, a tyrosine kinase inhibitor (TKI), was approved by the Food and Drug Administration (FDA) in 2011 for the treatment of advanced ALK-positive non-small-cell lung cancer (NSCLC).",
			"category": 2,
			"name": "Mohieldin Ahmed,2022"
		},
		{
			"PMID": 30326973,
			"title": "Microfluidics-based immunofluorescence for fast staining of ALK in lung adenocarcinoma.",
			"journal": "Diagnostic pathology",
			"authorList": [
				"Brajkovic Sa\u0161ka",
				"Pelz Benjamin",
				"Procopio Maria-Giuseppina",
				"Leblond Anne-Laure",
				"Repond Gr\u00e9goire",
				"Schaub-Clerigu\u00e9 Ariane",
				"Dupouy Diego G",
				"Soltermann Alex"
			],
			"DOI": "10.1186/s13000-018-0757-1",
			"date": "2019-01-30",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) is a key oncogenic driver in lung adenocarcinoma patients and its fusion proteins are routinely assessed. The microfluidic tissue processor (MTP) device is based on a chip-confined low-volume technology allowing for rapid immunohistochemistry/immunofluorescence (IHC/IF) stainings of formalin-fixed paraffin-embedded (FFPE) or frozen tissue samples.",
			"category": 2,
			"name": "Brajkovic Sa\u0161ka,2019"
		},
		{
			"PMID": 30210922,
			"title": "Pharmacologic characterization of CT-711, a novel dual inhibitor of ALK and c-Met.",
			"journal": "American journal of cancer research",
			"authorList": [
				"Wang Lei",
				"Gao Mingzhao",
				"Tong Mengya",
				"Xie Chengying",
				"He Ye",
				"Fu Li",
				"Li Yun",
				"Fu Haoyu",
				"Lou Liguang"
			],
			"DOI": "",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) is a validated molecular target for patients harboring ALK rearrangement, which triggers the development of ALK inhibitors. However, the activation of mesenchymal-epithelial transition factor (c-Met) has emerged as a common cause of acquired resistance induced by selective ALK inhibitors. Herein, we report the first preclinical characterization of CT-711, a novel dual inhibitor of ALK and c-Met. CT-711 demonstrates potent inhibitory activity against ALK kinase activity. Moreover, CT-711 profoundly inhibits ALK signal transduction and thereby induces G1 phase arrest and apoptosis, and results in remarkable anti-proliferative activity against ALK-driven cancer cells. Furthermore, CT-711 effectively inhibits c-Met kinase activity and potently overcomes the resistance mediated by c-Met activation. When orally administered to nude mice bearing xenografts, CT-711 exhibits favorable pharmacokinetic properties and robust antitumor activity. It is noteworthy that CT-711 is superior to crizotinib, the first-in-class ALK inhibitor, in the treatment of ALK-driven cancers in various models. The results of the current study provide a solid foundation for the clinical investigation of CT-711 in patients with tumors harboring ALK rearrangement.",
			"category": 2,
			"name": "Wang Lei,2020"
		},
		{
			"PMID": 30201071,
			"title": "[Current Status for Anaplastic Lymphoma Kinase in Non-small Cell Lung Cancer].",
			"journal": "Zhongguo fei ai za zhi = Chinese journal of lung cancer",
			"authorList": [
				"Song Peng",
				"Zhang Li",
				"Shang Congcong"
			],
			"DOI": "10.3779/j.issn.1009-3419.2018.09.10",
			"date": "2018-10-26",
			"PMC": "",
			"citation": "",
			"abstract": "The incidence of ALK gene rearrangement in non-small cell lung cancer (NSCLC) was about 3% to 5%. ALK gene inhibitors have made great breakthrough in recent years, significantly extending the survival period of patients with ALK(+) advanced NSCLC. But the majority of patients will be acquired drug resistance after treatment. This article has been explained separately from the ALK genetic background, the detection method, the treatment of the three generations of ALK inhibitors and the strategy after drug resistance. It is desire to have reference value and reference meaning for clinical work.\u2029.",
			"category": 2,
			"name": "Song Peng,2018"
		},
		{
			"PMID": 30174447,
			"title": "Spotlight on lorlatinib and its potential in the treatment of NSCLC: the evidence to date.",
			"journal": "OncoTargets and therapy",
			"authorList": [
				"Akamine Takaki",
				"Toyokawa Gouji",
				"Tagawa Tetsuzo",
				"Seto Takashi"
			],
			"DOI": "10.2147/OTT.S165511",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "The identification of anaplastic lymphoma kinase (",
			"category": 2,
			"name": "Akamine Takaki,2020"
		},
		{
			"PMID": 30146241,
			"title": "Combining Mutational Signatures, Clonal Fitness, and Drug Affinity to Define Drug-Specific Resistance Mutations in Cancer.",
			"journal": "Cell chemical biology",
			"authorList": [
				"Kaserer Teresa",
				"Blagg Julian"
			],
			"DOI": "10.1016/j.chembiol.2018.07.013",
			"date": "2019-07-01",
			"PMC": "",
			"citation": "",
			"abstract": "The emergence of mutations that confer resistance to molecularly targeted therapeutics is dependent upon the effect of each mutation on drug affinity for the target protein, the clonal fitness of cells harboring the mutation, and the probability that each variant can be generated by DNA codon base mutation. We present a computational workflow that combines these three factors to identify mutations likely to arise upon drug treatment in a particular tumor type. The Osprey-based workflow is validated using a comprehensive dataset of ERK2 mutations and is applied to small-molecule drugs and/or therapeutic antibodies targeting KIT, EGFR, Abl, and ALK. We identify major\u00a0clinically observed drug-resistant mutations for drug-target pairs and highlight the potential to\u00a0prospectively identify probable drug resistance mutations.",
			"category": 2,
			"name": "Kaserer Teresa,2019"
		},
		{
			"PMID": 30123543,
			"title": "(J)ALEX the great: a new era in the world of ALK inhibitors.",
			"journal": "Journal of thoracic disease",
			"authorList": [
				"Brosseau Solenn",
				"Gounant Val\u00e9rie",
				"Zalcman G\u00e9rard"
			],
			"DOI": "10.21037/jtd.2018.06.142",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Brosseau Solenn,2020"
		},
		{
			"PMID": 30123541,
			"title": "Is alectinib the new first line therapy in ALK-rearranged advanced non-small cell lung cancer?",
			"journal": "Journal of thoracic disease",
			"authorList": [
				"van der Wekken Anthonie J",
				"Kok Klaas",
				"Groen Harry J M"
			],
			"DOI": "10.21037/jtd.2018.06.45",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "van der Wekken Anthonie J,2020"
		},
		{
			"PMID": 30108712,
			"title": "Identification of a potent kinase inhibitor targeting EML4-ALK fusion protein in non-small cell lung cancer.",
			"journal": "MedChemComm",
			"authorList": [
				"Luo Lian-Xiang",
				"Li Ying",
				"Niu Yu-Zhen",
				"Wang Yu-Wei",
				"Wang Qian-Qian",
				"Fan Xing-Xing",
				"Xu Jia-Hui",
				"Liu Liang",
				"Leung Elaine Lai-Han",
				"Yao Xiao-Jun"
			],
			"DOI": "10.1039/c7md00305f",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "ALK-fusion proteins play a fundamental role in the development of about 5% of non-small cell lung cancers. Herein, we identified the compound 5067-0952 as a potent ALK inhibitor, which inhibited cell growth, induced apoptosis, and suppressed the phosphorylation of ALK, subsequently blocking its downstream signaling pathway.",
			"category": 2,
			"name": "Luo Lian-Xiang,2020"
		},
		{
			"PMID": 30098166,
			"title": "Optimizing Cancer Treatment Using Game Theory: A Review.",
			"journal": "JAMA oncology",
			"authorList": [
				"Stankov\u00e1 Katerina",
				"Brown Joel S",
				"Dalton William S",
				"Gatenby Robert A"
			],
			"DOI": "10.1001/jamaoncol.2018.3395",
			"date": "2019-12-19",
			"PMC": "",
			"citation": "",
			"abstract": "While systemic therapy for disseminated cancer is often initially successful, malignant cells, using diverse adaptive strategies encoded in the human genome, almost invariably evolve resistance, leading to treatment failure. Thus, the Darwinian dynamics of resistance are formidable barriers to all forms of systemic cancer treatment but rarely integrated into clinical trial design or included within precision oncology initiatives.",
			"category": 2,
			"name": "Stankov\u00e1 Katerina,2019"
		},
		{
			"PMID": 30089719,
			"title": "Personalized therapy for lung cancer: striking a moving target.",
			"journal": "JCI insight",
			"authorList": [
				"Pakkala Suchita",
				"Ramalingam Suresh S"
			],
			"DOI": "10.1172/jci.insight.120858",
			"date": "2019-12-20",
			"PMC": "",
			"citation": "",
			"abstract": "Molecular targeted therapy heralded a new era for the treatment of patients with oncogene-driven advanced-stage non-small-cell lung cancer (NSCLC). Molecular testing at the time of diagnosis guides therapy selection, and targeted therapies in patients with activating mutations in EGFR, BRAF, and rearrangements in anaplastic lymphoma kinase (ALK) and ROS1 have become part of routine care. These therapies have extended the median survival from a mere few months to greater than 3 years for patients with stage 4 disease. However, despite the initial success, these treatments are eventually met with molecular resistance. Selective pressure leads to cellular adaption to maintain cancer growth, making resistance complex and the treatment challenging. This review focuses on recent advances in targeted therapy, mechanisms of resistance, and therapeutic strategies to overcome resistance in patients with lung cancer.",
			"category": 2,
			"name": "Pakkala Suchita,2019"
		},
		{
			"PMID": 30066208,
			"title": "Sarcoid-like reaction mimicking disease progression in an ALK-positive lung cancer patient receiving lorlatinib.",
			"journal": "Investigational new drugs",
			"authorList": [
				"Facchinetti Francesco",
				"Gnetti Letizia",
				"Balestra Valeria",
				"Silva Mario",
				"Silini Enrico Maria",
				"Ventura Luigi",
				"Majori Maria",
				"Bordi Paola",
				"Tiseo Marcello"
			],
			"DOI": "10.1007/s10637-018-0652-3",
			"date": "2020-02-05",
			"PMC": "",
			"citation": "",
			"abstract": "The administration of target inhibitors is paramount to grant the longest survival in patients with ALK-positive non-small cell lung cancer (NSCLC). The eventual resistance to tyrosine kinase inhibitors (TKI) is monitored clinically and radiologically for prompt molecule shift to further generation TKI, if available. However, the early radiological detection of progression pattern (e.g. nodule onset) should be regarded with caution because overlaps exist with non-tumor cell proliferation and/or accumulation. Here we report the case of a stage IV ALK-rearranged NSCLC patient exposed to serial crizotinib, brigatinib, ceritinib, and lorlatinib (this latter brought to complete brain and leptomeningeal disease response), in a period of more than five years. During lorlatinib, the appearance of solid pulmonary nodules was obviously interpreted as disease progression. However, surgical biopsies of the pulmonary nodules revealed features of sarcoid-like granulomatous lymphadenitis, namely without tumor cell. This invasive approach, besides documenting for the first time a sarcoid-like reaction to ALK inhibitors, allowed to revert the radiological diagnosis and maintain lorlatinib, for the best patient outcome. The pragmatic relevance of these findings suggests a careful attitude towards the interpretation of radiologic patterns of disease progression in patients under TKI.",
			"category": 2,
			"name": "Facchinetti Francesco,2020"
		},
		{
			"PMID": 30006516,
			"title": "Structure and energy based quantitative missense variant effect analysis provides insights into drug resistance mechanisms of anaplastic lymphoma kinase mutations.",
			"journal": "Scientific reports",
			"authorList": [
				"Li Jianzong",
				"Huang Yue",
				"Wu Miaomiao",
				"Wu Chuanfang",
				"Li Xin",
				"Bao Jinku"
			],
			"DOI": "10.1038/s41598-018-28752-9",
			"date": "2019-11-25",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) is considered as a validated molecular target in multiple malignancies, such as non-small cell lung cancer (NSCLC). However, the effectiveness of molecularly targeted therapies using ALK inhibitors is almost universally limited by drug resistance. Drug resistance to molecularly targeted therapies has now become a major obstacle to effective cancer treatment and personalized medicine. It is of particular importance to provide an improved understanding on the mechanisms of resistance of ALK inhibitors, thus rational new therapeutic strategies can be developed to combat resistance. We used state-of-the-art computational approaches to systematically explore the mutational effects of ALK mutations on drug resistance properties. We found the activation of ALK was increased by substitution with destabilizing mutations, creating the capacity to confer drug resistance to inhibitors. In addition, results implied that evolutionary constraints might affect the drug resistance properties. Moreover, an extensive profile of drugs against ALK mutations was constructed to give better understanding of the mechanism of drug resistance based on structural transitions and energetic variation. Our work hopes to provide an up-to-date mechanistic framework for understanding the mechanisms of drug resistance induced by ALK mutations, thus tailor treatment decisions after the emergence of resistance in ALK-dependent diseases.",
			"category": 2,
			"name": "Li Jianzong,2019"
		},
		{
			"PMID": 29973561,
			"title": "Current Molecular-Targeted Therapies in NSCLC and Their Mechanism of Resistance.",
			"journal": "Cancers",
			"authorList": [
				"Schrank Zachary",
				"Chhabra Gagan",
				"Lin Leo",
				"Iderzorig Tsatsral",
				"Osude Chike",
				"Khan Nabiha",
				"Kuckovic Adijan",
				"Singh Sanjana",
				"Miller Rachel J",
				"Puri Neelu"
			],
			"DOI": "10.3390/cancers10070224",
			"date": "2023-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer is treated with many conventional therapies, such as surgery, radiation, and chemotherapy. However, these therapies have multiple undesirable side effects. To bypass the side effects elicited by these conventional treatments, molecularly-targeted therapies are currently in use or under development. Current molecularly-targeted therapies effectively target specific biomarkers, which are commonly overexpressed in lung cancers and can cause increased tumorigenicity. Unfortunately, several molecularly-targeted therapies are associated with initial dramatic responses followed by acquired resistance due to spontaneous mutations or activation of signaling pathways. Acquired resistance to molecularly targeted therapies presents a major clinical challenge in the treatment of lung cancer. Therefore, to address this clinical challenge and to improve lung cancer patient prognosis, we need to understand the mechanism of acquired resistance to current therapies and develop additional novel therapies. This review concentrates on various lung cancer biomarkers, including EGFR, ALK, and BRAF, as well as their potential mechanisms of drug resistance.",
			"category": 2,
			"name": "Schrank Zachary,2023"
		},
		{
			"PMID": 29932159,
			"title": "Understanding Intratumor Heterogeneity and Evolution in NSCLC and Potential New Therapeutic Approach.",
			"journal": "Cancers",
			"authorList": [
				"Goto Taichiro",
				"Hirotsu Yosuke",
				"Amemiya Kenji",
				"Mochizuki Hitoshi",
				"Omata Masao"
			],
			"DOI": "10.3390/cancers10070212",
			"date": "2020-09-29",
			"PMC": "",
			"citation": "",
			"abstract": "Advances in innovative technology, including next-generation sequencing, have allowed comprehensive genomic analysis and the elucidation of the genomic aspect of intratumor heterogeneity (ITH). Moreover, models of the evolution of the cancer genome have been proposed by integrating these analyses. Cancer has been considered to accumulate genetic abnormalities for clonal evolution in time and space, and these evolutionary patterns vary depending on the organs of primary sites. Selection pressure is an important determinant of such evolutionary patterns. With weak selection pressure, more diverse clones coexist, and heterogeneity increases. Heterogeneity is maximized when there is no selection pressure; in other words, neutral evolution occurs. Some types of cancer such as lung cancer evolve in conditions that have maintained close to neutral evolution and produce diverse variants. This ITH is a key factor contributing to the lethal outcome of cancer, therapeutic failure, and drug resistance. This factor reaffirms the complexity and subtle adaptability of cancer. It is expected that further understanding of ITH and cancer genome evolution will facilitate the development of new therapeutic strategies to overcome ITH.",
			"category": 2,
			"name": "Goto Taichiro,2020"
		},
		{
			"PMID": 29888064,
			"title": "A Computational Approach for Prioritizing Selection of Therapies Targeting Drug Resistant Variation in Anaplastic Lymphoma Kinase.",
			"journal": "AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science",
			"authorList": [
				"McCoy Matthew D",
				"Madhavan Subha"
			],
			"DOI": "",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase implicated as a driver of a number of cancer types, and activates cellular pathways involved in cell proliferation and differentiation. Tyrosine kinase inhibitors (TKIs) are a small molecule therapeutic that blocks ALK function, but tumor evolution leads to the rapid emergence of drug resistant somatic variation and necessitates selection of a new treatment strategy. Computational simulations of protein:drug interactions were used to investigate the impact of seven drug resistant mutations on binding to eleven TKIs approved, or under investigation, for treatment of ALK positive cancers. The results show variant specific disruptions to TKI molecular interactions, and demonstrate the potential to aid prioritization of therapeutic interventions. Validation remains a challenge due to the complex dependence of biomolecular interactions on the local biophysical environment, but improvements to the underlying structural model and continued curation efforts will improve the clinical utility of computational predictions.",
			"category": 2,
			"name": "McCoy Matthew D,2020"
		},
		{
			"PMID": 29862230,
			"title": "Treating ALK-positive non-small cell lung cancer.",
			"journal": "Annals of translational medicine",
			"authorList": [
				"Ziogas Dimitrios C",
				"Tsiara Anna",
				"Tsironis Georgios",
				"Lykka Maria",
				"Liontos Michalis",
				"Bamias Aristotelis",
				"Dimopoulos Meletios-Athanasios"
			],
			"DOI": "10.21037/atm.2017.11.34",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Targeting genomic alterations, such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements, have radically changed the treatment of patients with non-small cell lung cancer (NSCLC). In the case of ALK-rearranged gene, subsequent rapid development of effective genotype-directed therapies with ALK tyrosine kinase inhibitors (TKIs) triggered major advances in the personalized molecularly based approach of NSCLC. Crizotinib was the first-in-class ALK TKI with proven superiority over standard platinum-based chemotherapy for the 1st-line therapy of ALK-rearranged NSCLC patients. However, the acquired resistance to crizotinib and its diminished efficacy to the central nervous system (CNS) relapse led to the development of several novel ALK inhibitors, more potent and with different selectivity compared to crizotinib. To date, four ALK TKIs, crizotinib, ceritinib, alectinib and brigatinib have received approval from the Food and Drug Administration (FDA) and/or the European Medicines Agency (EMA) and even more agents are currently under investigation for the treatment of ALK-rearranged NSCLC. However, the optimal frontline approach and the exact sequence of ALK inhibitors are still under consideration. Recently announced results of phase III trials recognized higher efficacy of alectinib compared to crizotinib in first-line setting, even in patients with CNS involvement. In this review, we will discuss the current knowledge regarding the biology of the ALK-positive NSCLC, the available therapeutic inhibitors and we will focus on the raised issues from their use in clinical practise.",
			"category": 2,
			"name": "Ziogas Dimitrios C,2020"
		},
		{
			"PMID": 29808239,
			"title": "Management of Resistance to First-Line Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitor Therapy.",
			"journal": "Current treatment options in oncology",
			"authorList": [
				"Peters Solange",
				"Zimmermann Stefan"
			],
			"DOI": "10.1007/s11864-018-0553-x",
			"date": "2019-08-20",
			"PMC": "",
			"citation": "",
			"abstract": "A decade after the discovery of echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (EML4-ALK) rearrangements in non-small cell lung cancer (NSCLC), several inhibitors have gained regulatory approval, and their sequential use has deferred platinum-based chemotherapy to later lines of therapy. Nevertheless, although most ALK-driven tumors dramatically respond to ALK TKIs , all patients ultimately develop drug-resistant disease. Analysis of post-progression biopsy samples has provided invaluable insight into the mechanisms of resistance, now informing on subsequent therapeutic strategies. In particular, the identification of secondary ALK mutations, which are a common mechanism of resistance to both first-generation and to an even larger extent to second-generation ALK TKIs, may shape a personalized optimal treatment strategy beyond the current first-line choice. Alectinib has now become a preferred treatment option in the first line of therapy, and extrapolation of data obtained from post-progression samples after second-line next-generation ALK TKIs suggests that acquired resistance is likely to be mediated in more than half of patients by ALK resistance mutations. Nevertheless, clinical and preclinical evidence suggests that multiple resistance mechanisms may co-exist at different levels in the same TKI-resistant patient. Newer ALK tyrosine kinase inhibitors (TKIs) overcome some resistance mutations through higher exposure and potency, and generally present greater CNS activity, but are unlikely to overcome resistance mediated through separate oncogenic pathway activations, or epithelial to mesenchymal transition (EMT) and small cell lung cancer (SCLC) transformation. Furthermore, while resistance mutations can be detected through commonly available sequencing methods, the identification of other mechanisms of resistance is much less straightforward in the clinic. We hypothesize that the ALK resistance mutation status will likely be crucially important in the choice of second-line therapy after a second-generation TKI. Emerging clinical data also refines the optimal placing of PD-1- and PD-L1-directed immunotherapy in the treatment sequence.",
			"category": 2,
			"name": "Peters Solange,2019"
		},
		{
			"PMID": 29785088,
			"title": "Insight into resistance mechanism of anaplastic lymphoma kinase to alectinib and JH-VIII-157-02 caused by G1202R solvent front mutation.",
			"journal": "Drug design, development and therapy",
			"authorList": [
				"Wang Han",
				"Wang Yao",
				"Guo Wentao",
				"Du Bin",
				"Huang Xiaobing",
				"Wu Riping",
				"Yang Baoyu",
				"Lin Xiaoyan",
				"Wu Yilan"
			],
			"DOI": "10.2147/DDDT.S147104",
			"date": "2018-10-11",
			"PMC": "",
			"citation": "",
			"abstract": "Mutated anaplastic lymphoma kinase (ALK) drives the development of advanced non-small cell lung cancer (NSCLC). Most reported small-molecule inhibitors targeting the ALK domain do not display good inhibition of the G1202R solvent front mutation. The solvent front mutation was assumed to hinder drug binding. However, a different fact could be uncovered by the simulations reported in this study through a structural analog of alectinib (JH-VIII-157-02), which demonstrated potent effects against the G1202R mutation.",
			"category": 2,
			"name": "Wang Han,2018"
		},
		{
			"PMID": 29782561,
			"title": "Lorlatinib in ALK- and ROS1-positive NSCLC: the future has a start.",
			"journal": "Translational lung cancer research",
			"authorList": [
				"Facchinetti Francesco",
				"Friboulet Luc"
			],
			"DOI": "10.21037/tlcr.2018.02.04",
			"date": "2024-03-18",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Facchinetti Francesco,2024"
		},
		{
			"PMID": 29764517,
			"title": "New insights from the widening homogeneity perspective to target intratumor heterogeneity.",
			"journal": "Cancer communications (London, England)",
			"authorList": [
				"Tong Mengying",
				"Deng Ziqian",
				"Zhang Xiaolong",
				"He Bin",
				"Yang Mengying",
				"Cheng Wei",
				"Liu Quentin"
			],
			"DOI": "10.1186/s40880-018-0287-y",
			"date": "2019-02-25",
			"PMC": "",
			"citation": "",
			"abstract": "Precision medicine has shed new light on the treatment of heterogeneous cancer patients. However, intratumor heterogeneity strongly constrains the clinical benefit of precision medicine. Thus, rethinking therapeutic strategies from a different facet within the precision medicine framework will not only diversify clinical interventions, but also provide an avenue for precision medicine. Here, we explore the current approaches for targeting intratumor heterogeneity and their limitations. Furthermore, we propose a theoretical strategy with a \"homogenization\" feature based on iatrogenic evolutionary selection to target intratumor heterogeneity.",
			"category": 2,
			"name": "Tong Mengying,2019"
		},
		{
			"PMID": 29764505,
			"title": "Xenograft tumors derived from malignant pleural effusion of the patients with non-small-cell lung cancer as models to explore drug resistance.",
			"journal": "Cancer communications (London, England)",
			"authorList": [
				"Xu Yunhua",
				"Zhang Feifei",
				"Pan Xiaoqing",
				"Wang Guan",
				"Zhu Lei",
				"Zhang Jie",
				"Wen Danyi",
				"Lu Shun"
			],
			"DOI": "10.1186/s40880-018-0284-1",
			"date": "2019-02-25",
			"PMC": "",
			"citation": "",
			"abstract": "Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions show dramatic responses to specific tyrosine kinase inhibitors (TKIs); however, after 10-12\u00a0months, secondary mutations arise that confer resistance. We generated a murine xenograft model using patient-derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK- and EGFR-targeted TKIs crizotinib and osimertinib, respectively.",
			"category": 2,
			"name": "Xu Yunhua,2019"
		},
		{
			"PMID": 29708964,
			"title": "Antibiotic combination efficacy (ACE) networks for a Pseudomonas aeruginosa model.",
			"journal": "PLoS biology",
			"authorList": [
				"Barbosa Camilo",
				"Beardmore Robert",
				"Schulenburg Hinrich",
				"Jansen Gunther"
			],
			"DOI": "10.1371/journal.pbio.2004356",
			"date": "2019-03-27",
			"PMC": "",
			"citation": "",
			"abstract": "The spread of antibiotic resistance is always a consequence of evolutionary processes. The consideration of evolution is thus key to the development of sustainable therapy. Two main factors were recently proposed to enhance long-term effectiveness of drug combinations: evolved collateral sensitivities between the drugs in a pair and antagonistic drug interactions. We systematically assessed these factors by performing over 1,600 evolution experiments with the opportunistic nosocomial pathogen Pseudomonas aeruginosa in single- and multidrug environments. Based on the growth dynamics during these experiments, we reconstructed antibiotic combination efficacy (ACE) networks as a new tool for characterizing the ability of the tested drug combinations to constrain bacterial survival as well as drug resistance evolution across time. Subsequent statistical analysis of the influence of the factors on ACE network characteristics revealed that (i) synergistic drug interactions increased the likelihood of bacterial population extinction-irrespective of whether combinations were compared at the same level of inhibition or not-while (ii) the potential for evolved collateral sensitivities between 2 drugs accounted for a reduction in bacterial adaptation rates. In sum, our systematic experimental analysis allowed us to pinpoint 2 complementary determinants of combination efficacy and to identify specific drug pairs with high ACE scores. Our findings can guide attempts to further improve the sustainability of antibiotic therapy by simultaneously reducing pathogen load and resistance evolution.",
			"category": 2,
			"name": "Barbosa Camilo,2019"
		},
		{
			"PMID": 29660984,
			"title": "Chemically Induced Degradation of Anaplastic Lymphoma Kinase (ALK).",
			"journal": "Journal of medicinal chemistry",
			"authorList": [
				"Powell Chelsea E",
				"Gao Yang",
				"Tan Li",
				"Donovan Katherine A",
				"Nowak Rados\u0142aw P",
				"Loehr Amanda",
				"Bahcall Magda",
				"Fischer Eric S",
				"J\u00e4nne Pasi A",
				"George Rani E",
				"Gray Nathanael S"
			],
			"DOI": "10.1021/acs.jmedchem.7b01655",
			"date": "2019-05-28",
			"PMC": "",
			"citation": "",
			"abstract": "We present the development of the first small molecule degraders that can induce anaplastic lymphoma kinase (ALK) degradation, including in non-small-cell lung cancer (NSCLC), anaplastic large-cell lymphoma (ALCL), and neuroblastoma (NB) cell lines. These degraders were developed through conjugation of known pyrimidine-based ALK inhibitors, TAE684 or LDK378, and the cereblon ligand pomalidomide. We demonstrate that in some cell types degrader potency is compromised by expression of drug transporter ABCB1. In addition, proteomic profiling demonstrated that these compounds also promote the degradation of additional kinases including PTK2 (FAK), Aurora A, FER, and RPS6KA1 (RSK1).",
			"category": 2,
			"name": "Powell Chelsea E,2019"
		},
		{
			"PMID": 29650534,
			"title": "Sequential ALK Inhibitors Can Select for Lorlatinib-Resistant Compound ",
			"journal": "Cancer discovery",
			"authorList": [
				"Yoda Satoshi",
				"Lin Jessica J",
				"Lawrence Michael S",
				"Burke Benjamin J",
				"Friboulet Luc",
				"Langenbucher Adam",
				"Dardaei Leila",
				"Prutisto-Chang Kylie",
				"Dagogo-Jack Ibiayi",
				"Timofeevski Sergei",
				"Hubbeling Harper",
				"Gainor Justin F",
				"Ferris Lorin A",
				"Riley Amanda K",
				"Kattermann Krystina E",
				"Timonina Daria",
				"Heist Rebecca S",
				"Iafrate A John",
				"Benes Cyril H",
				"Lennerz Jochen K",
				"Mino-Kenudson Mari",
				"Engelman Jeffrey A",
				"Johnson Ted W",
				"Hata Aaron N",
				"Shaw Alice T"
			],
			"DOI": "10.1158/2159-8290.CD-17-1256",
			"date": "2019-09-06",
			"PMC": "",
			"citation": "",
			"abstract": "The cornerstone of treatment for advanced ALK-positive lung cancer is sequential therapy with increasingly potent and selective ALK inhibitors. The third-generation ALK inhibitor lorlatinib has demonstrated clinical activity in patients who failed previous ALK inhibitors. To define the spectrum of ",
			"category": 2,
			"name": "Yoda Satoshi,2019"
		},
		{
			"PMID": 29642598,
			"title": "ALK in Neuroblastoma: Biological and Therapeutic Implications.",
			"journal": "Cancers",
			"authorList": [
				"Trigg Ricky M",
				"Turner Suzanne D"
			],
			"DOI": "10.3390/cancers10040113",
			"date": "2020-09-29",
			"PMC": "",
			"citation": "",
			"abstract": "Neuroblastoma (NB) is the most common and deadly solid tumour in children. Despite the development of new treatment options for high-risk NB, over half of patients relapse and five-year survival remains at 40-50%. Therefore, novel treatment strategies aimed at providing long-term disease remission are urgently sought. ",
			"category": 2,
			"name": "Trigg Ricky M,2020"
		},
		{
			"PMID": 29636358,
			"title": "Resistance Mechanisms to Targeted Therapies in ",
			"journal": "Clinical cancer research : an official journal of the American Association for Cancer Research",
			"authorList": [
				"McCoach Caroline E",
				"Le Anh T",
				"Gowan Katherine",
				"Jones Kenneth",
				"Schubert Laura",
				"Doak Andrea",
				"Estrada-Bernal Adriana",
				"Davies Kurtis D",
				"Merrick Daniel T",
				"Bunn Paul A",
				"Purcell W Tom",
				"Dziadziuszko Rafal",
				"Varella-Garcia Marileila",
				"Aisner Dara L",
				"Camidge D Ross",
				"Doebele Robert C"
			],
			"DOI": "10.1158/1078-0432.CCR-17-2452",
			"date": "2019-12-20",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "McCoach Caroline E,2019"
		},
		{
			"PMID": 29601554,
			"title": "Treatment Options for Paediatric Anaplastic Large Cell Lymphoma (ALCL): Current Standard and beyond.",
			"journal": "Cancers",
			"authorList": [
				"Prokoph Nina",
				"Larose Hugo",
				"Lim Megan S",
				"Burke G A Amos",
				"Turner Suzanne D"
			],
			"DOI": "10.3390/cancers10040099",
			"date": "2024-03-14",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic Lymphoma Kinase (ALK)-positive Anaplastic Large Cell Lymphoma (ALCL), remains one of the most curable cancers in the paediatric setting; multi-agent chemotherapy cures approximately 65-90% of patients. Over the last two decades, major efforts have focused on improving the survival rate by intensification of combination chemotherapy regimens and employing stem cell transplantation for chemotherapy-resistant patients. More recently, several new and 'renewed' agents have offered the opportunity for a change in the paradigm for the management of both chemo-sensitive and chemo-resistant forms of ALCL. The development of ALK inhibitors following the identification of the EML4-ALK fusion gene in Non-Small Cell Lung Cancer (NSCLC) has opened new possibilities for ALK-positive ALCL. The uniform expression of CD30 on the cell surface of ALCL has given the opportunity for anti-CD30 antibody therapy. The re-evaluation of vinblastine, which has shown remarkable activity as a single agent even in the face of relapsed disease, has led to the consideration of a revised approach to frontline therapy. The advent of immune therapies such as checkpoint inhibition has provided another option for the treatment of ALCL. In fact, the number of potential new agents now presents a real challenge to the clinical community that must prioritise those thought to offer the most promise for the future. In this review, we will focus on the current status of paediatric ALCL therapy, explore how new and 'renewed' agents are re-shaping the therapeutic landscape for ALCL, and identify the strategies being employed in the next generation of clinical trials.",
			"category": 2,
			"name": "Prokoph Nina,2024"
		},
		{
			"PMID": 29599410,
			"title": "Clinical Utility of Cell-Free DNA for the Detection of ",
			"journal": "Clinical cancer research : an official journal of the American Association for Cancer Research",
			"authorList": [
				"McCoach Caroline E",
				"Blakely Collin M",
				"Banks Kimberly C",
				"Levy Benjamin",
				"Chue Ben M",
				"Raymond Victoria M",
				"Le Anh T",
				"Lee Christine E",
				"Diaz Joseph",
				"Waqar Saiama N",
				"Purcell William T",
				"Aisner Dara L",
				"Davies Kurtis D",
				"Lanman Richard B",
				"Shaw Alice T",
				"Doebele Robert C"
			],
			"DOI": "10.1158/1078-0432.CCR-17-2588",
			"date": "2019-11-19",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "McCoach Caroline E,2019"
		},
		{
			"PMID": 29559795,
			"title": "Reliability of using circulating tumor cells for detecting epidermal growth factor receptor mutation status in advanced non-small-cell lung cancer patients: a meta-analysis and systematic review.",
			"journal": "OncoTargets and therapy",
			"authorList": [
				"Hu Fang",
				"Mao Xiaowei",
				"Zhang Yujun",
				"Zheng Xiaoxuan",
				"Gu Ping",
				"Wang Huimin",
				"Zhang Xueyan"
			],
			"DOI": "10.2147/OTT.S158479",
			"date": "2022-03-16",
			"PMC": "",
			"citation": "",
			"abstract": "To evaluate the clinical value of circulating tumor cells as a surrogate to detect epidermal growth factor receptor mutation in advanced non-small-cell lung cancer (NSCLC) patients.",
			"category": 2,
			"name": "Hu Fang,2022"
		},
		{
			"PMID": 29489660,
			"title": "Primary pulmonary myoepithelial carcinoma in a young woman: A case report and review of literature.",
			"journal": "Medicine",
			"authorList": [
				"Zhou Xiaojuan",
				"Yu Min",
				"Zhuo Hongyu",
				"Zhang Shuang"
			],
			"DOI": "10.1097/MD.0000000000010049",
			"date": "2018-03-13",
			"PMC": "",
			"citation": "",
			"abstract": "Myoepithelial carcinoma mainly occurs in the salivary glands, but myoepithelial carcinoma of the lung is extremely rare neoplasm whose biological behavior and clinical course still remain to be fully elucidated. Although considered as low-grade carcinoma, these tumors have a high rate of recurrence or distant metastasis.",
			"category": 2,
			"name": "Zhou Xiaojuan,2018"
		},
		{
			"PMID": 29488070,
			"title": "Cost Effectiveness of Alectinib vs. Crizotinib in First-Line Anaplastic Lymphoma Kinase-Positive Advanced Non-Small-Cell Lung Cancer.",
			"journal": "PharmacoEconomics",
			"authorList": [
				"Carlson Josh J",
				"Suh Kangho",
				"Orfanos Panos",
				"Wong William"
			],
			"DOI": "10.1007/s40273-018-0625-6",
			"date": "2019-09-23",
			"PMC": "",
			"citation": "",
			"abstract": "The recently completed ALEX trial demonstrated that alectinib improved progression-free survival, and delayed time to central nervous system progression compared with crizotinib in patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer. However, the long-term clinical and economic impact of using alectinib vs. crizotinib has not been evaluated. The objective of this study was to determine the potential cost utility of alectinib vs. crizotinib from a US payer perspective.",
			"category": 2,
			"name": "Carlson Josh J,2019"
		},
		{
			"PMID": 29455675,
			"title": "The function and therapeutic targeting of anaplastic lymphoma kinase (ALK) in non-small cell lung cancer (NSCLC).",
			"journal": "Molecular cancer",
			"authorList": [
				"Golding Brandon",
				"Luu Anita",
				"Jones Robert",
				"Viloria-Petit Alicia M"
			],
			"DOI": "10.1186/s12943-018-0810-4",
			"date": "2019-01-16",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer is the leading cause of death by cancer in North America. A decade ago, genomic rearrangements in the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase were identified in a subset of non-small cell lung carcinoma (NSCLC) patients. Soon after, crizotinib, a small molecule ATP-competitive ALK inhibitor was proven to be more effective than chemotherapy in ALK-positive NSCLC patients. Crizotinib and two other ATP-competitive ALK inhibitors, ceritinib and alectinib, are approved for use as a first-line therapy in these patients, where ALK rearrangement is currently diagnosed by immunohistochemistry and in situ hybridization. The clinical success of these three ALK inhibitors has led to the development of next-generation ALK inhibitors with even greater potency and selectivity. However, patients inevitably develop resistance to ALK inhibitors leading to tumor relapse that commonly manifests in the form of brain metastasis. Several new approaches aim to overcome the various mechanisms of resistance that develop in ALK-positive NSCLC including the knowledge-based alternate and successive use of different ALK inhibitors, as well as combined therapies targeting ALK plus alternative signaling pathways. Key issues to resolve for the optimal implementation of established and emerging treatment modalities for ALK-rearranged NSCLC therapy include the high cost of the targeted inhibitors and the potential of exacerbated toxicities with combination therapies.",
			"category": 2,
			"name": "Golding Brandon,2019"
		},
		{
			"PMID": 29455642,
			"title": "Role and targeting of anaplastic lymphoma kinase in cancer.",
			"journal": "Molecular cancer",
			"authorList": [
				"Della Corte Carminia Maria",
				"Viscardi Giuseppe",
				"Di Liello Raimondo",
				"Fasano Morena",
				"Martinelli Erika",
				"Troiani Teresa",
				"Ciardiello Fortunato",
				"Morgillo Floriana"
			],
			"DOI": "10.1186/s12943-018-0776-2",
			"date": "2019-01-22",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) gene activation is involved in the carcinogenesis process of several human cancers such as anaplastic large cell lymphoma, lung cancer, inflammatory myofibroblastic tumors and neuroblastoma, as a consequence of fusion with other oncogenes (NPM, EML4, TIM, etc) or gene amplification, mutation or protein overexpression. ALK is a transmembrane tyrosine kinase receptor that, upon ligand binding to its extracellular domain, undergoes dimerization and subsequent autophosphorylation of the intracellular kinase domain. When activated in cancer it represents a target for specific inhibitors, such as crizotinib, ceritinib, alectinib etc. which use has demonstrated significant effectiveness in ALK-positive patients, in particular ALK-positive non- small cell lung cancer. Several mechanisms of resistance to these inhibitors have been described and new strategies are underway to overcome the limitations of current ALK inhibitors.",
			"category": 2,
			"name": "Della Corte Carminia Maria,2019"
		},
		{
			"PMID": 29400604,
			"title": "Capture-based ultra-deep sequencing in plasma ctDNA reveals the resistance mechanism of ALK inhibitors in a patient with advanced ALK-positive NSCLC.",
			"journal": "Cancer biology & therapy",
			"authorList": [
				"Guo Jing",
				"Guo Lihong",
				"Sun Li",
				"Wu Zhenzhen",
				"Ye Junyi",
				"Liu Jing",
				"Zuo Qiang"
			],
			"DOI": "10.1080/15384047.2018.1433496",
			"date": "2019-06-17",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) is a validated molecular target in non-small-cell lung cancer (NSCLC). However, the clinical benefits of ALK inhibitors are almost universally limited by the emergence of drug resistance.",
			"category": 2,
			"name": "Guo Jing,2019"
		},
		{
			"PMID": 29361925,
			"title": "Long-term progression-free survival in an advanced lung adenocarcinoma patient harboring EZR-ROS1 rearrangement: a case report.",
			"journal": "BMC pulmonary medicine",
			"authorList": [
				"Dong Liang",
				"Xia Jingwen",
				"Zhang Jing",
				"Zhang Yuanyuan",
				"Zhu Ning",
				"Zhang Peng",
				"Zhang Youzhi",
				"Zhang Xiujuan",
				"Li Shengqing"
			],
			"DOI": "10.1186/s12890-018-0585-9",
			"date": "2019-03-27",
			"PMC": "",
			"citation": "",
			"abstract": "Crizotinib is recommended as first-line therapy in ROS1-driven lung adenocarcinoma. However, the optimal first-line therapy for this subgroup of lung cancer is controversial according to the available clinical data.",
			"category": 2,
			"name": "Dong Liang,2019"
		},
		{
			"PMID": 29344953,
			"title": "Established, emerging and elusive molecular targets in the treatment of lung cancer.",
			"journal": "The Journal of pathology",
			"authorList": [
				"Gallant Jean-Nicolas",
				"Lovly Christine M"
			],
			"DOI": "10.1002/path.5038",
			"date": "2019-07-15",
			"PMC": "",
			"citation": "",
			"abstract": "Although histological subtype still underlies tumour classification and treatment, the recognition that lung cancer is, largely, a genetic disease has prompted a push to reconfigure cancer taxonomies according to molecular criteria. In this review, we discuss established (e.g. EGFR, ALK, ROS1, and programmed cell death 1/programmed death-ligand 1), emerging (e.g. MET, RET, and NTRK) and elusive (e.g. TP53, KRAS, and MYC) molecular targets in the treatment of lung cancer. We synthesize a large and rapidly growing body of literature regarding the discovery and therapeutic inhibition of these targets in lung cancer. Copyright \u00a9 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.",
			"category": 2,
			"name": "Gallant Jean-Nicolas,2019"
		},
		{
			"PMID": 29336091,
			"title": "Drug resistance in anaplastic lymphoma kinase-rearranged lung cancer.",
			"journal": "Cancer science",
			"authorList": [
				"Katayama Ryohei"
			],
			"DOI": "10.1111/cas.13504",
			"date": "2018-03-12",
			"PMC": "",
			"citation": "",
			"abstract": "The anaplastic lymphoma kinase (ALK) gene encodes a receptor tyrosine kinase, and many kinds of ALK fusion genes have been found in a variety of carcinomas. There is almost no detectable expression of ALK in adults. However, through ALK gene rearrangement, the resultant ALK fusion protein is aberrantly overexpressed and dimerized through the oligomerization domains, such as the coiled-coil domain, in the fusion partner that induces abnormal constitutive activation of ALK tyrosine kinase. This results in dysregulated cell proliferation. ALK gene rearrangement has been observed in 3%-5% of non-small-cell lung cancers, and multiple ALK inhibitors have been developed for the treatment of ALK-positive lung cancer. Among those inhibitors, in Japan, 3 (4 in the USA) ALK tyrosine kinase inhibitors (TKIs) have been approved and are currently used in clinics. All of the currently approved ALK-TKIs have been shown to induce marked tumor regression in ALK-rearranged non-small-cell lung cancer; however, tumors inevitably relapse because of acquired resistance within a few years. This review focuses on ALK-TKIs, their resistance mechanisms, and the potential therapeutic strategies to overcome resistance.",
			"category": 2,
			"name": "Katayama Ryohei,2018"
		},
		{
			"PMID": 29318404,
			"title": "Does ALK-rearrangement predict favorable response to the therapy of bevacizumab plus pemetrexed in advanced non-small-cell lung cancer? Case report and literature review.",
			"journal": "Clinical and translational medicine",
			"authorList": [
				"Liu Zhichao",
				"Bao Youting",
				"Li Butuo",
				"Sun Xindong",
				"Wang Linlin"
			],
			"DOI": "10.1186/s40169-017-0178-x",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Advanced ALK-rearranged non-small cell lung cancer (NSCLC) patients will develop acquired resistance after anaplastic lymphoma kinase (ALK) inhibitors therapies. Vascular endothelial growth factor-A (VEGF-A) production and tumor vessel formation were found to be more significantly enriched in ALK-rearrangement NSCLC than that in epidermal growth factor receptor or Kirsten rat sarcoma viral oncogene mutated NSCLC. However, the correlation between ALK rearrangement and the efficacy of bevacizumab (a recombinant humanized IgG1 monoclonal antibody targeting VEGF-A) was still elusive.",
			"category": 2,
			"name": "Liu Zhichao,2020"
		},
		{
			"PMID": 29290991,
			"title": "Early and late effects of pharmacological ALK inhibition on the neuroblastoma transcriptome.",
			"journal": "Oncotarget",
			"authorList": [
				"Claeys Shana",
				"Denecker Geertrui",
				"Cannoodt Robrecht",
				"Kumps Candy",
				"Durinck Kaat",
				"Speleman Frank",
				"De Preter Katleen"
			],
			"DOI": "10.18632/oncotarget.22423",
			"date": "2022-03-14",
			"PMC": "",
			"citation": "",
			"abstract": "Neuroblastoma is an aggressive childhood malignancy of the sympathetic nervous system. Despite multi-modal therapy, survival of high-risk patients remains disappointingly low, underscoring the need for novel treatment strategies. The discovery of ",
			"category": 2,
			"name": "Claeys Shana,2022"
		},
		{
			"PMID": 29263703,
			"title": "The applications of liquid biopsy in resistance surveillance of anaplastic lymphoma kinase inhibitor.",
			"journal": "Cancer management and research",
			"authorList": [
				"Chen Yating",
				"Guo Wenjie",
				"Fan Junsheng",
				"Chen Yuqing",
				"Zhang Xiaoli",
				"Chen Xin",
				"Luo Peng"
			],
			"DOI": "10.2147/CMAR.S151235",
			"date": "2022-03-16",
			"PMC": "",
			"citation": "",
			"abstract": "With the clinical promotion of precision medicine and individualized medical care, molecular targeted medicine has been used to treat non-small cell lung cancer (NSCLC) patients and proved to be significantly effective. Anaplastic lymphoma kinase (ALK) inhibitor is one of the most important specific therapeutic agents for patients with ALK-positive NSCLC. It can extend the survival of patients. However, resistance to the ALK inhibitor inevitably develops in the application process. So, the real-time resistance surveillance is particularly important, and liquid biopsy is one of the most potential inspection methods. Circulating tumor cells, circulating free tumor DNA and exosome in body fluid are used as the main detection biomarkers to reflect the occurrence of resistance in real time through sequencing or counting and then to guide the follow-up treatment.",
			"category": 2,
			"name": "Chen Yating,2022"
		},
		{
			"PMID": 29225694,
			"title": "Non-small cell lung cancer treatment (r)evolution: ten years of advances and more to come.",
			"journal": "Ecancermedicalscience",
			"authorList": [
				"Toschi Luca",
				"Rossi Sabrina",
				"Finocchiaro Giovanna",
				"Santoro Armando"
			],
			"DOI": "10.3332/ecancer.2017.787",
			"date": "2022-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "Diagnostic and treatment algorithms in non-small cell lung cancer (NSCLC) are evolving at a never-before-seen pace. Histological subtyping to maximise treatment efficacy and avoid toxicity has marked the beginning of the revolution, opening the way to molecular characterisation to guide genomically driven treatments with targeted agents, led by Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) inhibitors. More recently, agents against the Program Death 1 receptor (PD-1) and ligand 1 (PD-L1) have entered the clinical arena, offering new hope to NSCLC patients, although several uncertainties remain to be elucidated. Here, we review the most clinically relevant advances in the diagnosis and treatment of NSCLC in the past decade.",
			"category": 2,
			"name": "Toschi Luca,2022"
		},
		{
			"PMID": 29221246,
			"title": "Moving more potent and less toxic options to the frontline in the management of advanced lung cancer.",
			"journal": "Journal of thoracic disease",
			"authorList": [
				"Le Xiuning",
				"Rangachari Deepa",
				"Costa Daniel B"
			],
			"DOI": "10.21037/jtd.2017.08.79",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Le Xiuning,2020"
		},
		{
			"PMID": 29143897,
			"title": "Anaplastic Lymphoma Kinase Testing: IHC vs. FISH vs. NGS.",
			"journal": "Current treatment options in oncology",
			"authorList": [
				"Niu Xiaomin",
				"Chuang Jody C",
				"Berry Gerald J",
				"Wakelee Heather A"
			],
			"DOI": "10.1007/s11864-017-0513-x",
			"date": "2018-07-09",
			"PMC": "",
			"citation": "",
			"abstract": "Personalized targeted therapy has emerged as a promising strategy in lung cancer treatment, with current attention focused on elucidation and detection of oncogenic drivers responsible for tumor initiation and maintenance and development of drug resistance. In lung cancer, several oncogenic drivers have been reported, triggering the application of tyrosine kinase inhibitors (TKIs) to target these dysfunctional genes. The anaplastic lymphoma kinase (ALK) rearrangement is responsible for about 4-7% of all non-small cell lung cancers (NSCLCs) and perhaps as high as a third in specific patient populations such as younger, male, non-smokers with advanced stage, epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) wild type, and signet ring cell adenocarcinoma with abundant intracytoplasmic mucin. The selection of patients based on their ALK status is vital on account of the high response rates with the ALK-targeted agents in this subset of patients. Standardization and validation of ALK rearrangement detection methods is essential for accurate and reproducible results. There are currently three detection methods widely available in clinical practice, including fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), and polymerase chain reaction (PCR)-based next generation sequencing (NGS) technology. However, the choice of diagnostic methodology for ALK rearrangement detection in clinical practice remains a matter of debate. With accumulating data enumerating the advantages and disadvantages of each of the three methods, combining more than one testing method for ALK fusion detection may be beneficial for patients. In this review, we will discuss the current methods used in ALK rearrangement detection with emphasis on their key advantages and disadvantages.",
			"category": 2,
			"name": "Niu Xiaomin,2018"
		},
		{
			"PMID": 29143801,
			"title": "Novel Molecular Challenges in Targeting Anaplastic Lymphoma Kinase in ALK-Expressing Human Cancers.",
			"journal": "Cancers",
			"authorList": [
				"Alshareef Abdulraheem"
			],
			"DOI": "10.3390/cancers9110148",
			"date": "2020-09-29",
			"PMC": "",
			"citation": "",
			"abstract": "Targeting anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase receptor initially identified as a potent oncogenic driver in anaplastic large-cell lymphoma (ALCL) in the form of nucleophosmin (NPM)-ALK fusion protein, using tyrosine kinase inhibitors has shown to be a promising therapeutic approach for ALK-expressing tumors. However, clinical resistance to ALK inhibitors invariably occurs, and the molecular mechanisms are incompletely understood. Recent studies have clearly shown that clinical resistance to ALK inhibitors is a multifactorial and complex mechanism. While few of the mechanisms of clinical resistance to ALK inhibitors such as gene mutation are well known, there are others that are not well covered. In this review, the molecular mechanisms of cancer stem cells in mediating resistance to ALK inhibitors as well as the current understanding of the molecular challenges in targeting ALK in ALK-expressing human cancers will be discussed.",
			"category": 2,
			"name": "Alshareef Abdulraheem,2020"
		},
		{
			"PMID": 29117310,
			"title": "Sequencing and phasing cancer mutations in lung cancers using a long-read portable sequencer.",
			"journal": "DNA research : an international journal for rapid publication of reports on genes and genomes",
			"authorList": [
				"Suzuki Ayako",
				"Suzuki Mizuto",
				"Mizushima-Sugano Junko",
				"Frith Martin C",
				"Makalowski Wojciech",
				"Kohno Takashi",
				"Sugano Sumio",
				"Tsuchihara Katsuya",
				"Suzuki Yutaka"
			],
			"DOI": "10.1093/dnares/dsx027",
			"date": "2018-08-29",
			"PMC": "",
			"citation": "",
			"abstract": "Here, we employed cDNA amplicon sequencing using a long-read portable sequencer, MinION, to characterize various types of mutations in cancer-related genes, namely, EGFR, KRAS, NRAS and NF1. For homozygous SNVs, the precision and recall rates were 87.5% and 91.3%, respectively. For previously reported hotspot mutations, the precision and recall rates reached 100%. The precise junctions of EML4-ALK, CCDC6-RET and five other gene fusions were also detected. Taking advantages of long-read sequencing, we conducted phasing of EGFR mutations and elucidated the mutational allelic backgrounds of anti-tumor drug-sensitive and resistant mutations, which could provide useful information for selecting therapeutic approaches. In the H1975 cells, 72% of the reads harbored both L858R and T790M mutations, and 22% of the reads harbored neither mutation. To ensure that the clinical requirements can be met in potentially low cancer cell populations, we further conducted a serial dilution analysis of the template for EGFR mutations. Several percent of the mutant alleles could be detected depending on the yield and quality of the sequencing data. Finally, we characterized the mutation genotypes in eight clinical samples. This method could be a convenient long-read sequencing-based analytical approach and thus may change the current approaches used for cancer genome sequencing.",
			"category": 2,
			"name": "Suzuki Ayako,2018"
		},
		{
			"PMID": 29115304,
			"title": "Tumour heterogeneity and resistance to cancer therapies.",
			"journal": "Nature reviews. Clinical oncology",
			"authorList": [
				"Dagogo-Jack Ibiayi",
				"Shaw Alice T"
			],
			"DOI": "10.1038/nrclinonc.2017.166",
			"date": "2019-05-21",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a dynamic disease. During the course of disease, cancers generally become more heterogeneous. As a result of this heterogeneity, the bulk tumour might include a diverse collection of cells harbouring distinct molecular signatures with differential levels of sensitivity to treatment. This heterogeneity might result in a non-uniform distribution of genetically distinct tumour-cell subpopulations across and within disease sites (spatial heterogeneity) or temporal variations in the molecular makeup of cancer cells (temporal heterogeneity). Heterogeneity provides the fuel for resistance; therefore, an accurate assessment of tumour heterogeneity is essential for the development of effective therapies. Multiregion sequencing, single-cell sequencing, analysis of autopsy samples, and longitudinal analysis of liquid biopsy samples are all emerging technologies with considerable potential to dissect the complex clonal architecture of cancers. In this Review, we discuss the driving forces behind intratumoural heterogeneity and the current approaches used to combat this heterogeneity and its consequences. We also explore how clinical assessments of tumour heterogeneity might facilitate the development of more-effective personalized therapies.",
			"category": 2,
			"name": "Dagogo-Jack Ibiayi,2019"
		},
		{
			"PMID": 29093439,
			"title": "Combating subclonal evolution of resistant cancer phenotypes.",
			"journal": "Nature communications",
			"authorList": [
				"Brady Samuel W",
				"McQuerry Jasmine A",
				"Qiao Yi",
				"Piccolo Stephen R",
				"Shrestha Gajendra",
				"Jenkins David F",
				"Layer Ryan M",
				"Pedersen Brent S",
				"Miller Ryan H",
				"Esch Amanda",
				"Selitsky Sara R",
				"Parker Joel S",
				"Anderson Layla A",
				"Dalley Brian K",
				"Factor Rachel E",
				"Reddy Chakravarthy B",
				"Boltax Jonathan P",
				"Li Dean Y",
				"Moos Philip J",
				"Gray Joe W",
				"Heiser Laura M",
				"Buys Saundra S",
				"Cohen Adam L",
				"Johnson W Evan",
				"Quinlan Aaron R",
				"Marth Gabor",
				"Werner Theresa L",
				"Bild Andrea H"
			],
			"DOI": "10.1038/s41467-017-01174-3",
			"date": "2018-09-05",
			"PMC": "",
			"citation": "",
			"abstract": "Metastatic breast cancer remains challenging to treat, and most patients ultimately progress on therapy. This acquired drug resistance is largely due to drug-refractory sub-populations (subclones) within heterogeneous tumors. Here, we track the genetic and phenotypic subclonal evolution of four breast cancers through years of treatment to better understand how breast cancers become drug-resistant. Recurrently appearing post-chemotherapy mutations are rare. However, bulk and single-cell RNA sequencing reveal acquisition of malignant phenotypes after treatment, including enhanced mesenchymal and growth factor signaling, which may promote drug resistance, and decreased antigen presentation and TNF-\u03b1 signaling, which may enable immune system avoidance. Some of these phenotypes pre-exist in pre-treatment subclones that become dominant after chemotherapy, indicating selection for resistance phenotypes. Post-chemotherapy cancer cells are effectively treated with drugs targeting acquired phenotypes. These findings highlight cancer's ability to evolve phenotypically and suggest a phenotype-targeted treatment strategy that adapts to cancer as it evolves.",
			"category": 2,
			"name": "Brady Samuel W,2018"
		},
		{
			"PMID": 29061113,
			"title": "The emerging roles of NGS-based liquid biopsy in non-small cell lung cancer.",
			"journal": "Journal of hematology & oncology",
			"authorList": [
				"Zhang Yi-Chen",
				"Zhou Qing",
				"Wu Yi-Long"
			],
			"DOI": "10.1186/s13045-017-0536-6",
			"date": "2018-06-26",
			"PMC": "",
			"citation": "",
			"abstract": "The treatment paradigm of non-small cell lung cancer (NSCLC) has evolved into oncogene-directed precision medicine. Identifying actionable genomic alterations is the initial step towards precision medicine. An important scientific progress in molecular profiling of NSCLC over the past decade is the shift from the traditional piecemeal fashion to massively parallel sequencing with the use of next-generation sequencing (NGS). Another technical advance is the development of liquid biopsy with great potential in providing a dynamic and comprehensive genomic profiling of NSCLC in a minimally invasive manner. The integration of NGS with liquid biopsy has been demonstrated to play emerging roles in genomic profiling of NSCLC by increasing evidences. This review summarized the potential applications of NGS-based liquid biopsy in the diagnosis and treatment of NSCLC including identifying actionable genomic alterations, tracking spatiotemporal tumor evolution, dynamically monitoring response and resistance to targeted therapies, and diagnostic value in early-stage NSCLC, and discussed emerging challenges to overcome in order to facilitate clinical translation in future.",
			"category": 2,
			"name": "Zhang Yi-Chen,2018"
		},
		{
			"PMID": 29057238,
			"title": "Non-invasive diagnostic platforms in management of non-small cell lung cancer: opportunities and challenges.",
			"journal": "Annals of translational medicine",
			"authorList": [
				"Velcheti Vamsidhar",
				"Pennell Nathan A"
			],
			"DOI": "10.21037/atm.2017.08.24",
			"date": "2022-04-10",
			"PMC": "",
			"citation": "",
			"abstract": "Several non-invasive diagnostic platforms are already being incorporated in routine clinical practice in the work up and monitoring of patients with lung cancer. These approaches have great potential to improve patient selection and monitor patients while on therapy, however several challenges exist in clinical validation and standardization of such platforms. In this review, we summarize the current technologies available for non-invasive diagnostic evaluation from the blood of patients with non-small cell lung cancer (NSCLC), and discuss the technical and logistical challenges associated incorporating such testing in clinical practice.",
			"category": 2,
			"name": "Velcheti Vamsidhar,2022"
		},
		{
			"PMID": 28979145,
			"title": "Anaplastic lymphoma kinase inhibition in metastatic non-small cell lung cancer: clinical impact of alectinib.",
			"journal": "OncoTargets and therapy",
			"authorList": [
				"Muller Ittai B",
				"de Langen Adrianus J",
				"Giovannetti Elisa",
				"Peters Godefridus J"
			],
			"DOI": "10.2147/OTT.S109493",
			"date": "2022-04-10",
			"PMC": "",
			"citation": "",
			"abstract": "A subset of non-small cell lung cancer (NSCLC) tumors (5%) harbors an anaplastic lymphoma kinase (ALK) translocation that drives tumorigenesis. The clinically approved first-line treatment crizotinib specifically inhibits ALK and improves progression-free survival (PFS) in treated and untreated patients by 4 months compared to standard chemotherapy. While some patients relapse after crizotinib treatment due to resistance mutations in ALK, second-generation ALK inhibitors effectively induce tumor response and prolong PFS. Alectinib, a second-generation ALK inhibitor, has recently been approved for ALK-rearranged NSCLC after patients progressed on crizotinib. Alectinib is able to inhibit several crizotinib- and ceritinib-resistant ALK mutations in vitro. Furthermore, alectinib is a more potent tyrosine kinase inhibitor (TKI), with favorable safety profile, and has increased penetration into the central nervous system, inhibiting crizotinib-resistant brain metastases. The discovery of effective personalized therapies to combat ALK-rearranged NSCLC such as alectinib is an example of the importance of genomic profiling of NSCLC and provides an excellent template for future discoveries in managing these tumors.",
			"category": 2,
			"name": "Muller Ittai B,2022"
		},
		{
			"PMID": 28938646,
			"title": "Concordance between circulating tumor cells and clinical status during follow-up in anaplastic lymphoma kinase (ALK) non-small-cell lung cancer patients.",
			"journal": "Oncotarget",
			"authorList": [
				"Provencio Mariano",
				"P\u00e9rez-Callejo David",
				"Torrente Mar\u00eda",
				"Martin Paloma",
				"Calvo Virginia",
				"Guti\u00e9rrez Lourdes",
				"Franco Fernando",
				"Coronado Maria Jos\u00e9",
				"Cruz-Berm\u00fadez Juan Luis",
				"Ruiz-Valdepe\u00f1as Asunci\u00f3n Mart\u00edn",
				"Cruz-Berm\u00fadez Alberto",
				"S\u00e1nchez-Beato Margarita",
				"Romero Atocha",
				"Garc\u00eda-Grande Ar\u00e1nzazu"
			],
			"DOI": "10.18632/oncotarget.19722",
			"date": "2017-09-25",
			"PMC": "",
			"citation": "",
			"abstract": "The identification of anaplastic lymphoma kinase (ALK) rearrangements is found in approximately 5% of non-small-cell lung cancers (NSCLCs). However, the development of liquid biopsies as a diagnostic tool is less developed in these cases. This study investigates the use of CTCs during treatment, together with an extended follow-up to correlate with clinical evolution.",
			"category": 2,
			"name": "Provencio Mariano,2017"
		},
		{
			"PMID": 28904890,
			"title": "Biophysical technologies for understanding circulating tumor cell biology and metastasis.",
			"journal": "Translational lung cancer research",
			"authorList": [
				"Su Derrick W",
				"Nieva Jorge"
			],
			"DOI": "10.21037/tlcr.2017.05.08",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "An understanding of cancer evolution in lung cancer with its associated resistance to therapy can only be achieved with repeated sampling and analysis of the cancer. Given the high risks and costs associated with repeat physical biopsy, alternative technologies must be applied. Several modalities exist for analysis and re-analysis of cancer biology. Among them are the CellSearch platform, the CTC chip, and the high-definition CTC platform. While the former is primarily able to provide prognosticating information in the form of CTC enumeration, the latter two have the advantage of serving as a platform to study tumor biology. Techniques for analysis of single cell genomics, as well as protein expression on a single cell basis provide scientists with the capacity to understand cancer cell populations as a collection of individual cells, rather than as an average of all cells. A multimodal combination of circulating tumor DNAs (ctDNAs), CTCs, proteomics, and CTC-derived xenografts (CDXs) to create computational models useful in diagnosis, prognostication, and predictiveness to treatment is likely the future of tailoring individualized cancer care.",
			"category": 2,
			"name": "Su Derrick W,2020"
		},
		{
			"PMID": 28857077,
			"title": "Fusions in solid tumours: diagnostic strategies, targeted therapy, and acquired resistance.",
			"journal": "Nature reviews. Clinical oncology",
			"authorList": [
				"Schram Alison M",
				"Chang Matthew T",
				"Jonsson Philip",
				"Drilon Alexander"
			],
			"DOI": "10.1038/nrclinonc.2017.127",
			"date": "2017-12-04",
			"PMC": "",
			"citation": "",
			"abstract": "Structural gene rearrangements resulting in gene fusions are frequent events in solid tumours. The identification of certain activating fusions can aid in the diagnosis and effective treatment of patients with tumours harbouring these alterations. Advances in the techniques used to identify fusions have enabled physicians to detect these alterations in the clinic. Targeted therapies directed at constitutively activated oncogenic tyrosine kinases have proven remarkably effective against cancers with fusions involving ALK, ROS1, or PDGFB, and the efficacy of this approach continues to be explored in malignancies with RET, NTRK1/2/3, FGFR1/2/3, and BRAF/CRAF fusions. Nevertheless, prolonged treatment with such tyrosine-kinase inhibitors (TKIs) leads to the development of acquired resistance to therapy. This resistance can be mediated by mutations that alter drug binding, or by the activation of bypass pathways. Second-generation and third-generation TKIs have been developed to overcome resistance, and have variable levels of activity against tumours harbouring individual mutations that confer resistance to first-generation TKIs. The rational sequential administration of different inhibitors is emerging as a new treatment paradigm for patients with tumours that retain continued dependency on the downstream kinase of interest.",
			"category": 2,
			"name": "Schram Alison M,2017"
		},
		{
			"PMID": 28856564,
			"title": "The Current Landscape of Anaplastic Lymphoma Kinase (ALK) in Non-Small Cell Lung Cancer: Emerging Treatment Paradigms and Future Directions.",
			"journal": "Targeted oncology",
			"authorList": [
				"Qin Angel",
				"Gadgeel Shirish"
			],
			"DOI": "10.1007/s11523-017-0526-1",
			"date": "2018-08-02",
			"PMC": "",
			"citation": "",
			"abstract": "Tumorigenic rearrangements in anaplastic lymphoma kinase (ALK) account for 3-7% of all non-small cell lung cancers (NSCLC). Treatment with targeted tyrosine kinase inhibitors (TKIs) has shown impressive clinical responses. Crizotinib was the first agent approved for front-line therapy of ALK-rearranged NSCLC after it demonstrated superiority to chemotherapy in response rate, duration of response, and progression-free survival. However, eventually all patients progress on crizotinib therapy, with the central nervous system (CNS) being the most common site, which served as the impetus for the development of more potent next-generation ALK inhibitors. Currently, ceritinib, alectinib, and brigatinib are all approved for second-line therapy after progression on or intolerance to crizotinib. Investigations into whether the initiation of a second-generation ALK inhibitor as first-line therapy is the superior treatment paradigm has resulted in the approval of ceritinib as initial therapy. Alectinib has also shown impressive results as front-line therapy, as recently reported in two large randomized studies that compared it to crizotinib. There is a significant need to better understand the drivers of and mechanisms underlying resistance to ALK inhibitors. While specific mutations have been identified, there is currently only limited evidence that the identification of specific mutations should impact selection of the next ALK inhibitor. The best treatment option for patients who become TKI refractory is also unclear, though there is some evidence to suggests that these patients are not responsive to checkpoint inhibitors and may respond better to chemotherapy. Combination therapy with other classes of agents may help to overcome resistance mechanisms and should be investigated further.",
			"category": 2,
			"name": "Qin Angel,2018"
		},
		{
			"PMID": 28848676,
			"title": "A consensus on liquid biopsy from the 2016 Chinese Lung Cancer Summit expert panel.",
			"journal": "ESMO open",
			"authorList": [
				"Wu Yi-Long",
				"Wang Chang-Li",
				"Sun Yan",
				"Liao Mei-Lin",
				"Guan Zhong-Zhen",
				"Yang Zhi-Min",
				"Zhou Qing-Hua",
				"Lu Shun",
				"Cheng Ying",
				"Liu Xiao-Qing",
				"Zhang Xu-Chao",
				"Zhou Caicun",
				"Wang Jie",
				"Zhou Qing",
				"Song Yong",
				"Han Bao-Hui",
				"Ma Zhi-Yong",
				"Yang Fan",
				"Wang Qun",
				"Chuai Shao-Kun",
				"Shao Yang",
				"He Wei",
				"Zhu Guanshan",
				"Xiong Lei",
				"Wang Jian-Jun",
				"Chen Ke-Neng",
				"Zhang Li",
				"Mao Wei-Min",
				"Ma Sheng-Lin",
				"Feng Ji-Feng",
				"Yang Xue-Ning",
				"Xu Lin",
				"Chen Gang",
				"Zhao Jian",
				"Song Qi-Bin",
				"Shen-Tu Yang",
				"Qiao Gui-Bin",
				"Yu Ding",
				"Yu Shi-Ying",
				"Hu Yi",
				"Chen Ming",
				"Chen Gong-Yan",
				"Fan Yun",
				"Zhang He-Long",
				"Liang Jun",
				"Zhu Guang-Ying",
				"Cui Jiu-Wei",
				"Yang Jin-Ji",
				"Zhao Qiong",
				"Zhao Ming-Fang",
				"Lu You",
				"Chang Jian-Hua",
				"Li Jun-Ling",
				"Yang Yue",
				"Hu Jie",
				"Gu Chun-Dong",
				"Zhang Yi-Chen",
				"Zhong Wen-Zhao"
			],
			"DOI": "10.1136/esmoopen-2017-000174",
			"date": "2021-02-08",
			"PMC": "",
			"citation": "",
			"abstract": "The diagnosis and treatment of lung cancer have evolved into the era of precision medicine. Liquid biopsy, a minimally invasive approach, has emerged as a promising practice in genetic profiling and monitoring of lung cancer. Translating liquid biopsy from bench to bedside has encountered various challenges, including technique selection, protocol standardisation, data analysis and cost management. Regarding these challenges, the 2016 Chinese Lung Cancer Summit expert panel organised a trilateral forum involving oncologists, clinicians, clinical researchers, and industrial expertise on the 13th Chinese Lung Cancer Summit to formally discuss these controversies. Six consensuses were reached to guide the use of liquid biopsy and perform precision medicine in both clinic and research.",
			"category": 2,
			"name": "Wu Yi-Long,2021"
		},
		{
			"PMID": 28840024,
			"title": "Elucidation of radiation-resistant clones by a serial study of intratumor heterogeneity before and after stereotactic radiotherapy in lung cancer.",
			"journal": "Journal of thoracic disease",
			"authorList": [
				"Nakagomi Takahiro",
				"Goto Taichiro",
				"Hirotsu Yosuke",
				"Shikata Daichi",
				"Amemiya Kenji",
				"Oyama Toshio",
				"Mochizuki Hitoshi",
				"Omata Masao"
			],
			"DOI": "10.21037/jtd.2017.06.02",
			"date": "2020-09-29",
			"PMC": "",
			"citation": "",
			"abstract": "Stereotactic radiotherapy (SRT) for inoperable stage I non-small cell lung cancer has shown promising results and is now an alternative therapy for this disease. Several reports have detailed changes in mutation profiles after treatment with chemotherapy; however, such changes after SRT for lung cancer have not been reported. A patient who received SRT for lung cancer developed local recurrence 9 months after treatment and underwent surgery in our department. Using bronchoscopically biopsied and surgically resected specimens, we performed targeted sequencing of 53 lung cancer-related genes and compared the tumor mutation profiles before and after SRT. Identical mutations were detected from tumor specimens collected before and after SRT, and the specimens were confirmed to be clonal. However, the number of mutations decreased after SRT, suggesting that it induced mutation selection. Analyses of the statistical inference of clonal population structure showed that this evolving heterogeneous genomic landscape may be caused by heterogeneous responsiveness to SRT.",
			"category": 2,
			"name": "Nakagomi Takahiro,2020"
		},
		{
			"PMID": 28787259,
			"title": "Targeting ALK With Crizotinib in Pediatric Anaplastic Large Cell Lymphoma and Inflammatory Myofibroblastic Tumor: A Children's Oncology Group Study.",
			"journal": "Journal of clinical oncology : official journal of the American Society of Clinical Oncology",
			"authorList": [
				"Moss\u00e9 Yael P",
				"Voss Stephan D",
				"Lim Megan S",
				"Rolland Delphine",
				"Minard Charles G",
				"Fox Elizabeth",
				"Adamson Peter",
				"Wilner Keith",
				"Blaney Susan M",
				"Weigel Brenda J"
			],
			"DOI": "10.1200/JCO.2017.73.4830",
			"date": "2017-10-02",
			"PMC": "",
			"citation": "",
			"abstract": "Purpose Fusions involving the ALK gene are the predominant genetic lesion underlying pediatric anaplastic large cell lymphomas (ALCL) and inflammatory myofibroblastic tumors (IMTs). We assessed the activity of the ALK inhibitor crizotinib in patients who had no known curative treatment options at diagnosis or with relapsed/recurrent disease. Methods In this study, 26 patients with relapsed/refractory ALK-positive ALCL and 14 patients with metastatic or inoperable ALK-positive IMT received crizotinib orally twice daily. Study objectives were measurement of efficacy and safety. Correlative studies evaluated the serial detection of NPM-ALK fusion transcripts in patients with ALCL. Results The overall response rates for patients with ALCL treated at doses of 165 (ALCL165) and 280 (ALCL280) mg/m",
			"category": 2,
			"name": "Moss\u00e9 Yael P,2017"
		},
		{
			"PMID": 28740365,
			"title": "Spotlight on ceritinib in the treatment of ALK+ NSCLC: design, development and place in therapy.",
			"journal": "Drug design, development and therapy",
			"authorList": [
				"Santarpia Mariacarmela",
				"Daffin\u00e0 Maria Grazia",
				"D'Aveni Alessandro",
				"Marabello Grazia",
				"Liguori Alessia",
				"Giovannetti Elisa",
				"Karachaliou Niki",
				"Gonzalez Cao Maria",
				"Rosell Rafael",
				"Altavilla Giuseppe"
			],
			"DOI": "10.2147/DDDT.S113500",
			"date": "2018-06-14",
			"PMC": "",
			"citation": "",
			"abstract": "The identification of echinoderm microtubule-associated protein-like 4 (",
			"category": 2,
			"name": "Santarpia Mariacarmela,2018"
		},
		{
			"PMID": 28724631,
			"title": "The Axl kinase domain in complex with a macrocyclic inhibitor offers first structural insights into an active TAM receptor kinase.",
			"journal": "The Journal of biological chemistry",
			"authorList": [
				"Gajiwala Ketan S",
				"Grodsky Neil",
				"Bola\u00f1os Ben",
				"Feng Junli",
				"Ferre RoseAnn",
				"Timofeevski Sergei",
				"Xu Meirong",
				"Murray Brion W",
				"Johnson Ted W",
				"Stewart Al"
			],
			"DOI": "10.1074/jbc.M116.771485",
			"date": "2017-10-09",
			"PMC": "",
			"citation": "",
			"abstract": "The receptor tyrosine kinase family consisting of Tyro3, Axl, and Mer (TAM) is one of the most recently identified receptor tyrosine kinase families. TAM receptors are up-regulated postnatally and maintained at high levels in adults. They all play an important role in immunity, but Axl has also been implicated in cancer and therefore is a target in the discovery and development of novel therapeutics. However, of the three members of the TAM family, the Axl kinase domain is the only one that has so far eluded structure determination. To this end, using differential scanning fluorimetry and hydrogen-deuterium exchange mass spectrometry, we show here that a lower stability and greater dynamic nature of the Axl kinase domain may account for its poor crystallizability. We present the first structural characterization of the Axl kinase domain in complex with a small-molecule macrocyclic inhibitor. The Axl crystal structure revealed two distinct conformational states of the enzyme, providing a first glimpse of what an active TAM receptor kinase may look like and suggesting a potential role for the juxtamembrane region in enzyme activity. We noted that the ATP/inhibitor-binding sites of the TAM members closely resemble each other, posing a challenge for the design of a selective inhibitor. We propose that the differences in the conformational dynamics among the TAM family members could potentially be exploited to achieve inhibitor selectivity for targeted receptors.",
			"category": 2,
			"name": "Gajiwala Ketan S,2017"
		},
		{
			"PMID": 28561721,
			"title": "Managing Resistance to EFGR- and ALK-Targeted Therapies.",
			"journal": "American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting",
			"authorList": [
				"Lovly Christine M",
				"Iyengar Puneeth",
				"Gainor Justin F"
			],
			"DOI": "",
			"date": "2017-11-29",
			"PMC": "",
			"citation": "",
			"abstract": "Targeted therapies have transformed the management of non-small cell lung cancer (NSCLC) and placed an increased emphasis on stratifying patients on the basis of genetic alterations in oncogenic drivers. To date, the best characterized molecular targets in NSCLC are the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). Despite steady advances in targeted therapies within these molecular subsets, however, acquired resistance to therapy is near universal. Recent preclinical models and translational efforts have provided critical insights into the molecular mechanisms of resistance to EGFR and ALK inhibitors. In this review, we present a framework for understanding resistance to targeted therapies. We also provide overviews of the molecular mechanisms of resistance and strategies to overcome resistance among EGFR-mutant and ALK-rearranged lung cancers. To date, these strategies have centered on the development of novel next-generation inhibitors, rationale combinations, and use of local ablative therapies, such as radiotherapy.",
			"category": 2,
			"name": "Lovly Christine M,2017"
		},
		{
			"PMID": 28507205,
			"title": "A Case of Metastatic Atypical Neuroendocrine Tumor with ",
			"journal": "The oncologist",
			"authorList": [
				"Wang Victoria E",
				"Young Lauren",
				"Ali Siraj",
				"Miller Vincent A",
				"Urisman Anatoly",
				"Wolfe John",
				"Bivona Trever G",
				"Damato Bertil",
				"Fogh Shannon",
				"Bergsland Emily K"
			],
			"DOI": "10.1634/theoncologist.2017-0054",
			"date": "2018-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "A challenge in precision medicine requires identification of actionable driver mutations. Critical to such effort is the deployment of sensitive and well-validated assays for mutation detection. Although identification of such alterations within the tumor tissue remains the gold standard, many advanced non-small cell lung cancer cases have only limited tissue samples, derived from small biopsies or fine-needle aspirates, available for testing. More recently, noninvasive methods using either circulating tumor cells or tumor DNA (ctDNA) have become an alternative method for identifying molecular biomarkers and screening patients eligible for targeted therapies. In this article, we present a case of a 52-year-old never-smoking male who presented with widely metastatic atypical neuroendocrine tumor to the bones and the brain. Molecular genotyping using DNA harvested from a bone metastasis was unsuccessful due to limited material. Subsequent ctDNA analysis revealed an ",
			"category": 2,
			"name": "Wang Victoria E,2018"
		},
		{
			"PMID": 28490925,
			"title": "Management of ",
			"journal": "Current oncology (Toronto, Ont.)",
			"authorList": [
				"Cabanero M",
				"Sangha R",
				"Sheffield B S",
				"Sukhai M",
				"Pakkal M",
				"Kamel-Reid S",
				"Karsan A",
				"Ionescu D",
				"Juergens R A",
				"Butts C",
				"Tsao M S"
			],
			"DOI": "10.3747/co.24.3524",
			"date": "2022-03-17",
			"PMC": "",
			"citation": "",
			"abstract": "Starting in the early 2000s, non-small-cell lung cancer (nsclc) subtypes have evolved from being histologically described to molecularly defined. Management of lung adenocarcinomas now generally requires multiple molecular tests at baseline to define the optimal treatment strategy. More recently, second biopsies performed at progression in patients treated with tyrosine kinase inhibitors (tkis) have further defined the continued use of molecularly targeted therapy. In the present article, we focus on one molecular subtype: ",
			"category": 2,
			"name": "Cabanero M,2022"
		},
		{
			"PMID": 28450729,
			"title": "Collateral sensitivity networks reveal evolutionary instability and novel treatment strategies in ALK mutated non-small cell lung cancer.",
			"journal": "Scientific reports",
			"authorList": [
				"Dhawan Andrew",
				"Nichol Daniel",
				"Kinose Fumi",
				"Abazeed Mohamed E",
				"Marusyk Andriy",
				"Haura Eric B",
				"Scott Jacob G"
			],
			"DOI": "10.1038/s41598-017-00791-8",
			"date": "2018-09-04",
			"PMC": "",
			"citation": "",
			"abstract": "Drug resistance remains an elusive problem in cancer therapy, particularly for novel targeted therapies. Much work is focused upon the development of an arsenal of targeted therapies, towards oncogenic driver genes such as ALK-EML4, to overcome the inevitable resistance that develops over time. Currently, after failure of first line ALK TKI therapy, another ALK TKI is administered, though collateral sensitivity is not considered. To address this, we evolved resistance in an ALK rearranged non-small cell lung cancer line (H3122) to a panel of 4 ALK TKIs, and performed a collateral sensitivity analysis. All ALK inhibitor resistant cell lines displayed significant cross-resistance to all other ALK inhibitors. We then evaluated ALK-inhibitor sensitivities after drug holidays of varying length (1-21\u2009days), and observed dynamic patterns of resistance. This unpredictability led us to an expanded search for treatment options, where we tested 6 further anti-cancer agents for collateral sensitivity among resistant cells, uncovering possibilities for further treatment, including cross-sensitivity to standard cytotoxic therapies, as well as Hsp90 inhibitors. Taken together, these results imply that resistance to targeted therapy in non-small cell lung cancer is highly dynamic, and also one where there are many opportunities to re-establish sensitivities where there was once resistance. Drug resistance in cancer inevitably emerges during treatment; particularly with novel targeted therapies, designed to inhibit specific molecules. A clinically-relevant example of this phenomenon occurs in ALK-positive non-small cell lung cancer, where targeted therapies are used to inhibit the ALK-EML4 fusion protein. A potential solution to this may lie in finding drug sensitivities in the resistant population, termed collateral sensitivities, and then using these as second-line agents. This study shows how the evolution of resistance in ALK-positive lung cancer is a dynamic process through time, one in which patterns of drug resistance and collateral sensitivity change substantially, and therefore one where temporal regimens, such as drug cycling and drug holidays may have great benefit.",
			"category": 2,
			"name": "Dhawan Andrew,2018"
		},
		{
			"PMID": 28442018,
			"title": "[Recent Advances and Prospect of Advanced Non-small Cell Lung Cancer Targeted \u2029Therapy: Focus on Small Molecular Tyrosine Kinase Inhibitors].",
			"journal": "Zhongguo fei ai za zhi = Chinese journal of lung cancer",
			"authorList": [
				"Zhang Guowei",
				"Wang Huijuan",
				"Ma Zhiyong"
			],
			"DOI": "10.3779/j.issn.1009-3419.2017.04.09",
			"date": "2017-06-30",
			"PMC": "",
			"citation": "",
			"abstract": "At present the treatment of advanced non-small cell lung cancer enters a targeted era and develops rapidly. New drugs appear constantly. Small molecular tyrosine kinase inhibitors have occupied the biggest piece of the territory, which commonly have a clear biomarker as predictor, and show remarkable effect in specific molecular classification of patients. The epidermal growth factor tyrosine kinase inhibitors such as gefitinib, erlotinib, icotinib and anaplastic lymphoma kinase tyrosine kinase inhibitors crizotinib have brought a milestone advance. In recent years new generations of tyrosine kinase inhibitors have achieved a great success in patients with acquired resistance to the above two kinds of drugs. At the same time new therapeutic targets are constantly emerging. So in this paper, we reviewed and summarized the important drugs and clinical trails on this topic, and made a prospect of the future development.",
			"category": 2,
			"name": "Zhang Guowei,2017"
		},
		{
			"PMID": 28435288,
			"title": "The activity, safety, and evolving role of brigatinib in patients with ",
			"journal": "OncoTargets and therapy",
			"authorList": [
				"Sabari Joshua K",
				"Santini Fernando C",
				"Schram Alison M",
				"Bergagnini Isabella",
				"Chen Ruqin",
				"Mrad Chebli",
				"Lai W Victoria",
				"Arbour Kathryn C",
				"Drilon Alexander"
			],
			"DOI": "10.2147/OTT.S109295",
			"date": "2023-11-13",
			"PMC": "",
			"citation": "",
			"abstract": "Brigatinib (AP26113) is a dimethylphosphine oxide group-containing tyrosine kinase inhibitor (TKI) constructed around a bisanilinopyrimidine scaffold with potent activity against the anaplastic lymphoma kinase (ALK) and several other targets. Despite the activity of first- and second-generation ALK inhibitors in advanced ",
			"category": 2,
			"name": "Sabari Joshua K,2023"
		},
		{
			"PMID": 28431544,
			"title": "Strategies for monitoring and combating resistance to combination kinase inhibitors for cancer therapy.",
			"journal": "Genome medicine",
			"authorList": [
				"Ahronian Leanne G",
				"Corcoran Ryan B"
			],
			"DOI": "10.1186/s13073-017-0431-3",
			"date": "2017-09-01",
			"PMC": "",
			"citation": "",
			"abstract": "Targeted therapies such as kinase inhibitors and monoclonal antibodies have dramatically altered cancer care in recent decades. Although these targeted therapies have improved patient outcomes in several cancer types, resistance ultimately develops to these agents. One potential strategy proposed to overcome acquired resistance involves taking repeat tumor biopsies at the time of disease progression, to identify the specific molecular mechanism driving resistance in an individual patient and to select a new agent or combination of agents capable of surmounting that specific resistance mechanism. However, recent studies sampling multiple metastatic lesions upon acquired resistance, or employing \"liquid biopsy\" analyses of circulating tumor DNA, have revealed that multiple, heterogeneous resistance mechanisms can emerge in distinct tumor subclones in the same patient. This heterogeneity represents a major clinical challenge for devising therapeutic strategies to overcome resistance. In many cancers, multiple drug resistance mechanisms often converge to reactivate the original pathway targeted by the drug. This convergent evolution creates an opportunity to target a common signaling node to overcome resistance. Furthermore, integration of liquid biopsy approaches into clinical practice may allow real-time monitoring of emerging resistance alterations, allowing intervention prior to standard detection of radiographic progression. In this review, we discuss recent advances in understanding tumor heterogeneity and resistance to targeted therapies, focusing on combination kinase inhibitors, and we discuss approaches to address these issues in the clinic.",
			"category": 2,
			"name": "Ahronian Leanne G,2017"
		},
		{
			"PMID": 28422717,
			"title": "C3orf21 ablation promotes the proliferation of lung adenocarcinoma, and its mutation at the rs2131877 locus may serve as a susceptibility marker.",
			"journal": "Oncotarget",
			"authorList": [
				"Yang Litao",
				"Wang Ying",
				"Fang Meiyu",
				"Deng Douhou",
				"Zhang Yongjun"
			],
			"DOI": "10.18632/oncotarget.16798",
			"date": "2018-03-05",
			"PMC": "",
			"citation": "",
			"abstract": "In this study, we investigated the role of C3orf21 gene polymorphism at the rs2131877 locus and its contribution to lung adenocarcinoma pathogenesis. Normal lung and tumor tissue sections were collected from fifteen patients with lung adenocarcinoma for chromosome 3 open reading frame 21 (C3orf21) genotype analysis. In addition, a retrospective analysis was performed to assess the association between C3orf21 genotype and tumor markers from patient samples used in our previously published study. In parallel, we also manipulated C3orf21 gene expression either by overexpressing or ablating it in a MSTO-211H human lung cancer cell line to further understand its contribution to cell proliferation, apoptosis and migration. Our results indicated that the patients with smoking history had a significantly increased mutation (rs2131877 T/C+C/C genotype) rate (p = 0.025), in addition to higher values for the CYF211 and NSE tumor markers (p = 0.014 and p = 0.031, respectively). The retrospective analysis also confirmed that the NSE marker value was higher in patients with a C3orf21 rs2131877 T/C+C/C genotype. Furthermore, our in vitro data indicated that C3orf21 ablation promoted lung cancer cell proliferation, inhibited apoptosis and accelerated cell migration. Overall, our study concluded that C30rf21 rs 2131877 T/C+C/C genotype patients may experience increased nicotine addiction and that C30rf21 can likely serve as a susceptibility marker for lung adenocarcinoma with a higher degree of malignancy.",
			"category": 2,
			"name": "Yang Litao,2018"
		},
		{
			"PMID": 28373963,
			"title": "Current Treatment Algorithms for Patients with Metastatic Non-Small Cell, Non-Squamous Lung Cancer.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Melosky Barbara"
			],
			"DOI": "10.3389/fonc.2017.00038",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "The treatment paradigm for metastatic non-small cell, non-squamous lung cancer is continuously evolving due to new treatment options and our increasing knowledge of molecular signal pathways. As a result of treatments becoming more efficacious and more personalized, survival for selected groups of non-small cell lung cancer (NSCLC) patients is increasing. In this paper, three algorithms will be presented for treating patients with metastatic non-squamous, NSCLC. These include treatment algorithms for NSCLC patients whose tumors have ",
			"category": 2,
			"name": "Melosky Barbara,2020"
		},
		{
			"PMID": 28289245,
			"title": "Treatment-Induced Mutagenesis and Selective Pressures Sculpt Cancer Evolution.",
			"journal": "Cold Spring Harbor perspectives in medicine",
			"authorList": [
				"Venkatesan Subramanian",
				"Swanton Charles",
				"Taylor Barry S",
				"Costello Joseph F"
			],
			"DOI": "10.1101/cshperspect.a026617",
			"date": "2018-04-25",
			"PMC": "",
			"citation": "",
			"abstract": "Despite the great progress in our understanding of the molecular basis of human cancer, the heterogeneity of individual tumors and the evolutionary pressures imposed by therapy have hampered our ability to effectively eradicate and control this disease. How, therefore, do cancers evolve under the selective pressures of cancer therapy? Recent studies have linked both primary (or de novo) and acquired treatment resistance to intratumor heterogeneity and clonal evolution. Resistance to targeted therapies often includes mutation of the drug target itself and aberrations of pathways upstream of, downstream from, or parallel to the drug target. For systemic chemotherapies, discrete and recurrent resistance-conferring genetic aberrations have eluded the community, due in part to their wide-ranging mutagenic effects. In this review, we discuss different patterns of clonal evolution during treatment-specific selective pressures and focus on the genetic mechanisms of treatment resistance that have emerged to both targeted therapies and chemotherapies.",
			"category": 2,
			"name": "Venkatesan Subramanian,2018"
		},
		{
			"PMID": 28245558,
			"title": "L1198F Mutation Resensitizes Crizotinib to ALK by Altering the Conformation of Inhibitor and ATP Binding Sites.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Li Jian",
				"Sun Rong",
				"Wu Yuehong",
				"Song Mingzhu",
				"Li Jia",
				"Yang Qianye",
				"Chen Xiaoyi",
				"Bao Jinku",
				"Zhao Qi"
			],
			"DOI": "10.3390/ijms18030482",
			"date": "2017-04-28",
			"PMC": "",
			"citation": "",
			"abstract": "The efficacy of anaplastic lymphoma kinase (ALK) positive non-small-cell lung cancer (NSCLC) treatment with small molecule inhibitors is greatly challenged by acquired resistance. A recent study reported the newest generation inhibitor resistant mutation L1198F led to the resensitization to crizotinib, which is the first Food and Drug Administration (FDA) approved drug for the treatment of ALK-positive NSCLC. It is of great importance to understand how this extremely rare event occurred for the purpose of overcoming the acquired resistance of such inhibitors. In this study, we exploited molecular dynamics (MD) simulation to dissect the molecular mechanisms. Our MD results revealed that L1198F mutation of ALK resulted in the conformational change at the inhibitor site and altered the binding affinity of ALK to crizotinib and lorlatinib. L1198F mutation also affected the autoactivation of ALK as supported by the identification of His1124 and Tyr1278 as critical amino acids involved in ATP binding and phosphorylation. Our findings are valuable for designing more specific and potent inhibitors for the treatment of ALK-positive NSCLC and other types of cancer.",
			"category": 2,
			"name": "Li Jian,2017"
		},
		{
			"PMID": 28210164,
			"title": "Spotlight on crizotinib in the first-line treatment of ALK-positive advanced non-small-cell lung cancer: patients selection and perspectives.",
			"journal": "Lung Cancer (Auckland, N.Z.)",
			"authorList": [
				"Giroux-Leprieur Etienne",
				"Fallet Vincent",
				"Cadranel Jacques",
				"Wislez Marie"
			],
			"DOI": "10.2147/LCTT.S99303",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "Around 4% of advanced non-small-cell lung cancers (NSCLCs) have an ",
			"category": 2,
			"name": "Giroux-Leprieur Etienne,2020"
		},
		{
			"PMID": 28187282,
			"title": "Implementing Genome-Driven Oncology.",
			"journal": "Cell",
			"authorList": [
				"Hyman David M",
				"Taylor Barry S",
				"Baselga Jos\u00e9"
			],
			"DOI": "10.1016/j.cell.2016.12.015",
			"date": "2017-05-23",
			"PMC": "",
			"citation": "",
			"abstract": "Early successes in identifying and targeting individual oncogenic drivers, together with the increasing feasibility of sequencing tumor genomes, have brought forth the promise of genome-driven oncology care. As we expand the breadth and depth of genomic analyses, the biological and clinical complexity of its implementation will be unparalleled. Challenges include target credentialing and validation, implementing drug combinations, clinical trial designs, targeting tumor heterogeneity, and deploying technologies beyond DNA sequencing, among others. We review how contemporary approaches are tackling these challenges and will ultimately serve as an engine for biological discovery and increase our insight into cancer and its treatment.",
			"category": 2,
			"name": "Hyman David M,2017"
		},
		{
			"PMID": 28126915,
			"title": "Mixed Responses to Systemic Therapy Revealed Potential Genetic Heterogeneity and Poor Survival in Patients with Non-Small Cell Lung Cancer.",
			"journal": "The oncologist",
			"authorList": [
				"Dong Zhong-Yi",
				"Zhai Hao-Ran",
				"Hou Qing-Yi",
				"Su Jian",
				"Liu Si-Yang",
				"Yan Hong-Hong",
				"Li Yang-Si",
				"Chen Zhi-Yong",
				"Zhong Wen-Zhao",
				"Wu Yi-Long"
			],
			"DOI": "10.1634/theoncologist.2016-0150",
			"date": "2018-01-05",
			"PMC": "",
			"citation": "",
			"abstract": "A subset of patients with non-small cell lung cancer (NSCLC) fosters mixed responses (MRs) to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) or chemotherapy. However, little is known about the clinical and molecular features or the prognostic significance and potential mechanisms.",
			"category": 2,
			"name": "Dong Zhong-Yi,2018"
		},
		{
			"PMID": 28122866,
			"title": "Targeting ALK: Precision Medicine Takes on Drug Resistance.",
			"journal": "Cancer discovery",
			"authorList": [
				"Lin Jessica J",
				"Riely Gregory J",
				"Shaw Alice T"
			],
			"DOI": "10.1158/2159-8290.CD-16-1123",
			"date": "2017-11-03",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) is a validated molecular target in several ALK-rearranged malignancies, including non-small cell lung cancer. However, the clinical benefit of targeting ALK using tyrosine kinase inhibitors (TKI) is almost universally limited by the emergence of drug resistance. Diverse mechanisms of resistance to ALK TKIs have now been discovered, and these basic mechanisms are informing the development of novel therapeutic strategies to overcome resistance in the clinic. In this review, we summarize the current successes and challenges of targeting ALK.",
			"category": 2,
			"name": "Lin Jessica J,2017"
		},
		{
			"PMID": 28103976,
			"title": "[Research Progress of Targeted Therapy for Anaplastic Lymphoma Kinase and Other Rare Driver Genes in Advanced Non-small Cell Lung Cancer].",
			"journal": "Zhongguo fei ai za zhi = Chinese journal of lung cancer",
			"authorList": [
				"Zhang Quan",
				"Zhang Shucai"
			],
			"DOI": "10.3779/j.issn.1009-3419.2017.01.10",
			"date": "2017-04-03",
			"PMC": "",
			"citation": "",
			"abstract": "Targeted therapy was one of the major treatments in advanced non-small cell lung cancer (NSCLC) with positive driver genes. This area of research progresses day by day, with novel target discoveries, novel drug development, and use of novel combination treatments. Researchers have also undergone deep investigation about the molecular mechanisms underlying inherent or acquired resistance to these targeted therapies. This review aimed to summarize the advanced developments of targeted therapy for anaplastic lymphoma kinase (ALK) and other rare driver genes in NSCLC.",
			"category": 2,
			"name": "Zhang Quan,2017"
		},
		{
			"PMID": 28066567,
			"title": "Sequencing ALK inhibitors: alectinib in crizotinib-resistant patients, a phase 2 trial by Shaw ",
			"journal": "Journal of thoracic disease",
			"authorList": [
				"Mezquita Laura",
				"Besse Benjamin"
			],
			"DOI": "10.21037/jtd.2016.11.76",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Mezquita Laura,2020"
		},
		{
			"PMID": 28054318,
			"title": "Treating patients with ALK-rearranged non-small-cell lung cancer: mechanisms of resistance and strategies to overcome it.",
			"journal": "Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico",
			"authorList": [
				"Drizou M",
				"Kotteas E A",
				"Syrigos N"
			],
			"DOI": "10.1007/s12094-016-1605-y",
			"date": "2018-03-12",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) rearrangement is detected in 3-7% of patients with non-small-cell lung cancer. Crizotinib is an ALK inhibitor, which was approved in 2011 for the treatment of ALK-positive lung cancer. Despite the initial enthusiasm, most of the patients develop resistance within the first year of treatment. The main mechanisms are secondary mutations and bypass track activation. Moreover, crizotinib has low penetration into the central nervous system. The need to overcome these limitations has led to the development of second-generation inhibitors that have better effectiveness against crizotinib-resistant mutations and brain metastases. Ceritinib and alectinib are the only approved drugs of this group. Many ongoing trials try to define the most appropriate agent for the treatment of ALK-positive lung cancer depending on the responsible mechanism. This review focuses on the current data regarding the potential mechanisms of resistance to ALK inhibitors and the strategies to overcome it.",
			"category": 2,
			"name": "Drizou M,2018"
		},
		{
			"PMID": 28050598,
			"title": "ALK: a tyrosine kinase target for cancer therapy.",
			"journal": "Cold Spring Harbor molecular case studies",
			"authorList": [
				"Holla Vijaykumar R",
				"Elamin Yasir Y",
				"Bailey Ann Marie",
				"Johnson Amber M",
				"Litzenburger Beate C",
				"Khotskaya Yekaterina B",
				"Sanchez Nora S",
				"Zeng Jia",
				"Shufean Md Abu",
				"Shaw Kenna R",
				"Mendelsohn John",
				"Mills Gordon B",
				"Meric-Bernstam Funda",
				"Simon George R"
			],
			"DOI": "10.1101/mcs.a001115",
			"date": "2019-11-20",
			"PMC": "",
			"citation": "",
			"abstract": "The anaplastic lymphoma kinase (",
			"category": 2,
			"name": "Holla Vijaykumar R,2019"
		},
		{
			"PMID": 28030793,
			"title": "Anaplastic lymphoma kinase L1198F and G1201E mutations identified in anaplastic thyroid cancer patients are not ligand-independent.",
			"journal": "Oncotarget",
			"authorList": [
				"Guan Jikui",
				"Wolfstetter Georg",
				"Siaw Joachim",
				"Chand Damini",
				"Hugosson Fredrik",
				"Palmer Ruth H",
				"Hallberg Bengt"
			],
			"DOI": "10.18632/oncotarget.14141",
			"date": "2017-08-28",
			"PMC": "",
			"citation": "",
			"abstract": "Activating mutations in full length anaplastic lymphoma kinase (ALK) have been reported in neuroblastoma and in anaplastic thyroid cancer. ALK-L1198F and ALK-G1201E mutations were originally identified in anaplastic thyroid cancer (ATC) and characterized as constitutively activating mutations. In this study, we employed in vitro cell culture assays together with biochemical and in vivo Drosophila analyses to characterize their sensitivity to either activation by the FAM150A (AUG-\u03b2) and FAM150B (AUG-\u03b1) ALK ligands or inhibition by ALK inhibitors. Here we report that neither ALK-L1198F nor ALK-G1201E mutations result in ligand independent gain-of-function (GOF) activity in either in vitro biochemical analysis or the various model systems employed. ALK-L1198F is activated by the FAM150 (AUG) ligands and its ligand-dependant activity is similar to the wild type full length ALK receptor. ALK-G1201E is only very weakly activated by the FAM150 (AUG) ligands, most likely due to impaired protein stability. We conclude that neither ALK-L1198F nor ALK-G1201E displays ligand independent kinase activity, with ALK-L1198F belonging to the class of ligand dependent ALK mutations which are not constitutively active but that responds to ligand activation, while the ALK-G1201E mutation generates an unstable receptor with very low levels of kinase activity.",
			"category": 2,
			"name": "Guan Jikui,2017"
		},
		{
			"PMID": 28018791,
			"title": "Successful ceritinib treatment in a man with MPE and an ALK fusion gene mutation after multiple treatments.",
			"journal": "SpringerPlus",
			"authorList": [
				"Wei Hangping",
				"Du Fangming",
				"Lu Yifang",
				"Wei Juan",
				"Dong Xiaofang"
			],
			"DOI": "10.1186/s40064-016-3674-3",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "Ceritinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor. It inhibits two of the most common ALK-mutants that confer resistance to crizotinib. Ceritinib was approved by Food and Drug Administration in April 2014. However, the efficacy of ceritinib in Asian patients have not been widely studied. Decrease of malignant pleural effusion (MPE) has been rarely reported after treatment with ceritinib.",
			"category": 2,
			"name": "Wei Hangping,2020"
		},
		{
			"PMID": 27965961,
			"title": "Focus on Alectinib and Competitor Compounds for Second-Line Therapy in ",
			"journal": "Frontiers in medicine",
			"authorList": [
				"Tran Phu N",
				"Klempner Samuel J"
			],
			"DOI": "",
			"date": "2023-11-11",
			"PMC": "",
			"citation": "",
			"abstract": "The management of anaplastic lymphoma kinase rearranged (ALK+) non-small cell lung cancer (NSCLC) exemplifies the potential of a precision medicine approach to cancer care. The ALK inhibitor crizotinib has led to improved outcomes in the first- and second-line setting; however, toxicities, intracranial activity, and acquired resistance necessitated the advent of later generation ALK inhibitors. A large portion of acquired resistance to ALK inhibitors is caused by secondary mutations in the ALK kinase domain. Alectinib is a second-generation ALK inhibitor capable of overcoming multiple crizotinib-resistant ALK mutations and has demonstrated improved outcomes after crizotinib failure. Favorable toxicity profile and improved intracranial activity have spurred ongoing front-line trials and comparisons to other ALK inhibitors. However, important questions regarding comparability to competitor compounds, acquired alectinib resistance, and ALK inhibitor sequencing remain. Here, we review the key clinical data supporting alectinib in the second-line therapy of ALK+ NSCLC and provide context in comparison to other ALK inhibitors in development.",
			"category": 2,
			"name": "Tran Phu N,2023"
		},
		{
			"PMID": 27913999,
			"title": "The role of HER2, EGFR, and other receptor tyrosine kinases in breast cancer.",
			"journal": "Cancer metastasis reviews",
			"authorList": [
				"Hsu Jennifer L",
				"Hung Mien-Chie"
			],
			"DOI": "10.1007/s10555-016-9649-6",
			"date": "2017-10-31",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer affects approximately 1 in 8 women, and it is estimated that over 246,660 women in the USA will be diagnosed with breast cancer in 2016. Breast cancer mortality has decline over the last two decades due to early detection and improved treatment. Over the last few years, there is mounting evidence to demonstrate the prominent role of receptor tyrosine kinases (RTKs) in tumor initiation and progression, and targeted therapies against the RTKs have been developed, evaluated in clinical trials, and approved for many cancer types, including breast cancer. However, not all breast cancers are the same as evidenced by the multiple subtypes of the disease, with some more aggressive than others, showing differential treatment response to different types of drugs. Moreover, in addition to canonical signaling from the cell surface, many RTKs can be trafficked to various subcellular compartments, e.g., the multivesicular body and nucleus, where they carry out critical cellular functions, such as cell proliferation, DNA replication and repair, and therapeutic resistance. In this review, we provide a brief summary on the role of a selected number of RTKs in breast cancer and describe some mechanisms of resistance\u00a0to targeted therapies.",
			"category": 2,
			"name": "Hsu Jennifer L,2017"
		},
		{
			"PMID": 27819059,
			"title": "Resisting Resistance: Targeted Therapies in Lung Cancer.",
			"journal": "Trends in cancer",
			"authorList": [
				"Lin Jessica J",
				"Shaw Alice T"
			],
			"DOI": "",
			"date": "2018-01-25",
			"PMC": "",
			"citation": "",
			"abstract": "Drug resistance inevitably limits the efficacy of all targeted therapies including tyrosine kinase inhibitors (TKIs). Understanding the biological underpinnings of TKI resistance is key to the successful development of future therapeutic strategies. Traditionally, mechanisms of TKI resistance have been viewed under a dichotomous lens. Tumor cells are TKI-sensitive or TKI-refractory, exhibit intrinsic or acquired resistance, and accumulate alterations within or outside the target to promote their survival. Such classifications facilitate our comprehension of an otherwise complex biology, but are likely an oversimplification. Recent studies underscore the multifaceted, genetically heterogeneous nature of TKI resistance, which evolves dynamically with changes in therapy. In this Review, we provide a broad framework for understanding the diverse mechanisms of resistance at play in oncogene-driven lung cancers.",
			"category": 2,
			"name": "Lin Jessica J,2018"
		},
		{
			"PMID": 27799783,
			"title": "Personalized treatment in advanced ALK-positive non-small cell lung cancer: from bench to clinical practice.",
			"journal": "OncoTargets and therapy",
			"authorList": [
				"Passaro Antonio",
				"Lazzari Chiara",
				"Karachaliou Niki",
				"Spitaleri Gianluca",
				"Pochesci Alessia",
				"Catania Chiara",
				"Rosell Rafael",
				"de Marinis Filippo"
			],
			"DOI": "",
			"date": "2022-03-18",
			"PMC": "",
			"citation": "",
			"abstract": "The discovery of anaplastic lymphoma kinase (ALK) gene rearrangements and the development of tyrosine kinase inhibitors (TKI) that target them have achieved unprecedented success in the management of patients with ALK-positive non-small cell lung cancer (NSCLC). Despite the high efficacy of crizotinib, the first oral ALK TKI approved for the treatment of ALK-positive NSCLC, almost all patients inevitably develop acquired resistance, showing disease progression in the brain or in other parenchymal sites. Second- or third-generation ALK TKIs have shown to be active in crizotinib-pretreated or crizotinib-na\u00efve ALK-positive patients, even in those with brain metastases. In this review, the current knowledge regarding ALK-positive NSCLC, focusing on the biology of the disease and the available therapeutic options are discussed.",
			"category": 2,
			"name": "Passaro Antonio,2022"
		},
		{
			"PMID": 27698100,
			"title": "Cracking the Code of Resistance across Multiple Lines of ALK Inhibitor Therapy in Lung Cancer.",
			"journal": "Cancer discovery",
			"authorList": [
				"Qiao Huan",
				"Lovly Christine M"
			],
			"DOI": "",
			"date": "2017-12-05",
			"PMC": "",
			"citation": "",
			"abstract": "In the setting of recent exciting clinical results and numerous ongoing trials, Gainor and colleagues explored mechanisms of acquired resistance to first- and second-generation ALK inhibitors in ALK-rearranged non-small cell lung cancer and found that an increased frequency and distinct spectrums of resistance mutations emerged with the more potent second-generation inhibitors. Their findings have important and immediate clinical implications as the resistance mutations detected impart differential sensitivities to available ALK inhibitors, thereby highlighting the need for sequential biopsies with molecular testing to determine the most effective treatment strategy upon disease progression. Cancer Discov; 6(10); 1084-6. \u00a92016 AACRSee related article by Gainor et al., p. 1118.",
			"category": 2,
			"name": "Qiao Huan,2017"
		},
		{
			"PMID": 27662658,
			"title": "Synergistic activity of ALK and mTOR inhibitors for the treatment of NPM-ALK positive lymphoma.",
			"journal": "Oncotarget",
			"authorList": [
				"Redaelli Sara",
				"Ceccon Monica",
				"Antolini Laura",
				"Rigolio Roberta",
				"Pirola Alessandra",
				"Peronaci Marco",
				"Gambacorti-Passerini Carlo",
				"Mologni Luca"
			],
			"DOI": "10.18632/oncotarget.12128",
			"date": "2018-02-26",
			"PMC": "",
			"citation": "",
			"abstract": "ALK-positive Anaplastic Large Cell Lymphoma (ALCL) represents a subset of Non-Hodgkin Lymphoma whose treatment benefited from crizotinib development, a dual ALK/MET inhibitor. Crizotinib blocks ALK-triggered pathways such as PI3K/AKT/mTOR, indispensable for survival of ALK-driven tumors.Despite the positive impact of targeted treatment in ALCL, resistant clones are often selected during therapy. Strategies to overcome resistance include the design of second generation drugs and the use of combined therapies that simultaneously target multiple nodes essential for cells survival. We investigated the effects of combined ALK/mTOR inhibition. We observed a specific synergistic effect of combining ALK inhibitors with an mTOR inhibitor (temsirolimus), in ALK+ lymphoma cells. The positive cooperation resulted in an increased inhibition of mTOR effectors, compared to single treatments, a block in G0/G1 phase and induction of apoptosis. The combination was able to prevent the selection of resistant clones, while long-term exposure to single agents led to the establishment of resistant cell lines, with either ALK inhibitor or temsirolimus. In vivo, mice injected with Karpas 299 cells and treated with low dose combination showed complete regression of tumors, while only partial inhibition was obtained in single agents-treated mice. Upon treatment stop the combination was able to significantly delay tumor relapses. Re-challenge of relapsed tumors at a higher dose led to full regression of xenografts in the combination group, but not in mice treated with lorlatinib alone. In conclusion, our data suggest that the combination of ALK and mTOR inhibitors could be a valuable therapeutic option for ALK+ ALCL patients.",
			"category": 2,
			"name": "Redaelli Sara,2018"
		},
		{
			"PMID": 27620953,
			"title": "The pharmacogenomics of drug resistance to protein kinase inhibitors.",
			"journal": "Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy",
			"authorList": [
				"Gillis Nancy K",
				"McLeod Howard L"
			],
			"DOI": "10.1016/j.drup.2016.06.008",
			"date": "2018-01-19",
			"PMC": "",
			"citation": "",
			"abstract": "Dysregulation of growth factor cell signaling is a major driver of most human cancers. This has led to development of numerous drugs targeting protein kinases, with demonstrated efficacy in the treatment of a wide spectrum of cancers. Despite their high initial response rates and survival benefits, the majority of patients eventually develop resistance to these targeted therapies. This review article discusses examples of established mechanisms of drug resistance to anticancer therapies, including drug target mutations or gene amplifications, emergence of alternate signaling pathways, and pharmacokinetic variation. This reveals a role for pharmacogenomic analysis to identify and monitor for resistance, with possible therapeutic strategies to combat chemoresistance.",
			"category": 2,
			"name": "Gillis Nancy K,2018"
		},
		{
			"PMID": 27587193,
			"title": "[Targeted therapy and precision medicine : More than just words in the treatment of lung cancer].",
			"journal": "Der Internist",
			"authorList": [
				"Heigener D F",
				"Horn M",
				"Reck M"
			],
			"DOI": "10.1007/s00108-016-0121-z",
			"date": "2017-08-28",
			"PMC": "",
			"citation": "",
			"abstract": "Between 10 and 15\u2009% of non-small cell lung cancers (NSCLC) proliferate due to the presence of a\u00a0so-called driver mutation. This molecular alteration allows the cancer to continue to proliferate and can be deliberately inhibited. In addition to mutations in the epidermal growth factor receptor gene (EGFR) and translocations between the echinoderm microtubule-associated protein-like 4 gene (EML\u00a04) and the anaplastic lymphoma kinase gene (ALK), this applies to ROS1 gene translocations. For the former two alterations, many inhibitors are already available, whereas for ROS1 and other driving mutations the evidence is sparse due to the rare occurrence of these mutations in NSCLC.",
			"category": 2,
			"name": "Heigener D F,2017"
		},
		{
			"PMID": 27573756,
			"title": "Crizotinib resistance: implications for therapeutic strategies.",
			"journal": "Annals of oncology : official journal of the European Society for Medical Oncology",
			"authorList": [
				"Dagogo-Jack I",
				"Shaw A T"
			],
			"DOI": "10.1093/annonc/mdw305",
			"date": "2017-11-01",
			"PMC": "",
			"citation": "",
			"abstract": "In 2007, a chromosomal rearrangement resulting in a gene fusion leading to expression of a constitutively active anaplastic lymphoma kinase (ALK) fusion protein was identified as an oncogenic driver in non-small-cell lung cancer (NSCLC). ALK rearrangements are detected in 3%-7% of patients with NSCLC and are particularly enriched in younger patients with adenocarcinoma and a never or light smoking history. Fortuitously, crizotinib, a small molecule tyrosine kinase inhibitor initially developed to target cMET, was able to be repurposed for ALK-rearranged (ALK+) NSCLC. Despite dramatic and durable initial responses to crizotinib; however, the vast majority of patients will develop resistance within a few years. Diverse molecular mechanisms underlie resistance to crizotinib. This review will describe the clinical activity of crizotinib, review identified mechanisms of crizotinib resistance, and end with a survey of emerging therapeutic strategies aimed at overcoming crizotinib resistance.",
			"category": 2,
			"name": "Dagogo-Jack I,2017"
		},
		{
			"PMID": 27565908,
			"title": "De novo ALK kinase domain mutations are uncommon in kinase inhibitor-na\u00efve ALK rearranged lung cancers.",
			"journal": "Lung cancer (Amsterdam, Netherlands)",
			"authorList": [
				"Lucena-Araujo Antonio R",
				"Moran Jason P",
				"VanderLaan Paul A",
				"Dias-Santagata Dora",
				"Folch Erik",
				"Majid Adnan",
				"Kent Michael S",
				"Gangadharan Sidharta P",
				"Rangachari Deepa",
				"Huberman Mark S",
				"Kobayashi Susumu S",
				"Costa Daniel B"
			],
			"DOI": "10.1016/j.lungcan.2016.06.006",
			"date": "2017-12-07",
			"PMC": "",
			"citation": "",
			"abstract": "Anaplastic lymphoma kinase (ALK) rearranged lung adenocarcinomas are responsive to the multitargeted ALK inhibitor crizotinib. One of the common mechanisms of resistance to crizotinib is the acquisition of ALK kinase domain mutations. However, the presence of ALK mutations in crizotinib-na\u00efve tumors has not been widely reported and it is unclear if de novo ALK mutations affect the response to crizotinib.",
			"category": 2,
			"name": "Lucena-Araujo Antonio R,2017"
		},
		{
			"PMID": 27564104,
			"title": "Noninvasive genotyping and monitoring of anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer by capture-based next-generation sequencing.",
			"journal": "Oncotarget",
			"authorList": [
				"Wang Ye",
				"Tian Pan-Wen",
				"Wang Wei-Ya",
				"Wang Ke",
				"Zhang Zhou",
				"Chen Bo-Jiang",
				"He Yan-Qi",
				"Li Lei",
				"Liu Hao",
				"Chuai Shannon",
				"Li Wei-Min"
			],
			"DOI": "10.18632/oncotarget.11569",
			"date": "2018-02-23",
			"PMC": "",
			"citation": "",
			"abstract": "Noninvasive genotyping of driver genes and monitoring of tumor dynamics help make better personalized therapeutic decisions. However, neither PCR-based assays nor amplicon-based targeted sequencing can detect fusion genes like anaplastic lymphoma kinase (ALK) rearrangements in blood samples. To investigate the feasibility and performance of capture-based sequencing on ALK fusion detection, we developed a capture-based targeted sequencing panel to detect and quantify rearrangement events, along with other driver mutation variants in plasma. In this perspective study, we screened 364 patients with advanced non-small cell lung cancer (NSCLC) for ALK rearrangements, and collected blood samples from 24 of them with confirmed ALK rearrangements based on their tissue biopsies. ALK rearrangements were successfully detected in 19 of 24 patients at baseline with 79.2% (95% CI 57.9%, 92.9%) sensitivity and 100% (36/36) specificity. Among the 24 patients, we obtained longitudinal blood samples from 7 of them after either chemotherapy and/or Crizotinib treatment for disease monitoring. The by-sample detection rate of ALK rearrangements after treatment drops to 69.2% (9 of 13). In addition to detecting ALK rearrangements, we also detected 3 Crizotinib resistant mutations, ALK L1152R, ALK I1171T and ALK L1196M from patient P4. ctDNA concentration correlates with responses and disease progression, reflecting its ability as a biomarker. Our findings suggest capture-based sequencing can detect and quantify ALK rearrangements as well as other somatic mutations, including mutations mediated drug resistance, in plasma with high sensitivity, paving the way for its application in identifying driver fusion genes and monitoring tumor dynamics in the clinic.",
			"category": 2,
			"name": "Wang Ye,2018"
		},
		{
			"PMID": 27433281,
			"title": "Targeted therapies and immunotherapy in non-small-cell lung cancer.",
			"journal": "Ecancermedicalscience",
			"authorList": [
				"Cortinovis D",
				"Abbate M",
				"Bidoli P",
				"Capici S",
				"Canova S"
			],
			"DOI": "10.3332/ecancer.2016.648",
			"date": "2016-07-19",
			"PMC": "",
			"citation": "",
			"abstract": "Non-small-cell lung cancer is still considered a difficult disease to manage because of its aggressiveness and resistance to common therapies. Chemotherapy remains the gold standard in nearly 80% of lung cancers, but clinical outcomes are discouraging, and the impact on median overall survival (OS) barely reaches 12 months. At the end of the last century, the discovery of oncogene-driven tumours completely changed the therapeutic landscape in lung cancers, harbouring specific gene mutations/translocations. Epidermal growth factors receptor (EGFR) common mutations first and anaplastic lymphoma kinase (ALK) translocations later led new insights in lung cancer biology knowledge. The use of specific tyrosine kinases inhibitors overturned the biological behaviour of EGFR mutation positive tumours and became a preclinical model to understand the heterogeneity of lung cancers and the mechanisms of drug resistance. In this review, we summarise the employment of targeted agents against the most representative biomolecular alterations and provide some criticisms of the therapeutic strategies.",
			"category": 2,
			"name": "Cortinovis D,2016"
		},
		{
			"PMID": 27432227,
			"title": "Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer.",
			"journal": "Cancer discovery",
			"authorList": [
				"Gainor Justin F",
				"Dardaei Leila",
				"Yoda Satoshi",
				"Friboulet Luc",
				"Leshchiner Ignaty",
				"Katayama Ryohei",
				"Dagogo-Jack Ibiayi",
				"Gadgeel Shirish",
				"Schultz Katherine",
				"Singh Manrose",
				"Chin Emily",
				"Parks Melissa",
				"Lee Dana",
				"DiCecca Richard H",
				"Lockerman Elizabeth",
				"Huynh Tiffany",
				"Logan Jennifer",
				"Ritterhouse Lauren L",
				"Le Long P",
				"Muniappan Ashok",
				"Digumarthy Subba",
				"Channick Colleen",
				"Keyes Colleen",
				"Getz Gad",
				"Dias-Santagata Dora",
				"Heist Rebecca S",
				"Lennerz Jochen",
				"Sequist Lecia V",
				"Benes Cyril H",
				"Iafrate A John",
				"Mino-Kenudson Mari",
				"Engelman Jeffrey A",
				"Shaw Alice T"
			],
			"DOI": "",
			"date": "2017-10-27",
			"PMC": "",
			"citation": "",
			"abstract": "Advanced, anaplastic lymphoma kinase (ALK)-positive lung cancer is currently treated with the first-generation ALK inhibitor crizotinib followed by more potent, second-generation ALK inhibitors (e.g., ceritinib and alectinib) upon progression. Second-generation inhibitors are generally effective even in the absence of crizotinib-resistant ALK mutations, likely reflecting incomplete inhibition of ALK by crizotinib in many cases. Herein, we analyzed 103 repeat biopsies from ALK-positive patients progressing on various ALK inhibitors. We find that each ALK inhibitor is associated with a distinct spectrum of ALK resistance mutations and that the frequency of one mutation, ALK",
			"category": 2,
			"name": "Gainor Justin F,2017"
		},
		{
			"PMID": 27430024,
			"title": "Use of big data in drug development for precision medicine.",
			"journal": "Expert review of precision medicine and drug development",
			"authorList": [
				"Kim Rosa S",
				"Goossens Nicolas",
				"Hoshida Yujin"
			],
			"DOI": "",
			"date": "2022-04-09",
			"PMC": "",
			"citation": "",
			"abstract": "Drug development has been a costly and lengthy process with an extremely low success rate and lack of consideration of individual diversity in drug response and toxicity. Over the past decade, an alternative \"big data\" approach has been expanding at an unprecedented pace based on the development of electronic databases of chemical substances, disease gene/protein targets, functional readouts, and clinical information covering inter-individual genetic variations and toxicities. This paradigm shift has enabled systematic, high-throughput, and accelerated identification of novel drugs or repurposed indications of existing drugs for pathogenic molecular aberrations specifically present in each individual patient. The exploding interest from the information technology and direct-to-consumer genetic testing industries has been further facilitating the use of big data to achieve personalized Precision Medicine. Here we overview currently available resources and discuss future prospects.",
			"category": 2,
			"name": "Kim Rosa S,2022"
		},
		{
			"PMID": 27413712,
			"title": "Tackling ALK in non-small cell lung cancer: the role of novel inhibitors.",
			"journal": "Translational lung cancer research",
			"authorList": [
				"Facchinetti Francesco",
				"Tiseo Marcello",
				"Di Maio Massimo",
				"Graziano Paolo",
				"Bria Emilio",
				"Rossi Giulio",
				"Novello Silvia"
			],
			"DOI": "10.21037/tlcr.2016.06.10",
			"date": "2016-07-14",
			"PMC": "",
			"citation": "",
			"abstract": "Crizotinib is an oral inhibitor of anaplastic lymphoma kinase (ALK) with remarkable clinical activity in patients suffering from ALK-rearranged non-small cell lung cancer (NSCLC), accounting to its superiority compared to chemotherapy. Unfortunately, virtually all ALK-rearranged tumors acquire resistance to crizotinib, frequently within one year since the treatment initiation. To date, therapeutic strategies to overcome crizotinib resistance have focused on the use of more potent and structurally different compounds. Second-generation ALK inhibitors such as ceritinib (LDK378), alectinib (CH5424802/RO5424802) and brigatinib (AP26113) have shown relevant clinical activity, consequently fostering their rapid clinical development and their approval by health agencies. The third-generation inhibitor lorlatinib (PF-06463922), selectively active against ALK and ROS1, harbors impressive biological potency; its efficacy in reversing resistance to crizotinib and to other ALK inhibitors is being proven by early clinical trials. The NTRK1-3 and ROS1 inhibitor entrectinib (RXDX-101) has been reported to act against NSCLC harboring ALK fusion proteins too. Despite the quick development of these novel agents, several issues remain to be discussed in the treatment of patients suffering from ALK-rearranged NSCLC. This position paper will discuss the development, the current evidence and approvals, as long as the future perspectives of new ALK inhibitors beyond crizotinib. Clinical behaviors of ALK-rearranged NSCLC vary significantly among patients and differential molecular events responsible of crizotinib resistance account for the most important quote of this heterogeneity. The precious availability of a wide range of active anti-ALK compounds should be approached in a critical and careful perspective, in order to develop treatment strategies tailored on the disease evolution of every single patient.",
			"category": 2,
			"name": "Facchinetti Francesco,2016"
		},
		{
			"PMID": 27401214,
			"title": "Clinician Perspectives on Current Issues in Lung Cancer Drug Development.",
			"journal": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer",
			"authorList": [
				"Waqar Saiama N",
				"Bonomi Philip D",
				"Govindan Ramaswamy",
				"Hirsch Fred R",
				"Riely Gregory J",
				"Papadimitrakopoulou Vassiliki",
				"Kazandjian Dickran",
				"Khozin Sean",
				"Larkins Erin",
				"Dickson Dane J",
				"Malik Shakun",
				"Horn Leora",
				"Ferris Andrea",
				"Shaw Alice T",
				"J\u00e4nne Pasi A",
				"Mok Tony S K",
				"Herbst Roy",
				"Keegan Patricia",
				"Pazdur Richard",
				"Blumenthal Gideon M"
			],
			"DOI": "10.1016/j.jtho.2016.05.009",
			"date": "2017-11-06",
			"PMC": "",
			"citation": "",
			"abstract": "Recent advances in molecularly targeted therapy and immunotherapy offer a glimmer of hope for potentially realizing the dream of personalized therapy for lung cancer. This article highlights current questions in clinical trial design, enrollment strategies and patient focused drug development, with particular emphasis on unique issues in trials of targeted therapy and immunotherapy.",
			"category": 2,
			"name": "Waqar Saiama N,2017"
		},
		{
			"PMID": 27343444,
			"title": "Custom Gene Capture and Next-Generation Sequencing to Resolve Discordant ALK Status by FISH\u00a0and IHC in Lung Adenocarcinoma.",
			"journal": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer",
			"authorList": [
				"Jang Jin Sung",
				"Wang Xiaoke",
				"Vedell Peter T",
				"Wen Ji",
				"Zhang Jinghui",
				"Ellison David W",
				"Evans Jared M",
				"Johnson Sarah H",
				"Yang Ping",
				"Sukov William R",
				"Oliveira Andre M",
				"Vasmatzis George",
				"Sun Zhifu",
				"Jen Jin",
				"Yi Eunhee S"
			],
			"DOI": "10.1016/j.jtho.2016.06.001",
			"date": "2017-11-01",
			"PMC": "",
			"citation": "",
			"abstract": "We performed a genomic study in lung adenocarcinoma cases with discordant anaplastic lymphoma receptor tyrosine kinase gene (ALK) status by fluorescent in situ hybridization (FISH) and immunohistochemical (IHC) analysis.",
			"category": 2,
			"name": "Jang Jin Sung,2017"
		},
		{
			"PMID": 27335306,
			"title": "[Graphic Evolution Witness the Development of Lung Cancer Translational Research].",
			"journal": "Zhongguo fei ai za zhi = Chinese journal of lung cancer",
			"authorList": [
				"Zhang Chao",
				"Zhong Wenzhao"
			],
			"DOI": "10.3779/j.issn.1009-3419.2016.06.21",
			"date": "2017-03-27",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer treatment has altered from conventional chemotherapy to targeted treatment, which now has been turned to the immunotherapy. Translational research has played an irreplaceable role during this progression which graphic evolution has witnessed. The evolution has gone through forest plot, KM-curve, waterfall plot, spider plot and timeline-area, showing us the refining concept and gradual process of lung cancer treatment undergoing from community towards individual. Even though the latest immunotherapy is getting increasingly hot, the result isn't quite expected. Meanwhile, the limitations of conventional treatment still exist which require further research. This article will primarily illustrate the development of translational research of lung cancer via the aspect of curve evolution and analysis some abortive clinical trials in lung cancer surgery for inspiring the next graphic style and lung cancer treatment.",
			"category": 2,
			"name": "Zhang Chao,2017"
		},
		{
			"PMID": 27075079,
			"title": "Cancer therapy: an evolved approach.",
			"journal": "Nature",
			"authorList": [
				"Willyard Cassandra"
			],
			"DOI": "10.1038/532166a",
			"date": "2016-04-27",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Willyard Cassandra,2016"
		},
		{
			"PMID": 27045755,
			"title": "Genomic Aberrations in Crizotinib Resistant Lung Adenocarcinoma Samples Identified by Transcriptome Sequencing.",
			"journal": "PloS one",
			"authorList": [
				"Saber Ali",
				"van der Wekken Anthonie J",
				"Kok Klaas",
				"Terpstra M Martijn",
				"Bosman Lisette J",
				"Mastik Mirjam F",
				"Timens Wim",
				"Schuuring Ed",
				"Hiltermann T Jeroen N",
				"Groen Harry J M",
				"van den Berg Anke"
			],
			"DOI": "10.1371/journal.pone.0153065",
			"date": "2016-08-29",
			"PMC": "",
			"citation": "",
			"abstract": "ALK-break positive non-small cell lung cancer (NSCLC) patients initially respond to crizotinib, but resistance occurs inevitably. In this study we aimed to identify fusion genes in crizotinib resistant tumor samples. Re-biopsies of three patients were subjected to paired-end RNA sequencing to identify fusion genes using deFuse and EricScript. The IGV browser was used to determine presence of known resistance-associated mutations. Sanger sequencing was used to validate fusion genes and digital droplet PCR to validate mutations. ALK fusion genes were detected in all three patients with EML4 being the fusion partner. One patient had no additional fusion genes. Another patient had one additional fusion gene, but without a predicted open reading frame (ORF). The third patient had three additional fusion genes, of which two were derived from the same chromosomal region as the EML4-ALK. A predicted ORF was identified only in the CLIP4-VSNL1 fusion product. The fusion genes validated in the post-treatment sample were also present in the biopsy before crizotinib. ALK mutations (p.C1156Y and p.G1269A) detected in the re-biopsies of two patients, were not detected in pre-treatment biopsies. In conclusion, fusion genes identified in our study are unlikely to be involved in crizotinib resistance based on presence in pre-treatment biopsies. The detection of ALK mutations in post-treatment tumor samples of two patients underlines their role in crizotinib resistance.",
			"category": 2,
			"name": "Saber Ali,2016"
		},
		{
			"PMID": 27009859,
			"title": "TKI sensitivity patterns of novel kinase-domain mutations suggest therapeutic opportunities for patients with resistant ALK+ tumors.",
			"journal": "Oncotarget",
			"authorList": [
				"Amin Amit Dipak",
				"Li Lingxiao",
				"Rajan Soumya S",
				"Gokhale Vijay",
				"Groysman Matthew J",
				"Pongtornpipat Praechompoo",
				"Tapia Edgar O",
				"Wang Mengdie",
				"Schatz Jonathan H"
			],
			"DOI": "10.18632/oncotarget.8173",
			"date": "2018-02-07",
			"PMC": "",
			"citation": "",
			"abstract": "The anaplastic lymphoma kinase (ALK) protein drives tumorigenesis in subsets of several tumors through chromosomal rearrangements that express and activate its C-terminal kinase domain. In addition, germline predisposition alleles and acquired mutations are found in the full-length protein in the pediatric tumor neuroblastoma. ALK-specific tyrosine kinase inhibitors (TKIs) have become important new drugs for ALK-driven lung cancer, but acquired resistance via multiple mechanisms including kinase-domain mutations eventually develops, limiting median progression-free survival to less than a year. Here we assess the impact of several kinase-domain mutations that arose during TKI resistance selections of ALK+ anaplastic large-cell lymphoma (ALCL) cell lines. These include novel variants with respect to ALK-fusion cancers, R1192P and T1151M, and with respect to ALCL, F1174L and I1171S. We assess the effects of these mutations on the activity of six clinical inhibitors in independent systems engineered to depend on either the ALCL fusion kinase NPM-ALK or the lung-cancer fusion kinase EML4-ALK. Our results inform treatment strategies with a likelihood of bypassing mutations when detected in resistant patient samples and highlight differences between the effects of particular mutations on the two ALK fusions.",
			"category": 2,
			"name": "Amin Amit Dipak,2018"
		},
		{
			"PMID": 26951079,
			"title": "Second- and third-generation ALK inhibitors for non-small cell lung cancer.",
			"journal": "Journal of hematology & oncology",
			"authorList": [
				"Wu Jingjing",
				"Savooji John",
				"Liu Delong"
			],
			"DOI": "10.1186/s13045-016-0251-8",
			"date": "2016-10-24",
			"PMC": "",
			"citation": "",
			"abstract": "Crizotinib as the first-generation ALK inhibitor has shown significant activity in ALK-mutated non-small cell lung cancer (NSCLC). Second- and third-generation ALK inhibitors are entering clinical applications for ALK+ NSCLC. In addition, a third-generation ALK inhibitor, lorlatinib (PF-06463922), was reported to resensitize NSCLC to crizotinib. This review provided a summary of clinical development of alectinib, ceritinib, brigatinib (AP26113), and lorlatinib.",
			"category": 2,
			"name": "Wu Jingjing,2016"
		},
		{
			"PMID": 26806320,
			"title": "Lung cancer: Resolving resistance to ALK-targeted therapy.",
			"journal": "Nature reviews. Clinical oncology",
			"authorList": [
				"Hutchinson Lisa"
			],
			"DOI": "10.1038/nrclinonc.2016.8",
			"date": "2016-05-23",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Hutchinson Lisa,2016"
		},
		{
			"PMID": 26797648,
			"title": "Resistance: Crizotinib makes a comeback.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Shipman Lydia"
			],
			"DOI": "10.1038/nrc.2016.6",
			"date": "2016-05-31",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Shipman Lydia,2016"
		},
		{
			"PMID": 38717409,
			"title": "Dynamics of karyotype evolution.",
			"journal": "Chaos (Woodbury, N.Y.)",
			"authorList": [
				"Kuzmin Elena",
				"Baker Toby M",
				"Van Loo Peter",
				"Glass Leon"
			],
			"DOI": "10.1063/5.0206011",
			"date": "2024-05-08",
			"PMC": "",
			"citation": "",
			"abstract": "In the evolution of species, the karyotype changes with a timescale of tens to hundreds of thousand years. In the development of cancer, the karyotype often is modified in cancerous cells over the lifetime of an individual. Characterizing these changes and understanding the mechanisms leading to them has been of interest in a broad range of disciplines including evolution, cytogenetics, and cancer genetics. A central issue relates to the relative roles of random vs deterministic mechanisms in shaping the changes. Although it is possible that all changes result from random events followed by selection, many results point to other non-random factors that play a role in karyotype evolution. In cancer, chromosomal instability leads to characteristic changes in the karyotype, in which different individuals with a specific type of cancer display similar changes in karyotype structure over time. Statistical analyses of chromosome lengths in different species indicate that the length distribution of chromosomes is not consistent with models in which the lengths of chromosomes are random or evolve solely by simple random processes. A better understanding of the mechanisms underlying karyotype evolution should enable the development of quantitative theoretical models that combine the random and deterministic processes that can be compared to experimental determinations of the karyotype in diverse settings.",
			"category": 2,
			"name": "Kuzmin Elena,2024"
		},
		{
			"PMID": 38687804,
			"title": "Synergistic epistasis among cancer drivers can rescue early tumors from the accumulation of deleterious passengers.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Alejandre Carla",
				"Calle-Espinosa Jorge",
				"Iranzo Jaime"
			],
			"DOI": "10.1371/journal.pcbi.1012081",
			"date": "2024-05-10",
			"PMC": "",
			"citation": "",
			"abstract": "Epistasis among driver mutations is pervasive and explains relevant features of cancer, such as differential therapy response and convergence towards well-characterized molecular subtypes. Furthermore, a growing body of evidence suggests that tumor development could be hampered by the accumulation of slightly deleterious passenger mutations. In this work, we combined empirical epistasis networks, computer simulations, and mathematical models to explore how synergistic interactions among driver mutations affect cancer progression under the burden of slightly deleterious passengers. We found that epistasis plays a crucial role in tumor development by promoting the transformation of precancerous clones into rapidly growing tumors through a process that is analogous to evolutionary rescue. The triggering of epistasis-driven rescue is strongly dependent on the intensity of epistasis and could be a key rate-limiting step in many tumors, contributing to their unpredictability. As a result, central genes in cancer epistasis networks appear as key intervention targets for cancer therapy.",
			"category": 2,
			"name": "Alejandre Carla,2024"
		},
		{
			"PMID": 38553551,
			"title": "Label-free quantification of imaging features in the extracellular matrix of left and right-sided colon cancer tissues.",
			"journal": "Scientific reports",
			"authorList": [
				"Arora B",
				"Kulkarni A",
				"Markus M A",
				"Str\u00f6bel P",
				"Bohnenberger H",
				"Alves F",
				"Ramos-Gomes F"
			],
			"DOI": "10.1038/s41598-024-58231-3",
			"date": "2024-04-01",
			"PMC": "",
			"citation": "",
			"abstract": "The molecular pathogenesis of colorectal cancer is known to differ between the right and left side of the colon. Several previous studies have focussed on the differences in clinicopathological features, proteomic and genetic biomarkers, the composition of gut microbiota, response to therapy, and the characteristics of the tumour microenvironment. However, the morphology and density of collagen in the extracellular matrix (ECM) have not been studied intensively. In this study, we employed 2-photon laser scanning microscopy (2PLSM) to visualise the intrinsic second-harmonic generation (SHG) signal emitted by collagen fibres in the heterogeneous ECM of human colon tumour tissues. Through texture analysis of the SHG signal, we quantitatively distinguished the imaging features generated by structural differences of collagen fibres in healthy colon and cancers and found marked differences. The fibres inside of tumours exhibited a loss of organisation, particularly pronounced in right-sided colon cancer (RSCC), where the chaotic regions were significantly increased. In addition, a higher collagen content was found in left-sided colon cancer (LSCC). In future, this might aid in subclassification and therapeutic decisions or even in designing new therapy regimens by taking into account the differences between collagen fibres features between colon tumours located at different sides.",
			"category": 2,
			"name": "Arora B,2024"
		},
		{
			"PMID": 38502371,
			"title": "Impact of Resistance on Therapeutic Design: A Moran Model of Cancer Growth.",
			"journal": "Bulletin of mathematical biology",
			"authorList": [
				"Lacy Mason S",
				"Jenner Adrianne L"
			],
			"DOI": "10.1007/s11538-024-01272-6",
			"date": "2024-03-21",
			"PMC": "",
			"citation": "",
			"abstract": "Resistance of cancers to treatments, such as chemotherapy, largely arise due to cell mutations. These mutations allow cells to resist apoptosis and inevitably lead to recurrence and often progression to more aggressive cancer forms. Sustained-low dose therapies are being considered as an alternative over maximum tolerated dose treatments, whereby a smaller drug dosage is given over a longer period of time. However, understanding the impact that the presence of treatment-resistant clones may have on these new treatment modalities is crucial to validating them as a therapeutic avenue. In this study, a Moran process is used to capture stochastic mutations arising in cancer cells, inferring treatment resistance. The model is used to predict the probability of cancer recurrence given varying treatment modalities. The simulations predict that sustained-low dose therapies would be virtually ineffective for a cancer with a non-negligible probability of developing a sub-clone with resistance tendencies. Furthermore, calibrating the model to in vivo measurements for breast cancer treatment with Herceptin, the model suggests that standard treatment regimens are ineffective in this mouse model. Using a simple Moran model, it is possible to explore the likelihood of treatment success given a non-negligible probability of treatment resistant mutations and suggest more robust therapeutic schedules.",
			"category": 2,
			"name": "Lacy Mason S,2024"
		},
		{
			"PMID": 38424196,
			"title": "Regulatory T cell-mediated immunosuppression orchestrated by cancer: towards an immuno-genomic paradigm for precision medicine.",
			"journal": "Nature reviews. Clinical oncology",
			"authorList": [
				"Kumagai Shogo",
				"Itahashi Kota",
				"Nishikawa Hiroyoshi"
			],
			"DOI": "10.1038/s41571-024-00870-6",
			"date": "2024-04-24",
			"PMC": "",
			"citation": "",
			"abstract": "Accumulating evidence indicates that aberrant signalling stemming from genetic abnormalities in cancer cells has a fundamental role in their evasion of antitumour immunity. Immune escape mechanisms include enhanced expression of immunosuppressive molecules, such as immune-checkpoint proteins, and the accumulation of immunosuppressive cells, including regulatory T (T",
			"category": 2,
			"name": "Kumagai Shogo,2024"
		},
		{
			"PMID": 38407980,
			"title": "A pair of primary colorectal cancer-derived and corresponding synchronous liver metastasis-derived organoid cell lines.",
			"journal": "Aging",
			"authorList": [
				"Cheng Fangling",
				"Li Pengcheng",
				"Xu Sanpeng",
				"Zhang Chao",
				"Liang Huifang",
				"Ding Zeyang"
			],
			"DOI": "10.18632/aging.205595",
			"date": "2024-03-22",
			"PMC": "",
			"citation": "",
			"abstract": "Proper preclinical models for the research of colorectal cancer (CRC) and CRC liver metastases (CLM) are a clear and unmet need. Patient-derived organoids have recently emerged as a robust preclinical model, but are not available to all scientific researchers. Here, we present paired 3D organoid cell lines of CWH22 (CRC-derived) and CLM22 (CLM-derived) with sound background information and the short tandem repeats are identical to those of the normal tissue. Morphological and immunohistochemical staining, along with whole-exome sequencing (WES), confirmed that the organoids exhibited the same differentiation, molecular expression, and mutation status as the corresponding tumor tissue. Both organoids possessed mutated ",
			"category": 2,
			"name": "Cheng Fangling,2024"
		},
		{
			"PMID": 38047596,
			"title": "Cancer Evolution: A Multifaceted Affair.",
			"journal": "Cancer discovery",
			"authorList": [
				"Ciriello Giovanni",
				"Magnani Luca",
				"Aitken Sarah J",
				"Akkari Leila",
				"Behjati Sam",
				"Hanahan Douglas",
				"Landau Dan A",
				"Lopez-Bigas Nuria",
				"Lupi\u00e1\u00f1ez Dar\u00edo G",
				"Marine Jean-Christophe",
				"Martin-Villalba Ana",
				"Natoli Gioacchino",
				"Obenauf Anna C",
				"Oricchio Elisa",
				"Scaffidi Paola",
				"Sottoriva Andrea",
				"Swarbrick Alexander",
				"Tonon Giovanni",
				"Vanharanta Sakari",
				"Zuber Johannes"
			],
			"DOI": "10.1158/2159-8290.CD-23-0530",
			"date": "2024-01-15",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer cells adapt and survive through the acquisition and selection of molecular modifications. This process defines cancer evolution. Building on a theoretical framework based on heritable genetic changes has provided insights into the mechanisms supporting cancer evolution. However, cancer hallmarks also emerge via heritable nongenetic mechanisms, including epigenetic and chromatin topological changes, and interactions between tumor cells and the tumor microenvironment. Recent findings on tumor evolutionary mechanisms draw a multifaceted picture where heterogeneous forces interact and influence each other while shaping tumor progression. A comprehensive characterization of the cancer evolutionary toolkit is required to improve personalized medicine and biomarker discovery.",
			"category": 2,
			"name": "Ciriello Giovanni,2024"
		},
		{
			"PMID": 38009209,
			"title": "Molecular Diagnostics and [",
			"journal": "Thyroid : official journal of the American Thyroid Association",
			"authorList": [
				"de Koster Elizabeth J",
				"Morreau Hans",
				"Bleumink Gysele S",
				"van Engen-van Grunsven Adriana C H",
				"de Geus-Oei Lioe-Fee",
				"Links Thera P",
				"Wakelkamp Iris M M J",
				"Oyen Wim J G",
				"Vriens Dennis"
			],
			"DOI": "10.1089/thy.2023.0337",
			"date": "2024-01-29",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "de Koster Elizabeth J,2024"
		},
		{
			"PMID": 37938738,
			"title": "Scrambling the genome in cancer: causes and consequences of complex chromosome rearrangements.",
			"journal": "Nature reviews. Genetics",
			"authorList": [
				"Krupina Ksenia",
				"Goginashvili Alexander",
				"Cleveland Don W"
			],
			"DOI": "10.1038/s41576-023-00663-0",
			"date": "2024-02-22",
			"PMC": "",
			"citation": "",
			"abstract": "Complex chromosome rearrangements, known as chromoanagenesis, are widespread in cancer. Based on large-scale DNA sequencing of human tumours, the most frequent type of complex chromosome rearrangement is chromothripsis, a massive, localized and clustered rearrangement of one (or a few) chromosomes seemingly acquired in a single event. Chromothripsis can be initiated by mitotic errors that produce a micronucleus encapsulating a single chromosome or chromosomal fragment. Rupture of the unstable micronuclear envelope exposes its chromatin to cytosolic nucleases and induces chromothriptic shattering. Found in up to half of tumours included in pan-cancer genomic analyses, chromothriptic rearrangements can contribute to tumorigenesis through inactivation of tumour suppressor genes, activation of proto-oncogenes, or gene amplification through the production of self-propagating extrachromosomal circular DNAs encoding oncogenes or genes conferring anticancer drug resistance. Here, we discuss what has been learned about the mechanisms that enable these complex genomic rearrangements and their consequences in cancer.",
			"category": 2,
			"name": "Krupina Ksenia,2024"
		},
		{
			"PMID": 37895205,
			"title": "Decoding Cancer Evolution: Integrating Genetic and Non-Genetic Insights.",
			"journal": "Genes",
			"authorList": [
				"Ashouri Arghavan",
				"Zhang Chufan",
				"Gaiti Federico"
			],
			"DOI": "10.3390/genes14101856",
			"date": "2023-10-30",
			"PMC": "",
			"citation": "",
			"abstract": "The development of cancer begins with cells transitioning from their multicellular nature to a state akin to unicellular organisms. This shift leads to a breakdown in the crucial regulators inherent to multicellularity, resulting in the emergence of diverse cancer cell subpopulations that have enhanced adaptability. The presence of different cell subpopulations within a tumour, known as intratumoural heterogeneity (ITH), poses challenges for cancer treatment. In this review, we delve into the dynamics of the shift from multicellularity to unicellularity during cancer onset and progression. We highlight the role of genetic and non-genetic factors, as well as tumour microenvironment, in promoting ITH and cancer evolution. Additionally, we shed light on the latest advancements in omics technologies that allow for in-depth analysis of tumours at the single-cell level and their spatial organization within the tissue. Obtaining such detailed information is crucial for deepening our understanding of the diverse evolutionary paths of cancer, allowing for the development of effective therapies targeting the key drivers of cancer evolution.",
			"category": 2,
			"name": "Ashouri Arghavan,2023"
		},
		{
			"PMID": 37758711,
			"title": "Predictive modelling of response to neoadjuvant therapy in HER2+ breast cancer.",
			"journal": "NPJ breast cancer",
			"authorList": [
				"Cosgrove Nicola",
				"Eustace Alex J",
				"O'Donovan Peter",
				"Madden Stephen F",
				"Moran Bruce",
				"Crown John",
				"Moulton Brian",
				"Morris Patrick G",
				"Grogan Liam",
				"Breathnach Oscar",
				"Power Colm",
				"Allen Michael",
				"Walshe Janice M",
				"Hill Arnold D",
				"Bl\u00fcmel Anna",
				"O'Connor Darren",
				"Das Sudipto",
				"Milewska Ma\u0142gorzata",
				"Fay Joanna",
				"Kay Elaine",
				"Toomey Sinead",
				"Hennessy Bryan T",
				"Furney Simon J"
			],
			"DOI": "10.1038/s41523-023-00572-9",
			"date": "2024-02-12",
			"PMC": "",
			"citation": "",
			"abstract": "HER2-positive (HER2+) breast cancer accounts for 20-25% of all breast cancers. Predictive biomarkers of neoadjuvant therapy response are needed to better identify patients with early stage disease who may benefit from tailored treatments in the adjuvant setting. As part of the TCHL phase-II clinical trial (ICORG10-05/NCT01485926) whole exome DNA sequencing was carried out on normal-tumour pairs collected from 22 patients. Here we report predictive modelling of neoadjuvant therapy response using clinicopathological and genomic features of pre-treatment tumour biopsies identified age, estrogen receptor (ER) status and level of immune cell infiltration may together be important for predicting response. Clonal evolution analysis of longitudinally collected tumour samples show subclonal diversity and dynamics are evident with potential therapy resistant subclones detected. The sources of greater pre-treatment immunogenicity associated with a pathological complete response is largely unexplored in HER2+ tumours. However, here we point to the possibility of APOBEC associated mutagenesis, specifically in the ER-neg/HER2+ subtype as a potential mediator of this immunogenic phenotype.",
			"category": 2,
			"name": "Cosgrove Nicola,2024"
		},
		{
			"PMID": 37568187,
			"title": "Rapid assessment of 3-dimensional intra-tumor heterogeneity through cycling temperature capillary electrophoresis.",
			"journal": "BMC research notes",
			"authorList": [
				"Po\u0142e\u0107 Anna",
				"Ekstr\u00f8m Per Olaf",
				"Fougner Christian",
				"S\u00f8rlie Therese",
				"Norum Jens Henrik"
			],
			"DOI": "10.1186/s13104-023-06437-5",
			"date": "2023-11-27",
			"PMC": "",
			"citation": "",
			"abstract": "Tumors are heterogeneous three-dimensional masses populated by numerous cell types, including distinct sub-clones of cancerous cells. Various sub-clones within the same tumor mass may respond differently to cancer treatment, and intra-tumor heterogeneity contributes to acquired therapeutic resistance. Thus, one tissue biopsy will in most cases not be representative of the entire genetic landscape of a tumor mass. In this study, we aimed to establish an easily accessible, low cost method to address intra-tumor heterogeneity in three dimensions, for a limited number of DNA alterations.",
			"category": 2,
			"name": "Po\u0142e\u0107 Anna,2023"
		},
		{
			"PMID": 37560004,
			"title": "Development and validation of a N6 methylation regulator-related gene signature for prognostic and immune response prediction in non-small cell lung cancer.",
			"journal": "American journal of cancer research",
			"authorList": [
				"Li Xiang",
				"Ma Jinlong",
				"Sun Zhenqian",
				"Li Na",
				"Jiao Guangjun",
				"Zhang Tianqi",
				"Cao Hongxin"
			],
			"DOI": "",
			"date": "2023-08-11",
			"PMC": "",
			"citation": "",
			"abstract": "N6 methylation (m6A) has been reported to play an important role in tumor progression. Non-small cell lung cancer (NSCLC) is the predominant pathological type of lung cancer with a high mortality rate. The purpose of this study was to develop and validate a N6 methylation regulator-related gene signature for assessing prognosis and response to immunotherapy in NSCLC. Data from The Cancer Genome Atlas was used as the training cohort. Data from Gene Expression Omnibus and Xena served as the two validation cohorts. We performed Cox regression, last absolute shrinkage and selection operator, receiver operating characteristic curves and Kaplan-Meier survival analysis to generate and validate a prognostic signature based on m6A regulator-related genes. We explored the association between the signature and tumor microenvironment including genomic mutation, immune cell infiltration and tumor mutation burden. We also analyzed the association between the signature and immunotherapy. Finally, among the genes that constituted the signature, GGA2 was the only favorable factor for NSCLC prognosis. Molecular experiments were used to explore GGA2 function in NSCLC. We generated a prognostic signature based on seven m6A regulator-related genes (GGA2, CD70, BMP2, GPX8, YWHAZ, NOG and TEAD4). And the data from three cohorts showed that the signature could effectively assess prognosis in NSCLC. Patients with high risk scores had the higher mutational load and lower immune infiltration levels and were more likely to not respond to immunotherapy. The experiments revealed overexpression of GGA2 inhibited proliferation and motility of NSCLC cells. Mechanically, GGA2 downregulated METTL3 expression and thus reduced m6A abundance in NSCLC. This study developed and validated a prognostic signature based on m6A regulator-related genes, providing useful insights for the management of NSCLC. And GGA2 may be a target of m6A regulation.",
			"category": 2,
			"name": "Li Xiang,2023"
		},
		{
			"PMID": 37479705,
			"title": "Growth exponents reflect evolutionary processes and treatment response in brain metastases.",
			"journal": "NPJ systems biology and applications",
			"authorList": [
				"Oca\u00f1a-Tienda Beatriz",
				"P\u00e9rez-Beteta Juli\u00e1n",
				"Jim\u00e9nez-S\u00e1nchez Juan",
				"Molina-Garc\u00eda David",
				"Ortiz de Mendivil Ana",
				"Asenjo Beatriz",
				"Albillo David",
				"P\u00e9rez-Romasanta Luis A",
				"Valiente Manuel",
				"Zhu Luc\u00eda",
				"Garc\u00eda-G\u00f3mez Pedro",
				"Gonz\u00e1lez-Del Portillo Elisabet",
				"Llorente Manuel",
				"Carballo Natalia",
				"Arana Estanislao",
				"P\u00e9rez-Garc\u00eda V\u00edctor M"
			],
			"DOI": "10.1038/s41540-023-00298-1",
			"date": "2023-07-24",
			"PMC": "",
			"citation": "",
			"abstract": "Tumor growth is the result of the interplay of complex biological processes in huge numbers of individual cells living in changing environments. Effective simple mathematical laws have been shown to describe tumor growth in vitro, or simple animal models with bounded-growth dynamics accurately. However, results for the growth of human cancers in patients are scarce. Our study mined a large dataset of 1133 brain metastases (BMs) with longitudinal imaging follow-up to find growth laws for untreated BMs and recurrent treated BMs. Untreated BMs showed high growth exponents, most likely related to the underlying evolutionary dynamics, with experimental tumors in mice resembling accurately the disease. Recurrent BMs growth exponents were smaller, most probably due to a reduction in tumor heterogeneity after treatment, which may limit the tumor evolutionary capabilities. In silico simulations using a stochastic discrete mesoscopic model with basic evolutionary dynamics led to results in line with the observed data.",
			"category": 2,
			"name": "Oca\u00f1a-Tienda Beatriz,2023"
		},
		{
			"PMID": 37344104,
			"title": "Modeling and predicting cancer clonal evolution with reinforcement learning.",
			"journal": "Genome research",
			"authorList": [
				"Ivanovic Stefan",
				"El-Kebir Mohammed"
			],
			"DOI": "10.1101/gr.277672.123",
			"date": "2023-08-28",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer results from an evolutionary process that typically yields multiple clones with varying sets of mutations within the same tumor. Accurately modeling this process is key to understanding and predicting cancer evolution. Here, we introduce clone to mutation (CloMu), a flexible and low-parameter tree generative model of cancer evolution. CloMu uses a two-layer neural network trained via reinforcement learning to determine the probability of new mutations based on the existing mutations on a clone. CloMu supports several prediction tasks, including the determination of evolutionary trajectories, tree selection, causality and interchangeability between mutations, and mutation fitness. Importantly, previous methods support only some of these tasks, and many suffer from overfitting on data sets with a large number of mutations. Using simulations, we show that CloMu either matches or outperforms current methods on a wide variety of prediction tasks. In particular, for simulated data with interchangeable mutations, current methods are unable to uncover causal relationships as effectively as CloMu. On breast cancer and leukemia cohorts, we show that CloMu determines similarities and causal relationships between mutations as well as the fitness of mutations. We validate CloMu's inferred mutation fitness values for the leukemia cohort by comparing them to clonal proportion data not used during training, showing high concordance. In summary, CloMu's low-parameter model facilitates a wide range of prediction tasks regarding cancer evolution on increasingly available cohort-level data sets.",
			"category": 2,
			"name": "Ivanovic Stefan,2023"
		},
		{
			"PMID": 37302922,
			"title": "Clonal evolution and hierarchy in myeloid malignancies.",
			"journal": "Trends in cancer",
			"authorList": [
				"Takahashi Koichi",
				"Tanaka Tomoyuki"
			],
			"DOI": "10.1016/j.trecan.2023.05.004",
			"date": "2023-08-18",
			"PMC": "",
			"citation": "",
			"abstract": "Myeloid malignancies, a group of hematopoietic disorders that includes acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs), are caused by the accumulation of genetic and epigenetic changes in hematopoietic stem and progenitor cells (HSPCs) over time. Despite the relatively low number of genomic drivers compared with other forms of cancer, the process by which these changes shape the genomic architecture of myeloid malignancies remains elusive. Recent advancements in clonal hematopoiesis research and the use of cutting-edge single cell technologies have shed new light on the developmental process of myeloid malignancies. In this review, we delve into the intricacies of clonal evolution in myeloid malignancies and its implications for the development of new diagnostic and therapeutic approaches.",
			"category": 2,
			"name": "Takahashi Koichi,2023"
		},
		{
			"PMID": 37291246,
			"title": "Tumour mutations in long noncoding RNAs enhance cell fitness.",
			"journal": "Nature communications",
			"authorList": [
				"Esposito Roberta",
				"Lanz\u00f3s Andr\u00e9s",
				"Uroda Tina",
				"Ramnarayanan Sunandini",
				"B\u00fcchi Isabel",
				"Polidori Taisia",
				"Guillen-Ramirez Hugo",
				"Mihaljevic Ante",
				"Merlin Bernard Mefi",
				"Mela Lia",
				"Zoni Eugenio",
				"Hovhannisyan Lusine",
				"McCluggage Finn",
				"Medo Mat\u00fa\u0161",
				"Basile Giulia",
				"Meise Dominik F",
				"Zwyssig Sandra",
				"Wenger Corina",
				"Schwarz Kyriakos",
				"Vancura Adrienne",
				"Bosch-Guiteras N\u00faria",
				"Andrades \u00c1lvaro",
				"Tham Ai Ming",
				"Roemmele Michaela",
				"Medina Pedro P",
				"Ochsenbein Adrian F",
				"Riether Carsten",
				"Kruithof-de Julio Marianna",
				"Zimmer Yitzhak",
				"Medov\u00e1 Michaela",
				"Stroka Deborah",
				"Fox Archa",
				"Johnson Rory"
			],
			"DOI": "10.1038/s41467-023-39160-7",
			"date": "2023-06-12",
			"PMC": "",
			"citation": "",
			"abstract": "Long noncoding RNAs (lncRNAs) are linked to cancer via pathogenic changes in their expression levels. Yet, it remains unclear whether lncRNAs can also impact tumour cell fitness via function-altering somatic \"driver\" mutations. To search for such driver-lncRNAs, we here\u00a0perform a genome-wide analysis of fitness-altering single nucleotide variants (SNVs) across a cohort of 2583 primary and 3527 metastatic tumours. The resulting 54 mutated and positively-selected lncRNAs are significantly enriched for previously-reported cancer genes and a range of clinical and genomic features. A number of these lncRNAs promote tumour cell proliferation when overexpressed in in vitro models. Our results also highlight a dense SNV hotspot in the widely-studied NEAT1 oncogene. To directly evaluate the functional significance of NEAT1 SNVs, we use in cellulo mutagenesis to introduce tumour-like mutations in the gene and observe a significant and reproducible increase in cell fitness, both in vitro and in a mouse model. Mechanistic studies reveal that SNVs remodel the NEAT1 ribonucleoprotein and boost subnuclear paraspeckles. In summary, this work demonstrates the utility of driver analysis for mapping cancer-promoting lncRNAs, and provides experimental evidence that somatic mutations can act through lncRNAs to enhance pathological cancer cell fitness.",
			"category": 2,
			"name": "Esposito Roberta,2023"
		},
		{
			"PMID": 37246992,
			"title": "Unraveling the Drivers of Tumorigenesis in the Context of Evolution: Theoretical Models and Bioinformatics Tools.",
			"journal": "Journal of molecular evolution",
			"authorList": [
				"Zhu Xunuo",
				"Zhao Wenyi",
				"Zhou Zhan",
				"Gu Xun"
			],
			"DOI": "10.1007/s00239-023-10117-0",
			"date": "2023-06-20",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer originates from somatic cells that have accumulated mutations. These mutations alter the phenotype of the cells, allowing them to escape homeostatic regulation that maintains normal cell numbers. The emergence of malignancies is an evolutionary process in which the random accumulation of somatic mutations and sequential selection of dominant clones cause cancer cells to proliferate. The development of technologies such as high-throughput sequencing has provided a powerful means to measure subclonal evolutionary dynamics across space and time. Here, we review the patterns that may be observed in cancer evolution and the methods available for quantifying the evolutionary dynamics of cancer. An improved understanding of the evolutionary trajectories of cancer will enable us to explore the molecular mechanism of tumorigenesis and to design tailored treatment strategies.",
			"category": 2,
			"name": "Zhu Xunuo,2023"
		},
		{
			"PMID": 36925653,
			"title": "Single-Cell and Transcriptome-Based Immune Cell-Related Prognostic Model in Clear Cell Renal Cell Carcinoma.",
			"journal": "Journal of oncology",
			"authorList": [
				"Wu Guanlin",
				"Guo Weiming",
				"Zhu Shuai",
				"Fan Gang"
			],
			"DOI": "10.1155/2023/5355269",
			"date": "2023-03-18",
			"PMC": "",
			"citation": "",
			"abstract": "Traditional studies mostly focus on the role of single gene in regulating clear cell renal cell carcinoma (ccRCC), while it ignores the impact of tumour heterogeneity on disease progression. The purpose of this study is to construct a prognostic risk model for ccRCC by analysing the differential marker genes related to immune cells in the single-cell database to provide help in clinical diagnosis and targeted therapy. Single-cell data and ligand-receptor relationship pair data were downloaded from related publications, and ccRCC phenotype and expression profile data were downloaded from TCGA and CPTAC. Based on the DEGs of each cluster acquired from single-cell data, immune cell marker genes, and ligand-receptor gene data, we constructed a multilayer network. Then, the genes in the network and the genes in TCGA were used to construct the WGCNA network, which screened out prognosis-associated genes for subsequent analysis. Finally, a prognostic risk scoring model was obtained, and CPTAC data showed that the effectiveness of this model was good. A nomogram based on the predictive model for predicting the overall survival was established, and internal validation was performed well. Our findings suggest that the predictive model built and based on the immune cell scRNA-seq will enable us to judge the prognosis of patients with ccRCC and provide more accurate directions for basic relevant research and clinical practice.",
			"category": 2,
			"name": "Wu Guanlin,2023"
		},
		{
			"PMID": 36835493,
			"title": null,
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Ohguchi Yasuyo",
				"Ohguchi Hiroto"
			],
			"DOI": "10.3390/ijms24044079",
			"date": "2023-03-28",
			"PMC": "",
			"citation": "",
			"abstract": "Recent studies have revealed the genetic aberrations involved in the initiation and progression of various cancers, including multiple myeloma (MM), via next-generation sequencing analysis. Notably, ",
			"category": 2,
			"name": "Ohguchi Yasuyo,2023"
		},
		{
			"PMID": 36819584,
			"title": "The mitosis-related gene ",
			"journal": "Annals of translational medicine",
			"authorList": [
				"Pan Minghong",
				"Wang Yuanyong",
				"Wang Zhaoyang",
				"Duan Hongtao",
				"Shao Changjian",
				"Ding Peng",
				"Lei Jie",
				"Zhao Jinbo",
				"Ma Zhiqiang",
				"Zhang Fan",
				"Han Jing",
				"Yan Xiaolong"
			],
			"DOI": "10.21037/atm-22-6640",
			"date": "2023-02-24",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "Pan Minghong,2023"
		},
		{
			"PMID": 36761946,
			"title": "Yin and yang roles of B lymphocytes in solid tumors: Balance between antitumor immunity and immune tolerance/immunosuppression in tumor-draining lymph nodes.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Katakai Tomoya"
			],
			"DOI": "10.3389/fonc.2023.1088129",
			"date": "2023-02-11",
			"PMC": "",
			"citation": "",
			"abstract": "The role of B cells in antitumor immunity has been reported to be either promotive or suppressive, but the specific mechanism remains to be comprehensively understood. However, this complicated situation likely depends on the temporal and spatial relationship between the developing tumor and B cells that recognize tumor antigens. Unlike responses against microbial or pathogenic infections, tumor cells are derived from autologous cells that have mutated and become aberrant; thus, elimination by the adaptive immune system is essentially inefficient. If tumor cells can evade immune attack at an early stage, non-destructive responses, such as tolerance and immunosuppression, are established over time. In tumor-draining lymph nodes (TDLNs), tumor antigen-reactive B cells potentially acquire immunoregulatory phenotypes and contribute to an immunosuppressive microenvironment. Therefore, triggering and enhancing antitumor responses by immunotherapies require selective control of these regulatory B cell subsets in TDLNs. In contrast, B cell infiltration and formation of tertiary lymphoid structures in tumors are positively correlated with therapeutic prognosis, suggesting that tumor antigen-specific activation of B cells and antibody production are advantageous for antitumor immunity in mid- to late-stage tumors. Given that the presence of B cells in tumor tissues may reflect the ongoing antitumor response in TDLNs, therapeutic induction and enhancement of these lymphocytes are expected to increase the overall effectiveness of immunotherapy. Therefore, B cells are promising targets, but the spatiotemporal balance of the subsets that exhibit opposite characteristics, that is, the protumor or antitumor state in TDLNs, should be understood, and strategies to separately control their functions should be developed to maximize the clinical outcome.",
			"category": 2,
			"name": "Katakai Tomoya,2023"
		},
		{
			"PMID": 36543146,
			"title": "Genomic heterogeneity as a barrier to precision oncology in urothelial cancer.",
			"journal": "Cell reports",
			"authorList": [
				"Clinton Timothy N",
				"Chen Ziyu",
				"Wise Hannah",
				"Lenis Andrew T",
				"Chavan Shweta",
				"Donoghue Mark T A",
				"Almassi Nima",
				"Chu Carissa E",
				"Dason Shawn",
				"Rao Pavitra",
				"Rodrigues James A",
				"Vasani Naresh B",
				"Ridouani Fourat",
				"Rosenberg Jonathan E",
				"Bajorin Dean F",
				"Teo Min Yuen",
				"Bochner Bernard H",
				"Berger Michael F",
				"Ostrovnaya Irina",
				"Pietzak Eugene J",
				"Iyer Gopa",
				"Gao Sizhi Paul",
				"Hu Wenhuo",
				"Al-Ahmadie Hikmat A",
				"Solit David B"
			],
			"DOI": "10.1016/j.celrep.2022.111859",
			"date": "2022-12-23",
			"PMC": "",
			"citation": "",
			"abstract": "Precision oncology relies on the accurate molecular characterization of individual patients with cancer at the time of treatment initiation. However, tumor molecular profiles are not static, and cancers continually evolve because of ongoing mutagenesis and clonal selection. Here, we performed genomic analyses of primary tumors, metastases, and plasma collected from individual patients to define the concordance of actionable genomic alterations and to identify drivers of metastatic disease progression. We observed a high degree of discordance of actionable genomic alterations, with 23% discordant between primary and metastatic disease sites. Among chromatin-modifying genes, ARID1A mutations, when discordant, were exclusive to the metastatic tumor samples. Our findings indicate that the high degree of lesion-to-lesion genomic heterogeneity may be a barrier to precision oncology approaches for bladder cancer and that circulating tumor DNA profiling may be preferred to tumor sequencing for a subset of patients.",
			"category": 2,
			"name": "Clinton Timothy N,2022"
		},
		{
			"PMID": 36518303,
			"title": "Ferroptosis-related molecular patterns reveal immune escape, inflammatory development and lipid metabolism characteristics of the tumor microenvironment in acute myeloid leukemia.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Zhong Fang-Min",
				"Yao Fang-Yi",
				"Liu Jing",
				"Zhang Hai-Bin",
				"Zhang Jing",
				"Zhang Nan",
				"Lin Jin",
				"Li Shu-Qi",
				"Li Mei-Yong",
				"Jiang Jun-Yao",
				"Cheng Ying",
				"Xu Shuai",
				"Wen Wen",
				"Yang Yu-Lin",
				"Zhang Xue-Ru",
				"Cheng Xue-Xin",
				"Huang Bo",
				"Wang Xiao-Zhong"
			],
			"DOI": "10.3389/fonc.2022.888570",
			"date": "2022-12-22",
			"PMC": "",
			"citation": "",
			"abstract": "An increasing number of studies have revealed the influencing factors of ferroptosis. The influence of immune cell infiltration, inflammation development and lipid metabolism in the tumor microenvironment (TME) on the ferroptosis of tumor cells requires further research and discussion.",
			"category": 2,
			"name": "Zhong Fang-Min,2022"
		},
		{
			"PMID": 36497490,
			"title": "Cytoreductive Surgery (CRS) and HIPEC for Advanced Ovarian Cancer with Peritoneal Metastases: Italian PSM Oncoteam Evidence and Study Purposes.",
			"journal": "Cancers",
			"authorList": [
				"Marrelli Daniele",
				"Ansaloni Luca",
				"Federici Orietta",
				"Asero Salvatore",
				"Carbone Ludovico",
				"Marano Luigi",
				"Baiocchi Gianluca",
				"Vaira Marco",
				"Coccolini Federico",
				"Di Giorgio Andrea",
				"Framarini Massimo",
				"Gelmini Roberta",
				"Palopoli Carmen",
				"Accarpio Fabio",
				"Fagotti Anna"
			],
			"DOI": "10.3390/cancers14236010",
			"date": "2022-12-20",
			"PMC": "",
			"citation": "",
			"abstract": "Ovarian cancer is the eighth most common neoplasm in women with a high mortality rate mainly due to a marked propensity for peritoneal spread directly at diagnosis, as well as tumor recurrence after radical surgical treatment. Treatments for peritoneal metastases have to be designed from a patient's perspective and focus on meaningful measures of benefit. Hyperthermic intraperitoneal chemotherapy (HIPEC), a strategy combining maximal cytoreductive surgery with regional chemotherapy, has been proposed to treat advanced ovarian cancer. Preliminary results to date have shown promising results, with improved survival outcomes and tumor regression. As knowledge about the disease process increases, practice guidelines will continue to evolve. In this review, we have reported a broad overview of advanced ovarian cancer management, and an update of the current evidence. The future perspectives of the Italian Society of Surgical Oncology (SICO) are discussed conclusively.",
			"category": 2,
			"name": "Marrelli Daniele,2022"
		},
		{
			"PMID": 36324511,
			"title": "Exploration the global single-cell ecological landscape of adenomyosis-related cell clusters by single-cell RNA sequencing.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Lin Jiajing",
				"Liu Li",
				"Zheng Fengque",
				"Chen Saiqiong",
				"Yang Weiwei",
				"Li Jingjing",
				"Mo Steven",
				"Zeng Ding-Yuan"
			],
			"DOI": "10.3389/fgene.2022.1020757",
			"date": "2022-11-04",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "Lin Jiajing,2022"
		},
		{
			"PMID": 36138135,
			"title": "Artificial intelligence in histopathology: enhancing cancer research and clinical oncology.",
			"journal": "Nature cancer",
			"authorList": [
				"Shmatko Artem",
				"Ghaffari Laleh Narmin",
				"Gerstung Moritz",
				"Kather Jakob Nikolas"
			],
			"DOI": "10.1038/s43018-022-00436-4",
			"date": "2022-09-26",
			"PMC": "",
			"citation": "",
			"abstract": "Artificial intelligence (AI) methods have multiplied our capabilities to extract quantitative information from digital histopathology images. AI is expected to reduce workload for human experts, improve the objectivity and consistency of pathology reports, and have a clinical impact by extracting hidden information from routinely available data. Here, we describe how AI can be used to predict cancer outcome, treatment response, genetic alterations and gene expression from digitized histopathology slides. We summarize the underlying technologies and emerging approaches, noting limitations, including the need for data sharing and standards. Finally, we discuss the broader implications of AI in cancer research and oncology.",
			"category": 2,
			"name": "Shmatko Artem,2022"
		},
		{
			"PMID": 36130322,
			"title": "Inferring Epistasis from Genetic Time-series Data.",
			"journal": "Molecular biology and evolution",
			"authorList": [
				"Sohail Muhammad Saqib",
				"Louie Raymond H Y",
				"Hong Zhenchen",
				"Barton John P",
				"McKay Matthew R"
			],
			"DOI": "10.1093/molbev/msac199",
			"date": "2022-10-14",
			"PMC": "",
			"citation": "",
			"abstract": "Epistasis refers to fitness or functional effects of mutations that depend on the sequence background in which these mutations arise. Epistasis is prevalent in nature, including populations of viruses, bacteria, and cancers, and can contribute to the evolution of drug resistance and immune escape. However, it is difficult to directly estimate epistatic effects from sampled observations of a population. At present, there are very few methods that can disentangle the effects of selection (including epistasis), mutation, recombination, genetic drift, and genetic linkage in evolving populations. Here we develop a method to infer epistasis, along with the fitness effects of individual mutations, from observed evolutionary histories. Simulations show that we can accurately infer pairwise epistatic interactions provided that there is sufficient genetic diversity in the data. Our method also allows us to identify which fitness parameters can be reliably inferred from a particular data set and which ones are unidentifiable. Our approach therefore allows for the inference of more complex models of selection from time-series genetic data, while also quantifying uncertainty in the inferred parameters.",
			"category": 2,
			"name": "Sohail Muhammad Saqib,2022"
		},
		{
			"PMID": 36101394,
			"title": "Dynamic Co-Evolution of Cancer Cells and Cancer-Associated Fibroblasts: Role in Right- and Left-Sided Colon Cancer Progression and Its Clinical Relevance.",
			"journal": "Biology",
			"authorList": [
				"Ahmad Zawawi Sahira Syamimi",
				"Musa Marahaini"
			],
			"DOI": "10.3390/biology11071014",
			"date": "2022-09-17",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a result of a dynamic evolutionary process. It is composed of cancer cells and the tumour microenvironment (TME). One of the major cellular constituents of TME, cancer-associated fibroblasts (CAFs) are known to interact with cancer cells and promote colorectal carcinogenesis. The accumulation of these activated fibroblasts is linked to poor diagnosis in colorectal cancer (CRC) patients and recurrence of the disease. However, the interplay between cancer cells and CAFs is yet to be described, especially in relation to the sidedness of colorectal carcinogenesis. CRC, which is the third most commonly diagnosed cancer globally, can be classified according to the anatomical region from which they originate: left-sided (LCRC) and right-sided CRC (RCR). Both cancers differ in many aspects, including in histology, evolution, and molecular signatures. Despite occurring at lower frequency, RCRC is often associated with worse diagnosis compared to LCRC. The differences in molecular profiles between RCRC and LCRC also influence the mode of treatment that can be used to specifically target these cancer entities. A better understanding of the cancer cell-CAF interplay and its association with RCRC and LRCR progression will provide better insight into potential translational aspects of targeted treatment for CRC.",
			"category": 2,
			"name": "Ahmad Zawawi Sahira Syamimi,2022"
		},
		{
			"PMID": 36058001,
			"title": "Patient-Derived Organoids from Colorectal Cancer with Paired Liver Metastasis Reveal Tumor Heterogeneity and Predict Response to Chemotherapy.",
			"journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)",
			"authorList": [
				"Mo Shaobo",
				"Tang Peiyuan",
				"Luo Wenqin",
				"Zhang Long",
				"Li Yaqi",
				"Hu Xiang",
				"Ma Xiaoji",
				"Chen Yikuan",
				"Bao Yichao",
				"He Xingfeng",
				"Fu Guoxiang",
				"Xu Xiaoya",
				"Rao Xinxin",
				"Li Xiaomeng",
				"Guan Ruoyu",
				"Chen Shengzhi",
				"Deng Yun",
				"Lv Tao",
				"Mu Peiyuan",
				"Zheng Qiang",
				"Wang Simin",
				"Liu Fangqi",
				"Li Yiwei",
				"Sheng Weiqi",
				"Huang Dan",
				"Hu Chen",
				"Gao Jianjun",
				"Zhang Zhen",
				"Cai Sanjun",
				"Clevers Hans",
				"Peng Junjie",
				"Hua Guoqiang"
			],
			"DOI": "10.1002/advs.202204097",
			"date": "2022-11-04",
			"PMC": "",
			"citation": "",
			"abstract": "There is no effective method to predict chemotherapy response and postoperative prognosis of colorectal cancer liver metastasis (CRLM) patients. Patient-derived organoid (PDO) has become an important preclinical model. Herein, a living biobank with 50 CRLM organoids derived from primary tumors and paired liver metastatic lesions is successfully constructed. CRLM PDOs from the multiomics levels (histopathology, genome, transcriptome and single-cell sequencing) are comprehensively analyzed and confirmed that this organoid platform for CRLM could capture intra- and interpatient heterogeneity. The chemosensitivity data in vitro reveal the potential value of clinical application for PDOs to predict chemotherapy response (FOLFOX or FOLFIRI) and clinical prognosis of CRLM patients. Taken together, CRLM PDOs can be utilized to deliver a potential application for personalized medicine.",
			"category": 2,
			"name": "Mo Shaobo,2022"
		},
		{
			"PMID": 36038111,
			"title": "Dualistic classification of high grade serous ovarian carcinoma has its root in spatial heterogeneity.",
			"journal": "Journal of advanced research",
			"authorList": [
				"Sun Tingting",
				"Zhang Zuwei",
				"Tian Liming",
				"Zheng Yu",
				"Wu Linxiang",
				"Guo Yunyun",
				"Li Xiaohui",
				"Li Yuanyuan",
				"Shen Hongwei",
				"Lai Yingrong",
				"Liu Junfeng",
				"Cui Huanhuan",
				"He Shasha",
				"Ren Yufeng",
				"Yang Guofen"
			],
			"DOI": "10.1016/j.jare.2022.08.014",
			"date": "2023-06-05",
			"PMC": "",
			"citation": "",
			"abstract": "Widespread intra-peritoneal metastases is a main feature of high grade serous ovarian carcinoma (HGSOC). Recently, the extent of tumour heterogeneity was used to evaluate the cancer genomes among multi-regions in HGSOC. However, there is no consensus on the effect of tumour heterogeneity on the evolution of the tumour metastasis process in HGSOC.",
			"category": 2,
			"name": "Sun Tingting,2023"
		},
		{
			"PMID": 36000873,
			"title": "Single-cell mutation calling and phylogenetic tree reconstruction with loss and recurrence.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Kuipers Jack",
				"Singer Jochen",
				"Beerenwinkel Niko"
			],
			"DOI": "10.1093/bioinformatics/btac577",
			"date": "2022-10-18",
			"PMC": "",
			"citation": "",
			"abstract": "Tumours evolve as heterogeneous populations of cells, which may be distinguished by different genomic aberrations. The resulting intra-tumour heterogeneity plays an important role in cancer patient relapse and treatment failure, so that obtaining a clear understanding of each patient's tumour composition and evolutionary history is key for personalized therapies. Single-cell sequencing (SCS) now provides the possibility to resolve tumour heterogeneity at the highest resolution of individual tumour cells, but brings with it challenges related to the particular noise profiles of the sequencing protocols as well as the complexity of the underlying evolutionary process.",
			"category": 2,
			"name": "Kuipers Jack,2022"
		},
		{
			"PMID": 35996174,
			"title": "Evolution of intra-tumoral heterogeneity across different pathological stages in papillary thyroid carcinoma.",
			"journal": "Cancer cell international",
			"authorList": [
				"Affinito Ornella",
				"Orlandella Francesca Maria",
				"Luciano Neila",
				"Salvatore Marco",
				"Salvatore Giuliana",
				"Franzese Monica"
			],
			"DOI": "10.1186/s12935-022-02680-1",
			"date": "2022-09-05",
			"PMC": "",
			"citation": "",
			"abstract": "Intra-tumor heterogeneity (ITH) results from the continuous accumulation of mutations during disease progression, thus impacting patients' clinical outcome. How the ITH evolves across papillary thyroid carcinoma (PTC) different tumor stages is lacking.",
			"category": 2,
			"name": "Affinito Ornella,2022"
		},
		{
			"PMID": 35931318,
			"title": "Cancer: slaying the nine-headed Hydra.",
			"journal": "Annals of oncology : official journal of the European Society for Medical Oncology",
			"authorList": [
				"Adashek J J",
				"Subbiah V",
				"Westphalen C B",
				"Naing A",
				"Kato S",
				"Kurzrock R"
			],
			"DOI": "10.1016/j.annonc.2022.07.010",
			"date": "2023-01-03",
			"PMC": "",
			"citation": "",
			"abstract": "Modern medicine continues to evolve, and the treatment armamentarium for various diseases grows more individualized across a breadth of medical disciplines. Cure rates for infectious diseases that were previously pan-fatal approach 100% because of the identification of the specific pathogen(s) involved and the use of appropriate combinations of drugs, where needed, to completely extinguish infection and hence prevent emergence of resistant strains. Similarly, with the assistance of technologies such as next-generation sequencing and immunomic analysis as part of the contemporary oncology armory, therapies can be tailored to each tumor. Importantly, molecular interrogation has revealed that metastatic cancers are distinct from each other and complex. Therefore, it is conceivable that rational personalized drug combinations will be needed to eradicate cancers, and eradication will be necessary to mitigate clonal evolution and resistance.",
			"category": 2,
			"name": "Adashek J J,2023"
		},
		{
			"PMID": 35625573,
			"title": "Hepatocellular Carcinoma: The Role of MicroRNAs.",
			"journal": "Biomolecules",
			"authorList": [
				"Khare Sharad",
				"Khare Tripti",
				"Ramanathan Raghu",
				"Ibdah Jamal A"
			],
			"DOI": "10.3390/biom12050645",
			"date": "2022-05-31",
			"PMC": "",
			"citation": "",
			"abstract": "Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. HCC is diagnosed in its advanced stage when limited treatment options are available. Substantial morphologic, genetic and epigenetic heterogeneity has been reported in HCC, which poses a challenge for the development of a targeted therapy. In this review, we discuss the role and involvement of several microRNAs (miRs) in the heterogeneity and metastasis of hepatocellular carcinoma with a special emphasis on their possible role as a diagnostic and prognostic tool in the risk prediction, early detection, and treatment of hepatocellular carcinoma.",
			"category": 2,
			"name": "Khare Sharad,2022"
		},
		{
			"PMID": 35580068,
			"title": "Attribution of Cancer Origins to Endogenous, Exogenous, and Preventable Mutational Processes.",
			"journal": "Molecular biology and evolution",
			"authorList": [
				"Cannataro Vincent L",
				"Mandell Jeffrey D",
				"Townsend Jeffrey P"
			],
			"DOI": "10.1093/molbev/msac084",
			"date": "2022-05-19",
			"PMC": "",
			"citation": "",
			"abstract": "Mutational processes in tumors create distinctive patterns of mutations, composed of neutral \"passenger\" mutations and oncogenic drivers that have quantifiable effects on the proliferation and survival of cancer cell lineages. Increases in proliferation and survival are mediated by natural selection, which can be quantified by comparing the frequency at which we detect substitutions to the frequency at which we expect to detect substitutions assuming neutrality. Most of the variants detectable with whole-exome sequencing in tumors are neutral or nearly neutral in effect, and thus the processes generating the majority of mutations may not be the primary sources of the tumorigenic mutations. Across 24 cancer types, we identify the contributions of mutational processes to each oncogenic variant and quantify the degree to which each process contributes to tumorigenesis. We demonstrate that the origination of variants driving melanomas and lung cancers is predominantly attributable to the preventable, exogenous mutational processes associated with ultraviolet light and tobacco exposure, respectively, whereas the origination of selected variants in gliomas and prostate adenocarcinomas is largely attributable to endogenous processes associated with aging. Preventable mutations associated with pathogen exposure and apolipoprotein B mRNA-editing enzyme activity account for a large proportion of the cancer effect within head-and-neck, bladder, cervical, and breast cancers. These attributions complement epidemiological approaches-revealing the burden of cancer driven by single-nucleotide variants caused by either endogenous or exogenous, nonpreventable, or preventable processes, and crucially inform public health strategies.",
			"category": 2,
			"name": "Cannataro Vincent L,2022"
		},
		{
			"PMID": 35571400,
			"title": "The value of ",
			"journal": "Annals of translational medicine",
			"authorList": [
				"Feng Yingtong",
				"Wang Yuanyong",
				"Guo Kai",
				"Feng Junjun",
				"Shao Changjian",
				"Pan Minghong",
				"Ding Peng",
				"Liu Honggang",
				"Duan Hongtao",
				"Lu Di",
				"Wang Zhaoyang",
				"Zhang Yimeng",
				"Zhang Yujing",
				"Han Jing",
				"Li Xiaofei",
				"Yan Xiaolong"
			],
			"DOI": "10.21037/atm-22-1317",
			"date": "2022-05-19",
			"PMC": "",
			"citation": "",
			"abstract": "Finding new immune-related biomarkers is one of the promising research directions for tumor immunotherapy. The ",
			"category": 2,
			"name": "Feng Yingtong,2022"
		},
		{
			"PMID": 35546239,
			"title": "Immunogenomic intertumor heterogeneity across primary and metastatic sites in a patient with lung adenocarcinoma.",
			"journal": "Journal of experimental & clinical cancer research : CR",
			"authorList": [
				"Chen Runzhe",
				"Li Jun",
				"Fujimoto Junya",
				"Hong Lingzhi",
				"Hu Xin",
				"Quek Kelly",
				"Tang Ming",
				"Mitra Akash",
				"Behrens Carmen",
				"Chow Chi-Wan",
				"Jiang Peixin",
				"Little Latasha D",
				"Gumbs Curtis",
				"Song Xingzhi",
				"Zhang Jianhua",
				"Tan Dongfeng",
				"Heymach John V",
				"Wistuba Ignacio",
				"Futreal P Andrew",
				"Gibbons Don L",
				"Byers Lauren A",
				"Zhang Jianjun",
				"Reuben Alexandre"
			],
			"DOI": "10.1186/s13046-022-02361-x",
			"date": "2022-05-17",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer is the leading cause of cancer death, partially owing to its extensive heterogeneity. The analysis of intertumor heterogeneity has been limited by an inability to concurrently obtain tissue from synchronous metastases unaltered by multiple prior lines of therapy.",
			"category": 2,
			"name": "Chen Runzhe,2022"
		},
		{
			"PMID": 35438189,
			"title": "Leveraging single-cell sequencing to unravel intratumour heterogeneity and tumour evolution in human cancers.",
			"journal": "The Journal of pathology",
			"authorList": [
				"Bowes Amy L",
				"Tarabichi Maxime",
				"Pillay Nischalan",
				"Van Loo Peter"
			],
			"DOI": "10.1002/path.5914",
			"date": "2022-07-06",
			"PMC": "",
			"citation": "",
			"abstract": "Intratumour heterogeneity (ITH) and tumour evolution are well-documented phenomena in human cancers. While the advent of next-generation sequencing technologies has facilitated the large-scale capture of genomic data, the field of single-cell genomics is nascent but rapidly advancing and generating many new insights into the complex molecular mechanisms of tumour biology. In this review, we provide an overview of current single-cell DNA sequencing technologies, exploring how recent methodological advancements have enumerated new insights into ITH and tumour evolution. Areas highlighted include the potential power of single-cell genome sequencing studies to explore evolutionary dynamics contributing to tumourigenesis through to progression, metastasis, and therapy resistance. We also explore the use of in situ sequencing technologies to study ITH in a spatial context, as well as examining the use of single-cell genomics to perform lineage tracing in both normal and malignant tissues. Finally, we consider the use of multimodal single-cell sequencing technologies. Taken together, it is hoped that these many facets of single-cell genome sequencing will improve our understanding of tumourigenesis, progression, and lethality in cancer, leading to the development of novel therapies. \u00a9 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.",
			"category": 2,
			"name": "Bowes Amy L,2022"
		},
		{
			"PMID": 35346363,
			"title": "DNA in extracellular vesicles: from evolution to its current application in health and disease.",
			"journal": "Cell & bioscience",
			"authorList": [
				"Ghanam Jamal",
				"Chetty Venkatesh Kumar",
				"Barthel Lennart",
				"Reinhardt Dirk",
				"Hoyer Peter-Friedrich",
				"Thakur Basant Kumar"
			],
			"DOI": "10.1186/s13578-022-00771-0",
			"date": "2022-04-01",
			"PMC": "",
			"citation": "",
			"abstract": "Extracellular vesicle (EV) secretion is a highly conserved evolutionary trait in all organisms in the three domains of life. The packaging and release of EVs appears to be a bulk-flow process which takes place mainly under extreme conditions. EVs participate in horizontal gene transfer, which supports the survival of prokaryotic and eukaryotic microbes. In higher eukaryotes, almost all cells secrete a heterogeneous population of EVs loaded with various biomolecules. EV secretion is typically higher in cancer microenvironments, promoting tumor progression and metastasis. EVs are now recognized as additional mediators of autocrine and paracrine communication in health and disease. In this context, proteins and RNAs have been studied the most, but extracellular vesicle DNA (EV-DNA) has started to gain in importance in the last few years. In this review, we summarize new findings related to the loading mechanism(s), localization, and post-shedding function of EV-DNA. We also discuss the feasibility of using EV-DNA as a biomarker when performing a liquid biopsy, at the same time emphasizing the lack of data from clinical trials in this regard. Finally, we outline the potential of EV-DNA uptake and its interaction with the host genome as a promising tool for understanding the mechanisms of cancer evolution.",
			"category": 2,
			"name": "Ghanam Jamal,2022"
		},
		{
			"PMID": 35116635,
			"title": "Mutational status of main driver genes influences the prognosis of stage I-III lung adenocarcinoma patients underwent radical surgery.",
			"journal": "Translational cancer research",
			"authorList": [
				"Liao Hongliang",
				"Luo Xiaoyan",
				"Liang Yaqin",
				"Wan Renping",
				"Xu Meng"
			],
			"DOI": "10.21037/tcr-21-240",
			"date": "2022-05-01",
			"PMC": "",
			"citation": "",
			"abstract": "The therapeutic strategies and prognosis of local advanced and metastatic lung cancer have been extensively investigated. However, the prognosis of early-stage lung cancer patients undergoing radical surgery has not been fully studied due to the difficulties in follow-up and assessment.",
			"category": 2,
			"name": "Liao Hongliang,2022"
		},
		{
			"PMID": 35071438,
			"title": "Mitosis-related gene ",
			"journal": "Annals of translational medicine",
			"authorList": [
				"Shao Changjian",
				"Wang Yuanyong",
				"Duan Hongtao",
				"Ding Peng",
				"Zhang Yimeng",
				"Ning Jiayi",
				"Han Jing",
				"Jiang Tao",
				"Yan Xiaolong"
			],
			"DOI": "10.21037/atm-21-6516",
			"date": "2022-04-30",
			"PMC": "",
			"citation": "",
			"abstract": "Centromere protein U (",
			"category": 2,
			"name": "Shao Changjian,2022"
		},
		{
			"PMID": 34946794,
			"title": "RDAClone: Deciphering Tumor Heterozygosity through Single-Cell Genomics Data Analysis with Robust Deep Autoencoder.",
			"journal": "Genes",
			"authorList": [
				"Xia Jie",
				"Wang Lequn",
				"Zhang Guijun",
				"Zuo Chunman",
				"Chen Luonan"
			],
			"DOI": "10.3390/genes12121847",
			"date": "2022-02-21",
			"PMC": "",
			"citation": "",
			"abstract": "Rapid advances in single-cell genomics sequencing (SCGS) have allowed researchers to characterize tumor heterozygosity with unprecedented resolution and reveal the phylogenetic relationships between tumor cells or clones. However, high sequencing error rates of current SCGS data, i.e., false positives, false negatives, and missing bases, severely limit its application. Here, we present a deep learning framework, RDAClone, to recover genotype matrices from noisy data with an extended robust deep autoencoder, cluster cells into subclones by the Louvain-Jaccard method, and further infer evolutionary relationships between subclones by the minimum spanning tree. Studies on both simulated and real datasets demonstrate its robustness and superiority in data denoising, cell clustering, and evolutionary tree reconstruction, particularly for large datasets.",
			"category": 2,
			"name": "Xia Jie,2022"
		},
		{
			"PMID": 34944891,
			"title": "The Transmembrane Receptor TIRC7 Identifies a Distinct Subset of Immune Cells with Prognostic Implications in Cholangiocarcinoma.",
			"journal": "Cancers",
			"authorList": [
				"Albrecht Thomas",
				"Goeppert Benjamin",
				"Brinkmann Fritz",
				"Charbel Alphonse",
				"Zhang Qiangnu",
				"Schreck Johannes",
				"Wilhelm Nina",
				"Singer Stephan",
				"K\u00f6hler Bruno C",
				"Springfeld Christoph",
				"Mehrabi Arianeb",
				"Schirmacher Peter",
				"K\u00fchl Anja A",
				"Vogel Monika N",
				"Jansen Holger",
				"Utku Nal\u00e2n",
				"Roessler Stephanie"
			],
			"DOI": "10.3390/cancers13246272",
			"date": "2021-12-29",
			"PMC": "",
			"citation": "",
			"abstract": "Cholangiocarcinoma (CCA) is a heterogeneous malignancy with a dismal prognosis. Therapeutic options are largely limited to surgery and conventional chemotherapy offers limited benefit. As immunotherapy has proven highly effective in various cancer types, we have undertaken a quantitative immunohistopathological assessment of immune cells expressing the immunoinhibitory T cell immune response cDNA 7 receptor (TIRC7), an emerging immunoinhibitory receptor, in a cohort of 135 CCA patients. TIRC7",
			"category": 2,
			"name": "Albrecht Thomas,2021"
		},
		{
			"PMID": 34910733,
			"title": "Statistical tests for intra-tumour clonal co-occurrence and exclusivity.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Kuipers Jack",
				"Moore Ariane L",
				"Jahn Katharina",
				"Schraml Peter",
				"Wang Feng",
				"Morita Kiyomi",
				"Futreal P Andrew",
				"Takahashi Koichi",
				"Beisel Christian",
				"Moch Holger",
				"Beerenwinkel Niko"
			],
			"DOI": "10.1371/journal.pcbi.1009036",
			"date": "2022-02-14",
			"PMC": "",
			"citation": "",
			"abstract": "Tumour progression is an evolutionary process in which different clones evolve over time, leading to intra-tumour heterogeneity. Interactions between clones can affect tumour evolution and hence disease progression and treatment outcome. Intra-tumoural pairs of mutations that are overrepresented in a co-occurring or clonally exclusive fashion over a cohort of patient samples may be suggestive of a synergistic effect between the different clones carrying these mutations. We therefore developed a novel statistical testing framework, called GeneAccord, to identify such gene pairs that are altered in distinct subclones of the same tumour. We analysed our framework for calibration and power. By comparing its performance to baseline methods, we demonstrate that to control type I errors, it is essential to account for the evolutionary dependencies among clones. In applying GeneAccord to the single-cell sequencing of a cohort of 123 acute myeloid leukaemia patients, we find 1 clonally co-occurring and 8 clonally exclusive gene pairs. The clonally exclusive pairs mostly involve genes of the key signalling pathways.",
			"category": 2,
			"name": "Kuipers Jack,2022"
		},
		{
			"PMID": 34833475,
			"title": "A Portrait of Intratumoral Genomic and Transcriptomic Heterogeneity at Single-Cell Level in Colorectal Cancer.",
			"journal": "Medicina (Kaunas, Lithuania)",
			"authorList": [
				"Angius Andrea",
				"Scanu Antonio Mario",
				"Arru Caterina",
				"Muroni Maria Rosaria",
				"Carru Ciriaco",
				"Porcu Alberto",
				"Cossu-Rocca Paolo",
				"De Miglio Maria Rosaria"
			],
			"DOI": "10.3390/medicina57111257",
			"date": "2021-11-30",
			"PMC": "",
			"citation": "",
			"abstract": "In the study of cancer, omics technologies are supporting the transition from traditional clinical approaches to precision medicine. Intra-tumoral heterogeneity (ITH) is detectable within a single tumor in which cancer cell subpopulations with different genome features coexist in a patient in different tumor areas or may evolve/differ over time. Colorectal carcinoma (CRC) is characterized by heterogeneous features involving genomic, epigenomic, and transcriptomic alterations. The study of ITH is a promising new frontier to lay the foundation towards successful CRC diagnosis and treatment. Genome and transcriptome sequencing together with editing technologies are revolutionizing biomedical research, representing the most promising tools for overcoming unmet clinical and research challenges. Rapid advances in both bulk and single-cell next-generation sequencing (NGS) are identifying primary and metastatic intratumoral genomic and transcriptional heterogeneity. They provide critical insight in the origin and spatiotemporal evolution of genomic clones responsible for early and late therapeutic resistance and relapse. Single-cell technologies can be used to define subpopulations within a known cell type by searching for differential gene expression within the cell population of interest and/or effectively isolating signal from rare cell populations that would not be detectable by other methods. Each single-cell sequencing analysis is driven by clustering of cells based on their differentially expressed genes. Genes that drive clustering can be used as unique markers for a specific cell population. In this review we analyzed, starting from published data, the possible achievement of a transition from clinical CRC research to precision medicine with an emphasis on new single-cell based techniques; at the same time, we focused on all approaches and issues related to this promising technology. This transition might enable noninvasive screening for early diagnosis, individualized prediction of therapeutic response, and discovery of additional novel drug targets.",
			"category": 2,
			"name": "Angius Andrea,2021"
		},
		{
			"PMID": 34737276,
			"title": "Independent somatic evolution underlies clustered neuroendocrine tumors in the human small intestine.",
			"journal": "Nature communications",
			"authorList": [
				"Elias Erik",
				"Ardalan Arman",
				"Lindberg Markus",
				"Reinsbach Susanne E",
				"Muth Andreas",
				"Nilsson Ola",
				"Arvidsson Yvonne",
				"Larsson Erik"
			],
			"DOI": "10.1038/s41467-021-26581-5",
			"date": "2021-12-23",
			"PMC": "",
			"citation": "",
			"abstract": "Small intestine neuroendocrine tumor (SI-NET), the most common cancer of the small bowel, often displays a curious multifocal phenotype with several tumors clustered together in a limited intestinal segment. SI-NET also shows an unusual absence of driver mutations explaining tumor initiation and metastatic spread. The evolutionary trajectories that underlie multifocal SI-NET lesions could provide insight into the underlying tumor biology, but this question remains unresolved. Here, we determine the complete genome sequences of 61 tumors and metastases from 11 patients with multifocal SI-NET, allowing for elucidation of phylogenetic relationships between tumors within single patients. Intra-individual comparisons revealed a lack of shared somatic single-nucleotide variants among the sampled intestinal lesions, supporting an independent clonal origin. Furthermore, in three of the patients, two independent tumors had metastasized. We conclude that primary multifocal SI-NETs generally arise from clonally independent cells, suggesting a contribution from a cancer-priming local factor.",
			"category": 2,
			"name": "Elias Erik,2021"
		},
		{
			"PMID": 34573897,
			"title": "Breast Cancer Heterogeneity.",
			"journal": "Diagnostics (Basel, Switzerland)",
			"authorList": [
				"Fumagalli Caterina",
				"Barberis Massimo"
			],
			"DOI": "10.3390/diagnostics11091555",
			"date": "2021-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "Breast tumor heterogeneity is a major challenge in the clinical management of breast cancer patients. Both inter-tumor and intra-tumor heterogeneity imply that each breast cancer (BC) could have different prognosis and would benefit from specific therapy. Breast cancer is a dynamic entity, changing during tumor progression and metastatization and this poses fundamental issues to the feasibility of a personalized medicine approach. The most effective therapeutic strategy for patients with recurrent disease should be assessed evaluating biopsies obtained from metastatic sites. Furthermore, the tumor progression and the treatment response should be strictly followed and radiogenomics and liquid biopsy might be valuable tools to assess BC heterogeneity in a non-invasive way.",
			"category": 2,
			"name": "Fumagalli Caterina,2021"
		},
		{
			"PMID": 34503137,
			"title": "Emerging Role of Chimeric RNAs in Cell Plasticity and Adaptive Evolution of Cancer Cells.",
			"journal": "Cancers",
			"authorList": [
				"Mukherjee Sumit",
				"Heng Henry H",
				"Frenkel-Morgenstern Milana"
			],
			"DOI": "10.3390/cancers13174328",
			"date": "2023-09-21",
			"PMC": "",
			"citation": "",
			"abstract": "Gene fusions can give rise to somatic alterations in cancers. Fusion genes have the potential to create chimeric RNAs, which can generate the phenotypic diversity of cancer cells, and could be associated with novel molecular functions related to cancer cell survival and proliferation. The expression of chimeric RNAs in cancer cells might impact diverse cancer-related functions, including loss of apoptosis and cancer cell plasticity, and promote oncogenesis. Due to their recurrence in cancers and functional association with oncogenic processes, chimeric RNAs are considered biomarkers for cancer diagnosis. Several recent studies demonstrated that chimeric RNAs could lead to the generation of new functionality for the resistance of cancer cells against drug therapy. Therefore, targeting chimeric RNAs in drug resistance cancer could be useful for developing precision medicine. So, understanding the functional impact of chimeric RNAs in cancer cells from an evolutionary perspective will be helpful to elucidate cancer evolution, which could provide a new insight to design more effective therapies for cancer patients in a personalized manner.",
			"category": 2,
			"name": "Mukherjee Sumit,2023"
		},
		{
			"PMID": 34343239,
			"title": "Tracing the evolution of aneuploid cancers by multiregional sequencing with CRUST.",
			"journal": "Briefings in bioinformatics",
			"authorList": [
				"Chattopadhyay Subhayan",
				"Karlsson Jenny",
				"Valind Anders",
				"Andersson Natalie",
				"Gisselsson David"
			],
			"DOI": "10.1093/bib/bbab292",
			"date": "2022-03-10",
			"PMC": "",
			"citation": "",
			"abstract": "Clonal deconvolution of mutational landscapes is crucial to understand the evolutionary dynamics of cancer. Two limiting factors for clonal deconvolution that have remained unresolved are variation in purity and chromosomal copy number across different samples of the same tumor. We developed a semi-supervised algorithm that tracks variant calls through multi-sample spatiotemporal tumor data. While normalizing allele frequencies based on purity, it also adjusts for copy number changes at clonal deconvolution. Absent \u00e0 priori copy number data, it renders in silico copy number estimations from bulk sequences. Using published and simulated tumor sequences, we reliably segregated clonal/subclonal variants even at a low sequencing depth (~50\u00d7). Given at least one pure tumor sample (>70% purity), we could normalize and deconvolve paired samples down to a purity of 40%. This renders a reliable clonal reconstruction well adapted to multi-regionally sampled solid tumors, which are often aneuploid and contaminated by non-cancer cells.",
			"category": 2,
			"name": "Chattopadhyay Subhayan,2022"
		},
		{
			"PMID": 34321211,
			"title": "Regulation of telomere homeostasis and genomic stability in cancer by ",
			"journal": "Science advances",
			"authorList": [
				"Lee Ji Hoon",
				"Hong Juyeong",
				"Zhang Zhao",
				"de la Pe\u00f1a Avalos B\u00e1rbara",
				"Proietti Cecilia J",
				"Deamicis Agustina Rold\u00e1n",
				"Guzm\u00e1n G Pablo",
				"Lam Hung-Ming",
				"Garcia Jose",
				"Roudier Martine P",
				"Sisk Anthony E",
				"De La Rosa Richard",
				"Vu Kevin",
				"Yang Mei",
				"Liao Yiji",
				"Scheirer Jessica",
				"Pechacek Douglas",
				"Yadav Pooja",
				"Rao Manjeet K",
				"Zheng Siyuan",
				"Johnson-Pais Teresa L",
				"Leach Robin J",
				"Elizalde Patricia V",
				"Dray Elo\u00efse",
				"Xu Kexin"
			],
			"DOI": "10.1126/sciadv.abg7073",
			"date": "2021-08-12",
			"PMC": "",
			"citation": "",
			"abstract": "The role of RNA methylation on ",
			"category": 2,
			"name": "Lee Ji Hoon,2021"
		},
		{
			"PMID": 34316704,
			"title": "Cancer LncRNA Census 2 (CLC2): an enhanced resource reveals clinical features of cancer lncRNAs.",
			"journal": "NAR cancer",
			"authorList": [
				"Vancura Adrienne",
				"Lanz\u00f3s Andr\u00e9s",
				"Bosch-Guiteras N\u00faria",
				"Esteban M\u00f2nica Torres",
				"Gutierrez Alejandro H",
				"Haefliger Simon",
				"Johnson Rory"
			],
			"DOI": "10.1093/narcan/zcab013",
			"date": "2021-07-29",
			"PMC": "",
			"citation": "",
			"abstract": "Long non-coding RNAs (lncRNAs) play key roles in cancer and are at the vanguard of precision therapeutic development. These efforts depend on large and high-confidence collections of cancer lncRNAs. Here, we present the Cancer LncRNA Census 2 (CLC2). With 492 cancer lncRNAs, CLC2 is 4-fold greater in size than its predecessor, without compromising on strict criteria of confident functional/genetic roles and inclusion in the GENCODE annotation scheme. This increase was enabled by leveraging high-throughput transposon insertional mutagenesis screening data, yielding 92 novel cancer lncRNAs. CLC2 makes a valuable addition to existing collections: it is amongst the largest, contains numerous unique genes (not found in other databases) and carries functional labels (oncogene/tumour suppressor). Analysis of this dataset reveals that cancer lncRNAs are impacted by germline variants, somatic mutations and changes in expression consistent with inferred disease functions. Furthermore, we show how clinical/genomic features can be used to vet prospective gene sets from high-throughput sources. The combination of size and quality makes CLC2 a foundation for precision medicine, demonstrating cancer lncRNAs' evolutionary and clinical significance.",
			"category": 2,
			"name": "Vancura Adrienne,2021"
		},
		{
			"PMID": 34254208,
			"title": "Germline and tumor BRCA1/2 pathogenic variants in Chinese triple-negative breast carcinomas.",
			"journal": "Journal of cancer research and clinical oncology",
			"authorList": [
				"Ji Gang",
				"Bao Longlong",
				"Yao Qianlan",
				"Zhang Jing",
				"Zhu Xiaoli",
				"Bai Qianming",
				"Shao Zhiming",
				"Yang Wentao",
				"Zhou Xiaoyan"
			],
			"DOI": "10.1007/s00432-021-03696-2",
			"date": "2021-09-13",
			"PMC": "",
			"citation": "",
			"abstract": "BRCA1/2 screening for all triple-negative breast cancer (TNBC) patients younger than 60\u00a0years may still be an economic burden in China. Further evidences that include incidence and outcome of BRCA1/2 pathogenic variants (PV) screened based on younger age or family history (FH) are worth discussing for improving the cost-effectiveness of BRCA1/2 testing in Chinese TNBC. We aimed to investigate the prevalence of germline and tumor BRCA1/2 PV based on age screening in Chinese TNBC patients.",
			"category": 2,
			"name": "Ji Gang,2021"
		},
		{
			"PMID": 34205437,
			"title": "Transcriptomic Landscape of Lower Grade Glioma Based on Age-Related Non-Silent Somatic Mutations.",
			"journal": "Current oncology (Toronto, Ont.)",
			"authorList": [
				"Park YoungJoon",
				"Park JeongMan",
				"Ahn Ju Won",
				"Sim Jeong Min",
				"Kang Su Jung",
				"Kim Suwan",
				"Hwang So Jung",
				"Han Song-Hee",
				"Sung Kyoung Su",
				"Lim Jaejoon"
			],
			"DOI": "10.3390/curroncol28030210",
			"date": "2021-09-24",
			"PMC": "",
			"citation": "",
			"abstract": "Glioma accounts for 80% of all malignant brain tumours and is the most common adult primary brain tumour. Age is an important factor affecting the development of cancer, as somatic mutations accumulate with age. Here, we aimed to analyse the significance of age-dependent non-silent somatic mutations in glioma prognosis. Histological tumour grade depends on age at diagnosis in patients with ",
			"category": 2,
			"name": "Park YoungJoon,2021"
		},
		{
			"PMID": 34027407,
			"title": "Identification of combinations of somatic mutations that predict cancer survival and immunotherapy benefit.",
			"journal": "NAR cancer",
			"authorList": [
				"Gussow Ayal B",
				"Koonin Eugene V",
				"Auslander Noam"
			],
			"DOI": "10.1093/narcan/zcab017",
			"date": "2021-05-26",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer evolves through the accumulation of somatic mutations over time. Although several methods have been developed to characterize mutational processes in cancers, these have not been specifically designed to identify mutational patterns that predict patient prognosis. Here we present CLICnet, a method that utilizes mutational data to cluster patients by survival rate. CLICnet employs Restricted Boltzmann Machines, a type of generative neural network, which allows for the capture of complex mutational patterns associated with patient survival in different cancer types. For some cancer types, clustering produced by CLICnet also predicts benefit from anti-PD1 immune checkpoint blockade therapy, whereas for other cancer types, the mutational processes associated with survival are different from those associated with the improved anti-PD1 survival benefit. Thus, CLICnet has the ability to systematically identify and catalogue combinations of mutations that predict cancer survival, unveiling intricate associations between mutations, survival, and immunotherapy benefit.",
			"category": 2,
			"name": "Gussow Ayal B,2021"
		},
		{
			"PMID": 34026777,
			"title": "Clonal Evolution Dynamics in Primary and Metastatic Lesions of Pancreatic Neuroendocrine Neoplasms.",
			"journal": "Frontiers in medicine",
			"authorList": [
				"Tong Zhou",
				"Wang Lin",
				"Shi Weiwei",
				"Zeng Yanwu",
				"Zhang Hangyu",
				"Liu Lulu",
				"Zheng Yi",
				"Chen Chunlei",
				"Xia Weiliang",
				"Fang Weijia",
				"Zhao Peng"
			],
			"DOI": "10.3389/fmed.2021.620988",
			"date": "2021-05-26",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "Tong Zhou,2021"
		},
		{
			"PMID": 33897809,
			"title": "Identifying key questions in the ecology and evolution of cancer.",
			"journal": "Evolutionary applications",
			"authorList": [
				"Dujon Antoine M",
				"Aktipis Athena",
				"Alix-Panabi\u00e8res Catherine",
				"Amend Sarah R",
				"Boddy Amy M",
				"Brown Joel S",
				"Capp Jean-Pascal",
				"DeGregori James",
				"Ewald Paul",
				"Gatenby Robert",
				"Gerlinger Marco",
				"Giraudeau Mathieu",
				"Hamede Rodrigo K",
				"Hansen Elsa",
				"Kareva Irina",
				"Maley Carlo C",
				"Marusyk Andriy",
				"McGranahan Nicholas",
				"Metzger Michael J",
				"Nedelcu Aurora M",
				"Noble Robert",
				"Nunney Leonard",
				"Pienta Kenneth J",
				"Polyak Kornelia",
				"Pujol Pascal",
				"Read Andrew F",
				"Roche Benjamin",
				"Sebens Susanne",
				"Solary Eric",
				"Sta\u0148kov\u00e1 Kate\u0159ina",
				"Swain Ewald Holly",
				"Thomas Fr\u00e9d\u00e9ric",
				"Ujvari Beata"
			],
			"DOI": "10.1111/eva.13190",
			"date": "2023-09-20",
			"PMC": "",
			"citation": "",
			"abstract": "The application of evolutionary and ecological principles to cancer prevention and treatment, as well as recognizing cancer as a selection force in nature, has gained impetus over the last 50\u00a0years. Following the initial theoretical approaches that combined knowledge from interdisciplinary fields, it became clear that using the eco-evolutionary framework is of key importance to understand cancer. We are now at a pivotal point where accumulating evidence starts to steer the future directions of the discipline and allows us to underpin the key challenges that remain to be addressed. Here, we aim to assess current advancements in the field and to suggest future directions for research. First, we summarize cancer research areas that, so far, have assimilated ecological and evolutionary principles into their approaches and illustrate their key importance. Then, we assembled 33 experts and identified 84 key questions, organized around nine major themes, to pave the foundations for research to come. We highlight the urgent need for broadening the portfolio of research directions to stimulate novel approaches at the interface of oncology and ecological and evolutionary sciences. We conclude that progressive and efficient cross-disciplinary collaborations that draw on the expertise of the fields of ecology, evolution and cancer are essential in order to efficiently address current and future questions about cancer.",
			"category": 2,
			"name": "Dujon Antoine M,2023"
		},
		{
			"PMID": 33751828,
			"title": "The NFIB-ERO1A axis promotes breast cancer metastatic colonization of disseminated tumour cells.",
			"journal": "EMBO molecular medicine",
			"authorList": [
				"Zilli Federica",
				"Marques Ramos Pedro",
				"Auf der Maur Priska",
				"Jehanno Charly",
				"Sethi Atul",
				"Coissieux Marie-May",
				"Eichlisberger Tobias",
				"Sauteur Lo\u00efc",
				"Rouchon Adelin",
				"Bonapace Laura",
				"Pinto Couto Joana",
				"Rad Roland",
				"Jensen Michael Rugaard",
				"Banfi Andrea",
				"Stadler Michael B",
				"Bentires-Alj Mohamed"
			],
			"DOI": "10.15252/emmm.202013162",
			"date": "2021-10-25",
			"PMC": "",
			"citation": "",
			"abstract": "Metastasis is the main cause of deaths related to solid cancers. Active transcriptional programmes are known to regulate the metastatic cascade but the molecular determinants of metastatic colonization remain elusive. Using an inducible piggyBac (PB) transposon mutagenesis screen, we have shown that overexpression of the transcription factor nuclear factor IB (NFIB) alone is sufficient to enhance primary mammary tumour growth and lung metastatic colonization. Mechanistically and functionally, NFIB directly increases expression of the oxidoreductase ERO1A, which enhances HIF1\u03b1-VEGFA-mediated angiogenesis and colonization, the last and fatal step of the metastatic cascade. NFIB is thus clinically relevant: it is preferentially expressed in the poor-prognostic group of basal-like breast cancers, and high expression of the NFIB/ERO1A/VEGFA pathway correlates with reduced breast cancer patient survival.",
			"category": 2,
			"name": "Zilli Federica,2021"
		},
		{
			"PMID": 33745946,
			"title": "Sequential Administration of XPO1 and ATR Inhibitors Enhances Therapeutic Response in TP53-mutated Colorectal Cancer.",
			"journal": "Gastroenterology",
			"authorList": [
				"Inoue Akira",
				"Robinson Frederick S",
				"Minelli Rosalba",
				"Tomihara Hideo",
				"Rizi Bahar Salimian",
				"Rose Johnathon L",
				"Kodama Takahiro",
				"Srinivasan Sanjana",
				"Harris Angela L",
				"Zuniga Andy M",
				"Mullinax Robert A",
				"Ma Xiaoyan",
				"Seth Sahil",
				"Daniele Joseph R",
				"Peoples Michael D",
				"Loponte Sara",
				"Akdemir Kadir C",
				"Khor Tin Oo",
				"Feng Ningping",
				"Roszik Jason",
				"Sobieski Mary M",
				"Brunell David",
				"Stephan Clifford",
				"Giuliani Virginia",
				"Deem Angela K",
				"Shingu Takashi",
				"Deribe Yonathan Lissanu",
				"Menter David G",
				"Heffernan Timothy P",
				"Viale Andrea",
				"Bristow Christopher A",
				"Kopetz Scott",
				"Draetta Giulio F",
				"Genovese Giannicola",
				"Carugo Alessandro"
			],
			"DOI": "10.1053/j.gastro.2021.03.022",
			"date": "2021-10-25",
			"PMC": "",
			"citation": "",
			"abstract": "Understanding the mechanisms by which tumors adapt to therapy is critical for developing effective combination therapeutic approaches to improve clinical outcomes for patients with cancer.",
			"category": 2,
			"name": "Inoue Akira,2021"
		},
		{
			"PMID": 33641869,
			"title": "Application of Single-Cell Approaches to Study Myeloproliferative Neoplasm Biology.",
			"journal": "Hematology/oncology clinics of North America",
			"authorList": [
				"Royston Daniel",
				"Mead Adam J",
				"Psaila Bethan"
			],
			"DOI": "10.1016/j.hoc.2021.01.002",
			"date": "2022-03-03",
			"PMC": "",
			"citation": "",
			"abstract": "Philadelphia-negative myeloproliferative neoplasms (MPNs) are an excellent tractable disease model of a number of aspects of human cancer biology, including genetic evolution, tissue-associated fibrosis, and cancer stem cells. In this review, we discuss recent insights into MPN biology gained from the application of a number of new single-cell technologies to study human disease, with a specific focus on single-cell genomics, single-cell transcriptomics, and digital pathology.",
			"category": 2,
			"name": "Royston Daniel,2022"
		},
		{
			"PMID": 33606263,
			"title": "Multiregion Sequence Analysis to Predict Intratumor Heterogeneity and Clonal Evolution.",
			"journal": "Methods in molecular biology (Clifton, N.J.)",
			"authorList": [
				"Ahn Soyeon",
				"Huang Haiyan"
			],
			"DOI": "10.1007/978-1-0716-1103-6_14",
			"date": "2021-04-02",
			"PMC": "",
			"citation": "",
			"abstract": "Multiregion sequencing can advance our understanding of the intratumor heterogeneity and the clonal evolution. Here, we introduced multiple aspects of multiregion sequencing and its analysis, including the study design and sampling strategy, current understanding of the tumor evolution model, and a protocol for multiregion sequencing analysis of DNA-sequencing data.",
			"category": 2,
			"name": "Ahn Soyeon,2021"
		},
		{
			"PMID": 33602280,
			"title": "Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexity.",
			"journal": "Journal of experimental & clinical cancer research : CR",
			"authorList": [
				"Relecom Allan",
				"Merhi Maysaloun",
				"Inchakalody Varghese",
				"Uddin Shahab",
				"Rinchai Darawan",
				"Bedognetti Davide",
				"Dermime Said"
			],
			"DOI": "10.1186/s13046-021-01872-3",
			"date": "2021-10-19",
			"PMC": "",
			"citation": "",
			"abstract": "Immune checkpoint inhibitors provide considerable therapeutic benefit in a range of solid cancers as well as in a subgroup of hematological malignancies. Response rates are however suboptimal, and despite considerable efforts, predicting response to immune checkpoint inhibitors ahead of their administration in a given patient remains elusive. The study of the dynamics of the immune system and of the tumor under immune checkpoint blockade brought insight into the mechanisms of action of these therapeutic agents. Equally relevant are the mechanisms of adaptive resistance to immune checkpoint inhibitors that have been uncovered through this approach. In this review, we discuss the dynamics of the immune system and of the tumor under immune checkpoint blockade emanating from recent studies on animal models and humans. We will focus on mechanisms of action and of resistance conveying information predictive of therapeutic response.",
			"category": 2,
			"name": "Relecom Allan,2021"
		},
		{
			"PMID": 33584829,
			"title": "Clinical Perspectives on Liquid Biopsy in Metastatic Colorectal Cancer.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Gao Wei",
				"Chen Yigui",
				"Yang Jianwei",
				"Zhuo Changhua",
				"Huang Sha",
				"Zhang Hui",
				"Shi Yi"
			],
			"DOI": "10.3389/fgene.2021.634642",
			"date": "2021-02-16",
			"PMC": "",
			"citation": "",
			"abstract": "Liquid biopsy, which generally refers to the analysis of biological components such as circulating nuclear acids and circulating tumor cells in body fluids, particularly in peripheral blood, has shown good capacity to overcome several limitations faced by conventional tissue biopsies. Emerging evidence in recent decades has confirmed the promising role of liquid biopsy in the clinical management of various cancers, including colorectal cancer, which is one of the most prevalent cancers and the second leading cause of cancer-related deaths worldwide. Despite the challenges and poor clinical outcomes, patients with metastatic colorectal cancer can expect potential clinical benefits with liquid biopsy. Therefore, in this review, we focus on the clinical prospects of liquid biopsy in metastatic colorectal cancer, specifically with regard to the recently discovered various biomarkers identified on liquid biopsy. These biomarkers have been shown to be potentially useful in multiple aspects of metastatic colorectal cancer, such as auxiliary diagnosis of metastasis, prognosis prediction, and monitoring of therapy response.",
			"category": 2,
			"name": "Gao Wei,2021"
		},
		{
			"PMID": 33556087,
			"title": "Low immunogenicity of common cancer hot spot mutations resulting in false immunogenic selection signals.",
			"journal": "PLoS genetics",
			"authorList": [
				"Claeys Arne",
				"Luijts Tom",
				"Marchal Kathleen",
				"Van den Eynden Jimmy"
			],
			"DOI": "10.1371/journal.pgen.1009368",
			"date": "2021-06-21",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is driven by somatic mutations that result in a cellular fitness advantage. This selective advantage is expected to be counterbalanced by the immune system when these driver mutations simultaneously lead to the generation of neoantigens, novel peptides that are presented at the cancer cell membrane via HLA molecules from the MHC complex. The presentability of these peptides is determined by a patient's MHC genotype and it has been suggested that this results in MHC genotype-specific restrictions of the oncogenic mutational landscape. Here, we generated a set of virtual patients, each with an identical and prototypical MHC genotype, and show that the earlier reported HLA affinity differences between observed and unobserved mutations are unrelated to MHC genotype variation. We demonstrate how these differences are secondary to high frequencies of 13 hot spot driver mutations in 6 different genes. Several oncogenic mechanisms were identified that lower the peptides' HLA affinity, including phospho-mimicking substitutions in BRAF, destabilizing tyrosine mutations in TP53 and glycine-rich mutational contexts in the GTP-binding KRAS domain. In line with our earlier findings, our results emphasize that HLA affinity predictions are easily misinterpreted when studying immunogenic selection processes.",
			"category": 2,
			"name": "Claeys Arne,2021"
		},
		{
			"PMID": 33520605,
			"title": "Data-Driven Methods for Advancing Precision Oncology.",
			"journal": "Current pharmacology reports",
			"authorList": [
				"Nedungadi Prema",
				"Iyer Akshay",
				"Gutjahr Georg",
				"Bhaskar Jasmine",
				"Pillai Asha B"
			],
			"DOI": "10.1007/s40495-018-0127-4",
			"date": "2024-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "This article discusses the advances, methods, challenges, and future directions of data-driven methods in advancing precision oncology for biomedical research, drug discovery, clinical research, and practice.",
			"category": 2,
			"name": "Nedungadi Prema,2024"
		},
		{
			"PMID": 33489823,
			"title": "Future perspectives from lung cancer pre-clinical models: new treatments are coming?",
			"journal": "Translational lung cancer research",
			"authorList": [
				"Bersani Francesca",
				"Morena Deborah",
				"Picca Francesca",
				"Morotti Alessandro",
				"Tabb\u00f2 Fabrizio",
				"Bironzo Paolo",
				"Righi Luisella",
				"Taulli Riccardo"
			],
			"DOI": "10.21037/tlcr-20-189",
			"date": "2022-09-10",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer currently stands out as both the most common and the most lethal type of cancer, the latter feature being partly explained by the fact that the majority of lung cancer patients already display advanced disease at the time of diagnosis. In recent years, the development of specific tyrosine kinase inhibitors (TKI) for the therapeutic benefit of patients harboring certain molecular aberrations and the introduction of prospective molecular profiling in the clinical practice have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). However, the identification of the best strategies to enhance treatment effectiveness and to avoid the critical phenomenon of drug tolerance and acquired resistance in patients with lung cancer still remains an unmet medical need. Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are two complementary approaches to define tumor heterogeneity and clonal evolution in a non-invasive manner and to perform functional studies on metastatic cells. Finally, the recent discovery that the tumor microenvironment architecture can be faithfully recapitulated ",
			"category": 2,
			"name": "Bersani Francesca,2022"
		},
		{
			"PMID": 33489799,
			"title": "Predictive values of genomic variation, tumor mutational burden, and PD-L1 expression in advanced lung squamous cell carcinoma treated with immunotherapy.",
			"journal": "Translational lung cancer research",
			"authorList": [
				"Xu Yanjun",
				"Li Hui",
				"Huang Zhiyu",
				"Chen Kaiyan",
				"Yu Xiaoqing",
				"Sheng Jiamin",
				"Zhang Han-Han",
				"Fan Yun"
			],
			"DOI": "10.21037/tlcr-20-1130",
			"date": "2022-04-20",
			"PMC": "",
			"citation": "",
			"abstract": "Immune checkpoint inhibitors (ICIs) prolong overall survival (OS) in patients with advanced lung squamous cell carcinoma (LUSC). However, predictive and prognostic factors related to ICIs in LUSC remain elusive. This study aimed to identify predictors that are related to better clinical benefit and outcomes in LUSC patients treated with immunotherapy.",
			"category": 2,
			"name": "Xu Yanjun,2022"
		},
		{
			"PMID": 33473219,
			"title": "Liquid biopsy enters the clinic - implementation issues and future challenges.",
			"journal": "Nature reviews. Clinical oncology",
			"authorList": [
				"Ignatiadis Michail",
				"Sledge George W",
				"Jeffrey Stefanie S"
			],
			"DOI": "10.1038/s41571-020-00457-x",
			"date": "2021-07-21",
			"PMC": "",
			"citation": "",
			"abstract": "Historically, studies of disseminated tumour cells in bone marrow and circulating tumour cells in peripheral blood have provided crucial insights into cancer biology and the metastatic process. More recently, advances in the detection and characterization of circulating tumour DNA (ctDNA) have finally enabled the introduction of liquid biopsy assays into clinical practice. The FDA has already approved several single-gene assays and, more recently, multigene assays to detect genetic alterations in plasma cell-free DNA (cfDNA) for use as companion diagnostics matched to specific molecularly targeted therapies for cancer. These approvals mark a tipping point for the widespread use of liquid biopsy in the clinic, and mostly in patients with advanced-stage cancer. The next frontier for the clinical application of liquid biopsy is likely to be the systemic treatment of patients with 'ctDNA relapse', a term we introduce for ctDNA detection prior to imaging-detected relapse after curative-intent therapy for early stage disease. Cancer screening and diagnosis are other potential future applications. In this Perspective, we discuss key issues and gaps in technology, clinical trial methodologies and logistics for the eventual integration of liquid biopsy into the clinical workflow.",
			"category": 2,
			"name": "Ignatiadis Michail,2021"
		},
		{
			"PMID": 33414985,
			"title": "New insights of extrachromosomal DNA in tumorigenesis and therapeutic resistance of cancer.",
			"journal": "American journal of cancer research",
			"authorList": [
				"Qiu Hui",
				"Shao Zhi-Ying",
				"Wen Xin",
				"Zhang Long-Zhen"
			],
			"DOI": "",
			"date": "2021-03-27",
			"PMC": "",
			"citation": "",
			"abstract": "In the past few decades, the studies of extrachromosomal DNA (ecDNA), which existed independently of chromosomes, were tepid. However, recent studies on ecDNA rekindled the enthusiasm of oncologists for further studying ecDNA. In this review, we summarized the recent advances of ecDNA in oncogenesis and oncotherapy. ecDNA consists of highly open chromatin, and its circular structure enables ultra-long-range chromatin contacts. ecDNA is not inherited in accordance with Mendel's laws. Furthermore, ecDNA is widely existed in cancer cells, but almost never found in normal cells. It has been found that ecDNA played important roles in tumorigenesis and tumor progression, including oncogene amplification, tumor heterogeneity, enhancer hijacking and genomic rearrangement. More importantly, ecDNA is closely related to cancer treatment resistance. In hence, further understanding of ecDNA would contribute to developing innovative targeting ecDNA therapies.",
			"category": 2,
			"name": "Qiu Hui,2021"
		},
		{
			"PMID": 33253159,
			"title": "Inference of mutability landscapes of tumors from single cell sequencing data.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Tsyvina Viachaslau",
				"Zelikovsky Alex",
				"Snir Sagi",
				"Skums Pavel"
			],
			"DOI": "10.1371/journal.pcbi.1008454",
			"date": "2021-01-29",
			"PMC": "",
			"citation": "",
			"abstract": "One of the hallmarks of cancer is the extremely high mutability and genetic instability of tumor cells. Inherent heterogeneity of intra-tumor populations manifests itself in high variability of clone instability rates. Analogously to fitness landscapes, the instability rates of clonal populations form their mutability landscapes. Here, we present MULAN (MUtability LANdscape inference), a maximum-likelihood computational framework for inference of mutation rates of individual cancer subclones using single-cell sequencing data. It utilizes the partial information about the orders of mutation events provided by cancer mutation trees and extends it by inferring full evolutionary history and mutability landscape of a tumor. Evaluation of mutation rates on the level of subclones rather than individual genes allows to capture the effects of genomic interactions and epistasis. We estimate the accuracy of our approach and demonstrate that it can be used to study the evolution of genetic instability and infer tumor evolutionary history from experimental data. MULAN is available at https://github.com/compbel/MULAN.",
			"category": 2,
			"name": "Tsyvina Viachaslau,2021"
		},
		{
			"PMID": 33148332,
			"title": "Multiomics profiling of primary lung cancers and distant metastases reveals immunosuppression as a common characteristic of tumor cells with metastatic plasticity.",
			"journal": "Genome biology",
			"authorList": [
				"Lee Won-Chul",
				"Reuben Alexandre",
				"Hu Xin",
				"McGranahan Nicholas",
				"Chen Runzhe",
				"Jalali Ali",
				"Negrao Marcelo V",
				"Hubert Shawna M",
				"Tang Chad",
				"Wu Chia-Chin",
				"Lucas Anthony San",
				"Roh Whijae",
				"Suda Kenichi",
				"Kim Jihye",
				"Tan Aik-Choon",
				"Peng David H",
				"Lu Wei",
				"Tang Ximing",
				"Chow Chi-Wan",
				"Fujimoto Junya",
				"Behrens Carmen",
				"Kalhor Neda",
				"Fukumura Kazutaka",
				"Coyle Marcus",
				"Thornton Rebecca",
				"Gumbs Curtis",
				"Li Jun",
				"Wu Chang-Jiun",
				"Little Latasha",
				"Roarty Emily",
				"Song Xingzhi",
				"Lee J Jack",
				"Sulman Erik P",
				"Rao Ganesh",
				"Swisher Stephen",
				"Diao Lixia",
				"Wang Jing",
				"Heymach John V",
				"Huse Jason T",
				"Scheet Paul",
				"Wistuba Ignacio I",
				"Gibbons Don L",
				"Futreal P Andrew",
				"Zhang Jianhua",
				"Gomez Daniel",
				"Zhang Jianjun"
			],
			"DOI": "10.1186/s13059-020-02175-0",
			"date": "2021-11-30",
			"PMC": "",
			"citation": "",
			"abstract": "Metastasis is the primary cause of cancer mortality accounting for 90% of cancer deaths. Our understanding of the molecular mechanisms driving metastasis is rudimentary.",
			"category": 2,
			"name": "Lee Won-Chul,2021"
		},
		{
			"PMID": 33053644,
			"title": "The Impact of Next Generation Sequencing in Cancer Research.",
			"journal": "Cancers",
			"authorList": [
				"Nones Katia",
				"Patch Ann-Marie"
			],
			"DOI": "10.3390/cancers12102928",
			"date": "2020-11-01",
			"PMC": "",
			"citation": "",
			"abstract": "Next generation sequencing (NGS) describes the technical revolution that enabled massively parallel sequencing of fragmented nucleic acids, thus making possible our current genomic understanding of cancers [...].",
			"category": 2,
			"name": "Nones Katia,2020"
		},
		{
			"PMID": 32978398,
			"title": "Radiogenomic signatures reveal multiscale intratumour heterogeneity associated with biological functions and survival in breast cancer.",
			"journal": "Nature communications",
			"authorList": [
				"Fan Ming",
				"Xia Pingping",
				"Clarke Robert",
				"Wang Yue",
				"Li Lihua"
			],
			"DOI": "10.1038/s41467-020-18703-2",
			"date": "2020-10-14",
			"PMC": "",
			"citation": "",
			"abstract": "Advanced tumours are often heterogeneous, consisting of subclones with various genetic alterations and functional roles. The precise molecular features that characterize the contributions of multiscale intratumour heterogeneity to malignant progression, metastasis, and poor survival are largely unknown. Here, we address these challenges in breast cancer by defining the landscape of heterogeneous tumour subclones and their biological functions using radiogenomic signatures. Molecular heterogeneity is identified by a fully unsupervised deconvolution of gene expression data. Relative prevalence of two subclones associated with cell cycle and primary immunodeficiency pathways identifies patients with significantly different survival outcomes. Radiogenomic signatures of imaging scale heterogeneity are extracted and used to classify patients into groups with distinct subclone compositions. Prognostic value is confirmed by survival analysis accounting for clinical variables. These findings provide insight into how a radiogenomic analysis can identify the biological activities of specific subclones that predict prognosis in a noninvasive and clinically relevant manner.",
			"category": 2,
			"name": "Fan Ming,2020"
		},
		{
			"PMID": 32887686,
			"title": "Comprehensive analysis of structural variants in breast cancer genomes using single-molecule sequencing.",
			"journal": "Genome research",
			"authorList": [
				"Aganezov Sergey",
				"Goodwin Sara",
				"Sherman Rachel M",
				"Sedlazeck Fritz J",
				"Arun Gayatri",
				"Bhatia Sonam",
				"Lee Isac",
				"Kirsche Melanie",
				"Wappel Robert",
				"Kramer Melissa",
				"Kostroff Karen",
				"Spector David L",
				"Timp Winston",
				"McCombie W Richard",
				"Schatz Michael C"
			],
			"DOI": "10.1101/gr.260497.119",
			"date": "2021-10-29",
			"PMC": "",
			"citation": "",
			"abstract": "Improved identification of structural variants (SVs) in cancer can lead to more targeted and effective treatment options as well as advance our basic understanding of the disease and its progression. We performed whole-genome sequencing of the SKBR3 breast cancer cell line and patient-derived tumor and normal organoids from two breast cancer patients using Illumina/10x Genomics, Pacific Biosciences (PacBio), and Oxford Nanopore Technologies (ONT) sequencing. We then inferred SVs and large-scale allele-specific copy number variants (CNVs) using an ensemble of methods. Our findings show that long-read sequencing allows for substantially more accurate and sensitive SV detection, with between 90% and 95% of variants supported by each long-read technology also supported by the other. We also report high accuracy for long reads even at relatively low coverage (25\u00d7-30\u00d7). Furthermore, we integrated SV and CNV data into a unifying karyotype-graph structure to present a more accurate representation of the mutated cancer genomes. We find hundreds of variants within known cancer-related genes detectable only through long-read sequencing. These findings highlight the need for long-read sequencing of cancer genomes for the precise analysis of their genetic instability.",
			"category": 2,
			"name": "Aganezov Sergey,2021"
		},
		{
			"PMID": 32759358,
			"title": "Designing Evolutionary-based Interception Strategies to Block the Transition from Precursor Phases to Multiple Myeloma.",
			"journal": "Clinical cancer research : an official journal of the American Association for Cancer Research",
			"authorList": [
				"Maura Francesco",
				"Landgren Ola",
				"Morgan Gareth J"
			],
			"DOI": "10.1158/1078-0432.CCR-20-1395",
			"date": "2022-01-10",
			"PMC": "",
			"citation": "",
			"abstract": "The development of next-generation sequencing technology has dramatically improved our understanding of the genetic landscape of multiple myeloma. Several new drivers and recurrent events have been reported and linked to a potential driver role. This complex landscape is enhanced by intraclonal mutational heterogeneity and variability introduced through the dimensions of time and space. The evolutionary history of multiple myeloma is driven by both the accumulation of different genomic drivers and by the activity of different mutational processes active overtime. In this review, we describe how these new findings and sequencing technologies have been progressively allowed to understand and reshape our knowledge of the complexity of multiple myeloma at each of its developmental stages: premalignant, at diagnosis, and in relapsed/refractory states. We discuss how these evolutionary concepts can be utilized in the clinic to alter evolutionary trajectories providing a framework for therapeutic intervention at early-disease stages.",
			"category": 2,
			"name": "Maura Francesco,2022"
		},
		{
			"PMID": 32436146,
			"title": "HER2-targeted therapy influences CTC status in metastatic breast cancer.",
			"journal": "Breast cancer research and treatment",
			"authorList": [
				"Deutsch Thomas M",
				"Riethdorf Sabine",
				"Fremd Carlo",
				"Feisst Manuel",
				"Nees Juliane",
				"Fischer Chiara",
				"Hartkopf Andreas D",
				"Pantel Klaus",
				"Trumpp Andreas",
				"Sch\u00fctz Florian",
				"Schneeweiss Andreas",
				"Wallwiener Markus"
			],
			"DOI": "10.1007/s10549-020-05687-2",
			"date": "2021-01-04",
			"PMC": "",
			"citation": "",
			"abstract": "As an independent, negative-prognostic biomarker for progression-free survival (PFS) and overall survival (OS), circulating tumor cells (CTCs) constitute a promising component for developing a liquid biopsy for patients with metastatic breast cancer (MBC). The effects of HER2-targeted therapy such as trastuzumab, pertuzumab, T-DM1,\u00a0and lapatinib on CTC status and longitudinal enumeration were assessed in this trial.",
			"category": 2,
			"name": "Deutsch Thomas M,2021"
		},
		{
			"PMID": 32391102,
			"title": "Association of lncRNA-p53 regulatory network (lincRNA-p21, lincRNA-ROR and MALAT1) and p53 with the clinicopathological features of colorectal primary lesions and tumors.",
			"journal": "Oncology letters",
			"authorList": [
				"Chaleshi Vahid",
				"Irani Shiva",
				"Alebouyeh Masoud",
				"Mirfakhraie Reza",
				"Aghdaei Hamid Asadzadeh"
			],
			"DOI": "10.3892/ol.2020.11518",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Colorectal cancer (CRC) is a common intestinal cancer with a high mortality rate. Early detection of this type of cancer is fundamental to the prevention of the disease, which results in improved survival rates. In the human colon tissue, transition from normal epithelium to adenoma is considered to be caused by unknown molecular incidents occurring over 5-10 years. The detection of CRC has proved problematic when in the early stages of disease. In addition, identifying suitable biomarkers for the detection of CRC progress in patients remains one of the most significant challenges. Long non-coding RNAs have been demonstrated to contribute to the promotion of CRC. The aim of the present study was to investigate the clinical and biological significance of long intergenic non-coding (linc)RNA-p21, lincRNA-regulator of reprogramming (ROR) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the colon tumor and polyp tissue, and the association that these have with the expression of p53 at the mRNA level. Neoplastic and paired adjacent normal tissue samples were obtained from 72 patients (46 polyps and 26 tumors). Reverse transcription-quantitative PCR was performed to determine the relative fold changes in the expression of lincRNA-p21, lincRNA-RoR, MALAT1 and p53 in the samples. A significant association was observed between the levels of MALAT1 and p53 in neoplasm tissues (R=0.073; P<0.05). The relative expression of the MALAT1 gene revealed a statistically significant difference between the different polyp types and number of polyps (P=0.0028 and 0.022, respectively). Adjuvant therapy in patients with tumors revealed an association between the levels of lincRNA-ROR and lincRNA-p21 expression (P=0.015 and 0.038, respectively). MALAT1 may be selected as an early detection biomarker for CRC. Furthermore, lincRNA-ROR and lincRNA-p21 may serve as prognostic and therapeutic biomarkers in patients with CRC.",
			"category": 2,
			"name": "Chaleshi Vahid,2020"
		},
		{
			"PMID": 32317634,
			"title": "Timing the initiation of multiple myeloma.",
			"journal": "Nature communications",
			"authorList": [
				"Rustad Even H",
				"Yellapantula Venkata",
				"Leongamornlert Daniel",
				"Bolli Niccol\u00f2",
				"Ledergor Guy",
				"Nadeu Ferran",
				"Angelopoulos Nicos",
				"Dawson Kevin J",
				"Mitchell Thomas J",
				"Osborne Robert J",
				"Ziccheddu Bachisio",
				"Carniti Cristiana",
				"Montefusco Vittorio",
				"Corradini Paolo",
				"Anderson Kenneth C",
				"Moreau Philippe",
				"Papaemmanuil Elli",
				"Alexandrov Ludmil B",
				"Puente Xose S",
				"Campo Elias",
				"Siebert Reiner",
				"Avet-Loiseau Herve",
				"Landgren Ola",
				"Munshi Nikhil",
				"Campbell Peter J",
				"Maura Francesco"
			],
			"DOI": "10.1038/s41467-020-15740-9",
			"date": "2020-08-03",
			"PMC": "",
			"citation": "",
			"abstract": "The evolution and progression of multiple myeloma and its precursors over time is poorly understood. Here, we investigate the landscape and timing of mutational processes shaping multiple myeloma evolution in a large cohort of 89 whole genomes and 973 exomes. We identify eight processes, including a mutational signature caused by exposure to melphalan. Reconstructing the chronological activity of each mutational signature, we estimate that the initial transformation of a germinal center B-cell usually occurred during the first 2",
			"category": 2,
			"name": "Rustad Even H,2020"
		},
		{
			"PMID": 32296600,
			"title": "A unified simulation model for understanding the diversity of cancer evolution.",
			"journal": "PeerJ",
			"authorList": [
				"Niida Atsushi",
				"Hasegawa Takanori",
				"Innan Hideki",
				"Shibata Tatsuhiro",
				"Mimori Koshi",
				"Miyano Satoru"
			],
			"DOI": "10.7717/peerj.8842",
			"date": "2024-03-28",
			"PMC": "",
			"citation": "",
			"abstract": "Because cancer evolution underlies the therapeutic difficulties of cancer, it is clinically important to understand the evolutionary dynamics of cancer. Thus far, a number of evolutionary processes have been proposed to be working in cancer evolution. However, there exists no simulation model that can describe the different evolutionary processes in a unified manner. In this study, we constructed a unified simulation model for describing the different evolutionary processes and performed sensitivity analysis on the model to determine the conditions in which cancer growth is driven by each of the different evolutionary processes. Our sensitivity analysis has successfully provided a series of novel insights into the evolutionary dynamics of cancer. For example, we found that, while a high neutral mutation rate shapes neutral intratumor heterogeneity (ITH) characterized by a fractal-like pattern, a stem cell hierarchy can also contribute to shaping neutral ITH by apparently increasing the mutation rate. Although It has been reported that the evolutionary principle shaping ITH shifts from selection to accumulation of neutral mutations during colorectal tumorigenesis, our simulation revealed the possibility that this evolutionary shift is triggered by drastic evolutionary events that occur in a short time and confer a marked fitness increase on one or a few cells. This result helps us understand that each process works not separately but simultaneously and continuously as a series of phases of cancer evolution. Collectively, this study serves as a basis to understand in greater depth the diversity of cancer evolution.",
			"category": 2,
			"name": "Niida Atsushi,2024"
		},
		{
			"PMID": 32268084,
			"title": "Genome-wide Screens Implicate Loss of Cullin Ring Ligase 3 in Persistent Proliferation and Genome Instability in TP53-Deficient Cells.",
			"journal": "Cell reports",
			"authorList": [
				"Drainas Alexandros P",
				"Lambuta Ruxandra A",
				"Ivanova Irina",
				"Ser\u00e7in \u00d6zdemirhan",
				"Sarropoulos Ioannis",
				"Smith Mike L",
				"Efthymiopoulos Theocharis",
				"Raeder Benjamin",
				"St\u00fctz Adrian M",
				"Waszak Sebastian M",
				"Mardin Balca R",
				"Korbel Jan O"
			],
			"DOI": "10.1016/j.celrep.2020.03.029",
			"date": "2021-04-27",
			"PMC": "",
			"citation": "",
			"abstract": "TP53 deficiency is the most common alteration in cancer; however, this alone is typically insufficient to drive tumorigenesis. To identify genes promoting tumorigenesis in combination with TP53 deficiency, we perform genome-wide CRISPR-Cas9 knockout screens coupled with proliferation and transformation assays in isogenic cell lines. Loss of several known tumor suppressors enhances cellular proliferation and transformation. Loss of neddylation pathway genes promotes uncontrolled proliferation exclusively in TP53-deficient cells. Combined loss of CUL3 and TP53 activates an oncogenic transcriptional program governed by the nuclear factor \u03baB (NF-\u03baB), AP-1, and transforming growth factor \u03b2 (TGF-\u03b2) pathways. This program maintains persistent cellular proliferation, induces partial epithelial to mesenchymal transition, and increases DNA damage, genomic instability, and chromosomal rearrangements. Our findings reveal CUL3 loss as a key event stimulating persistent proliferation in TP53-deficient cells. These findings may be clinically relevant, since TP53-CUL3-deficient cells are highly sensitive to ataxia telangiectasia mutated (ATM) inhibition, exposing a vulnerability that could be exploited for cancer treatment.",
			"category": 2,
			"name": "Drainas Alexandros P,2021"
		},
		{
			"PMID": 32244556,
			"title": "Morphologic and Genomic Heterogeneity in the Evolution and Progression of Breast Cancer.",
			"journal": "Cancers",
			"authorList": [
				"Kutasovic Jamie R",
				"McCart Reed Amy E",
				"Sokolova Anna",
				"Lakhani Sunil R",
				"Simpson Peter T"
			],
			"DOI": "10.3390/cancers12040848",
			"date": "2023-11-03",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "Kutasovic Jamie R,2023"
		},
		{
			"PMID": 32117420,
			"title": "Phylogenetic Tree Inference: A Top-Down Approach to Track Tumor Evolution.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Wu Pin",
				"Hou Linjun",
				"Zhang Yingdong",
				"Zhang Liye"
			],
			"DOI": "10.3389/fgene.2019.01371",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Recently, an increasing number of studies sequence multiple biopsies of primary tumors, and even paired metastatic tumors to understand heterogeneity and the evolutionary trajectory of cancer progression. Although several algorithms are available to infer the phylogeny, most tools rely on accurate measurements of mutation allele frequencies from deep sequencing, which is often hard to achieve for clinical samples (especially FFPE samples). In this study, we present a novel and easy-to-use method, PTI (Phylogenetic Tree Inference), which use an iterative top-down approach to infer the phylogenetic tree structure of multiple tumor biopsies from same patient using just the presence or absence of somatic mutations without their allele frequencies. Therefore PTI can be used in a wide range of cases even when allele frequency data is not available. Comparison with existing state-of-the-art methods, such as LICHeE, Treeomics, and BAMSE, shows that PTI achieves similar or slightly better performance within a short run time. Moreover, this method is generally applicable to infer phylogeny for any other data sets (such as epigenetics) with a similar zero and one feature-by-sample matrix.",
			"category": 2,
			"name": "Wu Pin,2020"
		},
		{
			"PMID": 32024996,
			"title": "Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis.",
			"journal": "Communications biology",
			"authorList": [
				"Carlevaro-Fita Joana",
				"Lanz\u00f3s Andr\u00e9s",
				"Feuerbach Lars",
				"Hong Chen",
				"Mas-Ponte David",
				"Pedersen Jakob Skou",
				"PCAWG Drivers and Functional Interpretation Group",
				"Johnson Rory",
				"PCAWG Consortium"
			],
			"DOI": "10.1038/s42003-019-0741-7",
			"date": "2021-05-10",
			"PMC": "",
			"citation": "",
			"abstract": "Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis.",
			"category": 2,
			"name": "Carlevaro-Fita Joana,2021"
		},
		{
			"PMID": 31907488,
			"title": "Genomic evidence supports a clonal diaspora model for metastases of esophageal adenocarcinoma.",
			"journal": "Nature genetics",
			"authorList": [
				"Noorani Ayesha",
				"Li Xiaodun",
				"Goddard Martin",
				"Crawte Jason",
				"Alexandrov Ludmil B",
				"Secrier Maria",
				"Eldridge Matthew D",
				"Bower Lawrence",
				"Weaver Jamie",
				"Lao-Sirieix Pierre",
				"Martincorena Inigo",
				"Debiram-Beecham Irene",
				"Grehan Nicola",
				"MacRae Shona",
				"Malhotra Shalini",
				"Miremadi Ahmad",
				"Thomas Tabitha",
				"Galbraith Sarah",
				"Petersen Lorraine",
				"Preston Stephen D",
				"Gilligan David",
				"Hindmarsh Andrew",
				"Hardwick Richard H",
				"Stratton Michael R",
				"Wedge David C",
				"Fitzgerald Rebecca C"
			],
			"DOI": "10.1038/s41588-019-0551-3",
			"date": "2020-04-08",
			"PMC": "",
			"citation": "",
			"abstract": "The poor outcomes in esophageal adenocarcinoma (EAC) prompted us to interrogate the pattern and timing of metastatic spread. Whole-genome sequencing and phylogenetic analysis of 388 samples across 18 individuals with EAC showed, in 90% of patients, that multiple subclones from the primary tumor spread very rapidly from the primary site to form multiple metastases, including lymph nodes and distant tissues-a mode of dissemination that we term 'clonal diaspora'. Metastatic subclones at autopsy were present in tissue and blood samples from earlier time points. These findings have implications for our understanding and clinical evaluation of EAC.",
			"category": 2,
			"name": "Noorani Ayesha,2020"
		},
		{
			"PMID": 31907355,
			"title": "Identification of a transient state during the acquisition of temozolomide resistance in glioblastoma.",
			"journal": "Cell death & disease",
			"authorList": [
				"Rab\u00e9 Marion",
				"Dumont Solenne",
				"\u00c1lvarez-Arenas Arturo",
				"Janati Hicham",
				"Belmonte-Beitia Juan",
				"Calvo Gabriel F",
				"Thibault-Carpentier Christelle",
				"S\u00e9ry Quentin",
				"Chauvin Cynthia",
				"Joalland No\u00e9mie",
				"Briand Floriane",
				"Blandin St\u00e9phanie",
				"Scotet Emmanuel",
				"Pecqueur Claire",
				"Clairambault Jean",
				"Oliver Lisa",
				"Perez-Garcia Victor",
				"Nadaradjane Arulraj",
				"Cartron Pierre-Fran\u00e7ois",
				"Gratas Catherine",
				"Vallette Fran\u00e7ois M"
			],
			"DOI": "10.1038/s41419-019-2200-2",
			"date": "2021-01-15",
			"PMC": "",
			"citation": "",
			"abstract": "Drug resistance limits the therapeutic efficacy in cancers and leads to tumor recurrence through ill-defined mechanisms. Glioblastoma (GBM) are the deadliest brain tumors in adults. GBM, at diagnosis or after treatment, are resistant to temozolomide (TMZ), the standard chemotherapy. To better understand the acquisition of this resistance, we performed a longitudinal study, using a combination of mathematical models, RNA sequencing, single cell analyses, functional and drug assays in a human glioma cell line (U251). After an initial response characterized by cell death induction, cells entered a transient state defined by slow growth, a distinct morphology and a shift of metabolism. Specific genes expression associated to this population revealed chromatin remodeling. Indeed, the histone deacetylase inhibitor trichostatin (TSA), specifically eliminated this population and thus prevented the appearance of fast growing TMZ-resistant cells. In conclusion, we have identified in glioblastoma a population with tolerant-like features, which could constitute a therapeutic target.",
			"category": 2,
			"name": "Rab\u00e9 Marion,2021"
		},
		{
			"PMID": 31888619,
			"title": "Identifying driver genes involving gene dysregulated expression, tissue-specific expression and gene-gene network.",
			"journal": "BMC medical genomics",
			"authorList": [
				"Song Junrong",
				"Peng Wei",
				"Wang Feng",
				"Wang Jianxin"
			],
			"DOI": "10.1186/s12920-019-0619-z",
			"date": "2020-07-01",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer as a kind of genomic alteration disease each year deprives many people's life. The biggest challenge to overcome cancer is to identify driver genes that promote the cancer development from a huge amount of passenger mutations that have no effect on the selective growth advantage of cancer. In order to solve those problems, some researchers have started to focus on identification of driver genes by integrating networks with other biological information. However, more efforts should be needed to improve the prediction performance.",
			"category": 2,
			"name": "Song Junrong,2020"
		},
		{
			"PMID": 31861691,
			"title": "Are Leukaemic Stem Cells Restricted to a Single Cell Lineage?",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Brown Geoffrey",
				"S\u00e1nchez Luc\u00eda",
				"S\u00e1nchez-Garc\u00eda Isidro"
			],
			"DOI": "10.3390/ijms21010045",
			"date": "2020-05-04",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer-stem-cell theory states that most, if not all, cancers arise from a stem/uncommitted cell. This theory revolutionised our view to reflect that cancer consists of a hierarchy of cells that mimic normal cell development. Elegant studies of twins who both developed acute lymphoblastic leukaemia in childhood revealed that at least two genomic insults are required for cancer to develop. These 'hits' do not appear to confer a growth advantage to cancer cells, nor do cancer cells appear to be better equipped to survive than normal cells. Cancer cells created by investigators by introducing specific genomic insults generally belong to one cell lineage. For example, transgenic mice in which the LIM-only 2 (",
			"category": 2,
			"name": "Brown Geoffrey,2020"
		},
		{
			"PMID": 31852841,
			"title": "Secretome profiling identifies neuron-derived neurotrophic factor as a tumor-suppressive factor in lung cancer.",
			"journal": "JCI insight",
			"authorList": [
				"Zhang Ya",
				"Wu Xuefeng",
				"Kai Yan",
				"Lee Chia-Han",
				"Cheng Fengdong",
				"Li Yixuan",
				"Zhuang Yongbao",
				"Ghaemmaghami Javid",
				"Chuang Kun-Han",
				"Liu Zhuo",
				"Meng Yunxiao",
				"Keswani Meghana",
				"Gough Nancy R",
				"Wu Xiaojun",
				"Zhu Wenge",
				"Tzatsos Alexandros",
				"Peng Weiqun",
				"Seto Edward",
				"Sotomayor Eduardo M",
				"Zheng Xiaoyan"
			],
			"DOI": "10.1172/jci.insight.129344",
			"date": "2020-10-15",
			"PMC": "",
			"citation": "",
			"abstract": "Clinical and preclinical studies show tissue-specific differences in tumorigenesis. Tissue specificity is controlled by differential gene expression. We prioritized genes that encode secreted proteins according to their preferential expression in normal lungs to identify candidates associated with lung cancer. Indeed, most of the lung-enriched genes identified in our analysis have known or suspected roles in lung cancer. We focused on the gene encoding neuron-derived neurotrophic factor (NDNF), which had not yet been associated with lung cancer. We determined that NDNF was preferentially expressed in the normal adult lung and that its expression was decreased in human lung adenocarcinoma and a mouse model of this cancer. Higher expression of NDNF was associated with better clinical outcome of patients with lung adenocarcinoma. Purified NDNF inhibited proliferation of lung cancer cells, whereas silencing NDNF promoted tumor cell growth in culture and in xenograft models. We determined that NDNF is downregulated through DNA hypermethylation near CpG island shores in human lung adenocarcinoma. Furthermore, the lung cancer-related DNA hypermethylation sites corresponded to the methylation sites that occurred in tissues with low NDNF expression. Thus, by analyzing the tissue-specific secretome, we identified a tumor-suppressive factor, NDNF, which is associated with patient outcomes in lung adenocarcinoma.",
			"category": 2,
			"name": "Zhang Ya,2020"
		},
		{
			"PMID": 31701131,
			"title": "CancerTracer: a curated database for intrapatient tumor heterogeneity.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Wang Chen",
				"Yang Jian",
				"Luo Hong",
				"Wang Kun",
				"Wang Yu",
				"Xiao Zhi-Xiong",
				"Tao Xiang",
				"Jiang Hao",
				"Cai Haoyang"
			],
			"DOI": "10.1093/nar/gkz1061",
			"date": "2020-05-26",
			"PMC": "",
			"citation": "",
			"abstract": "Comprehensive genomic analyses of cancers have revealed substantial intrapatient molecular heterogeneities that may explain some instances of drug resistance and treatment failures. Examination of the clonal composition of an individual tumor and its evolution through disease progression and treatment may enable identification of precise therapeutic targets for drug design. Multi-region and single-cell sequencing are powerful tools that can be used to capture intratumor heterogeneity. Here, we present a database we've named CancerTracer (http://cailab.labshare.cn/cancertracer): a manually curated database designed to track and characterize the evolutionary trajectories of tumor growth in individual patients. We collected over 6000 tumor samples from 1548 patients corresponding to 45 different types of cancer. Patient-specific tumor phylogenetic trees were constructed based on somatic mutations or copy number alterations identified in multiple biopsies. Using the structured heterogeneity data, researchers can identify common driver events shared by all tumor regions, and the heterogeneous somatic events present in different regions of a tumor of interest. The database can also be used to investigate the phylogenetic relationships between primary and metastatic tumors. It is our hope that CancerTracer will significantly improve our understanding of the evolutionary histories of tumors, and may facilitate the identification of predictive biomarkers for personalized cancer therapies.",
			"category": 2,
			"name": "Wang Chen,2020"
		},
		{
			"PMID": 31628257,
			"title": "SiCloneFit: Bayesian inference of population structure, genotype, and phylogeny of tumor clones from single-cell genome sequencing data.",
			"journal": "Genome research",
			"authorList": [
				"Zafar Hamim",
				"Navin Nicholas",
				"Chen Ken",
				"Nakhleh Luay"
			],
			"DOI": "10.1101/gr.243121.118",
			"date": "2020-05-05",
			"PMC": "",
			"citation": "",
			"abstract": "Accumulation and selection of somatic mutations in a Darwinian framework result in intra-tumor heterogeneity (ITH) that poses significant challenges to the diagnosis and clinical therapy of cancer. Identification of the tumor cell populations (clones) and reconstruction of their evolutionary relationship can elucidate this heterogeneity. Recently developed single-cell DNA sequencing (SCS) technologies promise to resolve ITH to a single-cell level. However, technical errors in SCS data sets, including false-positives (FP) and false-negatives (FN) due to allelic dropout, and cell doublets, significantly complicate these tasks. Here, we propose a nonparametric Bayesian method that reconstructs the clonal populations as clusters of single cells, genotypes of each clone, and the evolutionary relationship between the clones. It employs a tree-structured Chinese restaurant process as the prior on the number and composition of clonal populations. The evolution of the clonal populations is modeled by a clonal phylogeny and a finite-site model of evolution to account for potential mutation recurrence and losses. We probabilistically account for FP and FN errors, and cell doublets are modeled by employing a Beta-binomial distribution. We develop a Gibbs sampling algorithm comprising partial reversible-jump and partial Metropolis-Hastings updates to explore the joint posterior space of all parameters. The performance of our method on synthetic and experimental data sets suggests that joint reconstruction of tumor clones and clonal phylogeny under a finite-site model of evolution leads to more accurate inferences. Our method is the first to enable this joint reconstruction in a fully Bayesian framework, thus providing measures of support of the inferences it makes.",
			"category": 2,
			"name": "Zafar Hamim,2020"
		},
		{
			"PMID": 31584621,
			"title": "Meltos: multi-sample tumor phylogeny reconstruction for structural variants.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Ricketts Camir",
				"Seidman Daniel",
				"Popic Victoria",
				"Hormozdiari Fereydoun",
				"Batzoglou Serafim",
				"Hajirasouliha Iman"
			],
			"DOI": "10.1093/bioinformatics/btz737",
			"date": "2020-09-15",
			"PMC": "",
			"citation": "",
			"abstract": "We propose Meltos, a novel computational framework to address the challenging problem of building tumor phylogeny trees using somatic structural variants (SVs) among multiple samples. Meltos leverages the tumor phylogeny tree built on somatic single nucleotide variants (SNVs) to identify high confidence SVs and produce a comprehensive tumor lineage tree, using a novel optimization formulation. While we do not assume the evolutionary progression of SVs is necessarily the same as SNVs, we show that a tumor phylogeny tree using high-quality somatic SNVs can act as a guide for calling and assigning somatic SVs on a tree. Meltos utilizes multiple genomic read signals for potential SV breakpoints in whole genome sequencing data and proposes a probabilistic formulation for estimating variant allele fractions (VAFs) of SV events.",
			"category": 2,
			"name": "Ricketts Camir,2020"
		},
		{
			"PMID": 31528343,
			"title": "Differences in mutational processes and intra-tumour heterogeneity between organs: The local selective filter hypothesis.",
			"journal": "Evolution, medicine, and public health",
			"authorList": [
				"Giraudeau Mathieu",
				"Sepp Tuul",
				"Ujvari Beata",
				"Renaud Fran\u00e7ois",
				"Tasiemski Aur\u00e9lie",
				"Roche Benjamin",
				"Capp Jean-Pascal",
				"Thomas Fr\u00e9d\u00e9ric"
			],
			"DOI": "10.1093/emph/eoz017",
			"date": "2024-07-20",
			"PMC": "",
			"citation": "",
			"abstract": "Extensive diversity (genetic, cytogenetic, epigenetic and phenotypic) exists within and between tumours, but reasons behind these variations, as well as their consistent hierarchical pattern between organs, are poorly understood at the moment. We argue that these phenomena are, at least partially, explainable by the evolutionary ecology of organs' theory, in the same way that environmental adversity shapes mutation rates and level of polymorphism in organisms. Organs in organisms can be considered as specialized ecosystems that are, for ecological and evolutionary reasons, more or less efficient at suppressing tumours. When a malignancy does arise in an organ applying strong selection pressure on tumours, its constituent cells are expected to display a large range of possible surviving strategies, from hyper mutator phenotypes relying on bet-hedging to persist (high mutation rates and high diversity), to few poorly variable variants that become invisible to natural defences. In contrast, when tumour suppression is weaker, selective pressure favouring extreme surviving strategies is relaxed, and tumours are moderately variable as a result. We provide a comprehensive overview of this hypothesis. Lay summary: Different levels of mutations and intra-tumour heterogeneity have been observed between cancer types and organs. Anti-cancer defences are unequal between our organs. We propose that mostly aggressive neoplasms (i.e. higher mutational and ITH levels), succeed in emerging and developing in organs with strong defences.",
			"category": 2,
			"name": "Giraudeau Mathieu,2024"
		},
		{
			"PMID": 31510696,
			"title": "Inference of clonal selection in cancer populations using single-cell sequencing data.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Skums Pavel",
				"Tsyvina Viachaslau",
				"Zelikovsky Alex"
			],
			"DOI": "10.1093/bioinformatics/btz392",
			"date": "2020-06-09",
			"PMC": "",
			"citation": "",
			"abstract": "Intra-tumor heterogeneity is one of the major factors influencing cancer progression and treatment outcome. However, evolutionary dynamics of cancer clone populations remain poorly understood. Quantification of clonal selection and inference of fitness landscapes of tumors is a key step to understanding evolutionary mechanisms driving cancer. These problems could be addressed using single-cell sequencing (scSeq), which provides an unprecedented insight into intra-tumor heterogeneity allowing to study and quantify selective advantages of individual clones. Here, we present Single Cell Inference of FItness Landscape (SCIFIL), a computational tool for inference of fitness landscapes of heterogeneous cancer clone populations from scSeq data. SCIFIL allows to estimate maximum likelihood fitnesses of clone variants, measure their selective advantages and order of appearance by fitting an evolutionary model into the tumor phylogeny. We demonstrate the accuracy our approach, and show how it could be applied to experimental tumor data to study clonal selection and infer evolutionary history. SCIFIL can be used to provide new insight into the evolutionary dynamics of cancer.",
			"category": 2,
			"name": "Skums Pavel,2020"
		},
		{
			"PMID": 31449515,
			"title": "Cooperative adaptation to therapy (CAT) confers resistance in heterogeneous non-small cell lung cancer.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Craig Morgan",
				"Kaveh Kamran",
				"Woosley Alec",
				"Brown Andrew S",
				"Goldman David",
				"Eton Elliot",
				"Mehta Ravindra M",
				"Dhawan Andrew",
				"Arai Kazuya",
				"Rahman M Mamunur",
				"Chen Sidi",
				"Nowak Martin A",
				"Goldman Aaron"
			],
			"DOI": "10.1371/journal.pcbi.1007278",
			"date": "2020-01-20",
			"PMC": "",
			"citation": "",
			"abstract": "Understanding intrinsic and acquired resistance is crucial to overcoming cancer chemotherapy failure. While it is well-established that intratumor, subclonal genetic and phenotypic heterogeneity significantly contribute to resistance, it is not fully understood how tumor sub-clones interact with each other to withstand therapy pressure. Here, we report a previously unrecognized behavior in heterogeneous tumors: cooperative adaptation to therapy (CAT), in which cancer cells induce co-resistant phenotypes in neighboring cancer cells when exposed to cancer therapy. Using a CRISPR/Cas9 toolkit we engineered phenotypically diverse non-small cell lung cancer (NSCLC) cells by conferring mutations in Dicer1, a type III cytoplasmic endoribonuclease involved in small non-coding RNA genesis. We monitored three-dimensional growth dynamics of fluorescently-labeled mutant and/or wild-type cells individually or in co-culture using a substrate-free NanoCulture system under unstimulated or drug pressure conditions. By integrating mathematical modeling with flow cytometry, we characterized the growth patterns of mono- and co-cultures using a mathematical model of intra- and interspecies competition. Leveraging the flow cytometry data, we estimated the model's parameters to reveal that the combination of WT and mutants in co-cultures allowed for beneficial growth in previously drug sensitive cells despite drug pressure via induction of cell state transitions described by a cooperative game theoretic change in the fitness values. Finally, we used an ex vivo human tumor model that predicts clinical response through drug sensitivity analyses and determined that cellular and morphologic heterogeneity correlates to prognostic failure of multiple clinically-approved and off-label drugs in individual NSCLC patient samples. Together, these findings present a new paradox in drug resistance implicating non-genetic cooperation among tumor cells to thwart drug pressure, suggesting that profiling for druggable targets (i.e. mutations) alone may be insufficient to assign effective therapy.",
			"category": 2,
			"name": "Craig Morgan,2020"
		},
		{
			"PMID": 31387980,
			"title": "Proteomic and genomic signatures of repeat instability in cancer and adjacent normal tissues.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Persi Erez",
				"Prandi Davide",
				"Wolf Yuri I",
				"Pozniak Yair",
				"Barnabas Georgina D",
				"Levanon Keren",
				"Barshack Iris",
				"Barbieri Christopher",
				"Gasperini Paola",
				"Beltran Himisha",
				"Faltas Bishoy M",
				"Rubin Mark A",
				"Geiger Tamar",
				"Koonin Eugene V",
				"Demichelis Francesca",
				"Horn David"
			],
			"DOI": "10.1073/pnas.1908790116",
			"date": "2020-03-23",
			"PMC": "",
			"citation": "",
			"abstract": "Repetitive sequences are hotspots of evolution at multiple levels. However, due to difficulties involved in their assembly and analysis, the role of repeats in tumor evolution is poorly understood. We developed a rigorous motif-based methodology to quantify variations in the repeat content, beyond microsatellites, in proteomes and genomes directly from proteomic and genomic raw data. This method was applied to a wide range of tumors and normal tissues. We identify high similarity between repeat instability patterns in tumors and their patient-matched adjacent normal tissues. Nonetheless, tumor-specific signatures both in protein expression and in the genome strongly correlate with cancer progression and robustly predict the tumorigenic state. In a patient, the hierarchy of genomic repeat instability signatures accurately reconstructs tumor evolution, with primary tumors differentiated from metastases. We observe an inverse relationship between repeat instability and point mutation load within and across patients independent of other somatic aberrations. Thus, repeat instability is a distinct, transient, and compensatory adaptive mechanism in tumor evolution and a potential signal for early detection.",
			"category": 2,
			"name": "Persi Erez,2020"
		},
		{
			"PMID": 31379741,
			"title": "Clonal Reconstruction of Thyroid Cancer: An Essential Strategy for Preventing Resistance to Ultra-Precision Therapy.",
			"journal": "Frontiers in endocrinology",
			"authorList": [
				"McGonagle Elizabeth R",
				"Nucera Carmelo"
			],
			"DOI": "10.3389/fendo.2019.00468",
			"date": "2020-02-25",
			"PMC": "",
			"citation": "",
			"abstract": "The introduction of ultra-precision targeted therapy has become a significant advancement in cancer therapeutics by creating treatments with less off target effects. Specifically with papillary thyroid carcinoma (PTC), the cancer's hallmark genetic mutation BRAF",
			"category": 2,
			"name": "McGonagle Elizabeth R,2020"
		},
		{
			"PMID": 31167132,
			"title": "Breakage-Fusion-Bridge Events Trigger Complex Genome Rearrangements and Amplifications in Developmentally Arrested T Cell Lymphomas.",
			"journal": "Cell reports",
			"authorList": [
				"Bianchi Joy J",
				"Murigneux Valentine",
				"Bedora-Faure Marie",
				"Lescale Chlo\u00e9",
				"Deriano Ludovic"
			],
			"DOI": "10.1016/j.celrep.2019.05.014",
			"date": "2020-08-05",
			"PMC": "",
			"citation": "",
			"abstract": "To reveal the relative contribution of the recombination activating gene (RAG)1/2 nuclease to lymphomagenesis, we conducted a genome-wide analysis of T\u00a0cell lymphomas from p53-deficient mice expressing or lacking RAG2. We found that while p53",
			"category": 2,
			"name": "Bianchi Joy J,2020"
		},
		{
			"PMID": 31080515,
			"title": "Quantifying local malignant adaptation in tissue-specific evolutionary trajectories by harnessing cancer's repeatability at the genetic level.",
			"journal": "Evolutionary applications",
			"authorList": [
				"Tokutomi Natsuki",
				"Moyret-Lalle Caroline",
				"Puisieux Alain",
				"Sugano Sumio",
				"Martinez Pierre"
			],
			"DOI": "10.1111/eva.12781",
			"date": "2023-10-11",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a potentially lethal disease, in which patients with nearly identical genetic backgrounds can develop a similar pathology through distinct combinations of genetic alterations. We aimed to reconstruct the evolutionary process underlying tumour initiation, using the combination of convergence and discrepancies observed across 2,742 cancer genomes from nine tumour types. We developed a framework using the repeatability of cancer development to score the local malignant adaptation (LMA) of genetic clones, as their potential to malignantly progress and invade their environment of origin. Using this framework, we found that premalignant skin and colorectal lesions appeared specifically adapted to their local environment, yet insufficiently for full cancerous transformation. We found that metastatic clones were more adapted to the site of origin than to the invaded tissue, suggesting that genetics may be more important for local progression than for the invasion of distant organs. In addition, we used network analyses to investigate evolutionary properties at the system-level, highlighting that different dynamics of malignant progression can be modelled by such a framework in tumour-type-specific fashion. We find that occurrence-based methods can be used to specifically recapitulate the process of cancer initiation and progression, as well as to evaluate the adaptation of genetic clones to given environments. The repeatability observed in the evolution of most tumour types could therefore be harnessed to better predict the trajectories likely to be taken by tumours and preneoplastic lesions in the future.",
			"category": 2,
			"name": "Tokutomi Natsuki,2023"
		},
		{
			"PMID": 30925887,
			"title": "Translating insights into tumor evolution to clinical practice: promises and challenges.",
			"journal": "Genome medicine",
			"authorList": [
				"Fittall Matthew W",
				"Van Loo Peter"
			],
			"DOI": "10.1186/s13073-019-0632-z",
			"date": "2019-12-27",
			"PMC": "",
			"citation": "",
			"abstract": "Accelerating technological advances have allowed the widespread genomic profiling of tumors. As yet, however, the vast catalogues of mutations that have been identified have made only a modest impact on clinical medicine. Massively parallel sequencing has informed our understanding of the genetic evolution and heterogeneity of cancers, allowing us to place these mutational catalogues into a meaningful context. Here, we review the methods used to measure tumor evolution and heterogeneity, and the potential and challenges for translating the insights gained to achieve clinical impact for cancer therapy, monitoring, early detection, risk stratification, and prevention. We discuss how tumor evolution can guide cancer therapy by targeting clonal and subclonal mutations both individually and in combination. Circulating tumor DNA and circulating tumor cells can be leveraged for monitoring the efficacy of therapy and for tracking the emergence of resistant subclones. The evolutionary history of tumors can be deduced for late-stage cancers, either directly by sampling precursor lesions or by leveraging computational approaches to infer the timing of driver events. This approach can identify recurrent early driver mutations that represent promising avenues for future early detection strategies. Emerging evidence suggests that mutational processes and complex clonal dynamics are active even in normal development and aging. This will make discriminating developing malignant neoplasms from normal aging cell lineages a challenge. Furthermore, insight into signatures of mutational processes that are active early in tumor evolution may allow the development of cancer-prevention approaches. Research and clinical studies that incorporate an appreciation of the complex evolutionary patterns in tumors will not only produce more meaningful genomic data, but also better exploit the vulnerabilities of cancer, resulting in improved treatment outcomes.",
			"category": 2,
			"name": "Fittall Matthew W,2019"
		},
		{
			"PMID": 30839720,
			"title": "Anastasis: recovery from the brink of cell death.",
			"journal": "Royal Society open science",
			"authorList": [
				"Tang Ho Man",
				"Tang Ho Lam"
			],
			"DOI": "10.1098/rsos.180442",
			"date": "2024-04-02",
			"PMC": "",
			"citation": "",
			"abstract": "Anastasis is a natural cell recovery phenomenon that rescues cells from the brink of death. Programmed cell death such as apoptosis has been traditionally assumed to be an intrinsically irreversible cascade that commits cells to a rapid and massive demolition. Interestingly, recent studies have demonstrated recovery of dying cells even at the late stages generally considered immutable. Here, we examine the evidence for anastasis in cultured cells and in animals, review findings illuminating the potential mechanisms of action, discuss the challenges of studying anastasis and explore new strategies to uncover the function and regulation of anastasis, the identification of which has wide-ranging physiological, pathological and therapeutic implications.",
			"category": 2,
			"name": "Tang Ho Man,2024"
		},
		{
			"PMID": 30782821,
			"title": "Ovarian insufficiency and CTNNB1 mutations drive malignant transformation of endometrial hyperplasia with altered PTEN/PI3K activities.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Terakawa Jumpei",
				"Serna Vanida Ann",
				"Taketo Makoto Mark",
				"Daikoku Takiko",
				"Suarez Adrian A",
				"Kurita Takeshi"
			],
			"DOI": "10.1073/pnas.1814506116",
			"date": "2020-04-06",
			"PMC": "",
			"citation": "",
			"abstract": "Endometrioid endometrial carcinomas (EECs) carry multiple driver mutations even when they are low grade. However, the biological significance of these concurrent mutations is unknown. We explored the interactions among three signature EEC mutations: loss-of-function (LOF) mutations in ",
			"category": 2,
			"name": "Terakawa Jumpei,2020"
		},
		{
			"PMID": 30674330,
			"title": "From tumors to species: a SCANDAL hypothesis.",
			"journal": "Biology direct",
			"authorList": [
				"Panchin A Y",
				"Aleoshin V V",
				"Panchin Y V"
			],
			"DOI": "10.1186/s13062-019-0233-1",
			"date": "2019-07-02",
			"PMC": "",
			"citation": "",
			"abstract": "\u115f: Some tumor cells can evolve into transmissible parasites. Notable examples include the Tasmanian devil facial tumor disease, the canine transmissible venereal tumor and transmissible cancers of mollusks. We present a hypothesis that such transmissible tumors existed in the past and that some modern animal taxa are descendants of these tumors. We expect potential candidates for SCANDALs (speciated by cancer development animals) to be simplified relatives of more complex metazoans and have genomic alterations typical for cancer progression (such as deletions of universal apoptosis genes). We considered several taxa of simplified animals for our hypothesis: dicyemida, orthonectida, myxosporea and trichoplax. Based on genomic analysis we conclude that Myxosporea appear to be the most suitable candidates for a tumor ancestry. They are simplified parasitic cnidarians that universally lack major genes implicated in cancer progression including all genes with Caspase and BCL2 domains as well as any p53 and apoptotic protease activating factor - 1 (Apaf-1) homologs, suggesting the disruption of main apoptotic pathways in their early evolutionary history. Further comparative genomics and single-cell transcriptomic studies may be helpful to test our hypothesis of speciation via a cancerous stage. REVIEWERS: This article was reviewed by Eugene Koonin, Mikhail Gelfand and Gregory M Woods.",
			"category": 2,
			"name": "Panchin A Y,2019"
		},
		{
			"PMID": 30615612,
			"title": "Mutation, drift and selection in single-driver hematologic malignancy: Example of secondary myelodysplastic syndrome following treatment of inherited neutropenia.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Wojdyla Tomasz",
				"Mehta Hrishikesh",
				"Glaubach Taly",
				"Bertolusso Roberto",
				"Iwanaszko Marta",
				"Braun Rosemary",
				"Corey Seth J",
				"Kimmel Marek"
			],
			"DOI": "10.1371/journal.pcbi.1006664",
			"date": "2019-02-28",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer development is driven by series of events involving mutations, which may become fixed in a tumor via genetic drift and selection. This process usually includes a limited number of driver (advantageous) mutations and a greater number of passenger (neutral or mildly deleterious) mutations. We focus on a real-world leukemia model evolving on the background of a germline mutation. Severe congenital neutropenia (SCN) evolves to secondary myelodysplastic syndrome (sMDS) and/or secondary acute myeloid leukemia (sAML) in 30-40%. The majority of SCN cases are due to a germline ELANE mutation. Acquired mutations in CSF3R occur in >70% sMDS/sAML associated with SCN. Hypotheses underlying our model are: an ELANE mutation causes SCN; CSF3R mutations occur spontaneously at a low rate; in fetal life, hematopoietic stem and progenitor cells expands quickly, resulting in a high probability of several tens to several hundreds of cells with CSF3R truncation mutations; therapeutic granulocyte colony-stimulating factor (G-CSF) administration early in life exerts a strong selective pressure, providing mutants with a growth advantage. Applying population genetics theory, we propose a novel two-phase model of disease development from SCN to sMDS. In Phase 1, hematopoietic tissues expand and produce tens to hundreds of stem cells with the CSF3R truncation mutation. Phase 2 occurs postnatally through adult stages with bone marrow production of granulocyte precursors and positive selection of mutants due to chronic G-CSF therapy to reverse the severe neutropenia. We predict the existence of the pool of cells with the mutated truncated receptor before G-CSF treatment begins. The model does not require increase in mutation rate under G-CSF treatment and agrees with age distribution of sMDS onset and clinical sequencing data.",
			"category": 2,
			"name": "Wojdyla Tomasz,2019"
		},
		{
			"PMID": 30563222,
			"title": "Defining a Characteristic Gene Expression Set Responsible for Cancer Stem Cell-Like Features in a Sub-Population of Ewing Sarcoma Cells CADO-ES1.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Hotfilder Marc",
				"Mallela Nikhil",
				"Seggewi\u00df Jochen",
				"Dirksen Uta",
				"Korsching Eberhard"
			],
			"DOI": "10.3390/ijms19123908",
			"date": "2019-03-28",
			"PMC": "",
			"citation": "",
			"abstract": "One of the still open questions in Ewing sarcoma, a rare bone tumor with weak therapeutic options, is to identify the tumor-driving cell (sub) population and to understand the specifics in the biological network of these cells. This basic scientific insight might foster the development of more specific therapeutic target patterns. The experimental approach is based on a side population (SP) of Ewing cells, based on the model cell line CADO-ES1. The SP is established by flow cytometry and defined by the idea that tumor stem-like cells can be identified by the time-course in clearing a given artificial dye. The SP was characterized by a higher colony forming activity, by a higher differentiation potential, by higher resistance to cytotoxic drugs, and by morphology. Several SP and non-SP cell fractions and bone marrow-derived mesenchymal stem cell reference were analyzed by short read sequencing of the full transcriptome. The double-differential analysis leads to an altered expression structure of SP cells centered around the AP-1 and APC/c complex. The SP cells share only a limited proportion of the full mesenchymal stem cell stemness set of genes. This is in line with the expectation that tumor stem-like cells share only a limited subset of stemness features which are relevant for tumor survival.",
			"category": 2,
			"name": "Hotfilder Marc,2019"
		},
		{
			"PMID": 30424545,
			"title": "miRNA Mediated Noise Making of 3'UTR Mutations in Cancer.",
			"journal": "Genes",
			"authorList": [
				"Wu Wei",
				"Wu Lingxiang",
				"Zhu Mengyan",
				"Wang Ziyu",
				"Wu Min",
				"Li Pengping",
				"Nie Yumin",
				"Lin Xue",
				"Hu Jie",
				"Eskilsson Eskil",
				"Wang Qh",
				"Shao Jiaofang",
				"Lyu Sali"
			],
			"DOI": "10.3390/genes9110545",
			"date": "2023-11-04",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic mutations in 3'-untranslated regions (3'UTR) do not alter amino acids and are considered to be silent in cancers. We found that such mutations can promote tumor progression by altering microRNA (miRNA) targeting efficiency and consequently affecting miRNA\u207bmRNA interactions. We identified 67,159 somatic mutations located in the 3'UTRs of messenger RNAs (mRNAs) which can alter miRNA\u207bmRNA interactions (functional somatic mutations, funcMutations), and 69.3% of these funcMutations (the degree of energy change > 12 kcal/mol) were identified to significantly promote loss of miRNA-mRNA binding. By integrating mRNA expression profiles of 21 cancer types, we found that the expression of target genes was positively correlated with the loss of absolute affinity level and negatively correlated with the gain of absolute affinity level. Functional enrichment analysis revealed that genes carrying funcMutations were significantly enriched in the MAPK and WNT signaling pathways, and analysis of regulatory modules identified eighteen miRNA modules involved with similar cellular functions. Our findings elucidate a complex relationship between miRNA, mRNA, and mutations, and suggest that 3'UTR mutations may play an important role in tumor development.",
			"category": 2,
			"name": "Wu Wei,2023"
		},
		{
			"PMID": 30424330,
			"title": "The Use of Microfluidic Technology for Cancer Applications and Liquid Biopsy.",
			"journal": "Micromachines",
			"authorList": [
				"Kulasinghe Arutha",
				"Wu Hanjie",
				"Punyadeera Chamindie",
				"Warkiani Majid Ebrahimi"
			],
			"DOI": "10.3390/mi9080397",
			"date": "2023-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "There is growing awareness for the need of early diagnostic tools to aid in point-of-care testing in cancer. Tumor biopsy remains the conventional means in which to sample a tumor and often presents with challenges and associated risks. Therefore, alternative sources of tumor biomarkers is needed. Liquid biopsy has gained attention due to its non-invasive sampling of tumor tissue and ability to serially assess disease via a simple blood draw over the course of treatment. Among the leading technologies developing liquid biopsy solutions, microfluidics has recently come to the fore. Microfluidic platforms offer cellular separation and analysis platforms that allow for high throughout, high sensitivity and specificity, low sample volumes and reagent costs and precise liquid controlling capabilities. These characteristics make microfluidic technology a promising tool in separating and analyzing circulating tumor biomarkers for diagnosis, prognosis and monitoring. In this review, the characteristics of three kinds of circulating tumor markers will be described in the context of cancer, circulating tumor cells (CTCs), exosomes, and circulating tumor DNA (ctDNA). The review will focus on how the introduction of microfluidic technologies has improved the separation and analysis of these circulating tumor markers.",
			"category": 2,
			"name": "Kulasinghe Arutha,2023"
		},
		{
			"PMID": 30404658,
			"title": "Recurrent mutations at estrogen receptor binding sites alter chromatin topology and distal gene expression in breast cancer.",
			"journal": "Genome biology",
			"authorList": [
				"Yang Jiekun",
				"Wei Xiaolong",
				"Tufan Turan",
				"Kuscu Cem",
				"Unlu Hayrunnisa",
				"Farooq Saadia",
				"Demirtas Elif",
				"Paschal Bryce M",
				"Adli Mazhar"
			],
			"DOI": "10.1186/s13059-018-1572-4",
			"date": "2019-02-05",
			"PMC": "",
			"citation": "",
			"abstract": "The mutational processes underlying non-coding cancer mutations and their biological significance in tumor evolution are poorly understood. To get better insights into the biological mechanisms of mutational processes in breast cancer, we integrate whole-genome level somatic mutations from breast cancer patients with chromatin states and transcription factor binding events.",
			"category": 2,
			"name": "Yang Jiekun,2019"
		},
		{
			"PMID": 30323172,
			"title": "High prevalence of focal and multi-focal somatic genetic variants in the human brain.",
			"journal": "Nature communications",
			"authorList": [
				"Keogh Michael J",
				"Wei Wei",
				"Aryaman Juvid",
				"Walker Lauren",
				"van den Ameele Jelle",
				"Coxhead Jon",
				"Wilson Ian",
				"Bashton Matthew",
				"Beck Jon",
				"West John",
				"Chen Richard",
				"Haudenschild Christian",
				"Bartha Gabor",
				"Luo Shujun",
				"Morris Chris M",
				"Jones Nick S",
				"Attems Johannes",
				"Chinnery Patrick F"
			],
			"DOI": "10.1038/s41467-018-06331-w",
			"date": "2018-12-31",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic mutations during stem cell division are responsible for several cancers. In principle, a similar process could occur during the intense cell proliferation accompanying human brain development, leading to the accumulation of regionally distributed foci of mutations. Using dual platform >5000-fold depth sequencing of 102 genes in 173 adult human brain samples, we detect and validate somatic mutations in 27 of 54 brains. Using a mathematical model of neurodevelopment and approximate Bayesian inference, we predict that macroscopic islands of pathologically mutated neurons are likely to be common in the general population. The detected mutation spectrum also includes DNMT3A and TET2 which are likely to have originated from blood cell lineages. Together, these findings establish developmental mutagenesis as a potential mechanism for neurodegenerative disorders, and provide a novel mechanism for the regional onset and focal pathology in sporadic cases.",
			"category": 2,
			"name": "Keogh Michael J,2018"
		},
		{
			"PMID": 30216655,
			"title": "A pan-cancer atlas of cancer hallmark-associated candidate driver lncRNAs.",
			"journal": "Molecular oncology",
			"authorList": [
				"Deng Yulan",
				"Luo Shangyi",
				"Zhang Xinxin",
				"Zou Chaoxia",
				"Yuan Huating",
				"Liao Gaoming",
				"Xu Liwen",
				"Deng Chunyu",
				"Lan Yujia",
				"Zhao Tingting",
				"Gao Xu",
				"Xiao Yun",
				"Li Xia"
			],
			"DOI": "10.1002/1878-0261.12381",
			"date": "2019-08-12",
			"PMC": "",
			"citation": "",
			"abstract": "Substantial cancer genome sequencing efforts have discovered many important driver genes contributing to tumorigenesis. However, very little is known about the genetic alterations of long non-coding RNAs (lncRNAs) in cancer. Thus, there is a need for systematic surveys of driver lncRNAs. Through integrative analysis of 5918 tumors across 11 cancer types, we revealed that lncRNAs have undergone dramatic genomic alterations, many of which are mutually exclusive with well-known cancer genes. Using the hypothesis of functional redundancy of mutual exclusivity, we developed a computational framework to identify driver lncRNAs associated with different cancer hallmarks. Applying it to pan-cancer data, we identified 378 candidate driver lncRNAs whose genomic features highly resemble the known cancer driver genes (e.g. high conservation and early replication). We further validated the candidate driver lncRNAs involved in 'Tissue Invasion and Metastasis' in lung adenocarcinoma and breast cancer, and also highlighted their potential roles in improving clinical outcomes. In summary, we have generated a comprehensive landscape of cancer candidate driver lncRNAs that could act as a starting point for future functional explorations, as well as the identification of biomarkers and lncRNA-based target therapy.",
			"category": 2,
			"name": "Deng Yulan,2019"
		},
		{
			"PMID": 30193109,
			"title": "The Multifaceted Role of Chromosomal Instability in Cancer and Its Microenvironment.",
			"journal": "Cell",
			"authorList": [
				"Bakhoum Samuel F",
				"Cantley Lewis C"
			],
			"DOI": "10.1016/j.cell.2018.08.027",
			"date": "2019-05-22",
			"PMC": "",
			"citation": "",
			"abstract": "Chromosomal instability (CIN) is a hallmark of human cancer, and it is associated with poor prognosis, metastasis, and therapeutic resistance. CIN results from errors in chromosome segregation during mitosis, leading to structural and numerical chromosomal abnormalities. In addition to generating genomic heterogeneity that acts as a substrate for natural selection, CIN promotes inflammatory\u00a0signaling by introducing double-stranded DNA into the cytosol, engaging the cGAS-STING anti-viral pathway. These multipronged effects distinguish CIN as a central driver of tumor evolution and as a genomic source for the crosstalk between the tumor and its microenvironment, in the course of immune editing and evasion.",
			"category": 2,
			"name": "Bakhoum Samuel F,2019"
		},
		{
			"PMID": 30123241,
			"title": "Using Supervised Learning Methods for Gene Selection in RNA-Seq Case-Control Studies.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Wenric Stephane",
				"Shemirani Ruhollah"
			],
			"DOI": "10.3389/fgene.2018.00297",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "Whole transcriptome studies typically yield large amounts of data, with expression values for all genes or transcripts of the genome. The search for genes of interest in a particular study setting can thus be a daunting task, usually relying on automated computational methods. Moreover, most biological questions imply that such a search should be performed in a multivariate setting, to take into account the inter-genes relationships. Differential expression analysis commonly yields large lists of genes deemed significant, even after adjustment for multiple testing, making the subsequent study possibilities extensive. Here, we explore the use of supervised learning methods to rank large ensembles of genes defined by their expression values measured with RNA-Seq in a typical 2 classes sample set. First, we use one of the variable importance measures generated by the random forests classification algorithm as a metric to rank genes. Second, we define the EPS (extreme pseudo-samples) pipeline, making use of VAEs (Variational Autoencoders) and regressors to extract a ranking of genes while leveraging the feature space of both virtual and comparable samples. We show that, on 12 cancer RNA-Seq data sets ranging from 323 to 1,210 samples, using either a random forests-based gene selection method or the EPS pipeline outperforms differential expression analysis for 9 and 8 out of the 12 datasets respectively, in terms of identifying subsets of genes associated with survival. These results demonstrate the potential of supervised learning-based gene selection methods in RNA-Seq studies and highlight the need to use such multivariate gene selection methods alongside the widely used differential expression analysis.",
			"category": 2,
			"name": "Wenric Stephane,2020"
		},
		{
			"PMID": 29976634,
			"title": "Comparing Clonality Between Components of Combined Hepatocellular Carcinoma and Cholangiocarcinoma by Targeted Sequencing.",
			"journal": "Cancer genomics & proteomics",
			"authorList": [
				"Jeon Jinyoung",
				"Maeng Lee-So",
				"Bae Yoon Jin",
				"Lee Eui-Jin",
				"Yoon Young Chul",
				"Yoon Nara"
			],
			"DOI": "10.21873/cgp.20087",
			"date": "2018-11-12",
			"PMC": "",
			"citation": "",
			"abstract": "Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a very rare type of tumor, comprising these two different components in a single mass. Although several studies have determined the genetic characteristics of cHCC-CC, next-generation sequencing (NGS) data for comparing clonality of cHCC-CC are currently unavailable.",
			"category": 2,
			"name": "Jeon Jinyoung,2018"
		},
		{
			"PMID": 29900125,
			"title": "Genome-Wide Analysis of Interchromosomal Interaction Probabilities Reveals Chained Translocations and Overrepresentation of Translocation Breakpoints in Genes in a Cutaneous T-Cell Lymphoma Cell Line.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Steininger Anne",
				"Ebert Grit",
				"Becker Benjamin V",
				"Assaf Chalid",
				"M\u00f6bs Markus",
				"Schmidt Christian A",
				"Grabarczyk Piotr",
				"Jensen Lars R",
				"Przybylski Grzegorz K",
				"Port Matthias",
				"Kuss Andreas W",
				"Ullmann Reinhard"
			],
			"DOI": "10.3389/fonc.2018.00183",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "In classical models of tumorigenesis, the accumulation of tumor promoting chromosomal aberrations is described as a gradual process. Next-generation sequencing-based methods have recently revealed complex patterns of chromosomal aberrations, which are beyond explanation by these classical models of karyotypic evolution of tumor genomes. Thus, the term chromothripsis has been introduced to describe a phenomenon, where temporarily and spatially confined genomic instability results in dramatic chromosomal rearrangements limited to segments of one or a few chromosomes. Simultaneously arising and misrepaired DNA double-strand breaks are also the cause of another phenomenon called chromoplexy, which is characterized by the presence of chained translocations and interlinking deletion bridges involving several chromosomes. In this study, we demonstrate the genome-wide identification of chromosomal translocations based on the analysis of translocation-associated changes in spatial proximities of chromosome territories on the example of the cutaneous T-cell lymphoma cell line Se-Ax. We have used alterations of intra- and interchromosomal interaction probabilities as detected by genome-wide chromosome conformation capture (Hi-C) to infer the presence of translocations and to fine-map their breakpoints. The outcome of this analysis was subsequently compared to datasets on DNA copy number alterations and gene expression. The presence of chained translocations within the Se-Ax genome, partly connected by intervening deletion bridges, indicates a role of chromoplexy in the etiology of this cutaneous T-cell lymphoma. Notably, translocation breakpoints were significantly overrepresented in genes, which highlight gene-associated biological processes like transcription or other gene characteristics as a possible cause of the observed complex rearrangements. Given the relevance of chromosomal aberrations for basic and translational research, genome-wide high-resolution analysis of structural chromosomal aberrations will gain increasing importance.",
			"category": 2,
			"name": "Steininger Anne,2020"
		},
		{
			"PMID": 29895694,
			"title": "Cancer-mutation network and the number and specificity of driver mutations.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Iranzo Jaime",
				"Martincorena I\u00f1igo",
				"Koonin Eugene V"
			],
			"DOI": "10.1073/pnas.1803155115",
			"date": "2018-09-04",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer genomics has produced extensive information on cancer-associated genes, but the number and specificity of cancer-driver mutations remains a matter of debate. We constructed a bipartite network in which 7,665 tumors from 30 cancer types are connected via shared mutations in 198 previously identified cancer genes. We show that about 27% of the tumors can be assigned to statistically supported modules, most of which encompass one or two cancer types. The rest of the tumors belong to a diffuse network component suggesting lower gene specificity of driver mutations. Linear regression of the mutational loads in cancer genes was used to estimate the number of drivers required for the onset of different cancers. The mean number of drivers in known cancer genes is approximately two, with a range of one to five. Cancers that are associated with modules had more drivers than those from the diffuse network component, suggesting that unidentified and/or interchangeable drivers exist in the latter.",
			"category": 2,
			"name": "Iranzo Jaime,2018"
		},
		{
			"PMID": 29872715,
			"title": "The potential of liquid biopsies for the early detection of cancer.",
			"journal": "NPJ precision oncology",
			"authorList": [
				"Heitzer Ellen",
				"Perakis Samantha",
				"Geigl Jochen B",
				"Speicher Michael R"
			],
			"DOI": "10.1038/s41698-017-0039-5",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "Precision medicine refers to the choosing of targeted therapies based on genetic data. Due to the increasing availability of data from large-scale tumor genome sequencing projects, genome-driven oncology may have enormous potential to change the clinical management of patients with cancer. To this end, components of tumors, which are shed into the circulation, i.e., circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), or extracellular vesicles, are increasingly being used for monitoring tumor genomes. A growing number of publications have documented that these \"liquid biopsies\" are informative regarding response to given therapies, are capable of detecting relapse with lead time compared to standard measures, and reveal mechanisms of resistance. However, the majority of published studies relate to advanced tumor stages and the use of liquid biopsies for detection of very early malignant disease stages is less well documented. In early disease stages, strategies for analysis are in principle relatively similar to advanced stages. However, at these early stages, several factors pose particular difficulties and challenges, including the lower frequency and volume of aberrations, potentially confounding phenomena such as clonal expansions of non-tumorous tissues or the accumulation of cancer-associated mutations with age, and the incomplete insight into driver alterations. Here we discuss biology, technical complexities and clinical significance for early cancer detection and their impact on precision oncology.",
			"category": 2,
			"name": "Heitzer Ellen,2020"
		},
		{
			"PMID": 29855388,
			"title": "Negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome.",
			"journal": "Genome biology",
			"authorList": [
				"Zapata Luis",
				"Pich Oriol",
				"Serrano Luis",
				"Kondrashov Fyodor A",
				"Ossowski Stephan",
				"Schaefer Martin H"
			],
			"DOI": "10.1186/s13059-018-1434-0",
			"date": "2018-09-03",
			"PMC": "",
			"citation": "",
			"abstract": "Natural selection shapes cancer genomes. Previous studies used signatures of positive selection to identify genes driving malignant transformation. However, the contribution of negative selection against somatic mutations that affect essential tumor functions or specific domains remains a controversial topic.",
			"category": 2,
			"name": "Zapata Luis,2018"
		},
		{
			"PMID": 29844525,
			"title": "Copy-number analysis and inference of subclonal populations in cancer genomes using Sclust.",
			"journal": "Nature protocols",
			"authorList": [
				"Cun Yupeng",
				"Yang Tsun-Po",
				"Achter Viktor",
				"Lang Ulrich",
				"Peifer Martin"
			],
			"DOI": "10.1038/nprot.2018.033",
			"date": "2019-04-15",
			"PMC": "",
			"citation": "",
			"abstract": "The genomes of cancer cells constantly change during pathogenesis. This evolutionary process can lead to the emergence of drug-resistant mutations in subclonal populations, which can hinder therapeutic intervention in patients. Data derived from massively parallel sequencing can be used to infer these subclonal populations using tumor-specific point mutations. The accurate determination of copy-number changes and tumor impurity is necessary to reliably infer subclonal populations by mutational clustering. This protocol describes how to use Sclust, a copy-number analysis method with a recently developed mutational clustering approach. In a series of simulations and comparisons with alternative methods, we have previously shown that Sclust accurately determines copy-number states and subclonal populations. Performance tests show that the method is computationally efficient, with copy-number analysis and mutational clustering taking <10 min. Sclust is designed such that even non-experts in computational biology or bioinformatics with basic knowledge of the Linux/Unix command-line syntax should be able to carry out analyses of subclonal populations.",
			"category": 2,
			"name": "Cun Yupeng,2019"
		},
		{
			"PMID": 29755565,
			"title": null,
			"journal": "Iranian journal of pharmaceutical research : IJPR",
			"authorList": [
				"Esmaeili-Mahani Saeed",
				"Samandari-Bahraseman Mohammad Rasoul",
				"Yaghoobi Mohammad Mehdi"
			],
			"DOI": "",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "Esmaeili-Mahani Saeed,2020"
		},
		{
			"PMID": 29718479,
			"title": "Complex repeat structure promotes hyper-amplification and amplicon evolution through rolling-circle replication.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Watanabe Takaaki",
				"Tanaka Hisashi",
				"Horiuchi Takashi"
			],
			"DOI": "10.1093/nar/gky275",
			"date": "2019-08-22",
			"PMC": "",
			"citation": "",
			"abstract": "Inverted repeats (IRs) are abundant in genomes and frequently serve as substrates for chromosomal aberrations, including gene amplification. In the early stage of amplification, repeated cycles of chromosome breakage and rearrangement, called breakage-fusion-bridge (BFB), generate a large inverted structure, which evolves into highly-amplified, complex end products. However, it remains to be determined how IRs mediate chromosome rearrangements and promote subsequent hyper-amplification and amplicon evolutions. To dissect the complex processes, we constructed repetitive structures in a yeast chromosome and selected amplified cells using genetic markers with limited expression. The genomic architecture was associated with replication stress and produced extra-/intra-chromosomal amplification. Genetic analysis revealed structure-specific endonucleases, Mus81 and Rad27, and post-replication DNA repair protein, Rad18, suppress the amplification processes. Following BFB cycles, the intra-chromosomal products undergo intensive rearrangements, such as frequent inversions and deletions, indicative of rolling-circle replication. This study presents an integrated view linking BFB cycles to hyper-amplification driven by rolling-circle replication.",
			"category": 2,
			"name": "Watanabe Takaaki,2019"
		},
		{
			"PMID": 29616301,
			"title": "Reconstructing the molecular life history of gliomas.",
			"journal": "Acta neuropathologica",
			"authorList": [
				"Barthel Floris P",
				"Wesseling Pieter",
				"Verhaak Roel G W"
			],
			"DOI": "10.1007/s00401-018-1842-y",
			"date": "2019-07-01",
			"PMC": "",
			"citation": "",
			"abstract": "At the time of their clinical manifestation, the heterogeneous group of adult and pediatric gliomas carries a wide range of diverse somatic genomic alterations, ranging from somatic single-nucleotide variants to structural chromosomal rearrangements. Somatic abnormalities may have functional consequences, such as a decrease, increase or change in mRNA transcripts, and cells pay a penalty for maintaining them. These abnormalities, therefore, must provide cells with a competitive advantage to become engrained into the glioma genome. Here, we propose a model of gliomagenesis consisting of the following five consecutive phases that glioma cells have traversed prior to clinical manifestation: (I) initial growth; (II) oncogene-induced senescence; (III) stressed growth; (IV) replicative senescence/crisis; (V) immortal growth. We have integrated the findings from a large number of studies in biology and (neuro)oncology and relate somatic alterations and other results discussed in these papers to each of these five phases. Understanding the story that each glioma tells at presentation may ultimately facilitate the design of novel, more effective therapeutic approaches.",
			"category": 2,
			"name": "Barthel Floris P,2019"
		},
		{
			"PMID": 29611034,
			"title": "Finding cancer driver mutations in the era of big data research.",
			"journal": "Biophysical reviews",
			"authorList": [
				"Poulos Rebecca C",
				"Wong Jason W H"
			],
			"DOI": "10.1007/s12551-018-0415-6",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "In the last decade, the costs of genome sequencing have decreased considerably. The commencement of large-scale cancer sequencing projects has enabled cancer genomics to join the big data revolution. One of the challenges still facing cancer genomics research is determining which are the driver mutations in an individual cancer, as these contribute only a small subset of the overall mutation profile of a tumour. Focusing primarily on somatic single nucleotide mutations in this review, we consider both coding and non-coding driver mutations, and discuss how such mutations might be identified from cancer sequencing datasets. We describe some of the tools and database that are available for the annotation of somatic variants and the identification of cancer driver genes. We also address the use of genome-wide variation in mutation load to establish background mutation rates from which to identify driver mutations under positive selection. Finally, we describe the ways in which mutational signatures can act as clues for the identification of cancer drivers, as these mutations may cause, or arise from, certain mutational processes. By defining the molecular changes responsible for driving cancer development, new cancer treatment strategies may be developed or novel preventative measures proposed.",
			"category": 2,
			"name": "Poulos Rebecca C,2020"
		},
		{
			"PMID": 29570743,
			"title": "Novel putative drivers revealed by targeted exome sequencing of advanced solid tumors.",
			"journal": "PloS one",
			"authorList": [
				"Pannuti Antonio",
				"Filipovic Aleksandra",
				"Hicks Chindo",
				"Lefkowitz Elliot",
				"Ptacek Travis",
				"Stebbing Justin",
				"Miele Lucio"
			],
			"DOI": "10.1371/journal.pone.0194790",
			"date": "2018-07-06",
			"PMC": "",
			"citation": "",
			"abstract": "Next generation sequencing (NGS) is becoming increasingly integrated into oncological practice and clinical research. NGS methods have also provided evidence for clonal evolution of cancers during disease progression and treatment. The number of variants associated with response to specific therapeutic agents keeps increasing. However, the identification of novel driver mutations as opposed to passenger (phenotypically silent or clinically irrelevant) mutations remains a major challenge. We conducted targeted exome sequencing of advanced solid tumors from 44 pre-treated patients with solid tumors including breast, colorectal and lung carcinomas, neuroendocrine tumors, sarcomas and others. We catalogued established driver mutations and putative new drivers as predicted by two distinct algorithms. The established drivers we detected were consistent with published observations. However, we also detected a significant number of mutations with driver potential never described before in each tumor type we studied. These putative drivers belong to key cell fate regulatory networks, including potentially druggable pathways. Should our observations be confirmed, they would support the hypothesis that new driver mutations are selected by treatment in clinically aggressive tumors, and indicate a need for longitudinal genomic testing of solid tumors to inform second line cancer treatment.",
			"category": 2,
			"name": "Pannuti Antonio,2018"
		},
		{
			"PMID": 29564184,
			"title": "How does the tumor microenvironment play a role in hepatobiliary tumors?",
			"journal": "Journal of gastrointestinal oncology",
			"authorList": [
				"Kamil Fathima",
				"Rowe Julie H"
			],
			"DOI": "10.21037/jgo.2017.06.09",
			"date": "2024-03-14",
			"PMC": "",
			"citation": "",
			"abstract": "The tumor microenvironment (TME) is defined as the structural and dynamic network of cellular and non-cellular interactions between malignant cells and the surrounding non-malignant matrix. Hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC) are two of the most challenging gastrointestinal malignancies. Despite clinical advancements in understanding tumor biology and growth of the chemotherapeutic industry, there have been no corresponding improvements in prognosis and overall survival of HCC and PDAC. Both of these cancers have a very intimate relationship with their surrounding environment; the TME is thought to actively participate in initiating and sustaining these malignancies. Individual TME constituents play a vital role in chemoresistance and recurrence after surgery and have been established as independent prognostic factors. This review article will highlight the diverse structural components, key signaling pathways, and extracellular matrices of HCC and PDAC and discuss their crosstalk with tumor cells to promote growth and metastasis. The article will also summarize the latest laboratory and clinical research based on therapeutic targets identified within the TME of both HCC and PDAC.",
			"category": 2,
			"name": "Kamil Fathima,2024"
		},
		{
			"PMID": 29466995,
			"title": "Nothing in cancer makes sense except\u2026.",
			"journal": "BMC biology",
			"authorList": [
				"Greaves Mel"
			],
			"DOI": "10.1186/s12915-018-0493-8",
			"date": "2019-03-25",
			"PMC": "",
			"citation": "",
			"abstract": "Paraphrasing Dobzhansky's famous dictum, I discuss how interrogating cancer through the lens of evolution has transformed our understanding of its development, causality and treatment resistance. The emerging picture of cancer captures its extensive diversity and therapeutic resilience, highlighting the need for more innovative approaches to control.",
			"category": 2,
			"name": "Greaves Mel,2019"
		},
		{
			"PMID": 29464062,
			"title": "Cell-cell fusion as a mechanism of DNA exchange in cancer.",
			"journal": "Oncotarget",
			"authorList": [
				"Searles Stephen C",
				"Santosa Endi K",
				"Bui Jack D"
			],
			"DOI": "10.18632/oncotarget.23715",
			"date": "2020-03-06",
			"PMC": "",
			"citation": "",
			"abstract": "Cell-cell fusion describes the process by which two cells combine their plasma membranes and become a single cell, possessing and retaining certain genetic information from each parent cell. Here, using a Cre-",
			"category": 2,
			"name": "Searles Stephen C,2020"
		},
		{
			"PMID": 29422598,
			"title": "Genetic insights into the morass of metastatic heterogeneity.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Hunter Kent W",
				"Amin Ruhul",
				"Deasy Sarah",
				"Ha Ngoc-Han",
				"Wakefield Lalage"
			],
			"DOI": "10.1038/nrc.2017.126",
			"date": "2019-05-20",
			"PMC": "",
			"citation": "",
			"abstract": "Tumour heterogeneity poses a substantial problem for the clinical management of cancer. Somatic evolution of the cancer genome results in genetically distinct subclones in the primary tumour with different biological properties and therapeutic sensitivities. The problem of heterogeneity is compounded in metastatic disease owing to the complexity of the metastatic process and the multiple biological hurdles that the tumour cell must overcome to establish a clinically overt metastatic lesion. New advances in sequencing technology and clinical sample acquisition are providing insights into the phylogenetic relationship of metastases and primary tumours at the level of somatic tumour genetics while also illuminating fundamental mechanisms of the metastatic process. In addition to somatically acquired genetic heterogeneity in the tumour cells, inherited population-based genetic heterogeneity can profoundly modify metastatic biology and further complicate the development of effective, broadly applicable antimetastatic therapies. Here, we examine how genetic heterogeneity impacts metastatic disease and the implications of current knowledge for future research endeavours and therapeutic interventions.",
			"category": 2,
			"name": "Hunter Kent W,2019"
		},
		{
			"PMID": 29399660,
			"title": "Stress-Induced Mutagenesis: Implications in Cancer and Drug Resistance.",
			"journal": "Annual review of cancer biology",
			"authorList": [
				"Fitzgerald Devon M",
				"Hastings P J",
				"Rosenberg Susan M"
			],
			"DOI": "10.1146/annurev-cancerbio-050216-121919",
			"date": "2024-03-13",
			"PMC": "",
			"citation": "",
			"abstract": "Genomic instability underlies many cancers and generates genetic variation that drives cancer initiation, progression, and therapy resistance. In contrast with classical assumptions that mutations occur purely stochastically at constant, gradual rates, microbes, plants, flies, and human cancer cells possess mechanisms of mutagenesis that are upregulated by stress responses. These generate transient, genetic-diversity bursts that can propel evolution, specifically when cells are poorly adapted to their environments-that is, when stressed. We review molecular mechanisms of stress-response-dependent (stress-induced) mutagenesis that occur from bacteria to cancer, and are activated by starvation, drugs, hypoxia, and other stressors. We discuss mutagenic DNA break repair in ",
			"category": 2,
			"name": "Fitzgerald Devon M,2024"
		},
		{
			"PMID": 29361790,
			"title": "Single-Cell Genomic Analysis in Plants.",
			"journal": "Genes",
			"authorList": [
				"Yuan Yuxuan",
				"Lee HueyTyng",
				"Hu Haifei",
				"Scheben Armin",
				"Edwards David"
			],
			"DOI": "10.3390/genes9010050",
			"date": "2019-11-20",
			"PMC": "",
			"citation": "",
			"abstract": "Individual cells in an organism are variable, which strongly impacts cellular processes. Advances in sequencing technologies have enabled single-cell genomic analysis to become widespread, addressing shortcomings of analyses conducted on populations of bulk cells. While the field of single-cell plant genomics is in its infancy, there is great potential to gain insights into cell lineage and functional cell types to help understand complex cellular interactions in plants. In this review, we discuss current approaches for single-cell plant genomic analysis, with a focus on single-cell isolation, DNA amplification, next-generation sequencing, and bioinformatics analysis. We outline the technical challenges of analysing material from a single plant cell, and then examine applications of single-cell genomics and the integration of this approach with genome editing. Finally, we indicate future directions we expect in the rapidly developing field of plant single-cell genomic analysis.",
			"category": 2,
			"name": "Yuan Yuxuan,2019"
		},
		{
			"PMID": 29354286,
			"title": "Pan-cancer screen for mutations in non-coding elements with conservation and cancer specificity reveals correlations with expression and survival.",
			"journal": "NPJ genomic medicine",
			"authorList": [
				"Hornsh\u00f8j Henrik",
				"Nielsen Morten Muhlig",
				"Sinnott-Armstrong Nicholas A",
				"\u015awitnicki Micha\u0142 P",
				"Juul Malene",
				"Madsen Tobias",
				"Sallari Richard",
				"Kellis Manolis",
				"\u00d8rntoft Torben",
				"Hobolth Asger",
				"Pedersen Jakob Skou"
			],
			"DOI": "10.1038/s41525-017-0040-5",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer develops by accumulation of somatic driver mutations, which impact cellular function. Mutations in non-coding regulatory regions can now be studied genome-wide and further characterized by correlation with gene expression and clinical outcome to identify driver candidates. Using a new two-stage procedure, called ncDriver, we first screened 507 ICGC whole-genomes from 10 cancer types for non-coding elements, in which mutations are both recurrent and have elevated conservation or cancer specificity. This identified 160 significant non-coding elements, including the ",
			"category": 2,
			"name": "Hornsh\u00f8j Henrik,2020"
		},
		{
			"PMID": 29351238,
			"title": "Telomeres: Implications for Cancer Development.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Bernal Aina",
				"Tusell Laura"
			],
			"DOI": "10.3390/ijms19010294",
			"date": "2018-08-13",
			"PMC": "",
			"citation": "",
			"abstract": "Telomeres facilitate the protection of natural ends of chromosomes from constitutive exposure to the DNA damage response (DDR). This is most likely achieved by a lariat structure that hides the linear telomeric DNA through protein-protein and protein-DNA interactions. The telomere shortening associated with DNA replication in the absence of a compensatory mechanism culminates in unmasked telomeres. Then, the subsequent activation of the DDR will define the fate of cells according to the functionality of cell cycle checkpoints. Dysfunctional telomeres can suppress cancer development by engaging replicative senescence or apoptotic pathways, but they can also promote tumour initiation. Studies in telomere dynamics and karyotype analysis underpin telomere crisis as a key event driving genomic instability. Significant attainment of telomerase or alternative lengthening of telomeres (ALT)-pathway to maintain telomere length may be permissive and required for clonal evolution of genomically-unstable cells during progression to malignancy. We summarise current knowledge of the role of telomeres in the maintenance of chromosomal stability and carcinogenesis.",
			"category": 2,
			"name": "Bernal Aina,2018"
		},
		{
			"PMID": 29344272,
			"title": "Cancer vaccine: learning lessons from immune checkpoint inhibitors.",
			"journal": "Journal of Cancer",
			"authorList": [
				"Ye ZhenLong",
				"Qian Qiming",
				"Jin HuaJun",
				"Qian QiJun"
			],
			"DOI": "10.7150/jca.20059",
			"date": "2021-01-03",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer vaccines have been exclusively studied all through the past decades, and have made exceptional achievements in cancer treatment. Few cancer vaccines have been approved by the US Food and Drug Administration (FDA), for instance, Provenge, which was approved for the treatment of prostate carcinoma in 2012. Moreover, more recently, T-VEC got approval for the treatment of melanoma. While, the overall therapeutic effects of cancer vaccines have been taken into consideration as below expectations, low antigenicity of targeting antigen and tumor heterogeneity are the two key limiting barriers encountered by the cancer vaccines. Nonetheless, recent developments in cancer immune-therapies together with associated technologies, for instance the unparalleled achievements bagged by immune checkpoint inhibitor based therapies and neo-antigen identification tools, envisage potential improvements in cancer vaccines in respect to the treatments of malignancies. This review brings forth measures for the purpose of refining therapeutic cancer vaccines by learning lessons from the success of PD-1 inhibitor based immune-therapies.",
			"category": 2,
			"name": "Ye ZhenLong,2021"
		},
		{
			"PMID": 29295957,
			"title": "The depalmitoylase APT1 directs the asymmetric partitioning of Notch and Wnt signaling during cell division.",
			"journal": "Science signaling",
			"authorList": [
				"Stypulkowski Ewa",
				"Asangani Irfan A",
				"Witze Eric S"
			],
			"DOI": "10.1126/scisignal.aam8705",
			"date": "2019-05-09",
			"PMC": "",
			"citation": "",
			"abstract": "Asymmetric cell division results in two distinctly fated daughter cells. A molecular hallmark of asymmetric division is the unequal partitioning of cell fate determinants. We have previously established that growth factor signaling promotes protein depalmitoylation to foster polarized protein localization, which, in turn, drives migration and metastasis. We report protein palmitoylation as a key mechanism for the asymmetric partitioning of the cell fate determinants Numb and \u03b2-catenin through the activity of the depalmitoylating enzyme APT1. Using point mutations, we showed that specific palmitoylated residues on Numb were required for its asymmetric localization. By live-cell imaging, we showed that reciprocal interactions between APT1 and the Rho family GTPase CDC42 promoted the asymmetric localization of Numb and \u03b2-catenin to the plasma membrane. This, in turn, restricted Notch- or Wnt-responsive transcriptional activity to one daughter cell. Moreover, we showed that altering APT1 abundance changed the transcriptional signatures of MDA-MB-231 triple receptor-negative breast cancer cells, similar to changes in Notch and \u03b2-catenin-mediated Wnt signaling. We also showed that loss of APT1 depleted a specific subpopulation of tumorigenic cells in colony formation assays. Together, our findings suggest that APT1-mediated depalmitoylation is a major mechanism of asymmetric cell division that maintains Notch- and Wnt-associated protein dynamics, gene expression, and cellular functions.",
			"category": 2,
			"name": "Stypulkowski Ewa,2019"
		},
		{
			"PMID": 29293529,
			"title": "Identification of metastasis driver genes by massive parallel sequencing of successive steps of breast cancer progression.",
			"journal": "PloS one",
			"authorList": [
				"Kr\u00f8ig\u00e5rd Anne Bruun",
				"Larsen Martin Jakob",
				"L\u00e6nkholm Anne-Vibeke",
				"Knoop Ann S",
				"Jensen Jeanette Dupont",
				"Bak Martin",
				"Mollenhauer Jan",
				"Thomassen Mads",
				"Kruse Torben A"
			],
			"DOI": "10.1371/journal.pone.0189887",
			"date": "2018-01-29",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer results from alterations at essential genomic sites and is characterized by uncontrolled cell proliferation, invasion and metastasis. Identification of driver genes of metastatic progression is essential, as metastases, not primary tumors, are fatal. To gain insight into the mutational concordance between different steps of malignant progression we performed exome sequencing and validation with targeted deep sequencing of successive steps of malignant progression from pre-invasive stages to asynchronous distant metastases in six breast cancer patients. Using the ratio of non-synonymous to synonymous mutations, a surprisingly large number of cancer driver genes, ranging between 3 and 145, were estimated to confer a selective advantage in the studied primary tumors. We report a substantial amount of metastasis specific mutations and a number of novel putative metastasis driver genes. Most notable are the DCC, ABCA13, TIAM2, CREBBP, BCL6B and ZNF185 genes, mainly mutated exclusively in metastases and highly likely driver genes of metastatic progression. We find different genes and pathways to be affected at different steps of malignant progression. The Adherens junction pathway is affected in four of the six studied patients and this pathway most likely plays a vital role in the metastatic process.",
			"category": 2,
			"name": "Kr\u00f8ig\u00e5rd Anne Bruun,2018"
		},
		{
			"PMID": 29203377,
			"title": "Proposed Terminology and Classification of Pre-Malignant Neoplastic Conditions: A Consensus Proposal.",
			"journal": "EBioMedicine",
			"authorList": [
				"Valent Peter",
				"Akin Cem",
				"Arock Michel",
				"Bock Christoph",
				"George Tracy I",
				"Galli Stephen J",
				"Gotlib Jason",
				"Haferlach Torsten",
				"Hoermann Gregor",
				"Hermine Olivier",
				"J\u00e4ger Ulrich",
				"Kenner Lukas",
				"Kreipe Hans",
				"Majeti Ravindra",
				"Metcalfe Dean D",
				"Orfao Alberto",
				"Reiter Andreas",
				"Sperr Wolfgang R",
				"Staber Philipp B",
				"Sotlar Karl",
				"Schiffer Charles",
				"Superti-Furga Giulio",
				"Horny Hans-Peter"
			],
			"DOI": "10.1016/j.ebiom.2017.11.024",
			"date": "2018-07-20",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer evolution is a step-wise non-linear process that may start early in life or later in adulthood, and includes pre-malignant (indolent) and malignant phases. Early somatic changes may not be detectable or are found by chance in apparently healthy individuals. The same lesions may be detected in pre-malignant clonal conditions. In some patients, these lesions may never become relevant clinically whereas in others, they act together with additional pro-oncogenic hits and thereby contribute to the formation of an overt malignancy. Although some pre-malignant stages of a malignancy have been characterized, no global system to define and to classify these conditions is available. To discuss open issues related to pre-malignant phases of neoplastic disorders, a working conference was organized in Vienna in August 2015. The outcomes of this conference are summarized herein and include a basic proposal for a nomenclature and classification of pre-malignant conditions. This proposal should assist in the communication among patients, physicians and scientists, which is critical as genome-sequencing will soon be offered widely for early cancer-detection.",
			"category": 2,
			"name": "Valent Peter,2018"
		},
		{
			"PMID": 29190940,
			"title": "Elevation of MAP17 enhances the malignant behavior of cells via the Akt/mTOR pathway in hepatocellular carcinoma.",
			"journal": "Oncotarget",
			"authorList": [
				"Chen Xinhuang",
				"Liao Yan",
				"Yu Yaqun",
				"Zhu Pengpeng",
				"Li Jun",
				"Qin Liling",
				"Liao Weijia",
				"Huang Zhaoquan"
			],
			"DOI": "10.18632/oncotarget.21506",
			"date": "2019-11-20",
			"PMC": "",
			"citation": "",
			"abstract": "MAP17, a small non-glycosylated membrane protein, was significantly up-regulated in hepatocellular carcinoma (HCC) tissues in our previous genome-wide microarray analysis. In this study, quantitative real-time RT-PCR and immunohistochemistry were applied to examine MAP17 mRNA and protein expression in primary HCC and matched peritumoral tissues. The disease-free survival (DFS) and overall survival (OS) was estimated using the Kaplan-Meier analysis. The expression of MAP17 was significantly higher in HCC tissues compared to the paired peritumoral tissues at both mRNA and protein levels. High MAP17 expression was positively correlated with gender, distant metastasis, early recurrence (\u2264 2 year), and serum alpha-fetoprotein (all ",
			"category": 2,
			"name": "Chen Xinhuang,2019"
		},
		{
			"PMID": 29148540,
			"title": "Single-cell heterogeneity in ductal carcinoma in situ of breast.",
			"journal": "Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc",
			"authorList": [
				"Gerdes Michael J",
				"G\u00f6kmen-Polar Yesim",
				"Sui Yunxia",
				"Pang Alberto Santamaria",
				"LaPlante Nicole",
				"Harris Adrian L",
				"Tan Puay-Hoon",
				"Ginty Fiona",
				"Badve Sunil S"
			],
			"DOI": "10.1038/modpathol.2017.143",
			"date": "2019-06-21",
			"PMC": "",
			"citation": "",
			"abstract": "Heterogeneous patterns of mutations and RNA expression have been well documented in invasive cancers. However, technological challenges have limited the ability to study heterogeneity of protein expression. This is particularly true for pre-invasive lesions such as ductal carcinoma in situ of the breast. Cell-level heterogeneity in ductal carcinoma in situ was analyzed in a single 5\u2009\u03bcm tissue section using a multiplexed immunofluorescence analysis of 11 disease-related markers (EGFR, HER2, HER4, S6, pmTOR, CD44v6, SLC7A5 and CD10, CD4, CD8 and CD20, plus pan-cytokeratin, pan-cadherin, DAPI, and Na+K+ATPase for cell segmentation). Expression was quantified at cell level using a single-cell segmentation algorithm. K-means clustering was used to determine co-expression patterns of epithelial cell markers and immune markers. We document for the first time the presence of epithelial cell heterogeneity within ducts, between ducts and between patients with ductal carcinoma in situ. There was moderate heterogeneity in a distribution of eight clusters within each duct (average Shannon index 0.76; range 0-1.61). Furthermore, within each patient, the average Shannon index across all ducts ranged from 0.33 to 1.02 (s.d. 0.09-0.38). As the distribution of clusters within ducts was uneven, the analysis of eight ducts might be sufficient to represent all the clusters ie within- and between-duct heterogeneity. The pattern of epithelial cell clustering was associated with the presence and type of immune infiltrates, indicating a complex interaction between the epithelial tumor and immune system for each patient. This analysis also provides the first evidence that simultaneous analysis of both the epithelial and immune/stromal components might be necessary to understand the complex milieu in ductal carcinoma in situ lesions.",
			"category": 2,
			"name": "Gerdes Michael J,2019"
		},
		{
			"PMID": 29088721,
			"title": "Proposed minimal diagnostic criteria for myelodysplastic syndromes (MDS) and potential pre-MDS conditions.",
			"journal": "Oncotarget",
			"authorList": [
				"Valent Peter",
				"Orazi Attilio",
				"Steensma David P",
				"Ebert Benjamin L",
				"Haase Detlef",
				"Malcovati Luca",
				"van de Loosdrecht Arjan A",
				"Haferlach Torsten",
				"Westers Theresia M",
				"Wells Denise A",
				"Giagounidis Aristoteles",
				"Loken Michael",
				"Orfao Alberto",
				"L\u00fcbbert Michael",
				"Ganser Arnold",
				"Hofmann Wolf-Karsten",
				"Ogata Kiyoyuki",
				"Schanz Julie",
				"B\u00e9n\u00e9 Marie C",
				"Hoermann Gregor",
				"Sperr Wolfgang R",
				"Sotlar Karl",
				"Bettelheim Peter",
				"Stauder Reinhard",
				"Pfeilst\u00f6cker Michael",
				"Horny Hans-Peter",
				"Germing Ulrich",
				"Greenberg Peter",
				"Bennett John M"
			],
			"DOI": "10.18632/oncotarget.19008",
			"date": "2019-11-20",
			"PMC": "",
			"citation": "",
			"abstract": "Myelodysplastic syndromes (MDS) comprise a heterogeneous group of myeloid neoplasms characterized by peripheral cytopenia, dysplasia, and a variable clinical course with about 30% risk to transform to secondary acute myeloid leukemia (AML). In the past 15 years, diagnostic evaluations, prognostication, and treatment of MDS have improved substantially. However, with the discovery of molecular markers and advent of novel targeted therapies, new challenges have emerged in the complex field of MDS. For example, MDS-related molecular lesions may be detectable in healthy individuals and increase in prevalence with age. Other patients exhibit persistent cytopenia of unknown etiology without dysplasia. Although these conditions are potential pre-phases of MDS they may also transform into other bone marrow neoplasms. Recently identified molecular, cytogenetic, and flow-based parameters may add in the delineation and prognostication of these conditions. However, no generally accepted integrated classification and no related criteria are as yet available. In an attempt to address this challenge, an international consensus group discussed these issues in a working conference in July 2016. The outcomes of this conference are summarized in the present article which includes criteria and a proposal for the classification of pre-MDS conditions as well as updated minimal diagnostic criteria of MDS. Moreover, we propose diagnostic standards to delineate between \u00b4normal\u00b4, pre-MDS, and MDS. These standards and criteria should facilitate diagnostic and prognostic evaluations in clinical studies as well as in clinical practice.",
			"category": 2,
			"name": "Valent Peter,2019"
		},
		{
			"PMID": 29069402,
			"title": "SEECancer: a resource for somatic events in evolution of cancer genome.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Zhang Hongyi",
				"Luo Shangyi",
				"Zhang Xinxin",
				"Liao Jianlong",
				"Quan Fei",
				"Zhao Erjie",
				"Zhou Chenfen",
				"Yu Fulong",
				"Yin Wenkang",
				"Zhang Yunpeng",
				"Xiao Yun",
				"Li Xia"
			],
			"DOI": "10.1093/nar/gkx964",
			"date": "2019-07-31",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer cells progressively evolve from a premalignant to a malignant state, which is driven by accumulating somatic alterations that confer normal cells a fitness advantage. Improvements in high-throughput sequencing techniques have led to an increase in construction of tumor phylogenetics and identification of somatic driver events that specifically occurred in different tumor progression stages. Here, we developed the SEECancer database (http://biocc.hrbmu.edu.cn/SEECancer), which aims to present the comprehensive cancer evolutionary stage-specific somatic events (including early-specific, late-specific, relapse-specific, metastasis-specific, drug-resistant and drug-induced genomic events) and their temporal orders. By manually curating over 10 000 published articles, 1231 evolutionary stage-specific genomic events and 5772 temporal orders involving 82 human cancers and 23 tissue origins were collected and deposited in the SEECancer database. Each entry contains the somatic event, evolutionary stage, cancer type, detection approach and relevant evidence. SEECancer provides a user-friendly interface for browsing, searching and downloading evolutionary stage-specific somatic events and temporal relationships in various cancers. With increasing attention on cancer genome evolution, the necessary information in SEECancer will facilitate understanding of cancer etiology and development of evolutionary therapeutics, and help clinicians to discover biomarkers for monitoring tumor progression.",
			"category": 2,
			"name": "Zhang Hongyi,2019"
		},
		{
			"PMID": 28968631,
			"title": "Computational approaches for discovery of mutational signatures in cancer.",
			"journal": "Briefings in bioinformatics",
			"authorList": [
				"Baez-Ortega Adrian",
				"Gori Kevin"
			],
			"DOI": "10.1093/bib/bbx082",
			"date": "2019-07-19",
			"PMC": "",
			"citation": "",
			"abstract": "The accumulation of somatic mutations in a genome is the result of the activity of one or more mutagenic processes, each of which leaves its own imprint. The study of these DNA fingerprints, termed mutational signatures, holds important potential for furthering our understanding of the causes and evolution of cancer, and can provide insights of relevance for cancer prevention and treatment. In this review, we focus our attention on the mathematical models and computational techniques that have driven recent advances in the field.",
			"category": 2,
			"name": "Baez-Ortega Adrian,2019"
		},
		{
			"PMID": 28938635,
			"title": "Distribution of circulating tumor DNA in lung cancer: analysis of the primary lung and bone marrow along with the pulmonary venous and peripheral blood.",
			"journal": "Oncotarget",
			"authorList": [
				"Goto Taichiro",
				"Hirotsu Yosuke",
				"Amemiya Kenji",
				"Nakagomi Takahiro",
				"Shikata Daichi",
				"Yokoyama Yujiro",
				"Okimoto Kenichiro",
				"Oyama Toshio",
				"Mochizuki Hitoshi",
				"Omata Masao"
			],
			"DOI": "10.18632/oncotarget.19538",
			"date": "2017-09-25",
			"PMC": "",
			"citation": "",
			"abstract": "Circulating tumor DNA (ctDNA), extracted from plasma, is a non-invasive surrogate biomarker. However, the distribution of ctDNA in the body still remains to be elucidated. In this study, resected lung tumors, with simultaneous blood and bone marrow samples, were analyzed to elucidate the distribution of ctDNA. Rib bone marrow, pulmonary venous blood (Pul.V) and peripheral blood (Peri.B) were obtained from 30 patients. The liquid samples were divided into cell pellets and supernatant by centrifugation; a total of 212 DNA samples were subjected to massively parallel sequencing. ctDNA was detected in 5 patients. Given that the frequency of mutations in the primary tumor was considered to be 100%, those in the other specimens were as follows; Pul.V plasma 20%, Peri.B plasma 11%, and the other samples 0%. Furthermore, ctDNA reflected the predominant mutations in the primary lesion. Clinically, the presence of ctDNA was associated with significantly poorer survival. These results suggest ctDNA \"spill over\" into an immediate outflow tract (Pul.V), and from there is disseminated to the entire body. Thus, it can be inferred that ctDNA reflects the cancer progression and could function as a prognostic marker.",
			"category": 2,
			"name": "Goto Taichiro,2017"
		},
		{
			"PMID": 28938601,
			"title": "Mutation-profile-based methods for understanding selection forces in cancer somatic mutations: a comparative analysis.",
			"journal": "Oncotarget",
			"authorList": [
				"Zhou Zhan",
				"Zou Yangyun",
				"Liu Gangbiao",
				"Zhou Jingqi",
				"Wu Jingcheng",
				"Zhao Shimin",
				"Su Zhixi",
				"Gu Xun"
			],
			"DOI": "10.18632/oncotarget.19371",
			"date": "2017-09-25",
			"PMC": "",
			"citation": "",
			"abstract": "Human genes exhibit different effects on fitness in cancer and normal cells. Here, we present an evolutionary approach to measure the selection pressure on human genes, using the well-known ratio of the nonsynonymous to synonymous substitution rate in both cancer genomes (",
			"category": 2,
			"name": "Zhou Zhan,2017"
		},
		{
			"PMID": 28927434,
			"title": "SiFit: inferring tumor trees from single-cell sequencing data under finite-sites models.",
			"journal": "Genome biology",
			"authorList": [
				"Zafar Hamim",
				"Tzen Anthony",
				"Navin Nicholas",
				"Chen Ken",
				"Nakhleh Luay"
			],
			"DOI": "10.1186/s13059-017-1311-2",
			"date": "2018-05-23",
			"PMC": "",
			"citation": "",
			"abstract": "Single-cell sequencing enables the inference of tumor phylogenies that provide insights on intra-tumor heterogeneity and evolutionary trajectories. Recently introduced methods perform this task under the infinite-sites assumption, violations of which, due to chromosomal deletions and loss of heterozygosity, necessitate the development of inference methods that utilize finite-sites models. We propose a statistical inference method for tumor phylogenies from noisy single-cell sequencing data under a finite-sites model. The performance of our method on synthetic and experimental data sets from two colorectal cancer patients to trace evolutionary lineages in primary and metastatic tumors suggests that employing a finite-sites model leads to improved inference of tumor phylogenies.",
			"category": 2,
			"name": "Zafar Hamim,2018"
		},
		{
			"PMID": 28877206,
			"title": "Simulation framework for generating intratumor heterogeneity patterns in a cancer cell population.",
			"journal": "PloS one",
			"authorList": [
				"Iwasaki Watal M",
				"Innan Hideki"
			],
			"DOI": "10.1371/journal.pone.0184229",
			"date": "2017-10-06",
			"PMC": "",
			"citation": "",
			"abstract": "As cancer cell populations evolve, they accumulate a number of somatic mutations, resulting in heterogeneous subclones in the final tumor. Understanding the mechanisms that produce intratumor heterogeneity is important for selecting the best treatment. Although some studies have involved intratumor heterogeneity simulations, their model settings differed substantially. Thus, only limited conditions were explored in each. Herein, we developed a general framework for simulating intratumor heterogeneity patterns and a simulator (tumopp). Tumopp offers many setting options so that simulations can be carried out under various settings. Setting options include how the cell division rate is determined, how daughter cells are placed, and how driver mutations are treated. Furthermore, to account for the cell cycle, we introduced a gamma function for the waiting time involved in cell division. Tumopp also allows simulations in a hexagonal lattice, in addition to a regular lattice that has been used in previous simulation studies. A hexagonal lattice produces a more biologically reasonable space than a regular lattice. Using tumopp, we investigated how model settings affect the growth curve and intratumor heterogeneity pattern. It was found that, even under neutrality (with no driver mutations), tumopp produced dramatically variable patterns of intratumor heterogeneity and tumor morphology, from tumors in which cells with different genetic background are well intermixed to irregular shapes of tumors with a cluster of closely related cells. This result suggests a caveat in analyzing intratumor heterogeneity with simulations with limited settings, and tumopp will be useful to explore intratumor heterogeneity patterns in various conditions.",
			"category": 2,
			"name": "Iwasaki Watal M,2017"
		},
		{
			"PMID": 28863981,
			"title": "Single cell analysis of normal and leukemic hematopoiesis.",
			"journal": "Molecular aspects of medicine",
			"authorList": [
				"Povinelli Benjamin J",
				"Rodriguez-Meira Alba",
				"Mead Adam J"
			],
			"DOI": "10.1016/j.mam.2017.08.006",
			"date": "2019-02-04",
			"PMC": "",
			"citation": "",
			"abstract": "The hematopoietic system is well established as a paradigm for the study of cellular hierarchies, their disruption in disease and therapeutic use in regenerative medicine. Traditional approaches to study hematopoiesis involve purification of cell populations based on a small number of surface markers. However, such population-based analysis obscures underlying heterogeneity contained within any phenotypically defined cell population. This heterogeneity can only be resolved through single cell analysis. Recent advances in single cell techniques allow analysis of the genome, transcriptome, epigenome and proteome in single cells at an unprecedented scale. The application of these new single cell methods to investigate the hematopoietic system has led to paradigm shifts in our understanding of cellular heterogeneity in hematopoiesis and how this is disrupted in disease. In this review, we summarize how single cell techniques have been applied to the analysis of hematopoietic stem/progenitor cells in normal and malignant hematopoiesis, with a particular focus on recent advances in single-cell genomics, including how these might be utilized for clinical application.",
			"category": 2,
			"name": "Povinelli Benjamin J,2019"
		},
		{
			"PMID": 28835719,
			"title": "Unravelling biology and shifting paradigms in cancer with single-cell sequencing.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Baslan Timour",
				"Hicks James"
			],
			"DOI": "10.1038/nrc.2017.58",
			"date": "2017-09-12",
			"PMC": "",
			"citation": "",
			"abstract": "The fundamental operative unit of a cancer is the genetically and epigenetically innovative single cell. Whether proliferating or quiescent, in the primary tumour mass or disseminated elsewhere, single cells govern the parameters that dictate all facets of the biology of cancer. Thus, single-cell analyses provide the ultimate level of resolution in our quest for a fundamental understanding of this disease. Historically, this quest has been hampered by technological shortcomings. In this Opinion article, we argue that the rapidly evolving field of single-cell sequencing has unshackled the cancer research community of these shortcomings. From furthering an elemental understanding of intra-tumoural genetic heterogeneity and cancer genome evolution to illuminating the governing principles of disease relapse and metastasis, we posit that single-cell sequencing promises to unravel the biology of all facets of this disease.",
			"category": 2,
			"name": "Baslan Timour,2017"
		},
		{
			"PMID": 28794264,
			"title": "Liquid-phase electron microscopy of molecular drug response in breast cancer cells reveals irresponsive cell subpopulations related to lack of HER2 homodimers.",
			"journal": "Molecular biology of the cell",
			"authorList": [
				"Peckys Diana B",
				"Korf Ulrike",
				"Wiemann Stefan",
				"de Jonge Niels"
			],
			"DOI": "10.1091/mbc.E17-06-0381",
			"date": "2024-02-27",
			"PMC": "",
			"citation": "",
			"abstract": "The development of drug resistance in cancer poses a major clinical problem. An example is human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer often treated with anti-HER2 antibody therapies, such as trastuzumab. Since drug resistance is rooted mainly in tumor cell heterogeneity, we examined the drug effect in different subpopulations of SKBR3 breast cancer cells, and compared the results with a drug resistant cell line, HCC1954. Correlative light microscopy and liquid-phase scanning transmission electron microscopy (STEM) were used to quantitatively analyze HER2 responses upon drug binding, whereby many tens of whole cells were imaged. Trastuzumab was found to selectively cross-link and down regulate HER2 homodimers from the plasma membranes of bulk cancer cells. In contrast, HER2 resided mainly as monomers in rare subpopulations of resting- and cancer stem cells (CSCs), and these monomers were not internalized after drug binding. The HER2 distribution was hardly influenced by trastuzumab for the HCC1954 cells. These findings show that resting cells and CSCs are irresponsive to the drug, and thus point towards a molecular explanation behind the origin of drug resistance. This analytical method is broadly applicable to study membrane protein interactions in the intact plasma membrane, while accounting for cell heterogeneity.",
			"category": 2,
			"name": "Peckys Diana B,2024"
		},
		{
			"PMID": 28775779,
			"title": "GSK-3\u03b2 suppresses HCC cell dissociation ",
			"journal": "Journal of Cancer",
			"authorList": [
				"Zhang Jing-Hua",
				"Jiao Li-Yan",
				"Li Tie-Jun",
				"Zhu York Yuanyuan",
				"Zhou Jian-Wei",
				"Tian Jian"
			],
			"DOI": "10.7150/jca.18744",
			"date": "2023-01-20",
			"PMC": "",
			"citation": "",
			"abstract": "Glycogen synthase kinase-3\u03b2 (GSK-3\u03b2) is required in the expression of epithelial junction proteins. It was found downregulated in hepatocellular carcinoma (HCC) tissues. The purpose of this study was to investigate the role of GSK-3\u03b2 in modulating the metastatic behaviors of human HCC cell lines ",
			"category": 2,
			"name": "Zhang Jing-Hua,2023"
		},
		{
			"PMID": 28710406,
			"title": "Comprehensive circular RNA profiling reveals the regulatory role of the circRNA-100338/miR-141-3p pathway in hepatitis B-related hepatocellular carcinoma.",
			"journal": "Scientific reports",
			"authorList": [
				"Huang Xiu-Yan",
				"Huang Zi-Li",
				"Xu Yong-Hua",
				"Zheng Qi",
				"Chen Zi",
				"Song Wei",
				"Zhou Jian",
				"Tang Zhao-You",
				"Huang Xin-Yu"
			],
			"DOI": "10.1038/s41598-017-05432-8",
			"date": "2019-01-28",
			"PMC": "",
			"citation": "",
			"abstract": "Circular RNAs (circRNAs) represent a class of endogenous noncoding RNAs that have recently been recognized as important regulators of gene expression and pathological networks. However, their transcriptional activities and functional mechanisms in cancer remain largely unknown. Here, we present results from a global circRNA expression and functional analysis of patients with hepatocellular carcinoma (HCC). Using a circRNA microarray, we identified 226 differentially expressed circRNAs, of which 189 were significantly upregulated and 37 were downregulated. High expression of circRNA_100338, one of the upregulated circRNAs in HCC, is closely correlated with a low cumulative survival rate and metastatic progression in HCC patients with hepatitis B. Furthermore, our in silico and experimental analyses identified miR-141-3p as a direct target of circRNA_100338. Thus, circRNA_100338 functions as an endogenous sponge for miR-141-3p in HCC. In addition, we identified the crucial antagonistic roles of circRNA_100338 and miR-141-3p in the regulation of invasive potential in liver cancer cells. Overall, the differential expression of multiple circRNAs in HCC tissues and their clinical significance in hepatitis B-related HCC patients as revealed by our study suggests that circRNA_100338 is a potentially valuable biomarker for HCC diagnosis and target for HCC therapeutics.",
			"category": 2,
			"name": "Huang Xiu-Yan,2019"
		},
		{
			"PMID": 28710260,
			"title": "Big Bang Tumor Growth and Clonal Evolution.",
			"journal": "Cold Spring Harbor perspectives in medicine",
			"authorList": [
				"Sun Ruping",
				"Hu Zheng",
				"Curtis Christina"
			],
			"DOI": "10.1101/cshperspect.a028381",
			"date": "2019-05-31",
			"PMC": "",
			"citation": "",
			"abstract": "The advent and application of next-generation sequencing (NGS) technologies to tumor genomes has reinvigorated efforts to understand clonal evolution. Although tumor progression has traditionally been viewed as a gradual stepwise process, recent studies suggest that evolutionary rates in tumors can be variable with periods of punctuated mutational bursts and relative stasis. For example, Big Bang dynamics have been reported, wherein after transformation, growth occurs in the absence of stringent selection, consistent with effectively neutral evolution. Although first noted in colorectal tumors, effective neutrality may be relatively common. Additionally, punctuated evolution resulting from mutational bursts and cataclysmic genomic alterations have been described. In this review, we contrast these findings with the conventional gradualist view of clonal evolution and describe potential clinical and therapeutic implications of different evolutionary modes and tempos.",
			"category": 2,
			"name": "Sun Ruping,2019"
		},
		{
			"PMID": 28664449,
			"title": "Analysis of BRCA1/2 mutation spectrum and prevalence in unselected Chinese breast cancer patients by next-generation sequencing.",
			"journal": "Journal of cancer research and clinical oncology",
			"authorList": [
				"Li Guoli",
				"Guo Xinwu",
				"Tang Lili",
				"Chen Ming",
				"Luo Xipeng",
				"Peng Limin",
				"Xu Xunxun",
				"Wang Shouman",
				"Xiao Zhi",
				"Yi Wenjun",
				"Dai Lizhong",
				"Wang Jun"
			],
			"DOI": "10.1007/s00432-017-2465-8",
			"date": "2017-11-20",
			"PMC": "",
			"citation": "",
			"abstract": "BRCA1 and BRCA2 (BRCA1/2) are two major high-penetrance breast cancer predisposition genes, mutations in which can lead to high risks and early onset of breast cancer. This study was performed to comprehensively investigate the spectrum and prevalence of BRCA1/2 mutations in unselected Chinese breast cancer patients and evaluate the associations of BRCA1/2 mutations with related clinicopathological characteristics of the tumors.",
			"category": 2,
			"name": "Li Guoli,2017"
		},
		{
			"PMID": 28659971,
			"title": "Computational Methods for Characterizing Cancer Mutational Heterogeneity.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Vandin Fabio"
			],
			"DOI": "10.3389/fgene.2017.00083",
			"date": "2024-03-26",
			"PMC": "",
			"citation": "",
			"abstract": "Advances in DNA sequencing technologies have allowed the characterization of somatic mutations in a large number of cancer genomes at an unprecedented level of detail, revealing the extreme genetic heterogeneity of cancer at two different levels: inter-tumor, with different patients of the same cancer type presenting different collections of somatic mutations, and intra-tumor, with different clones coexisting within the same tumor. Both inter-tumor and intra-tumor heterogeneity have crucial implications for clinical practices. Here, we review computational methods that use somatic alterations measured through next-generation DNA sequencing technologies for characterizing tumor heterogeneity and its association with clinical variables. We first review computational methods for studying inter-tumor heterogeneity, focusing on methods that attempt to summarize cancer heterogeneity by discovering pathways that are commonly mutated across different patients of the same cancer type. We then review computational methods for characterizing intra-tumor heterogeneity using information from bulk sequencing data or from single cell sequencing data. Finally, we present some of the recent computational methodologies that have been proposed to identify and assess the association between inter- or intra-tumor heterogeneity with clinical variables.",
			"category": 2,
			"name": "Vandin Fabio,2024"
		},
		{
			"PMID": 28629429,
			"title": "Linked read sequencing resolves complex genomic rearrangements in gastric cancer metastases.",
			"journal": "Genome medicine",
			"authorList": [
				"Greer Stephanie U",
				"Nadauld Lincoln D",
				"Lau Billy T",
				"Chen Jiamin",
				"Wood-Bouwens Christina",
				"Ford James M",
				"Kuo Calvin J",
				"Ji Hanlee P"
			],
			"DOI": "10.1186/s13073-017-0447-8",
			"date": "2017-09-01",
			"PMC": "",
			"citation": "",
			"abstract": "Genome rearrangements are critical oncogenic driver events in many malignancies. However, the identification and resolution of the structure of cancer genomic rearrangements remain challenging even with whole genome sequencing.",
			"category": 2,
			"name": "Greer Stephanie U,2017"
		},
		{
			"PMID": 28614790,
			"title": "Genomic landscape and evolution of metastatic chromophobe renal cell carcinoma.",
			"journal": "JCI insight",
			"authorList": [
				"Casuscelli Jozefina",
				"Weinhold Nils",
				"Gundem Gunes",
				"Wang Lu",
				"Zabor Emily C",
				"Drill Esther",
				"Wang Patricia I",
				"Nanjangud Gouri J",
				"Redzematovic Almedina",
				"Nargund Amrita M",
				"Manley Brandon J",
				"Arcila Maria E",
				"Donin Nicholas M",
				"Cheville John C",
				"Thompson R Houston",
				"Pantuck Allan J",
				"Russo Paul",
				"Cheng Emily H",
				"Lee William",
				"Tickoo Satish K",
				"Ostrovnaya Irina",
				"Creighton Chad J",
				"Papaemmanuil Elli",
				"Seshan Venkatraman E",
				"Hakimi A Ari",
				"Hsieh James J"
			],
			"DOI": "10.1172/jci.insight.92688",
			"date": "2024-02-10",
			"PMC": "",
			"citation": "",
			"abstract": "Chromophobe renal cell carcinoma (chRCC) typically shows ~7 chromosome losses (1, 2, 6, 10, 13, 17, and 21) and ~31 exonic somatic mutations, yet carries ~5%-10% metastatic incidence. Since extensive chromosomal losses can generate proteotoxic stress and compromise cellular proliferation, it is intriguing how chRCC, a tumor with extensive chromosome losses and a low number of somatic mutations, can develop lethal metastases. Genomic features distinguishing metastatic from nonmetastatic chRCC are unknown. An integrated approach, including whole-genome sequencing (WGS), targeted ultradeep cancer gene sequencing, and chromosome analyses (FACETS, OncoScan, and FISH), was performed on 79 chRCC patients including 38 metastatic (M-chRCC) cases. We demonstrate that TP53 mutations (58%), PTEN mutations (24%), and imbalanced chromosome duplication (ICD, duplication of \u2265 3 chromosomes) (25%) were enriched in M-chRCC. Reconstruction of the subclonal composition of paired primary-metastatic chRCC tumors supports the role of TP53, PTEN, and ICD in metastatic evolution. Finally, the presence of these 3 genomic features in primary tumors of both The Cancer Genome Atlas kidney chromophobe (KICH) (n = 64) and M-chRCC (n = 35) cohorts was associated with worse survival. In summary, our study provides genomic insights into the metastatic progression of chRCC and identifies TP53 mutations, PTEN mutations, and ICD as high-risk features.",
			"category": 2,
			"name": "Casuscelli Jozefina,2024"
		},
		{
			"PMID": 28546418,
			"title": "Single-cell DNA sequencing reveals a late-dissemination model in metastatic colorectal cancer.",
			"journal": "Genome research",
			"authorList": [
				"Leung Marco L",
				"Davis Alexander",
				"Gao Ruli",
				"Casasent Anna",
				"Wang Yong",
				"Sei Emi",
				"Vilar Eduardo",
				"Maru Dipen",
				"Kopetz Scott",
				"Navin Nicholas E"
			],
			"DOI": "10.1101/gr.209973.116",
			"date": "2018-05-30",
			"PMC": "",
			"citation": "",
			"abstract": "Metastasis is a complex biological process that has been difficult to delineate in human colorectal cancer (CRC) patients. A major obstacle in understanding metastatic lineages is the extensive intra-tumor heterogeneity at the primary and metastatic tumor sites. To address this problem, we developed a highly multiplexed single-cell DNA sequencing approach to trace the metastatic lineages of two CRC patients with matched liver metastases. Single-cell copy number or mutational profiling was performed, in addition to bulk exome and targeted deep-sequencing. In the first patient, we observed monoclonal seeding, in which a single clone evolved a large number of mutations prior to migrating to the liver to establish the metastatic tumor. In the second patient, we observed polyclonal seeding, in which two independent clones seeded the metastatic liver tumor after having diverged at different time points from the primary tumor lineage. The single-cell data also revealed an unexpected independent tumor lineage that did not metastasize, and early progenitor clones with the \"first hit\" mutation in ",
			"category": 2,
			"name": "Leung Marco L,2018"
		},
		{
			"PMID": 28503910,
			"title": "Postzygotic single-nucleotide mosaicisms contribute to the etiology of autism spectrum disorder and autistic traits and the origin of mutations.",
			"journal": "Human mutation",
			"authorList": [
				"Dou Yanmei",
				"Yang Xiaoxu",
				"Li Ziyi",
				"Wang Sheng",
				"Zhang Zheng",
				"Ye Adam Yongxin",
				"Yan Linlin",
				"Yang Changhong",
				"Wu Qixi",
				"Li Jiarui",
				"Zhao Boxun",
				"Huang August Yue",
				"Wei Liping"
			],
			"DOI": "10.1002/humu.23255",
			"date": "2018-04-30",
			"PMC": "",
			"citation": "",
			"abstract": "The roles and characteristics of postzygotic single-nucleotide mosaicisms (pSNMs) in autism spectrum disorders (ASDs) remain unclear. In this study of the whole exomes of 2,361 families in the Simons Simplex Collection, we identified 1,248 putative pSNMs in children and 285 de\u00a0novo SNPs in children with detectable parental mosaicism. Ultra-deep amplicon resequencing suggested a validation rate of 51%. Analyses of validated pSNMs revealed that missense/loss-of-function (LoF) pSNMs with a high mutant allele fraction (MAF\u2265 0.2) contributed to ASD diagnoses (P = 0.022, odds ratio [OR] = 5.25), whereas missense/LoF pSNMs with a low MAF (MAF<0.2) contributed to autistic traits in male non-ASD siblings (P = 0.033). LoF pSNMs in parents were less likely to be transmitted to offspring than neutral pSNMs (P = 0.037), and missense/LoF pSNMs in parents with a low MAF were transmitted more to probands than to siblings (P = 0.016, OR = 1.45). We estimated that pSNMs in probands or de\u00a0novo mutations inherited from parental pSNMs increased the risk of ASD by approximately 6%. Adding pSNMs into the transmission and de\u00a0novo association test model revealed 13 new ASD risk genes. These results expand the existing repertoire of genes involved in ASD and shed new light on the contribution of genomic mosaicisms to ASD diagnoses and autistic traits.",
			"category": 2,
			"name": "Dou Yanmei,2018"
		},
		{
			"PMID": 28497793,
			"title": "Image-guided genomics of phenotypically heterogeneous populations reveals vascular signalling during symbiotic collective cancer invasion.",
			"journal": "Nature communications",
			"authorList": [
				"Konen J",
				"Summerbell E",
				"Dwivedi B",
				"Galior K",
				"Hou Y",
				"Rusnak L",
				"Chen A",
				"Saltz J",
				"Zhou W",
				"Boise L H",
				"Vertino P",
				"Cooper L",
				"Salaita K",
				"Kowalski J",
				"Marcus A I"
			],
			"DOI": "10.1038/ncomms15078",
			"date": "2018-11-26",
			"PMC": "",
			"citation": "",
			"abstract": "Phenotypic heterogeneity is widely observed in cancer cell populations. Here, to probe this heterogeneity, we developed an image-guided genomics technique termed spatiotemporal genomic and cellular analysis (SaGA) that allows for precise selection and amplification of living and rare cells. SaGA was used on collectively invading 3D cancer cell packs to create purified leader and follower cell lines. The leader cell cultures are phenotypically stable and highly invasive in contrast to follower cultures, which show phenotypic plasticity over time and minimally invade in a sheet-like pattern. Genomic and molecular interrogation reveals an atypical VEGF-based vasculogenesis signalling that facilitates recruitment of follower cells but not for leader cell motility itself, which instead utilizes focal adhesion kinase-fibronectin signalling. While leader cells provide an escape mechanism for followers, follower cells in turn provide leaders with increased growth and survival. These data support a symbiotic model of collective invasion where phenotypically distinct cell types cooperate to promote their escape.",
			"category": 2,
			"name": "Konen J,2018"
		},
		{
			"PMID": 28490542,
			"title": "Evolution of Premalignant Disease.",
			"journal": "Cold Spring Harbor perspectives in medicine",
			"authorList": [
				"Curtius Kit",
				"Wright Nicholas A",
				"Graham Trevor A"
			],
			"DOI": "10.1101/cshperspect.a026542",
			"date": "2018-08-28",
			"PMC": "",
			"citation": "",
			"abstract": "Where does cancer come from? Although the cell-of-origin is difficult to pinpoint, cancer clones harbor information about their clonal ancestries. In an effort to find cells before they evolve into a life-threatening cancer, physicians currently diagnose premalignant diseases at frequencies that substantially exceed those of clinical cancers. Cancer risk prediction relies on our ability to distinguish between which premalignant features will lead to cancer mortality and which are characteristic of inconsequential disease. Here, we review the evolution of cancer from premalignant disease, and discuss the concept that even phenotypically normal cell progenies inherently gain more malignant potential with age. We describe the hurdles of prognosticating cancer risk in premalignant disease by making reference to the underlying continuous and multivariate natures of genotypes and phenotypes and the particular challenge inherent in defining a cell lineage as \"cancerized.\"",
			"category": 2,
			"name": "Curtius Kit,2018"
		},
		{
			"PMID": 28344344,
			"title": "Detecting truly clonal alterations from multi-region profiling of tumours.",
			"journal": "Scientific reports",
			"authorList": [
				"Werner Benjamin",
				"Traulsen Arne",
				"Sottoriva Andrea",
				"Dingli David"
			],
			"DOI": "10.1038/srep44991",
			"date": "2018-11-14",
			"PMC": "",
			"citation": "",
			"abstract": "Modern cancer therapies aim at targeting tumour-specific alterations, such as mutations or neo-antigens, and maximal treatment efficacy requires that targeted alterations are present in all tumour cells. Currently, treatment decisions are based on one or a few samples per tumour, creating uncertainty on whether alterations found in those samples are actually present in all tumour cells. The probability of classifying clonal versus sub-clonal alterations from multi-region profiling of tumours depends on the earliest phylogenetic branching event during tumour growth. By analysing 181 samples from 10 renal carcinoma and 11 colorectal cancers we demonstrate that the information gain from additional sampling falls onto a simple universal curve. We found that in colorectal cancers, 30% of alterations identified as clonal with one biopsy proved sub-clonal when 8 samples were considered. The probability to overestimate clonal alterations fell below 1% in 7/11 patients with 8 samples per tumour. In renal cell carcinoma, 8 samples reduced the list of clonal alterations by 40% with respect to a single biopsy. The probability to overestimate clonal alterations remained as high as 92% in 7/10 renal cancer patients. Furthermore, treatment was associated with more unbalanced tumour phylogenetic trees, suggesting the need of denser sampling of tumours at relapse.",
			"category": 2,
			"name": "Werner Benjamin,2018"
		},
		{
			"PMID": 28298214,
			"title": "CLImAT-HET: detecting subclonal copy number alterations and loss of heterozygosity in heterogeneous tumor samples from whole-genome sequencing data.",
			"journal": "BMC medical genomics",
			"authorList": [
				"Yu Zhenhua",
				"Li Ao",
				"Wang Minghui"
			],
			"DOI": "10.1186/s12920-017-0255-4",
			"date": "2017-10-27",
			"PMC": "",
			"citation": "",
			"abstract": "Copy number alterations (CNA) and loss of heterozygosity (LOH) represent a large proportion of genetic structural variations of cancer genomes. These aberrations are continuously accumulated during the procedure of clonal evolution and patterned by phylogenetic branching. This invariably results in the emergence of multiple cell populations with distinct complement of mutational landscapes in tumor sample. With the advent of next-generation sequencing technology, inference of subclonal populations has become one of the focused interests in cancer-associated studies, and is usually based on the assessment of combinations of somatic single-nucleotide variations (SNV), CNA and LOH. However, cancer samples often have several inherent issues, such as contamination of normal stroma, tumor aneuploidy and intra-tumor heterogeneity. Addressing these critical issues is imperative for accurate profiling of clonal architecture.",
			"category": 2,
			"name": "Yu Zhenhua,2017"
		},
		{
			"PMID": 28276433,
			"title": "Renal cell carcinoma.",
			"journal": "Nature reviews. Disease primers",
			"authorList": [
				"Hsieh James J",
				"Purdue Mark P",
				"Signoretti Sabina",
				"Swanton Charles",
				"Albiges Laurence",
				"Schmidinger Manuela",
				"Heng Daniel Y",
				"Larkin James",
				"Ficarra Vincenzo"
			],
			"DOI": "10.1038/nrdp.2017.9",
			"date": "2018-07-10",
			"PMC": "",
			"citation": "",
			"abstract": "Renal cell carcinoma (RCC) denotes cancer originated from the renal epithelium and accounts for >90% of cancers in the kidney. The disease encompasses >10 histological and molecular subtypes, of which clear cell RCC (ccRCC) is most common and accounts for most cancer-related deaths. Although somatic VHL mutations have been described for some time, more-recent cancer genomic studies have identified mutations in epigenetic regulatory genes and demonstrated marked intra-tumour heterogeneity, which could have prognostic, predictive and therapeutic relevance. Localized RCC can be successfully managed with surgery, whereas metastatic RCC is refractory to conventional chemotherapy. However, over the past decade, marked advances in the treatment of metastatic RCC have been made, with targeted agents including sorafenib, sunitinib, bevacizumab, pazopanib and axitinib, which inhibit vascular endothelial growth factor (VEGF) and its receptor (VEGFR), and everolimus and temsirolimus, which inhibit mechanistic target of rapamycin complex 1 (mTORC1), being approved. Since 2015, agents with additional targets aside from VEGFR have been approved, such as cabozantinib and lenvatinib; immunotherapies, such as nivolumab, have also been added to the armamentarium for metastatic RCC. Here, we provide an overview of the biology of RCC, with a focus on ccRCC, as well as updates to complement the current clinical guidelines and an outline of potential future directions for RCC research and therapy.",
			"category": 2,
			"name": "Hsieh James J,2018"
		},
		{
			"PMID": 28274726,
			"title": "A population genetics perspective on the determinants of intra-tumor heterogeneity.",
			"journal": "Biochimica et biophysica acta. Reviews on cancer",
			"authorList": [
				"Hu Zheng",
				"Sun Ruping",
				"Curtis Christina"
			],
			"DOI": "10.1016/j.bbcan.2017.03.001",
			"date": "2017-08-24",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer results from the acquisition of somatic alterations in a microevolutionary process that typically occurs over many years, much of which is occult. Understanding the evolutionary dynamics that are operative at different stages of progression in individual tumors might inform the earlier detection, diagnosis, and treatment of cancer. Although these processes cannot be directly observed, the resultant spatiotemporal patterns of genetic variation amongst tumor cells encode their evolutionary histories. Such intra-tumor heterogeneity is pervasive not only at the genomic level, but also at the transcriptomic, phenotypic, and cellular levels. Given the implications for precision medicine, the accurate quantification of heterogeneity within and between tumors has become a major focus of current research. In this review, we provide a population genetics perspective on the determinants of intra-tumor heterogeneity and approaches to quantify genetic diversity. We summarize evidence for different modes of evolution based on recent cancer genome sequencing studies and discuss emerging evolutionary strategies to therapeutically exploit tumor heterogeneity. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby.",
			"category": 2,
			"name": "Hu Zheng,2017"
		},
		{
			"PMID": 28213433,
			"title": "Chromosomal Instability as a Driver of Tumor Heterogeneity and Evolution.",
			"journal": "Cold Spring Harbor perspectives in medicine",
			"authorList": [
				"Bakhoum Samuel F",
				"Landau Dan Avi"
			],
			"DOI": "10.1101/cshperspect.a029611",
			"date": "2018-03-16",
			"PMC": "",
			"citation": "",
			"abstract": "Large-scale, massively parallel sequencing of human cancer samples has revealed tremendous genetic heterogeneity within individual tumors. Indeed, tumors are composed of an admixture of diverse subpopulations-subclones-that vary in space and time. Here, we discuss a principal driver of clonal diversification in cancer known as chromosomal instability (CIN), which complements other modes of genetic diversification creating the multilayered genomic instability often seen in human cancer. Cancer cells have evolved to fine-tune chromosome missegregation rates to balance the acquisition of heterogeneity while preserving favorable genotypes, a dependence that can be exploited for a therapeutic benefit. We discuss how whole-genome doubling events accelerate clonal evolution in a subset of tumors by providing a viable path toward favorable near-triploid karyotypes and present evidence for CIN-induced clonal speciation that can overcome the dependence on truncal initiating events.",
			"category": 2,
			"name": "Bakhoum Samuel F,2018"
		},
		{
			"PMID": 28193548,
			"title": "Advances in understanding tumour evolution through single-cell\u00a0sequencing.",
			"journal": "Biochimica et biophysica acta. Reviews on cancer",
			"authorList": [
				"Kuipers Jack",
				"Jahn Katharina",
				"Beerenwinkel Niko"
			],
			"DOI": "10.1016/j.bbcan.2017.02.001",
			"date": "2017-08-24",
			"PMC": "",
			"citation": "",
			"abstract": "The mutational heterogeneity observed within tumours poses additional challenges to the development of effective cancer treatments. A thorough understanding of a tumour's subclonal composition and its mutational history is essential to open up the design of treatments tailored to individual patients. Comparative studies on a large number of tumours permit the identification of mutational patterns which may refine forecasts of cancer progression, response to treatment and metastatic potential. The composition of tumours is shaped by evolutionary processes. Recent advances in next-generation sequencing offer the possibility to analyse the evolutionary history and accompanying heterogeneity of tumours at an unprecedented resolution, by sequencing single cells. New computational challenges arise when moving from bulk to single-cell sequencing data, leading to the development of novel modelling frameworks. In this review, we present the state of the art methods for understanding the phylogeny encoded in bulk or single-cell sequencing data, and highlight future directions for developing more comprehensive and informative pictures of tumour evolution. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby.",
			"category": 2,
			"name": "Kuipers Jack,2017"
		},
		{
			"PMID": 28187431,
			"title": "Recombinant adeno-associated virus expressing a p53-derived apoptotic peptide (37AA) inhibits HCC cells growth in vitro and in vivo.",
			"journal": "Oncotarget",
			"authorList": [
				"Zhang Hongyong",
				"Wang Yufeng",
				"Bai Yanxia",
				"Shao Yuan",
				"Bai Jigang",
				"Ma Zhenhua",
				"Liu Qingguang",
				"Wu Shengli"
			],
			"DOI": "10.18632/oncotarget.15160",
			"date": "2017-08-24",
			"PMC": "",
			"citation": "",
			"abstract": "Recent studies have confirmed that a p53-derived apoptotic peptide (37AA) could act as a tumor suppressor inducing apoptosis in multiple tumor cells through derepressing p73. However, the tumor suppressive effects of recombinant adeno-associated virus (rAAV) expressing 37AA on HCC cells are still unknown. In this study, we successfully constructed a recombinant rAAV expressing 37AA. In vitro and in vivo assays showed that transfection of NT4-37AA/rAAV in HCC cells strongly suppressed cell proliferation, induced apoptosis, and up-regulated the cellular expression of p73. NT4-37AA/rAAV transfection markedly slowed Huh-7 xenografted tumor growth in murine. Pretreatment of HCC cells with p73 siRNA abrogated these effects of NT4-37AA/rAAV. Furthermore, we found that expression of p73 was upregulated and the formation of P73/iASSP complex was prevented when 37AA was introduced into HCC cells. Taken together, these results indicate that introduction of 37AA into HCC cells with a rAAV vector may lead to the development of broadly applicable agents for the treatment of HCC, and the mechanism may, at least in part, be associated with the upregulation of p73 expression and reduced level of P73/iASSP complex.",
			"category": 2,
			"name": "Zhang Hongyong,2017"
		},
		{
			"PMID": 28187169,
			"title": "Prognostic value of circulating tumor DNA in patients with colon cancer: Systematic review.",
			"journal": "PloS one",
			"authorList": [
				"Fan Gaowei",
				"Zhang Kuo",
				"Yang Xin",
				"Ding Jiansheng",
				"Wang Zujian",
				"Li Jinming"
			],
			"DOI": "10.1371/journal.pone.0171991",
			"date": "2017-08-09",
			"PMC": "",
			"citation": "",
			"abstract": "The application of circulating tumor DNA(ctDNA) represents a non-invasive method for tumor detection. Its prognostic significance in patients with colorectal cancer is controversial. We performed a systematic review of data from published studies to assess the prognostic values of ctDNA in patients with colorectal cancer. We searched Medline, Embase, Web of Science, the Cochrane Library, and Scopus databases to identify eligible studies reporting disease-free survival (DFS) and overall survival (OS) stratified by ctDNA prior to December 6, 2016. We evaluated the quality and design of these studies. A total of 22 studies were eligible for systematic review. Among them, 11 studies investigated the prognostic value of ctDNA on disease-free survival (DFS). Seven of 11 studies showed that ctDNA was an independent variable to estimate the probability of DFS by multivariate analyses. Thirteen studies assessed the relationship between ctDNA and overall survival (OS). Eight of 13 studies showed that ctDNA was an independent predictor of worse OS through the use of multivariate analyses. This analysis provides evidence that ctDNA may be a prognostic biomarker, negatively correlated with the survival of patients with colorectal cancer.",
			"category": 2,
			"name": "Fan Gaowei,2017"
		},
		{
			"PMID": 28178237,
			"title": "Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity.",
			"journal": "Nature",
			"authorList": [
				"Turner Kristen M",
				"Deshpande Viraj",
				"Beyter Doruk",
				"Koga Tomoyuki",
				"Rusert Jessica",
				"Lee Catherine",
				"Li Bin",
				"Arden Karen",
				"Ren Bing",
				"Nathanson David A",
				"Kornblum Harley I",
				"Taylor Michael D",
				"Kaushal Sharmeela",
				"Cavenee Webster K",
				"Wechsler-Reya Robert",
				"Furnari Frank B",
				"Vandenberg Scott R",
				"Rao P Nagesh",
				"Wahl Geoffrey M",
				"Bafna Vineet",
				"Mischel Paul S"
			],
			"DOI": "10.1038/nature21356",
			"date": "2017-07-18",
			"PMC": "",
			"citation": "",
			"abstract": "Human cells have twenty-three pairs of chromosomes. In cancer, however, genes can be amplified in chromosomes or in circular extrachromosomal DNA (ecDNA), although the frequency and functional importance of ecDNA are not understood. We performed whole-genome sequencing, structural modelling and cytogenetic analyses of 17 different cancer types, including analysis of the structure and function of chromosomes during metaphase of 2,572 dividing cells, and developed a software package called ECdetect to conduct unbiased, integrated ecDNA detection and analysis. Here we show that ecDNA was found in nearly half of human cancers; its frequency varied by tumour type, but it was almost never found in normal cells. Driver oncogenes were amplified most commonly in ecDNA, thereby increasing transcript level. Mathematical modelling predicted that ecDNA amplification would increase oncogene copy number and intratumoural heterogeneity more effectively than chromosomal amplification. We validated these predictions by quantitative analyses of cancer samples. The results presented here suggest that ecDNA contributes to accelerated evolution in cancer.",
			"category": 2,
			"name": "Turner Kristen M,2017"
		},
		{
			"PMID": 28154415,
			"title": "Genomic variants in mouse model induced by azoxymethane and dextran sodium sulfate improperly mimic human colorectal cancer.",
			"journal": "Scientific reports",
			"authorList": [
				"Pan Qingfei",
				"Lou Xiaomin",
				"Zhang Ju",
				"Zhu Yinghui",
				"Li Fuqiang",
				"Shan Qiang",
				"Chen Xianwei",
				"Xie Yingying",
				"Su Siyuan",
				"Wei Hanfu",
				"Lin Liang",
				"Wu Lin",
				"Liu Siqi"
			],
			"DOI": "10.1038/s41598-017-00057-3",
			"date": "2019-02-05",
			"PMC": "",
			"citation": "",
			"abstract": "Mouse model induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) is generally accepted as an ideal object to study on the carcinogenesis mechanisms of human colorectal cancer (CRC). The genomic responses to the AOM/DSS treatment in mouse that possibly lead to elucidation of CRC pathological mechanism are still poorly understood. For the first time, we investigated the cancer genome landscape of AOM/DSS mouse model by exome sequencing, to testify its molecular faithfulness to human CRC. Of 14 neoplastic samples, 7575 somatic variants were identified, which resulted in 2507 mutant genes and exhibited a large diversity in both colorectal aberrant crypt foci (ACF) and tumors even those tissues that were gained from the similar morphology or same treatment period. Cross-species comparison of the somatic variants demonstrated the totally different patterns of variable sites, mutant genes and perturbed pathways between mouse and human CRC. We therefore come to a conclusion that the tumorigenesis at genomic level in AOM/DSS model may not be properly comparable with that in human CRC, and the molecular mechanism elicited from this animal model should be carefully evaluated.",
			"category": 2,
			"name": "Pan Qingfei,2019"
		},
		{
			"PMID": 28108658,
			"title": "Computational approach for deriving cancer progression roadmaps from static sample data.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Sun Yijun",
				"Yao Jin",
				"Yang Le",
				"Chen Runpu",
				"Nowak Norma J",
				"Goodison Steve"
			],
			"DOI": "10.1093/nar/gkx003",
			"date": "2017-08-29",
			"PMC": "",
			"citation": "",
			"abstract": "As with any biological process, cancer development is inherently dynamic. While major efforts continue to catalog the genomic events associated with human cancer, it remains difficult to interpret and extrapolate the accumulating data to provide insights into the dynamic aspects of the disease. Here, we present a computational strategy that enables the construction of a cancer progression model using static tumor sample data. The developed approach overcame many technical limitations of existing methods. Application of the approach to breast cancer data revealed a linear, branching model with two distinct trajectories for malignant progression. The validity of the constructed model was demonstrated in 27 independent breast cancer data sets, and through visualization of the data in the context of disease progression we were able to identify a number of potentially key molecular events in the advance of breast cancer to malignancy.",
			"category": 2,
			"name": "Sun Yijun,2017"
		},
		{
			"PMID": 28096526,
			"title": "Telomeres in cancer: tumour suppression and genome instability.",
			"journal": "Nature reviews. Molecular cell biology",
			"authorList": [
				"Maciejowski John",
				"de Lange Titia"
			],
			"DOI": "10.1038/nrm.2016.171",
			"date": "2017-05-26",
			"PMC": "",
			"citation": "",
			"abstract": "The shortening of human telomeres has two opposing effects during cancer development. On the one hand, telomere shortening can exert a tumour-suppressive effect through the proliferation arrest induced by activating the kinases ATM and ATR at unprotected chromosome ends. On the other hand, loss of telomere protection can lead to telomere crisis, which is a state of extensive genome instability that can promote cancer progression. Recent data, reviewed here, provide new evidence for the telomere tumour suppressor pathway and has revealed that telomere crisis can induce numerous cancer-relevant changes, including chromothripsis, kataegis and tetraploidization.",
			"category": 2,
			"name": "Maciejowski John,2017"
		},
		{
			"PMID": 28089370,
			"title": "Single-Cell Multiomics: Multiple Measurements from Single Cells.",
			"journal": "Trends in genetics : TIG",
			"authorList": [
				"Macaulay Iain C",
				"Ponting Chris P",
				"Voet Thierry"
			],
			"DOI": "10.1016/j.tig.2016.12.003",
			"date": "2017-11-20",
			"PMC": "",
			"citation": "",
			"abstract": "Single-cell sequencing provides information that is not confounded by genotypic or phenotypic heterogeneity of bulk samples. Sequencing of one molecular type (RNA, methylated DNA or open chromatin) in a single cell, furthermore, provides insights into the cell's phenotype and links to its genotype. Nevertheless, only by taking measurements of these phenotypes and genotypes from the same single cells can such inferences be made unambiguously. In this review, we survey the first experimental approaches that assay, in parallel, multiple molecular types from the same single cell, before considering the challenges and opportunities afforded by these and future technologies.",
			"category": 2,
			"name": "Macaulay Iain C,2017"
		},
		{
			"PMID": 28069394,
			"title": "Catch my drift? Making sense of genomic intra-tumour heterogeneity.",
			"journal": "Biochimica et biophysica acta. Reviews on cancer",
			"authorList": [
				"Sottoriva Andrea",
				"Barnes Chris P",
				"Graham Trevor A"
			],
			"DOI": "10.1016/j.bbcan.2016.12.003",
			"date": "2017-08-24",
			"PMC": "",
			"citation": "",
			"abstract": "The cancer genome is shaped by three components of the evolutionary process: mutation, selection and drift. While many studies have focused on the first two components, the role of drift in cancer evolution has received little attention. Drift occurs when all individuals in the population have the same likelihood of producing surviving offspring, and so by definition a drifting population is one that is evolving neutrally. Here we focus on how neutral evolution is manifested in the cancer genome. We discuss how neutral passenger mutations provide a magnifying glass that reveals the evolutionary dynamics underpinning cancer development, and outline how statistical inference can be used to quantify these dynamics from sequencing data. We argue that only after we understand the impact of neutral drift on the genome can we begin to make full sense of clonal selection. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer? Edited by Dr. Robert A. Gatenby.",
			"category": 2,
			"name": "Sottoriva Andrea,2017"
		},
		{
			"PMID": 27933214,
			"title": "Integrating next-generation sequencing into clinical oncology: strategies, promises and pitfalls.",
			"journal": "ESMO open",
			"authorList": [
				"Horak Peter",
				"Fr\u00f6hling Stefan",
				"Glimm Hanno"
			],
			"DOI": "",
			"date": "2022-03-31",
			"PMC": "",
			"citation": "",
			"abstract": "We live in an era of genomic medicine. The past five\u2005years brought about many significant achievements in the field of cancer genetics, driven by rapidly evolving technologies and plummeting costs of next-generation sequencing (NGS). The official completion of the Cancer Genome Project in 2014 led many to envision the clinical implementation of cancer genomic data as the next logical step in cancer therapy. Stemming from this vision, the term 'precision oncology' was coined to illustrate the novelty of this individualised approach. The basic assumption of precision oncology is that molecular markers detected by NGS will predict response to targeted therapies independently from tumour histology. However, along with a ubiquitous availability of NGS, the complexity and heterogeneity at the individual patient level had to be acknowledged. Not only does the latter present challenges to clinical decision-making based on sequencing data, it is also an obstacle to the rational design of clinical trials. Novel tissue-agnostic trial designs were quickly developed to overcome these challenges. Results from some of these trials have recently demonstrated the feasibility and efficacy of this approach. On the other hand, there is an increasing amount of whole-exome and whole-genome NGS data which allows us to assess ever smaller differences between individual patients with cancer. In this review, we highlight different tumour sequencing strategies currently used for precision oncology, describe their individual strengths and weaknesses, and emphasise their feasibility in different clinical settings. Further, we evaluate the possibility of NGS implementation in current and future clinical trials, and point to the significance of NGS for translational research.",
			"category": 2,
			"name": "Horak Peter,2022"
		},
		{
			"PMID": 27931250,
			"title": "Tracing the origin of disseminated tumor cells in breast cancer using single-cell sequencing.",
			"journal": "Genome biology",
			"authorList": [
				"Demeulemeester Jonas",
				"Kumar Parveen",
				"M\u00f8ller Elen K",
				"Nord Silje",
				"Wedge David C",
				"Peterson April",
				"Mathiesen Randi R",
				"Fjelldal Renathe",
				"Zamani Esteki Masoud",
				"Theunis Koen",
				"Fernandez Gallardo Elia",
				"Grundstad A Jason",
				"Borgen Elin",
				"Baumbusch Lars O",
				"B\u00f8rresen-Dale Anne-Lise",
				"White Kevin P",
				"Kristensen Vessela N",
				"Van Loo Peter",
				"Voet Thierry",
				"Naume Bj\u00f8rn"
			],
			"DOI": "",
			"date": "2017-07-10",
			"PMC": "",
			"citation": "",
			"abstract": "Single-cell micro-metastases of solid tumors often occur in the bone marrow. These disseminated tumor cells (DTCs) may resist therapy and lay dormant or progress to cause overt bone and visceral metastases. The molecular nature of DTCs remains elusive, as well as when and from where in the tumor they originate. Here, we apply single-cell sequencing to identify and trace the origin of DTCs in breast cancer.",
			"category": 2,
			"name": "Demeulemeester Jonas,2017"
		},
		{
			"PMID": 27899621,
			"title": "Cooperative genomic alteration network reveals molecular classification across 12 major cancer types.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Zhang Hongyi",
				"Deng Yulan",
				"Zhang Yong",
				"Ping Yanyan",
				"Zhao Hongying",
				"Pang Lin",
				"Zhang Xinxin",
				"Wang Li",
				"Xu Chaohan",
				"Xiao Yun",
				"Li Xia"
			],
			"DOI": "10.1093/nar/gkw1087",
			"date": "2017-06-15",
			"PMC": "",
			"citation": "",
			"abstract": "The accumulation of somatic genomic alterations that enables cells to gradually acquire growth advantage contributes to tumor development. This has the important implication of the widespread existence of cooperative genomic alterations in the accumulation process. Here, we proposed a computational method HCOC that simultaneously consider genetic context and downstream functional effects on cancer hallmarks to uncover somatic cooperative events in human cancers. Applying our method to 12 TCGA cancer types, we totally identified 1199 cooperative events with high heterogeneity across human cancers, and then constructed a pan-cancer cooperative alteration network. These cooperative events are associated with genomic alterations of some high-confident cancer drivers, and can trigger the dysfunction of hallmark associated pathways in a co-defect way rather than single alterations. We found that these cooperative events can be used to produce a prognostic classification that can provide complementary information with tissue-of-origin. In a further case study of glioblastoma, using 23 cooperative events identified, we stratified patients into molecularly relevant subtypes with a prognostic significance independent of the Glioma-CpG Island Methylator Phenotype (GCIMP). In summary, our method can be effectively used to discover cancer-driving cooperative events that can be valuable clinical markers for patient stratification.",
			"category": 2,
			"name": "Zhang Hongyi,2017"
		},
		{
			"PMID": 27766604,
			"title": "A braided cancer river connects tumor heterogeneity and precision medicine.",
			"journal": "Clinical and translational medicine",
			"authorList": [
				"Hsieh James J",
				"Cheng Emily H"
			],
			"DOI": "",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "With the ever-increasing complexity of tumor heterogeneity (TH) discovered through cancer genome sequencing, it is apparent that TH has become the biggest hurdle for precision cancer therapeutics. Through studying the genomics of exceptional responders to targeted therapeutic agents in kidney cancer, we demonstrated parallel convergent gene/pathway/capability/function evolution of kidney cancer in the context of TH, which prompted us to propose a new cancer evolution model \"the braided cancer river model\". Based on this model, we might be able to outsmart a given cancer type within an individual patient through simultaneously inhibiting preferred parallel pathways or sequential nodes. Thus, the goals of this perspective are to define tumor heterogeneity, discuss tumor evolution, introduce braided cancer river model, and improve precision medicine.",
			"category": 2,
			"name": "Hsieh James J,2020"
		},
		{
			"PMID": 27688796,
			"title": "Analysis of gene copy number changes in tumor phylogenetics.",
			"journal": "Algorithms for molecular biology : AMB",
			"authorList": [
				"Zhou Jun",
				"Lin Yu",
				"Rajan Vaibhav",
				"Hoskins William",
				"Feng Bing",
				"Tang Jijun"
			],
			"DOI": "10.1186/s13015-016-0088-2",
			"date": "2016-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "Evolution of cancer cells is characterized by large scale and rapid changes in the chromosomal \u00a0landscape. The fluorescence in situ hybridization (FISH) technique provides a way to measure the copy numbers of preselected genes in a group of cells and has been found to be a reliable source of data to model the evolution of tumor cells. Chowdhury et al. (Bioinformatics 29(13):189-98, 23; PLoS Comput Biol 10(7):1003740, 24) recently develop a computational model for tumor progression driven by gains and losses in cell count patterns obtained by FISH probes. Their model aims to find the rectilinear Steiner minimum tree (RSMT) (Chowdhury et al. in Bioinformatics 29(13):189-98, 23) and the duplication Steiner minimum tree (DSMT) (Chowdhury et al. in PLoS Comput Biol 10(7):1003740, 24) that describe the progression of FISH cell count patterns over its branches in a parsimonious manner. Both the RSMT and DSMT problems are NP-hard and heuristics are required to solve the problems efficiently.",
			"category": 2,
			"name": "Zhou Jun,2016"
		},
		{
			"PMID": 27615548,
			"title": "Overcome tumor heterogeneity-imposed therapeutic barriers through convergent genomic biomarker discovery: A braided cancer river model of kidney cancer.",
			"journal": "Seminars in cell & developmental biology",
			"authorList": [
				"Hsieh James J",
				"Manley Brandon J",
				"Khan Nabeela",
				"Gao JianJiong",
				"Carlo Maria I",
				"Cheng Emily H"
			],
			"DOI": "10.1016/j.semcdb.2016.09.002",
			"date": "2017-12-25",
			"PMC": "",
			"citation": "",
			"abstract": "Tumor heterogeneity, encompassing genetic, epigenetic, and microenvironmental variables, is extremely complex and presents challenges to cancer diagnosis and therapy. Genomic efforts on genetic intratumor heterogeneity (G-ITH) confirm branched evolution, support the trunk-branch cancer model, and present a seemingly insurmountable obstacle to conquering cancers. G-ITH is conspicuous in clear cell renal cell carcinoma (ccRCC), where its presence complicates identification and validation of biomarkers and thwarts efforts in advancing precision cancer therapeutics. However, long-term clinical benefits on targeted therapy are not uncommon in metastatic ccRCC patients, implicating that there are underlying constraints during ccRCC evolution, which in turn force a nonrandom sequence of parallel gene/pathway/function/phenotype convergence within individual tumors. Accordingly, we proposed a \"braided cancer river model\" depicting ccRCC evolution, which deduces cancer development based on multiregion tumor genomics of exceptional mTOR inhibitor (mTORi) responders. Furthermore, we employ an outlier case to explore the river model and highlight the importance of \"Five NGS Matters: Number, Frequency, Position, Site and Time\" in assessing cancer genomics for precision medicine. This mutable cancer river model may capture clinically significant phenotype-convergent events, predict vulnerability/resistance mechanisms, and guide effective therapeutic strategies. Our model originates from studying exceptional responders in ccRCC, which warrants further refinement and future validation concerning its applicability to other cancer types. The goal of this review is employing kidney cancer as an example to illustrate critical issues concerning tumor heterogeneity.",
			"category": 2,
			"name": "Hsieh James J,2017"
		},
		{
			"PMID": 27538953,
			"title": "Shifting patterns of genomic variation in the somatic evolution of papillary thyroid carcinoma.",
			"journal": "BMC cancer",
			"authorList": [
				"Rubinstein Jill C",
				"Brown Taylor C",
				"Christison-Lagay Emily R",
				"Zhang Yawei",
				"Kunstman John W",
				"Juhlin C Christofer",
				"Nelson-Williams Carol",
				"Goh Gerald",
				"Quinn Courtney E",
				"Callender Glenda G",
				"Udelsman Robert",
				"Lifton Richard P",
				"Korah Reju",
				"Carling Tobias"
			],
			"DOI": "10.1186/s12885-016-2665-7",
			"date": "2017-09-26",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is increasingly understood to arise in the context of dynamically evolving genomes with continuously generated variants subject to selective pressures. Diverse mutations have been identified in papillary thyroid carcinoma (PTC), but unifying theories underlying genomic change are lacking. Applying a framework of somatic evolution, we sought to broaden understanding of the PTC genome through identification of global trends that help explain risk of tumorigenesis.",
			"category": 2,
			"name": "Rubinstein Jill C,2017"
		},
		{
			"PMID": 27516729,
			"title": "Circulating Tumor Cells Versus Circulating Tumor DNA in Colorectal Cancer: Pros and Cons.",
			"journal": "Current colorectal cancer reports",
			"authorList": [
				"Tan Carlyn Rose C",
				"Zhou Lanlan",
				"El-Deiry Wafik S"
			],
			"DOI": "",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are emerging noninvasive multifunctional biomarkers in liquid biopsy allowing for early diagnosis, accurate prognosis, therapeutic target selection, spatiotemporal monitoring of metastasis, as well as monitoring response and resistance to treatment. CTCs and ctDNA are released from different tumor types at different stages and contribute complementary information for clinical decision. Although big strides have been taken in technology development for detection, isolation and characterization of CTCs and sensitive and specific detection of ctDNA, CTC-, and ctDNA-based liquid biopsies may not be widely adopted for routine cancer patient care until the suitability, accuracy, and reliability of these tests are validated and more standardized protocols are corroborated in large, independent, prospectively designed trials. This review covers CTC- and ctDNA-related technologies and their application in colorectal cancer. The promise of CTC-and ctDNA-based liquid biopsies is envisioned.",
			"category": 2,
			"name": "Tan Carlyn Rose C,2020"
		},
		{
			"PMID": 27513638,
			"title": "Prevalent Accumulation of Non-Optimal Codons through Somatic Mutations in Human Cancers.",
			"journal": "PloS one",
			"authorList": [
				"Wu Xudong",
				"Li Guohui"
			],
			"DOI": "10.1371/journal.pone.0160463",
			"date": "2017-07-27",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is characterized by uncontrolled cell growth, and the cause of different cancers is generally attributed to checkpoint dysregulation of cell proliferation and apoptosis. Recent studies have shown that non-optimal codons were preferentially adopted by genes to generate cell cycle-dependent oscillations in protein levels. This raises the intriguing question of how dynamic changes of codon usage modulate the cancer genome to cope with a non-controlled proliferative cell cycle. In this study, we comprehensively analyzed the somatic mutations of codons in human cancers, and found that non-optimal codons tended to be accumulated through both synonymous and non-synonymous mutations compared with other types of genomic substitution. We further demonstrated that non-optimal codons were prevalently accumulated across different types of cancers, amino acids, and chromosomes, and genes with accumulation of non-optimal codons tended to be involved in protein interaction/signaling networks and encoded important enzymes in metabolic networks that played roles in cancer-related pathways. This study provides insights into the dynamics of codons in the cancer genome and demonstrates that accumulation of non-optimal codons may be an adaptive strategy for cancerous cells to win the competition with normal cells. This deeper interpretation of the patterns and the functional characterization of somatic mutations of codons will help to broaden the current understanding of the molecular basis of cancers.",
			"category": 2,
			"name": "Wu Xudong,2017"
		},
		{
			"PMID": 27377132,
			"title": "Combine and conquer: challenges for targeted therapy combinations in early phase trials.",
			"journal": "Nature reviews. Clinical oncology",
			"authorList": [
				"Lopez Juanita S",
				"Banerji Udai"
			],
			"DOI": "10.1038/nrclinonc.2016.96",
			"date": "2017-05-22",
			"PMC": "",
			"citation": "",
			"abstract": "Our increasing understanding of cancer biology has led to the development of molecularly targeted anticancer drugs. The full potential of these agents has not, however, been realised, owing to the presence of de novo (intrinsic) resistance, often resulting from compensatory signalling pathways, or the development of acquired resistance in cancer cells via clonal evolution under the selective pressures of treatment. Combinations of targeted treatments can circumvent some mechanisms of resistance to yield a clinical benefit. We explore the challenges in identifying the best drug combinations and the best combination strategies, as well as the complexities of delivering these treatments to patients. Recognizing treatment-induced toxicity and the inability to use continuous pharmacodynamically effective doses of many targeted treatments necessitates creative intermittent scheduling. Serial tumour profiling and the use of parallel co-clinical trials can contribute to understanding mechanisms of resistance, and will guide the development of adaptive clinical trial designs that can accommodate hypothesis testing, in order to realize the full potential of combination therapies.",
			"category": 2,
			"name": "Lopez Juanita S,2017"
		},
		{
			"PMID": 27313981,
			"title": "Single-Cell Sequencing Technology in Oncology: Applications for Clinical Therapies and Research.",
			"journal": "Analytical cellular pathology (Amsterdam)",
			"authorList": [
				"Ye Baixin",
				"Gao Qingping",
				"Zeng Zhi",
				"Stary Creed M",
				"Jian Zhihong",
				"Xiong Xiaoxing",
				"Gu Lijuan"
			],
			"DOI": "10.1155/2016/9369240",
			"date": "2016-12-13",
			"PMC": "",
			"citation": "",
			"abstract": "Cellular heterogeneity is a fundamental characteristic of many cancers. A lack of cellular homogeneity contributes to difficulty in designing targeted oncological therapies. Therefore, the development of novel methods to determine and characterize oncologic cellular heterogeneity is a critical next step in the development of novel cancer therapies. Single-cell sequencing (SCS) technology has been recently employed for analyzing the genetic polymorphisms of individual cells at the genome-wide level. SCS requires (1) precise isolation of the single cell of interest; (2) isolation and amplification of genetic material; and (3) descriptive analysis of genomic, transcriptomic, and epigenomic data. In addition to targeted analysis of single cells isolated from tumor biopsies, SCS technology may be applied to circulating tumor cells, which may aid in predicting tumor progression and metastasis. In this paper, we provide an overview of SCS technology and review the current literature on the potential application of SCS to clinical oncology and research.",
			"category": 2,
			"name": "Ye Baixin,2016"
		},
		{
			"PMID": 27311963,
			"title": "OncodriveFML: a general framework to identify coding and non-coding regions with cancer driver mutations.",
			"journal": "Genome biology",
			"authorList": [
				"Mularoni Loris",
				"Sabarinathan Radhakrishnan",
				"Deu-Pons Jordi",
				"Gonzalez-Perez Abel",
				"L\u00f3pez-Bigas N\u00faria"
			],
			"DOI": "10.1186/s13059-016-0994-0",
			"date": "2017-06-21",
			"PMC": "",
			"citation": "",
			"abstract": "Distinguishing the driver mutations from somatic mutations in a tumor genome is one of the major challenges of cancer research. This challenge is more acute and far from solved for non-coding mutations. Here we present OncodriveFML, a method designed to analyze the pattern of somatic mutations across tumors in both coding and non-coding genomic regions to identify signals of positive selection, and therefore, their involvement in tumorigenesis. We describe the method and illustrate its usefulness to identify protein-coding genes, promoters, untranslated regions, intronic splice regions, and lncRNAs-containing driver mutations in several malignancies.",
			"category": 2,
			"name": "Mularoni Loris,2017"
		},
		{
			"PMID": 27270107,
			"title": "Clonal evolution of glioblastoma under therapy.",
			"journal": "Nature genetics",
			"authorList": [
				"Wang Jiguang",
				"Cazzato Emanuela",
				"Ladewig Erik",
				"Frattini Veronique",
				"Rosenbloom Daniel I S",
				"Zairis Sakellarios",
				"Abate Francesco",
				"Liu Zhaoqi",
				"Elliott Oliver",
				"Shin Yong-Jae",
				"Lee Jin-Ku",
				"Lee In-Hee",
				"Park Woong-Yang",
				"Eoli Marica",
				"Blumberg Andrew J",
				"Lasorella Anna",
				"Nam Do-Hyun",
				"Finocchiaro Gaetano",
				"Iavarone Antonio",
				"Rabadan Raul"
			],
			"DOI": "10.1038/ng.3590",
			"date": "2017-09-08",
			"PMC": "",
			"citation": "",
			"abstract": "Glioblastoma (GBM) is the most common and aggressive primary brain tumor. To better understand how GBM evolves, we analyzed longitudinal genomic and transcriptomic data from 114 patients. The analysis shows a highly branched evolutionary pattern in which 63% of patients experience expression-based subtype changes. The branching pattern, together with estimates of evolutionary rate, suggests that relapse-associated clones typically existed years before diagnosis. Fifteen percent of tumors present hypermutation at relapse in highly expressed genes, with a clear mutational signature. We find that 11% of recurrence tumors harbor mutations in LTBP4, which encodes a protein binding to TGF-\u03b2. Silencing LTBP4 in GBM cells leads to suppression of TGF-\u03b2 activity and decreased cell proliferation. In recurrent GBM with wild-type IDH1, high LTBP4 expression is associated with worse prognosis, highlighting the TGF-\u03b2 pathway as a potential therapeutic target in GBM.",
			"category": 2,
			"name": "Wang Jiguang,2017"
		},
		{
			"PMID": 27182434,
			"title": "Circulating tumor DNA in hepatocellular carcinoma: trends and challenges.",
			"journal": "Cell & bioscience",
			"authorList": [
				"Tang Jia-Cheng",
				"Feng Yi-Li",
				"Guo Tao",
				"Xie An-Yong",
				"Cai Xiu-Jun"
			],
			"DOI": "10.1186/s13578-016-0100-z",
			"date": "2016-05-16",
			"PMC": "",
			"citation": "",
			"abstract": "Molecular characterization of individual patients' tumor cells is becoming increasingly important in offering effective treatment for patients in clinical practice. Recent advances in the field have indicated that circulating tumor DNA (ctDNA) has huge potential to serve as a biomarker for early detection and precision treatment as well as prognosis of hepatocellular carcinoma (HCC). As ctDNA in HCC patients harbors the molecular characteristics of HCC tumor cells, ctDNA analysis in the blood may be sufficient for convenient, non-invasive and accurate detection, providing information for HCC diagnosis, treatment and prognosis. In this review, we will summarize and discuss current trends and challenges of ctDNA application in HCC.",
			"category": 2,
			"name": "Tang Jia-Cheng,2016"
		},
		{
			"PMID": 27175599,
			"title": "The chronological sequence of somatic mutations in early gastric carcinogenesis inferred from multiregion sequencing of gastric adenomas.",
			"journal": "Oncotarget",
			"authorList": [
				"Lim Chul-Hyun",
				"Cho Yu Kyung",
				"Kim Sang Woo",
				"Choi Myung-Gyu",
				"Rhee Je-Keun",
				"Chung Yeun-Jun",
				"Lee Sug-Hyung",
				"Kim Tae-Min"
			],
			"DOI": "10.18632/oncotarget.9250",
			"date": "2018-01-12",
			"PMC": "",
			"citation": "",
			"abstract": "Mutation profiles and intratumoral heterogeneity are not well understood for benign gastric adenomas, some of which progress into malignant gastric adenocarcinomas. In this study, we performed whole-exome sequencing of three microsatellite stable (MSS) and two microsatellite instability-high (MSI-H) gastric adenomas with three regional tumor biopsies per case. We observed that the mutation abundance of benign gastric adenomas was comparable to those of gastric adenocarcinomas, suggesting that the mutational makeup for gastric carcinogenesis may already be achieved in benign adenomas. The extent of intratumoral heterogeneity was more substantial for MSS genomes in that only 1% - 14% of somatic mutations were common across the regional biopsies or 'public', while 50% - 94% of mutations were public in MSI-H gastric adenomas. We observed biallelic, loss-of-functional events of APC with truncating mutations and/or 5q losses for all cases, mostly as public events. All MSS gastric adenomas also harbored ARID2 truncating mutations, often as multiple, region-specific ones indicative of convergent evolution. Hotspot missense mutations on known cancer genes such as ERBB2 and KRAS were largely observed as region-specific aberrations. These findings suggest that biallelic functional APC inactivation initiates the gastric carcinogenesis and is followed by mutations of histone modifiers and then activation of known cancer-related genes. As the first exome-wide multi-region mutational profiling of gastric adenomas, our study provides clues on the chronological sequence of somatic mutations and their clonal architectures in early gastric carcinogenesis.",
			"category": 2,
			"name": "Lim Chul-Hyun,2018"
		},
		{
			"PMID": 27149953,
			"title": "Tree inference for single-cell data.",
			"journal": "Genome biology",
			"authorList": [
				"Jahn Katharina",
				"Kuipers Jack",
				"Beerenwinkel Niko"
			],
			"DOI": "10.1186/s13059-016-0936-x",
			"date": "2017-02-27",
			"PMC": "",
			"citation": "",
			"abstract": "Understanding the mutational heterogeneity within tumors is a keystone for the development of efficient cancer therapies. Here, we present SCITE, a stochastic search algorithm to identify the evolutionary history of a tumor from noisy and incomplete mutation profiles of single cells. SCITE comprises a flexible Markov chain Monte Carlo sampling scheme that allows the user to compute the maximum-likelihood mutation history, to sample from the posterior probability distribution, and to estimate the error rates of the underlying sequencing experiments. Evaluation on real cancer data and on simulation studies shows the scalability of SCITE to present-day single-cell sequencing data and improved reconstruction accuracy compared to existing approaches.",
			"category": 2,
			"name": "Jahn Katharina,2017"
		},
		{
			"PMID": 27108385,
			"title": "Complex Chromosomal Rearrangements in B-Cell Lymphoma: Evidence of Chromoanagenesis? A Case Report.",
			"journal": "Neoplasia (New York, N.Y.)",
			"authorList": [
				"Ortega Veronica",
				"Chaubey Alka",
				"Mendiola Christina",
				"Ehman William",
				"Vadlamudi Kumari",
				"Dupont Barbara",
				"Velagaleti Gopalrao"
			],
			"DOI": "10.1016/j.neo.2016.02.004",
			"date": "2017-05-04",
			"PMC": "",
			"citation": "",
			"abstract": "Genomic instability is a well-known hallmark of cancer. Recent genome sequencing studies have led to the identification of novel phenomena called chromothripsis and chromoanasynthesis in which complex genomic rearrangements are thought to be derived from a single catastrophic event rather than by several incremental steps. A new term chromoanagenesis or chromosomal rebirth was coined recently to group these two one-step catastrophic events together. These phenomena suggest an evolutionary modality for cancer cells to circumvent individual mutational events with one simultaneous shattering of chromosomes resulting in the random reassembling of segmented genetic material to form complex derivative chromosomes. We report a case of possible chromoanagenesis in a patient with diffuse large B-cell lymphoma. Chromosome analysis from the biopsy showed a complex karyotype with multiple numerical and structural rearrangements including a translocation of chromosomes 3 and 7 involving the BCL6 gene region, with the derivative chromosome further rearranging with chromosomes 14, 7, and 22 with involvement of the IGH gene region. Fluorescence in situ hybridization studies confirmed these findings. Chromosomal microarray studies showed multiple complex copy number variations including a chromosome 12 abnormality, the complexity of which appears to suggest the phenomenon of chromoanagenesis. Our case further illustrates that lymphomagenesis can be complex and may arise from a catastrophic event resulting in multiple complex chromosome rearrangements.",
			"category": 2,
			"name": "Ortega Veronica,2017"
		},
		{
			"PMID": 27088115,
			"title": "Combination of Sonodynamic and Photodynamic Therapy against Cancer Would Be Effective through Using a Regulated Size of Nanoparticles.",
			"journal": "Nanoscience and nanoengineering",
			"authorList": [
				"Miyoshi N",
				"Kundu S K",
				"Tuziuti T",
				"Yasui K",
				"Shimada I",
				"Ito Y"
			],
			"DOI": "",
			"date": "2024-03-25",
			"PMC": "",
			"citation": "",
			"abstract": "Nanoparticles have been used for many functional materials in nano-sciences and photo-catalyzing surface chemistry. The titanium oxide nanoparticles will be useful for the treatment of tumor by laser and/or ultrasound as the sensitizers in nano-medicine. We have studied the combination therapy of photo- and sono-dynamic therapies in an animal tumor model. Oral-administration of two sensitizers titanium oxide, 0.2%-TiO",
			"category": 2,
			"name": "Miyoshi N,2024"
		},
		{
			"PMID": 27075101,
			"title": "Nucleotide excision repair is impaired by binding of transcription factors to DNA.",
			"journal": "Nature",
			"authorList": [
				"Sabarinathan Radhakrishnan",
				"Mularoni Loris",
				"Deu-Pons Jordi",
				"Gonzalez-Perez Abel",
				"L\u00f3pez-Bigas N\u00faria"
			],
			"DOI": "10.1038/nature17661",
			"date": "2016-04-27",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic mutations are the driving force of cancer genome evolution. The rate of somatic mutations appears to be greatly variable across the genome due to variations in chromatin organization, DNA accessibility and replication timing. However, other variables that may influence the mutation rate locally are unknown, such as a role for DNA-binding proteins, for example. Here we demonstrate that the rate of somatic mutations in melanomas is highly increased at active transcription factor binding sites and nucleosome embedded DNA, compared to their flanking regions. Using recently available excision-repair sequencing (XR-seq) data, we show that the higher mutation rate at these sites is caused by a decrease of the levels of nucleotide excision repair (NER) activity. Our work demonstrates that DNA-bound proteins interfere with the NER machinery, which results in an increased rate of DNA mutations at the protein binding sites. This finding has important implications for our understanding of mutational and DNA repair processes and in the identification of cancer driver mutations.",
			"category": 2,
			"name": "Sabarinathan Radhakrishnan,2016"
		},
		{
			"PMID": 27071093,
			"title": "The tandem duplicator phenotype as a distinct genomic configuration in cancer.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Menghi Francesca",
				"Inaki Koichiro",
				"Woo XingYi",
				"Kumar Pooja A",
				"Grzeda Krzysztof R",
				"Malhotra Ankit",
				"Yadav Vinod",
				"Kim Hyunsoo",
				"Marquez Eladio J",
				"Ucar Duygu",
				"Shreckengast Phung T",
				"Wagner Joel P",
				"MacIntyre George",
				"Murthy Karuturi Krishna R",
				"Scully Ralph",
				"Keck James",
				"Chuang Jeffrey H",
				"Liu Edison T"
			],
			"DOI": "10.1073/pnas.1520010113",
			"date": "2016-12-13",
			"PMC": "",
			"citation": "",
			"abstract": "Next-generation sequencing studies have revealed genome-wide structural variation patterns in cancer, such as chromothripsis and chromoplexy, that do not engage a single discernable driver mutation, and whose clinical relevance is unclear. We devised a robust genomic metric able to identify cancers with a chromotype called tandem duplicator phenotype (TDP) characterized by frequent and distributed tandem duplications (TDs). Enriched only in triple-negative breast cancer (TNBC) and in ovarian, endometrial, and liver cancers, TDP tumors conjointly exhibit tumor protein p53 (TP53) mutations, disruption of breast cancer 1 (BRCA1), and increased expression of DNA replication genes pointing at rereplication in a defective checkpoint environment as a plausible causal mechanism. The resultant TDs in TDP augment global oncogene expression and disrupt tumor suppressor genes. Importantly, the TDP strongly correlates with cisplatin sensitivity in both TNBC cell lines and primary patient-derived xenografts. We conclude that the TDP is a common cancer chromotype that coordinately alters oncogene/tumor suppressor expression with potential as a marker for chemotherapeutic response.",
			"category": 2,
			"name": "Menghi Francesca,2016"
		},
		{
			"PMID": 27056366,
			"title": "Cell-free circulating tumor DNA in cancer.",
			"journal": "Chinese journal of cancer",
			"authorList": [
				"Qin Zhen",
				"Ljubimov Vladimir A",
				"Zhou Cuiqi",
				"Tong Yunguang",
				"Liang Jimin"
			],
			"DOI": "10.1186/s40880-016-0092-4",
			"date": "2016-12-30",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a common cause of death worldwide. Despite significant advances in cancer treatments, the morbidity and mortality are still enormous. Tumor heterogeneity, especially intratumoral heterogeneity, is a significant reason underlying difficulties in tumor treatment and failure of a number of current therapeutic modalities, even of molecularly targeted therapies. The development of a virtually noninvasive \"liquid biopsy\" from the blood has been attempted to characterize tumor heterogeneity. This review focuses on cell-free circulating tumor DNA (ctDNA) in the bloodstream as a versatile biomarker. ctDNA analysis is an evolving field with many new methods being developed and optimized to be able to successfully extract and analyze ctDNA, which has vast clinical applications. ctDNA has the potential to accurately genotype the tumor and identify personalized genetic and epigenetic alterations of the entire tumor. In addition, ctDNA has the potential to accurately monitor tumor burden and treatment response, while also being able to monitor minimal residual disease, reducing the need for harmful adjuvant chemotherapy and allowing more rapid detection of relapse. There are still many challenges that need to be overcome prior to this biomarker getting wide adoption in the clinical world, including optimization, standardization, and large multicenter trials.",
			"category": 2,
			"name": "Qin Zhen,2016"
		},
		{
			"PMID": 26911190,
			"title": "Leukaemia 'firsts' in cancer research and treatment.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Greaves Mel"
			],
			"DOI": "10.1038/nrc.2016.3",
			"date": "2016-07-06",
			"PMC": "",
			"citation": "",
			"abstract": "Our understanding of cancer biology has been radically transformed over recent years with a more realistic grasp of its multilayered cellular and genetic complexity. These advances are being translated into more selective and effective treatment of cancers and, although there are still considerable challenges, particularly with drug resistance and metastatic disease, many patients with otherwise lethal malignancies now enjoy protracted remissions or cure. One largely unheralded theme of this story is the extent to which new biological insights and novel clinical applications have their origins with leukaemia and related blood cell cancers, including lymphoma. In this Timeline article, I review the remarkable and ground-breaking role that studies in leukaemia have had at the forefront of this progress.",
			"category": 2,
			"name": "Greaves Mel,2016"
		},
		{
			"PMID": 26845763,
			"title": "Computational Cancer Biology: An Evolutionary Perspective.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Beerenwinkel Niko",
				"Greenman Chris D",
				"Lagergren Jens"
			],
			"DOI": "10.1371/journal.pcbi.1004717",
			"date": "2016-06-13",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Beerenwinkel Niko,2016"
		},
		{
			"PMID": 26833260,
			"title": "COSMOS: accurate detection of somatic structural variations through asymmetric comparison between tumor and normal samples.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Yamagata Koichi",
				"Yamanishi Ayako",
				"Kokubu Chikara",
				"Takeda Junji",
				"Sese Jun"
			],
			"DOI": "10.1093/nar/gkw026",
			"date": "2017-07-06",
			"PMC": "",
			"citation": "",
			"abstract": "An important challenge in cancer genomics is precise detection of structural variations (SVs) by high-throughput short-read sequencing, which is hampered by the high false discovery rates of existing analysis tools. Here, we propose an accurate SV detection method named COSMOS, which compares the statistics of the mapped read pairs in tumor samples with isogenic normal control samples in a distinct asymmetric manner. COSMOS also prioritizes the candidate SVs using strand-specific read-depth information. Performance tests on modeled tumor genomes revealed that COSMOS outperformed existing methods in terms of F-measure. We also applied COSMOS to an experimental mouse cell-based model, in which SVs were induced by genome engineering and gamma-ray irradiation, followed by polymerase chain reaction-based confirmation. The precision of COSMOS was 84.5%, while the next best existing method was 70.4%. Moreover, the sensitivity of COSMOS was the highest, indicating that COSMOS has great potential for cancer genome analysis.",
			"category": 2,
			"name": "Yamagata Koichi,2017"
		},
		{
			"PMID": 26812134,
			"title": "A holistic view of cancer bioenergetics: mitochondrial function and respiration play fundamental roles in the development and progression of diverse tumors.",
			"journal": "Clinical and translational medicine",
			"authorList": [
				"Alam Md Maksudul",
				"Lal Sneha",
				"FitzGerald Keely E",
				"Zhang Li"
			],
			"DOI": "10.1186/s40169-016-0082-9",
			"date": "2016-01-27",
			"PMC": "",
			"citation": "",
			"abstract": "Since Otto Warburg made the first observation that tumor cells exhibit altered metabolism and bioenergetics in the 1920s, many scientists have tried to further the understanding of tumor bioenergetics. Particularly, in the past decade, the application of the state-of the-art metabolomics and genomics technologies has revealed the remarkable plasticity of tumor metabolism and bioenergetics. Firstly, a wide array of tumor cells have been shown to be able to use not only glucose, but also glutamine for generating cellular energy, reducing power, and metabolic building blocks for biosynthesis. Secondly, many types of cancer cells generate most of their cellular energy via mitochondrial respiration and oxidative phosphorylation. Glutamine is the preferred substrate for oxidative phosphorylation in tumor cells. Thirdly, tumor cells exhibit remarkable versatility in using bioenergetics substrates. Notably, tumor cells can use metabolic substrates donated by stromal cells for cellular energy generation via oxidative phosphorylation. Further, it has been shown that mitochondrial transfer is a critical mechanism for tumor cells with defective mitochondria to restore oxidative phosphorylation. The restoration is necessary for tumor cells to gain tumorigenic and metastatic potential. It is also worth noting that heme is essential for the biogenesis and proper functioning of mitochondrial respiratory chain complexes. Hence, it is not surprising that recent experimental data showed that heme flux and function are elevated in non-small cell lung cancer (NSCLC) cells and that elevated heme function promotes intensified oxygen consumption, thereby fueling tumor cell proliferation and function. Finally, emerging evidence increasingly suggests that clonal evolution and tumor genetic heterogeneity contribute to bioenergetic versatility of tumor cells, as well as tumor recurrence and drug resistance. Although mutations are found only in several metabolic enzymes in tumors, diverse mutations in signaling pathways and networks can cause changes in the expression and activity of metabolic enzymes, which likely enable tumor cells to gain their bioenergetic versatility. A better understanding of tumor bioenergetics should provide a more holistic approach to investigate cancer biology and therapeutics. This review therefore attempts to comprehensively consider and summarize the experimental data supporting our latest view of cancer bioenergetics.",
			"category": 2,
			"name": "Alam Md Maksudul,2016"
		},
		{
			"PMID": 26811604,
			"title": "Adjuvant chemotherapy for resected colorectal cancer metastases: Literature review and meta-analysis.",
			"journal": "World journal of gastroenterology",
			"authorList": [
				"Brandi Giovanni",
				"De Lorenzo Stefania",
				"Nannini Margherita",
				"Curti Stefania",
				"Ottone Marta",
				"Dall'Olio Filippo Gustavo",
				"Barbera Maria Aurelia",
				"Pantaleo Maria Abbondanza",
				"Biasco Guido"
			],
			"DOI": "10.3748/wjg.v22.i2.519",
			"date": "2017-01-17",
			"PMC": "",
			"citation": "",
			"abstract": "Surgical resection is the only option of cure for patients with metastatic colorectal cancer (CRC). However, the risk of recurrence within 18 mo after metastasectomy is around 75% and the liver is the most frequent site of relapse. The current international guidelines recommend an adjuvant therapy after surgical resection of CRC metastases despite the lower level of evidence (based on the quality of studies in this setting). However, there is still no standard treatment and the effective role of an adjuvant therapy remains controversial. The aim of this review is to report the state-of-art of systemic chemotherapy and regional chemotherapy with hepatic arterial infusion in the management of patients after resection of metastases from CRC, with a literature review and meta-analysis of the relevant randomized controlled trials.",
			"category": 2,
			"name": "Brandi Giovanni,2017"
		},
		{
			"PMID": 26798491,
			"title": "Cancer Stem Cells: Plasticity Works against Therapy.",
			"journal": "Acta naturae",
			"authorList": [
				"Vinogradova T V",
				"Chernov I P",
				"Monastyrskaya G S",
				"Kondratyeva L G",
				"Sverdlov E D"
			],
			"DOI": "",
			"date": "2016-01-22",
			"PMC": "",
			"citation": "",
			"abstract": "Great successes in identification and deciphering of mechanisms of the adult stem cells regulation have given rise to the idea that stem cells can also function in tumors as central elements of their development, starting from the initial stage and continuing until metastasis. Such cells were called cancer stem cells (CSCs). Over the course of intense discussion, the CSCs hypothesis gradually began to be perceived as an obvious fact. Recently, the existence of CSCs has been indeed confirmed in a number of works. However, when are CSCs universal prerequisites of tumors and to what extent their role is essential for tumor evolution remains an issue far from resolved. Likewise, the problem of potential use of CSCs as therapeutic targets remains unsolved. The present review attempts to analyze the issue of cancer stem cells and the potential of targeting them in tumor therapy.",
			"category": 2,
			"name": "Vinogradova T V,2016"
		},
		{
			"PMID": 26695660,
			"title": "Mutational Landscapes of Sequential Prostate Metastases and Matched Patient Derived Xenografts during Enzalutamide Therapy.",
			"journal": "PloS one",
			"authorList": [
				"Kohli Manish",
				"Wang Liguo",
				"Xie Fang",
				"Sicotte Hugues",
				"Yin Ping",
				"Dehm Scott M",
				"Hart Steven N",
				"Vedell Peter T",
				"Barman Poulami",
				"Qin Rui",
				"Mahoney Douglas W",
				"Carlson Rachel E",
				"Eckel-Passow Jeanette E",
				"Atwell Thomas D",
				"Eiken Patrick W",
				"McMenomy Brendan P",
				"Wieben Eric D",
				"Jha Gautam",
				"Jimenez Rafael E",
				"Weinshilboum Richard",
				"Wang Liewei"
			],
			"DOI": "10.1371/journal.pone.0145176",
			"date": "2016-06-24",
			"PMC": "",
			"citation": "",
			"abstract": "Developing patient derived models from individual tumors that capture the biological heterogeneity and mutation landscape in advanced prostate cancer is challenging, but essential for understanding tumor progression and delivery of personalized therapy in metastatic castrate resistant prostate cancer stage. To demonstrate the feasibility of developing patient derived xenograft models in this stage, we present a case study wherein xenografts were derived from cancer metastases in a patient progressing on androgen deprivation therapy and prior to initiating pre-chemotherapy enzalutamide treatment. Tissue biopsies from a metastatic rib lesion were obtained for sequencing before and after initiating enzalutamide treatment over a twelve-week period and also implanted subcutaneously as well as under the renal capsule in immuno-deficient mice. The genome and transcriptome landscapes of xenografts and the original patient tumor tissues were compared by performing whole exome and transcriptome sequencing of the metastatic tumor tissues and the xenografts at both time points. After comparing the somatic mutations, copy number variations, gene fusions and gene expression we found that the patient's genomic and transcriptomic alterations were preserved in the patient derived xenografts with high fidelity. These xenograft models provide an opportunity for predicting efficacy of existing and potentially novel drugs that is based on individual metastatic tumor expression signature and molecular pharmacology for delivery of precision medicine.",
			"category": 2,
			"name": "Kohli Manish,2016"
		},
		{
			"PMID": 26640285,
			"title": "Advances in Breast Cancer - Looking Back over the Year.",
			"journal": "Geburtshilfe und Frauenheilkunde",
			"authorList": [
				"L\u00fcftner D",
				"Lux M P",
				"Maass N",
				"Sch\u00fctz F",
				"Schwidde I",
				"Fasching P A",
				"Fehm T",
				"Janni W",
				"K\u00fcmmel S",
				"Kolberg H-C"
			],
			"DOI": "",
			"date": "2023-11-11",
			"PMC": "",
			"citation": "",
			"abstract": "Treatment options as well as the characteristics for therapeutic decisions in patients with primary and advanced breast cancer are increasing in number and variety. New targeted therapies in combination with established chemotherapy schemes are broadening the spectrum, yet not every new, promising combination achieves a better result. New data from the field of pharmacogenomics point to prognostic and predictive factors that take not only the properties of the tumour but also the genetic disposition of the patient into consideration. Current therapeutic decision-making is thus based on a combination of classical clinical and modern molecular biomarkers. Health-economic concerns are also being taken into consideration more frequently, meaning political decisions may also become a factor. This review presents the trends over the past year.",
			"category": 2,
			"name": "L\u00fcftner D,2023"
		},
		{
			"PMID": 26636033,
			"title": "Current Challenges in Glioblastoma: Intratumour Heterogeneity, Residual Disease, and Models to Predict Disease Recurrence.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Ellis Hayley P",
				"Greenslade Mark",
				"Powell Ben",
				"Spiteri Inmaculada",
				"Sottoriva Andrea",
				"Kurian Kathreena M"
			],
			"DOI": "10.3389/fonc.2015.00251",
			"date": "2015-12-04",
			"PMC": "",
			"citation": "",
			"abstract": "Glioblastoma (GB) is the most common primary malignant brain tumor, and despite the availability of chemotherapy and radiotherapy to combat the disease, overall survival remains low with a high incidence of tumor recurrence. Technological advances are continually improving our understanding of the disease, and in particular, our knowledge of clonal evolution, intratumor heterogeneity, and possible reservoirs of residual disease. These may inform how we approach clinical treatment and recurrence in GB. Mathematical modeling (including neural networks) and strategies such as multiple sampling during tumor resection and genetic analysis of circulating cancer cells, may be of great future benefit to help predict the nature of residual disease and resistance to standard and molecular therapies in GB.",
			"category": 2,
			"name": "Ellis Hayley P,2015"
		},
		{
			"PMID": 26600436,
			"title": "Reliably Detecting Clinically Important Variants Requires Both Combined Variant Calls and Optimized Filtering Strategies.",
			"journal": "PloS one",
			"authorList": [
				"Field Matthew A",
				"Cho Vicky",
				"Andrews T Daniel",
				"Goodnow Chris C"
			],
			"DOI": "10.1371/journal.pone.0143199",
			"date": "2016-06-20",
			"PMC": "",
			"citation": "",
			"abstract": "A diversity of tools is available for identification of variants from genome sequence data. Given the current complexity of incorporating external software into a genome analysis infrastructure, a tendency exists to rely on the results from a single tool alone. The quality of the output variant calls is highly variable however, depending on factors such as sequence library quality as well as the choice of short-read aligner, variant caller, and variant caller filtering strategy. Here we present a two-part study first using the high quality 'genome in a bottle' reference set to demonstrate the significant impact the choice of aligner, variant caller, and variant caller filtering strategy has on overall variant call quality and further how certain variant callers outperform others with increased sample contamination, an important consideration when analyzing sequenced cancer samples. This analysis confirms previous work showing that combining variant calls of multiple tools results in the best quality resultant variant set, for either specificity or sensitivity, depending on whether the intersection or union, of all variant calls is used respectively. Second, we analyze a melanoma cell line derived from a control lymphocyte sample to determine whether software choices affect the detection of clinically important melanoma risk-factor variants finding that only one of the three such variants is unanimously detected under all conditions. Finally, we describe a cogent strategy for implementing a clinical variant detection pipeline; a strategy that requires careful software selection, variant caller filtering optimizing, and combined variant calls in order to effectively minimize false negative variants. While implementing such features represents an increase in complexity and computation the results offer indisputable improvements in data quality.",
			"category": 2,
			"name": "Field Matthew A,2016"
		},
		{
			"PMID": 26561834,
			"title": "Revealing the Complexity of Breast Cancer by Next Generation Sequencing.",
			"journal": "Cancers",
			"authorList": [
				"Verigos John",
				"Magklara Angeliki"
			],
			"DOI": "10.3390/cancers7040885",
			"date": "2015-11-13",
			"PMC": "",
			"citation": "",
			"abstract": "Over the last few years the increasing usage of \"-omic\" platforms, supported by next-generation sequencing, in the analysis of breast cancer samples has tremendously advanced our understanding of the disease. New driver and passenger mutations, rare chromosomal rearrangements and other genomic aberrations identified by whole genome and exome sequencing are providing missing pieces of the genomic architecture of breast cancer. High resolution maps of breast cancer methylomes and sequencing of the miRNA microworld are beginning to paint the epigenomic landscape of the disease. Transcriptomic profiling is giving us a glimpse into the gene regulatory networks that govern the fate of the breast cancer cell. At the same time, integrative analysis of sequencing data confirms an extensive intertumor and intratumor heterogeneity and plasticity in breast cancer arguing for a new approach to the problem. In this review, we report on the latest findings on the molecular characterization of breast cancer using NGS technologies, and we discuss their potential implications for the improvement of existing therapies.",
			"category": 2,
			"name": "Verigos John,2015"
		},
		{
			"PMID": 26559503,
			"title": "Testing for oncogenic molecular aberrations in cell-free DNA-based liquid biopsies in the clinic: are we there yet?",
			"journal": "Expert review of molecular diagnostics",
			"authorList": [
				"Polivka Jiri",
				"Pesta Martin",
				"Janku Filip"
			],
			"DOI": "10.1586/14737159.2015.1110021",
			"date": "2016-09-15",
			"PMC": "",
			"citation": "",
			"abstract": "The optimal choice of cancer therapy depends upon analysis of the tumor genome for druggable molecular alterations. The spatial and temporal intratumor heterogeneity of cancers creates substantial challenges, as molecular profile depends on time and site of tumor tissue collection. To capture the entire molecular profile, multiple biopsies from primary and metastatic sites at different time points would be required, which is not feasible for ethical or economic reasons. Molecular analysis of circulating cell-free DNA offers a novel, minimally invasive method that can be performed at multiple time-points and plausibly better represents the prevailing molecular profile of the cancer. Molecular analysis of this cell-free DNA offers multiple clinically useful applications, such as identification of molecular targets for cancer therapy, monitoring of tumor molecular profile in real time, detection of emerging molecular aberrations associated with resistance to particular therapy, determination of cancer prognosis and diagnosis of cancer recurrence or progression.",
			"category": 2,
			"name": "Polivka Jiri,2016"
		},
		{
			"PMID": 26540282,
			"title": "Genomic DNA Copy Number Aberrations, Histological Diagnosis, Oral Subsite and Aneuploidy in OPMDs/OSCCs.",
			"journal": "PloS one",
			"authorList": [
				"Castagnola Patrizio",
				"Zoppoli Gabriele",
				"Gandolfo Sergio",
				"Monticone Massimiliano",
				"Malacarne Davide",
				"Cirmena Gabriella",
				"Brown David",
				"Aiello Cinzia",
				"Maffei Massimo",
				"Marino Roberto",
				"Giaretti Walter",
				"Pentenero Monica"
			],
			"DOI": "10.1371/journal.pone.0142294",
			"date": "2016-06-14",
			"PMC": "",
			"citation": "",
			"abstract": "Oral potentially malignant disorders (OPMDs) characterized by the presence of dysplasia and DNA copy number aberrations (CNAs), may reflect chromosomal instability (CIN) and predispose to oral squamous cell carcinoma (OSCC). Early detection of OPMDs with such characteristics may play a crucial role in OSCC prevention. The aim of this study was to explore the relationship between CNAs, histological diagnosis, oral subsite and aneuploidy in OPMDs/OSCCs. Samples from OPMDs and OSCCs were processed by high-resolution DNA flow cytometry (hr DNA-FCM) to determine the relative nuclear DNA content. Additionally, CNAs were obtained for a subset of these samples by genome-wide array comparative genomic hybridization (aCGH) using DNA extracted from either diploid or aneuploid nuclei suspension sorted by FCM. Our study shows that: i) aneuploidy, global genomic imbalance (measured as the total number of CNAs) and specific focal CNAs occur early in the development of oral cancer and become more frequent at later stages; ii) OPMDs limited to tongue (TNG) mucosa display a higher frequency of aneuploidy compared to OPMDs confined to buccal mucosa (BM) as measured by DNA-FCM; iii) TNG OPMDs/OSCCs show peculiar features of CIN compared to BM OPMDs/OSCCs given the preferential association with total broad and specific focal CNA gains. Follow-up studies are warranted to establish whether the presence of DNA aneuploidy and specific focal or broad CNAs may predict cancer development in non-dysplastic OPMDs.",
			"category": 2,
			"name": "Castagnola Patrizio,2016"
		},
		{
			"PMID": 26512044,
			"title": "Genomic Profiling in Gastrointestinal Cancer: Are We Ready To Use These Data to Make Treatment Decisions?",
			"journal": "The oncologist",
			"authorList": [
				"Goldberg Richard M"
			],
			"DOI": "10.1634/theoncologist.2015-0263",
			"date": "2016-09-21",
			"PMC": "",
			"citation": "",
			"abstract": "Remarkable strides have been made in the past 10-15 years in identifying the molecular events that drive cancer. With an enormous amount of new data, including those from The Cancer Genome Atlas Project, therapies are increasingly being developed and tested in clinical trials specifically designed to target some of these molecular events. Often, molecular signatures have become more important than the histologic features in making treatment choices. The success rate of these therapies depends on many factors but, perhaps most importantly, on patient selection according to the genetic analysis results of their individual tumors.",
			"category": 2,
			"name": "Goldberg Richard M,2016"
		},
		{
			"PMID": 26457018,
			"title": "Genetic and epigenetic aspects of initiation and progression of hepatocellular carcinoma.",
			"journal": "World journal of gastroenterology",
			"authorList": [
				"Kanda Mitsuro",
				"Sugimoto Hiroyuki",
				"Kodera Yasuhiro"
			],
			"DOI": "10.3748/wjg.v21.i37.10584",
			"date": "2016-05-24",
			"PMC": "",
			"citation": "",
			"abstract": "Hepatocellular carcinoma (HCC) is a primary cancer of the liver that is predominant in developing countries and is responsible for nearly 600000 deaths each year worldwide. Similar to many other tumors, the development of HCC must be understood as a multistep process involving the accumulation of genetic and epigenetic alterations in regulatory genes, leading to the activation of oncogenes and the inactivation or loss of tumor suppressor genes. Extensive research over the past decade has identified a number of molecular biomarkers, including aberrant expression of HCC-related genes and microRNAs. The challenge facing HCC research and clinical care at this time is to address the heterogeneity and complexity of these genetic and epigenetic alterations and to use this information to direct rational diagnosis and treatment strategies. The multikinase inhibitor sorafenib was the first molecularly targeted drug for HCC to show some extent of survival benefits in patients with advanced tumors. Although the results obtained using sorafenib support the importance of molecular therapies in the treatment of HCC, there is still room for improvement. In addition, no molecular markers for drug sensitivity, recurrence and prognosis are currently clinically available. In this review, we provide an overview of recently published articles addressing HCC-related genes and microRNAs to update what is currently known regarding genetic and epigenetic aspects of the pathogenesis of HCC and propose novel promising candidates for use as diagnostic and therapeutic targets in HCC.",
			"category": 2,
			"name": "Kanda Mitsuro,2016"
		},
		{
			"PMID": 26457012,
			"title": "Challenges of deciphering gastric cancer heterogeneity.",
			"journal": "World journal of gastroenterology",
			"authorList": [
				"Hudler Petra"
			],
			"DOI": "10.3748/wjg.v21.i37.10510",
			"date": "2016-05-24",
			"PMC": "",
			"citation": "",
			"abstract": "Gastric cancer is in decline in most developed countries; however, it still accounts for a notable fraction of global mortality and morbidity related to cancer. High-throughput methods are rapidly changing our view and understanding of the molecular basis of gastric carcinogenesis. Today, it is widely accepted that the molecular complexity and heterogeneity, both inter- and intra-tumour, of gastric adenocarcinomas present significant obstacles in elucidating specific biomarkers for early detection of the disease. Although genome-wide sequencing and gene expression studies have revealed the intricate nature of the molecular changes that occur in tumour landscapes, the collected data and results are complex and sometimes contradictory. Several aberrant molecules have already been tested in clinical trials, although their diagnostic and prognostic utilities have not been confirmed thus far. The gold standard for the detection of sporadic gastric cancer is still the gastric endoscopy, which is considered invasive. In addition, genome-wide association studies have confirmed that genetic variations are important contributors to increased cancer risk and could participate in the initiation of malignant transformation. This hypothesis could in part explain the late onset of sporadic gastric cancers. The elaborate interplay of polymorphic low penetrance genes and lifestyle and environmental risk factors requires additional research to decipher their relative impacts on tumorigenesis. The purpose of this article is to present details of the molecular heterogeneity of sporadic gastric cancers at the DNA, RNA, and proteome levels and to discuss issues relevant to the translation of basic research data to clinically valuable tools. The focus of this work is the identification of relevant molecular changes that could be detected non-invasively.",
			"category": 2,
			"name": "Hudler Petra,2016"
		},
		{
			"PMID": 26427655,
			"title": "Quality assurance in clinical trials--the role of pathology.",
			"journal": "Virchows Archiv : an international journal of pathology",
			"authorList": [
				"R\u00f6cken Christoph"
			],
			"DOI": "10.1007/s00428-015-1857-x",
			"date": "2016-08-10",
			"PMC": "",
			"citation": "",
			"abstract": "In the last two decades, our knowledge about cancer genetics and cancer biology increased exponentially. Deep sequencing now allows rapid and cost-effective analysis of entire cancer genomes. Dysregulation of cell growth, cell survival, tissue homeostasis, and immune surveillance have been recognized as hallmarks of cancer. In parallel, diagnostic surgical pathology has been harmonized and consensus diagnostic criteria for cancer classification have been developed by initiatives of the World Health Organization, the International Agency for Research on Cancer, and the Union for International Cancer Control. Pharmaceutical companies developed novel drugs targeting specific molecules in signaling pathways, which has allowed the development of the concept of precision medicine. Now, we are facing a large number of clinical trials which bring together these advances and will explore efficacy of novel treatment regimens. Assessment of the efficacy of a new drug is often coupled with the simultaneous assessment of the capacity of tissue-based biomarkers to predict response of individual patients (companion diagnostics/precision medicine). Patients with histologically similar tumors might respond differently to the same drug. This review summarizes the diverse roles played by surgical pathologists involved in clinical trials, with a special focus on quality assurance of diagnostic, laboratory, and reporting standards.",
			"category": 2,
			"name": "R\u00f6cken Christoph,2016"
		},
		{
			"PMID": 26354865,
			"title": "Mammalian RAD51 paralogs protect nascent DNA at stalled forks and mediate replication restart.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Somyajit Kumar",
				"Saxena Sneha",
				"Babu Sharath",
				"Mishra Anup",
				"Nagaraju Ganesh"
			],
			"DOI": "10.1093/nar/gkv880",
			"date": "2016-03-29",
			"PMC": "",
			"citation": "",
			"abstract": "Mammalian RAD51 paralogs are implicated in the repair of collapsed replication forks by homologous recombination. However, their physiological roles in replication fork maintenance prior to fork collapse remain obscure. Here, we report on the role of RAD51 paralogs in short-term replicative stress devoid of DSBs. We show that RAD51 paralogs localize to nascent DNA and common fragile sites upon replication fork stalling. Strikingly, RAD51 paralogs deficient cells exhibit elevated levels of 53BP1 nuclear bodies and increased DSB formation, the latter being attributed to extensive degradation of nascent DNA at stalled forks. RAD51C and XRCC3 promote the restart of stalled replication in an ATP hydrolysis dependent manner by disengaging RAD51 and other RAD51 paralogs from the halted forks. Notably, we find that Fanconi anemia (FA)-like disorder and breast and ovarian cancer patient derived mutations of RAD51C fails to protect replication fork, exhibit under-replicated genomic regions and elevated micro-nucleation. Taken together, RAD51 paralogs prevent degradation of stalled forks and promote the restart of halted replication to avoid replication fork collapse, thereby maintaining genomic integrity and suppressing tumorigenesis.",
			"category": 2,
			"name": "Somyajit Kumar,2016"
		},
		{
			"PMID": 26193902,
			"title": "Evolutionary determinants of cancer.",
			"journal": "Cancer discovery",
			"authorList": [
				"Greaves Mel"
			],
			"DOI": "10.1158/2159-8290.CD-15-0439",
			"date": "2016-05-05",
			"PMC": "",
			"citation": "",
			"abstract": "Our understanding of cancer is being transformed by exploring clonal diversity, drug resistance, and causation within an evolutionary framework. The therapeutic resilience of advanced cancer is a consequence of its character as a complex, dynamic, and adaptive ecosystem engendering robustness, underpinned by genetic diversity and epigenetic plasticity. The risk of mutation-driven escape by self-renewing cells is intrinsic to multicellularity but is countered by multiple restraints, facilitating increasing complexity and longevity of species. But our own species has disrupted this historical narrative by rapidly escalating intrinsic risk. Evolutionary principles illuminate these challenges and provide new avenues to explore for more effective control.",
			"category": 2,
			"name": "Greaves Mel,2016"
		},
		{
			"PMID": 26191234,
			"title": "Gene mutation profiling of primary glioblastoma through multiple tumor biopsy guided by 1H-magnetic resonance spectroscopy.",
			"journal": "International journal of clinical and experimental pathology",
			"authorList": [
				"Tang Chao",
				"Guo Jun",
				"Chen Hong",
				"Yao Cheng-Jun",
				"Zhuang Dong-Xiao",
				"Wang Yin",
				"Tang Wei-Jun",
				"Ren Guang",
				"Yao Yu",
				"Wu Jin-Song",
				"Mao Ying",
				"Zhou Liang-Fu"
			],
			"DOI": "",
			"date": "2016-04-19",
			"PMC": "",
			"citation": "",
			"abstract": "Genetic mutation has served as the biomarkers for the diagnosis and treatment of glioblastoma multiforme (GBM). However, intra-tumor heterogeneity may interfere with personalized treatment strategies based on mutation analysis. This study aimed to characterize somatic mutation profiling of GBM. We collected 33 samples from 7 patients with the primary GBM associated with different Choline (Cho) to N-acetylaspartate (NAA) index (CNI) through the frameless proton magnetic resonance spectroscopy (1H-MRS) guided biopsies and investigated multiple somatic mutations profiling using the AmpliSeq cancer hotspot panel V2. We identified 53 missense or nonsense mutations in 27 genes including some novel mutations such as APC and IDH2. The mutations in EGFR, TP53, PTEN, PIK3CA genes were presented with different frequency and the majority of the mutated gene was only shared by 1-2 samples from one patient. Moreover, we found the association of CNI with histological grade, but there was no significant change of CNI in the presence of TP53, EGFR and PTEN mutations. These data suggest that gene mutations constitute a heterogeneous marker for primary GBM which may be independent of intra-tumor morphological phenotypes of GBM; therefore, gene mutation markers could not be determined from a small number of needle biopsies or only confined to the high-grade region.",
			"category": 2,
			"name": "Tang Chao,2016"
		},
		{
			"PMID": 26166838,
			"title": "Chemotherapy for Metastatic Breast Cancer - An Anachronism in the Era of Personalised and Targeted Oncological Therapy?",
			"journal": "Geburtshilfe und Frauenheilkunde",
			"authorList": [
				"Schneeweiss A",
				"Ruckh\u00e4berle E",
				"Huober J"
			],
			"DOI": "",
			"date": "2019-11-20",
			"PMC": "",
			"citation": "",
			"abstract": "Based on the findings of modern molecular biology, breast cancer is nowadays considered to be a heterogeneous disease. This leads to the objective of an individualised, more patient-oriented therapy. A series of target molecules for this purpose has already been identified. The principle of targeted oncological therapy was realised decades ago with the introduction of endocrine therapy for patients with hormone receptor-positive tumours. The modern therapy for HER2-positive tumours is a further example for the translation of targeted therapy into clinical routine. For patients with HER2-negative metastatic breast cancer, to date two targeted drugs, bevacizumab and everolimus, are available for routine clinical use. Many other substances are still undergoing clinical development. However, validated predictive markers to aid in therapeutic decision-making and therapy control are still lacking. Chemotherapy constitutes an effective palliative therapy with proven efficacy for the patients. In this process strategies have also been realised for a targeted therapy against tumour cells with the help of chemotherapeutic agents such as, for example, the intracellular activation of the prodrug capecitabine or the active albumin-mediated transport of nab-paclitaxel which leads to higher peri- and intratumoural enrichments. The continuing unchanged relevance of chemotherapy is often underestimated in the current discussions and will be comprehensively evaluated in this review.",
			"category": 2,
			"name": "Schneeweiss A,2019"
		},
		{
			"PMID": 26142706,
			"title": "Genetic heterogeneity in cholangiocarcinoma: a major challenge for targeted therapies.",
			"journal": "Oncotarget",
			"authorList": [
				"Brandi Giovanni",
				"Farioli Andrea",
				"Astolfi Annalisa",
				"Biasco Guido",
				"Tavolari Simona"
			],
			"DOI": "",
			"date": "2016-04-18",
			"PMC": "",
			"citation": "",
			"abstract": "Cholangiocarcinoma (CC) encompasses a group of related but distinct malignancies whose lack of a stereotyped genetic signature makes challenging the identification of genomic landscape and the development of effective targeted therapies. Accumulated evidences strongly suggest that the remarkable genetic heterogeneity of CC may be the result of a complex interplay among different causative factors, some shared by most human cancers while others typical of this malignancy. Currently, considerable efforts are ongoing worldwide for the genetic characterization of CC, also using advanced technologies such as next-generation sequencing (NGS). Undoubtedly this technology could offer an unique opportunity to broaden our understanding on CC molecular pathogenesis. Despite this great potential, however, the high complexity in terms of factors potentially contributing to genetic variability in CC calls for a more cautionary application of NGS to this malignancy, in order to avoid possible biases and criticisms in the identification of candidate actionable targets. This approach is further justified by the urgent need to develop effective targeted therapies in this disease. A multidisciplinary approach integrating genomic, functional and clinical studies is therefore mandatory to translate the results obtained by NGS into effective targeted therapies for this orphan disease.",
			"category": 2,
			"name": "Brandi Giovanni,2016"
		},
		{
			"PMID": 26113645,
			"title": "Application of single-cell genomics in cancer: promise and challenges.",
			"journal": "Human molecular genetics",
			"authorList": [
				"Wills Quin F",
				"Mead Adam J"
			],
			"DOI": "10.1093/hmg/ddv235",
			"date": "2016-06-28",
			"PMC": "",
			"citation": "",
			"abstract": "Recent advances in single-cell genomics are opening up unprecedented opportunities to transform cancer genomics. While bulk tissue genomic analysis across large populations of tumour cells has provided key insights into cancer biology, this approach does not provide the resolution that is critical for understanding the interaction between different genetic events within the cellular hierarchy of the tumour during disease initiation, evolution, relapse and metastasis. Single-cell genomic approaches are uniquely placed to definitively unravel complex clonal structures and tissue hierarchies, account for spatiotemporal cell interactions and discover rare cells that drive metastatic disease, drug resistance and disease progression. Here we present five challenges that need to be met for single-cell genomics to fulfil its potential as a routine tool alongside bulk sequencing. These might be thought of as being challenges related to samples (processing and scale for analysis), sensitivity and specificity of mutation detection, sources of heterogeneity (biological and technical), synergies (from data integration) and systems modelling. We discuss these in the context of recent advances in technologies and data modelling, concluding with implications for moving cancer research into the clinic.",
			"category": 2,
			"name": "Wills Quin F,2016"
		},
		{
			"PMID": 26106142,
			"title": "Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.",
			"journal": "Carcinogenesis",
			"authorList": [
				"Goodson William H",
				"Lowe Leroy",
				"Carpenter David O",
				"Gilbertson Michael",
				"Manaf Ali Abdul",
				"Lopez de Cerain Salsamendi Adela",
				"Lasfar Ahmed",
				"Carnero Amancio",
				"Azqueta Amaya",
				"Amedei Amedeo",
				"Charles Amelia K",
				"Collins Andrew R",
				"Ward Andrew",
				"Salzberg Anna C",
				"Colacci Annamaria",
				"Olsen Ann-Karin",
				"Berg Arthur",
				"Barclay Barry J",
				"Zhou Binhua P",
				"Blanco-Aparicio Carmen",
				"Baglole Carolyn J",
				"Dong Chenfang",
				"Mondello Chiara",
				"Hsu Chia-Wen",
				"Naus Christian C",
				"Yedjou Clement",
				"Curran Colleen S",
				"Laird Dale W",
				"Koch Daniel C",
				"Carlin Danielle J",
				"Felsher Dean W",
				"Roy Debasish",
				"Brown Dustin G",
				"Ratovitski Edward",
				"Ryan Elizabeth P",
				"Corsini Emanuela",
				"Rojas Emilio",
				"Moon Eun-Yi",
				"Laconi Ezio",
				"Marongiu Fabio",
				"Al-Mulla Fahd",
				"Chiaradonna Ferdinando",
				"Darroudi Firouz",
				"Martin Francis L",
				"Van Schooten Frederik J",
				"Goldberg Gary S",
				"Wagemaker Gerard",
				"Nangami Gladys N",
				"Calaf Gloria M",
				"Williams Graeme",
				"Wolf Gregory T",
				"Koppen Gudrun",
				"Brunborg Gunnar",
				"Lyerly H Kim",
				"Krishnan Harini",
				"Ab Hamid Hasiah",
				"Yasaei Hemad",
				"Sone Hideko",
				"Kondoh Hiroshi",
				"Salem Hosni K",
				"Hsu Hsue-Yin",
				"Park Hyun Ho",
				"Koturbash Igor",
				"Miousse Isabelle R",
				"Scovassi A Ivana",
				"Klaunig James E",
				"Vondr\u00e1\u010dek Jan",
				"Raju Jayadev",
				"Roman Jesse",
				"Wise John Pierce",
				"Whitfield Jonathan R",
				"Woodrick Jordan",
				"Christopher Joseph A",
				"Ochieng Josiah",
				"Martinez-Leal Juan Fernando",
				"Weisz Judith",
				"Kravchenko Julia",
				"Sun Jun",
				"Prudhomme Kalan R",
				"Narayanan Kannan Badri",
				"Cohen-Solal Karine A",
				"Moorwood Kim",
				"Gonzalez Laetitia",
				"Soucek Laura",
				"Jian Le",
				"D'Abronzo Leandro S",
				"Lin Liang-Tzung",
				"Li Lin",
				"Gulliver Linda",
				"McCawley Lisa J",
				"Memeo Lorenzo",
				"Vermeulen Louis",
				"Leyns Luc",
				"Zhang Luoping",
				"Valverde Mahara",
				"Khatami Mahin",
				"Romano Maria Fiammetta",
				"Chapellier Marion",
				"Williams Marc A",
				"Wade Mark",
				"Manjili Masoud H",
				"Lleonart Matilde E",
				"Xia Menghang",
				"Gonzalez Michael J",
				"Karamouzis Michalis V",
				"Kirsch-Volders Micheline",
				"Vaccari Monica",
				"Kuemmerle Nancy B",
				"Singh Neetu",
				"Cruickshanks Nichola",
				"Kleinstreuer Nicole",
				"van Larebeke Nik",
				"Ahmed Nuzhat",
				"Ogunkua Olugbemiga",
				"Krishnakumar P K",
				"Vadgama Pankaj",
				"Marignani Paola A",
				"Ghosh Paramita M",
				"Ostrosky-Wegman Patricia",
				"Thompson Patricia A",
				"Dent Paul",
				"Heneberg Petr",
				"Darbre Philippa",
				"Sing Leung Po",
				"Nangia-Makker Pratima",
				"Cheng Qiang Shawn",
				"Robey R Brooks",
				"Al-Temaimi Rabeah",
				"Roy Rabindra",
				"Andrade-Vieira Rafaela",
				"Sinha Ranjeet K",
				"Mehta Rekha",
				"Vento Renza",
				"Di Fiore Riccardo",
				"Ponce-Cusi Richard",
				"Dornetshuber-Fleiss Rita",
				"Nahta Rita",
				"Castellino Robert C",
				"Palorini Roberta",
				"Abd Hamid Roslida",
				"Langie Sabine A S",
				"Eltom Sakina E",
				"Brooks Samira A",
				"Ryeom Sandra",
				"Wise Sandra S",
				"Bay Sarah N",
				"Harris Shelley A",
				"Papagerakis Silvana",
				"Romano Simona",
				"Pavanello Sofia",
				"Eriksson Staffan",
				"Forte Stefano",
				"Casey Stephanie C",
				"Luanpitpong Sudjit",
				"Lee Tae-Jin",
				"Otsuki Takemi",
				"Chen Tao",
				"Massfelder Thierry",
				"Sanderson Thomas",
				"Guarnieri Tiziana",
				"Hultman Tove",
				"Dormoy Val\u00e9rian",
				"Odero-Marah Valerie",
				"Sabbisetti Venkata",
				"Maguer-Satta Veronique",
				"Rathmell W Kimryn",
				"Engstr\u00f6m Wilhelm",
				"Decker William K",
				"Bisson William H",
				"Rojanasakul Yon",
				"Luqmani Yunus",
				"Chen Zhenbang",
				"Hu Zhiwei"
			],
			"DOI": "10.1093/carcin/bgv039",
			"date": "2015-09-09",
			"PMC": "",
			"citation": "",
			"abstract": "Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.",
			"category": 2,
			"name": "Goodson William H,2015"
		},
		{
			"PMID": 26017310,
			"title": "Chromothripsis from DNA damage in micronuclei.",
			"journal": "Nature",
			"authorList": [
				"Zhang Cheng-Zhong",
				"Spektor Alexander",
				"Cornils Hauke",
				"Francis Joshua M",
				"Jackson Emily K",
				"Liu Shiwei",
				"Meyerson Matthew",
				"Pellman David"
			],
			"DOI": "10.1038/nature14493",
			"date": "2015-07-02",
			"PMC": "",
			"citation": "",
			"abstract": "Genome sequencing has uncovered a new mutational phenomenon in cancer and congenital disorders called chromothripsis. Chromothripsis is characterized by extensive genomic rearrangements and an oscillating pattern of DNA copy number levels, all curiously restricted to one or a few chromosomes. The mechanism for chromothripsis is unknown, but we previously proposed that it could occur through the physical isolation of chromosomes in aberrant nuclear structures called micronuclei. Here, using a combination of live cell imaging and single-cell genome sequencing, we demonstrate that micronucleus formation can indeed generate a spectrum of genomic rearrangements, some of which recapitulate all known features of chromothripsis. These events are restricted to the mis-segregated chromosome and occur within one cell division. We demonstrate that the mechanism for chromothripsis can involve the fragmentation and subsequent reassembly of a single chromatid from a micronucleus. Collectively, these experiments establish a new mutational process of which chromothripsis is one extreme outcome.",
			"category": 2,
			"name": "Zhang Cheng-Zhong,2015"
		},
		{
			"PMID": 26003801,
			"title": "Tracking the genomic evolution of esophageal adenocarcinoma through neoadjuvant chemotherapy.",
			"journal": "Cancer discovery",
			"authorList": [
				"Murugaesu Nirupa",
				"Wilson Gareth A",
				"Birkbak Nicolai J",
				"Watkins Thomas",
				"McGranahan Nicholas",
				"Kumar Sacheen",
				"Abbassi-Ghadi Nima",
				"Salm Max",
				"Mitter Richard",
				"Horswell Stuart",
				"Rowan Andrew",
				"Phillimore Benjamin",
				"Biggs Jennifer",
				"Begum Sharmin",
				"Matthews Nik",
				"Hochhauser Daniel",
				"Hanna George B",
				"Swanton Charles"
			],
			"DOI": "10.1158/2159-8290.CD-15-0412",
			"date": "2016-05-05",
			"PMC": "",
			"citation": "",
			"abstract": "Esophageal adenocarcinomas are associated with a dismal prognosis. Deciphering the evolutionary history of this disease may shed light on therapeutically tractable targets and reveal dynamic mutational processes during the disease course and following neoadjuvant chemotherapy (NAC). We exome sequenced 40 tumor regions from 8 patients with operable esophageal adenocarcinomas, before and after platinum-containing NAC. This revealed the evolutionary genomic landscape of esophageal adenocarcinomas with the presence of heterogeneous driver mutations, parallel evolution, early genome-doubling events, and an association between high intratumor heterogeneity and poor response to NAC. Multiregion sequencing demonstrated a significant reduction in thymine to guanine mutations within a CpTpT context when comparing early and late mutational processes and the presence of a platinum signature with enrichment of cytosine to adenine mutations within a CpC context following NAC. Esophageal adenocarcinomas are characterized by early chromosomal instability leading to amplifications containing targetable oncogenes persisting through chemotherapy, providing a rationale for future therapeutic approaches.",
			"category": 2,
			"name": "Murugaesu Nirupa,2016"
		},
		{
			"PMID": 25946211,
			"title": "Comparison of genetic and epigenetic alterations of primary tumors and matched plasma samples in patients with colorectal cancer.",
			"journal": "PloS one",
			"authorList": [
				"Danese Elisa",
				"Minicozzi Anna Maria",
				"Benati Marco",
				"Montagnana Martina",
				"Paviati Elisa",
				"Salvagno Gian Luca",
				"Lima-Oliveira Gabriel",
				"Gusella Milena",
				"Pasini Felice",
				"Lippi Giuseppe",
				"Guidi Gian Cesare"
			],
			"DOI": "10.1371/journal.pone.0126417",
			"date": "2016-04-25",
			"PMC": "",
			"citation": "",
			"abstract": "Although recent advances in circulating DNA analysis allow the prediction of tumor genomes by noninvasive means, some challenges remain, which limit the widespread introduction of cfDNA in cancer diagnostics. We analyzed the status of the two best characterized colorectal cancer (CRC) genetic and epigenetic alterations in a cohort of CRC patients, and then compared the degree to which the two patterns move from tissue to plasma in order to improve our understanding of biology modulating the concordance between tissues and plasma methylation and mutation profiles.",
			"category": 2,
			"name": "Danese Elisa,2016"
		},
		{
			"PMID": 25944252,
			"title": "Fast and scalable inference of multi-sample cancer lineages.",
			"journal": "Genome biology",
			"authorList": [
				"Popic Victoria",
				"Salari Raheleh",
				"Hajirasouliha Iman",
				"Kashef-Haghighi Dorna",
				"West Robert B",
				"Batzoglou Serafim"
			],
			"DOI": "10.1186/s13059-015-0647-8",
			"date": "2016-06-01",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic variants can be used as lineage markers for the phylogenetic reconstruction of cancer evolution. Since somatic phylogenetics is complicated by sample heterogeneity, novel specialized tree-building methods are required for cancer phylogeny reconstruction. We present LICHeE (Lineage Inference for Cancer Heterogeneity and Evolution), a novel method that automates the phylogenetic inference of cancer progression from multiple somatic samples. LICHeE uses variant allele frequencies of somatic single nucleotide variants obtained by deep sequencing to reconstruct multi-sample cell lineage trees and infer the subclonal composition of the samples. LICHeE is open source and available at http://viq854.github.io/lichee .",
			"category": 2,
			"name": "Popic Victoria,2016"
		},
		{
			"PMID": 25928234,
			"title": "Darwin and Fisher meet at biotech: on the potential of computational molecular evolution in industry.",
			"journal": "BMC evolutionary biology",
			"authorList": [
				"Anisimova Maria"
			],
			"DOI": "10.1186/s12862-015-0352-y",
			"date": "2015-07-27",
			"PMC": "",
			"citation": "",
			"abstract": "Today computational molecular evolution is a vibrant research field that benefits from the availability of large and complex new generation sequencing data - ranging from full genomes and proteomes to microbiomes, metabolomes and epigenomes. The grounds for this progress were established long before the discovery of the DNA structure. Specifically, Darwin's theory of evolution by means of natural selection not only remains relevant today, but also provides a solid basis for computational research with a variety of applications. But a long-term progress in biology was ensured by the mathematical sciences, as exemplified by Sir R. Fisher in early 20th century. Now this is true more than ever: The data size and its complexity require biologists to work in close collaboration with experts in computational sciences, modeling and statistics.",
			"category": 2,
			"name": "Anisimova Maria,2015"
		},
		{
			"PMID": 25905041,
			"title": "The importance of being dead: cell death mechanisms assessment in anti-sarcoma therapy.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Rello-Varona Santiago",
				"Herrero-Mart\u00edn David",
				"Lagares-Tena Laura",
				"L\u00f3pez-Alemany Roser",
				"Mulet-Margalef N\u00faria",
				"Huertas-Mart\u00ednez Juan",
				"Garcia-Moncl\u00fas Silvia",
				"Garc\u00eda Del Muro Xavier",
				"Mu\u00f1oz-Pinedo Cristina",
				"Tirado Oscar Mart\u00ednez"
			],
			"DOI": "10.3389/fonc.2015.00082",
			"date": "2015-04-23",
			"PMC": "",
			"citation": "",
			"abstract": "Cell death can occur through different mechanisms, defined by their nature and physiological implications. Correct assessment of cell death is crucial for cancer therapy success. Sarcomas are a large and diverse group of neoplasias from mesenchymal origin. Among cell death types, apoptosis is by far the most studied in sarcomas. Albeit very promising in other fields, regulated necrosis and other cell death circumstances (as so-called \"autophagic cell death\" or \"mitotic catastrophe\") have not been yet properly addressed in sarcomas. Cell death is usually quantified in sarcomas by unspecific assays and in most cases the precise sequence of events remains poorly characterized. In this review, our main objective is to put into context the most recent sarcoma cell death findings in the more general landscape of different cell death modalities.",
			"category": 2,
			"name": "Rello-Varona Santiago,2015"
		},
		{
			"PMID": 25895611,
			"title": "Clinical management of breast cancer heterogeneity.",
			"journal": "Nature reviews. Clinical oncology",
			"authorList": [
				"Zardavas Dimitrios",
				"Irrthum Alexandre",
				"Swanton Charles",
				"Piccart Martine"
			],
			"DOI": "10.1038/nrclinonc.2015.73",
			"date": "2016-03-21",
			"PMC": "",
			"citation": "",
			"abstract": "Traditionally, intertumour heterogeneity in breast cancer has been documented in terms of different histological subtypes, treatment sensitivity profiles, and clinical outcomes among different patients. Results of high-throughput molecular profiling studies have subsequently revealed the true extent of this heterogeneity. Further complicating this scenario, the heterogeneous expression of the oestrogen receptor (ER), progesterone receptor (PR), and HER2 has been reported in different areas of the same tumour. Furthermore, discordance, in terms of ER, PR and HER2 expression, has also been reported between primary tumours and their matched metastatic lesions. High-throughput molecular profiling studies have confirmed that spatial and temporal intratumour heterogeneity of breast cancers exist at a level beyond common expectations. We describe the different levels of tumour heterogeneity, and discuss the strategies that can be adopted by clinicians to tackle treatment response and resistance issues associated with such heterogeneity, including a rationally selected combination of agents that target driver mutations, the targeting of deleterious passenger mutations, identifying and eradicating the 'lethal' clone, targeting the tumour microenvironment, or using adaptive treatments and immunotherapy. The identification of the most-appropriate strategies and their implementation in the clinic will prove highly challenging and necessitate the adoption of radically new practices for the optimal clinical management of breast malignancies.",
			"category": 2,
			"name": "Zardavas Dimitrios,2016"
		},
		{
			"PMID": 25895610,
			"title": "Mouse hospital and co-clinical trial project--from bench to bedside.",
			"journal": "Nature reviews. Clinical oncology",
			"authorList": [
				"Clohessy John G",
				"Pandolfi Pier Paolo"
			],
			"DOI": "10.1038/nrclinonc.2015.62",
			"date": "2016-03-21",
			"PMC": "",
			"citation": "",
			"abstract": "Owing to the molecular complexity of cancer and the cost of therapy, researchers have begun looking to in vivo functional genomics to inform patient care. Unfortunately, xenographs of established tumour cell lines in immunodeficient mice fail to recapitulate many critical features of human primary tumours. By contrast, mouse models of cancer often faithfully recapitulate basic biology, tumour-microenvironment interactions, drug responses and therapy resistance similar to human disease. Thus, we established the co-clinical trial project, and in doing so developed the concept of the mouse hospital, whereby in vivo preclinical and early clinical studies are closely aligned, enabling in vivo testing of drugs in a multitude of cancer subtypes using mouse models, while minimizing the cost and time required to study responses in thousands of human patients. This approach can inform enrollment of patients in clinical trials, and can enable repositioning and/or repurposing of previously approved drugs.",
			"category": 2,
			"name": "Clohessy John G,2016"
		},
		{
			"PMID": 25877892,
			"title": "Clonal status of actionable driver events and the timing of mutational processes in cancer evolution.",
			"journal": "Science translational medicine",
			"authorList": [
				"McGranahan Nicholas",
				"Favero Francesco",
				"de Bruin Elza C",
				"Birkbak Nicolai Juul",
				"Szallasi Zoltan",
				"Swanton Charles"
			],
			"DOI": "10.1126/scitranslmed.aaa1408",
			"date": "2016-01-12",
			"PMC": "",
			"citation": "",
			"abstract": "Deciphering whether actionable driver mutations are found in all or a subset of tumor cells will likely be required to improve drug development and precision medicine strategies. We analyzed nine cancer types to determine the subclonal frequencies of driver events, to time mutational processes during cancer evolution, and to identify drivers of subclonal expansions. Although mutations in known driver genes typically occurred early in cancer evolution, we also identified later subclonal \"actionable\" mutations, including BRAF (V600E), IDH1 (R132H), PIK3CA (E545K), EGFR (L858R), and KRAS (G12D), which may compromise the efficacy of targeted therapy approaches. More than 20% of IDH1 mutations in glioblastomas, and 15% of mutations in genes in the PI3K (phosphatidylinositol 3-kinase)-AKT-mTOR (mammalian target of rapamycin) signaling axis across all tumor types were subclonal. Mutations in the RAS-MEK (mitogen-activated protein kinase kinase) signaling axis were less likely to be subclonal than mutations in genes associated with PI3K-AKT-mTOR signaling. Analysis of late mutations revealed a link between APOBEC-mediated mutagenesis and the acquisition of subclonal driver mutations and uncovered putative cancer genes involved in subclonal expansions, including CTNNA2 and ATXN1. Our results provide a pan-cancer census of driver events within the context of intratumor heterogeneity and reveal patterns of tumor evolution across cancers. The frequent presence of subclonal driver mutations suggests the need to stratify targeted therapy response according to the proportion of tumor cells in which the driver is identified.",
			"category": 2,
			"name": "McGranahan Nicholas,2016"
		},
		{
			"PMID": 25858951,
			"title": "Optimizing sparse sequencing of single cells for highly multiplex copy number profiling.",
			"journal": "Genome research",
			"authorList": [
				"Baslan Timour",
				"Kendall Jude",
				"Ward Brian",
				"Cox Hilary",
				"Leotta Anthony",
				"Rodgers Linda",
				"Riggs Michael",
				"D'Italia Sean",
				"Sun Guoli",
				"Yong Mao",
				"Miskimen Kristy",
				"Gilmore Hannah",
				"Saborowski Michael",
				"Dimitrova Nevenka",
				"Krasnitz Alexander",
				"Harris Lyndsay",
				"Wigler Michael",
				"Hicks James"
			],
			"DOI": "10.1101/gr.188060.114",
			"date": "2016-01-18",
			"PMC": "",
			"citation": "",
			"abstract": "Genome-wide analysis at the level of single cells has recently emerged as a powerful tool to dissect genome heterogeneity in cancer, neurobiology, and development. To be truly transformative, single-cell approaches must affordably accommodate large numbers of single cells. This is feasible in the case of copy number variation (CNV), because CNV determination requires only sparse sequence coverage. We have used a combination of bioinformatic and molecular approaches to optimize single-cell DNA amplification and library preparation for highly multiplexed sequencing, yielding a method that can produce genome-wide CNV profiles of up to a hundred individual cells on a single lane of an Illumina HiSeq instrument. We apply the method to human cancer cell lines and biopsied cancer tissue, thereby illustrating its efficiency, reproducibility, and power to reveal underlying genetic heterogeneity and clonal phylogeny. The capacity of the method to facilitate the rapid profiling of hundreds to thousands of single-cell genomes represents a key step in making single-cell profiling an easily accessible tool for studying cell lineage.",
			"category": 2,
			"name": "Baslan Timour,2016"
		},
		{
			"PMID": 25849937,
			"title": "Structural variation discovery in the cancer genome using next generation sequencing: computational solutions and perspectives.",
			"journal": "Oncotarget",
			"authorList": [
				"Liu Biao",
				"Conroy Jeffrey M",
				"Morrison Carl D",
				"Odunsi Adekunle O",
				"Qin Maochun",
				"Wei Lei",
				"Trump Donald L",
				"Johnson Candace S",
				"Liu Song",
				"Wang Jianmin"
			],
			"DOI": "",
			"date": "2016-03-03",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic Structural Variations (SVs) are a complex collection of chromosomal mutations that could directly contribute to carcinogenesis. Next Generation Sequencing (NGS) technology has emerged as the primary means of interrogating the SVs of the cancer genome in recent investigations. Sophisticated computational methods are required to accurately identify the SV events and delineate their breakpoints from the massive amounts of reads generated by a NGS experiment. In this review, we provide an overview of current analytic tools used for SV detection in NGS-based cancer studies. We summarize the features of common SV groups and the primary types of NGS signatures that can be used in SV detection methods. We discuss the principles and key similarities and differences of existing computational programs and comment on unresolved issues related to this research field. The aim of this article is to provide a practical guide of relevant concepts, computational methods, software tools and important factors for analyzing and interpreting NGS data for the detection of SVs in the cancer genome.",
			"category": 2,
			"name": "Liu Biao,2016"
		},
		{
			"PMID": 25806684,
			"title": "Experimental evolution reveals hidden diversity in evolutionary pathways.",
			"journal": "eLife",
			"authorList": [
				"Lind Peter A",
				"Farr Andrew D",
				"Rainey Paul B"
			],
			"DOI": "10.7554/eLife.07074",
			"date": "2015-12-23",
			"PMC": "",
			"citation": "",
			"abstract": "Replicate populations of natural and experimental organisms often show evidence of parallel genetic evolution, but the causes are unclear. The wrinkly spreader morph of Pseudomonas fluorescens arises repeatedly during experimental evolution. The mutational causes reside exclusively within three pathways. By eliminating these, 13 new mutational pathways were discovered with the newly arising WS types having fitnesses similar to those arising from the commonly passaged routes. Our findings show that parallel genetic evolution is strongly biased by constraints and we reveal the genetic bases. From such knowledge, and in instances where new phenotypes arise via gene activation, we suggest a set of principles: evolution proceeds firstly via pathways subject to negative regulation, then via promoter mutations and gene fusions, and finally via activation by intragenic gain-of-function mutations. These principles inform evolutionary forecasting and have relevance to interpreting the diverse array of mutations associated with clinically identical instances of disease in humans.",
			"category": 2,
			"name": "Lind Peter A,2015"
		},
		{
			"PMID": 25768946,
			"title": "Clonality and evolutionary history of rhabdomyosarcoma.",
			"journal": "PLoS genetics",
			"authorList": [
				"Chen Li",
				"Shern Jack F",
				"Wei Jun S",
				"Yohe Marielle E",
				"Song Young K",
				"Hurd Laura",
				"Liao Hongling",
				"Catchpoole Daniel",
				"Skapek Stephen X",
				"Barr Frederic G",
				"Hawkins Douglas S",
				"Khan Javed"
			],
			"DOI": "10.1371/journal.pgen.1005075",
			"date": "2015-12-14",
			"PMC": "",
			"citation": "",
			"abstract": "To infer the subclonality of rhabdomyosarcoma (RMS) and predict the temporal order of genetic events for the tumorigenic process, and to identify novel drivers, we applied a systematic method that takes into account germline and somatic alterations in 44 tumor-normal RMS pairs using deep whole-genome sequencing. Intriguingly, we find that loss of heterozygosity of 11p15.5 and mutations in RAS pathway genes occur early in the evolutionary history of the PAX-fusion-negative-RMS (PFN-RMS) subtype. We discover several early mutations in non-RAS mutated samples and predict them to be drivers in PFN-RMS including recurrent mutation of PKN1. In contrast, we find that PAX-fusion-positive (PFP) subtype tumors have undergone whole-genome duplication in the late stage of cancer evolutionary history and have acquired fewer mutations and subclones than PFN-RMS. Moreover we predict that the PAX3-FOXO1 fusion event occurs earlier than the whole genome duplication. Our findings provide information critical to the understanding of tumorigenesis of RMS.",
			"category": 2,
			"name": "Chen Li,2015"
		},
		{
			"PMID": 25740784,
			"title": "Somatic POLE mutations cause an ultramutated giant cell high-grade glioma subtype with better prognosis.",
			"journal": "Neuro-oncology",
			"authorList": [
				"Erson-Omay E Zeynep",
				"\u00c7a\u011flayan Ahmet Okay",
				"Schultz Nikolaus",
				"Weinhold Nils",
				"Omay S B\u00fclent",
				"\u00d6zduman Koray",
				"K\u00f6ksal Yavuz",
				"Li Jie",
				"Serin Harmanc\u0131 Akdes",
				"Clark Victoria",
				"Carri\u00f3n-Grant Geneive",
				"Baranoski Jacob",
				"\u00c7a\u011flar Caner",
				"Barak Tanyeri",
				"Co\u015fkun S\u00fcleyman",
				"Baran Bur\u00e7in",
				"K\u00f6se Do\u011fan",
				"Sun Jia",
				"Bak\u0131rc\u0131o\u011flu Mehmet",
				"Moliterno G\u00fcnel Jennifer",
				"Pamir M Necmettin",
				"Mishra-Gorur Ketu",
				"Bilguvar Kaya",
				"Yasuno Katsuhito",
				"Vortmeyer Alexander",
				"Huttner Anita J",
				"Sander Chris",
				"G\u00fcnel Murat"
			],
			"DOI": "10.1093/neuonc/nov027",
			"date": "2016-06-24",
			"PMC": "",
			"citation": "",
			"abstract": "Malignant high-grade gliomas (HGGs), including the most aggressive form, glioblastoma multiforme, show significant clinical and genomic heterogeneity. Despite recent advances, the overall survival of HGGs and their response to treatment remain poor. In order to gain further insight into disease pathophysiology by correlating genomic landscape with clinical behavior, thereby identifying distinct HGG molecular subgroups associated with improved prognosis, we performed a comprehensive genomic analysis.",
			"category": 2,
			"name": "Erson-Omay E Zeynep,2016"
		},
		{
			"PMID": 25730902,
			"title": "Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis.",
			"journal": "Oncotarget",
			"authorList": [
				"Kr\u00f8ig\u00e5rd Anne Bruun",
				"Larsen Martin Jakob",
				"L\u00e6nkholm Anne-Vibeke",
				"Knoop Ann S",
				"Jensen Jeanette D",
				"Bak Martin",
				"Mollenhauer Jan",
				"Kruse Torben A",
				"Thomassen Mads"
			],
			"DOI": "",
			"date": "2016-03-03",
			"PMC": "",
			"citation": "",
			"abstract": "Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer necessitates knowledge of the degree of genomic concordance between different steps of malignant progression as primary tumors often are used as surrogates of systemic disease. Based on exome sequencing we performed copy number profiling and point mutation detection on successive steps of breast cancer progression from one breast cancer patient, including two different regions of Ductal Carcinoma In Situ (DCIS), primary tumor and an asynchronous metastasis. We identify a remarkable landscape of somatic mutations, retained throughout breast cancer progression and with new mutational events emerging at each step. Our data, contrary to the proposed model of early dissemination of metastatic cells and parallel progression of primary tumors and metastases, provide evidence of linear progression of breast cancer with relatively late dissemination from the primary tumor. The genomic discordance between the different stages of tumor evolution in this patient emphasizes the importance of molecular profiling of metastatic tissue directing molecularly targeted therapy at recurrence.",
			"category": 2,
			"name": "Kr\u00f8ig\u00e5rd Anne Bruun,2016"
		},
		{
			"PMID": 25713148,
			"title": "Primary tumor location as a prognostic factor in metastatic colorectal cancer.",
			"journal": "Journal of the National Cancer Institute",
			"authorList": [
				"Loupakis Fotios",
				"Yang Dongyun",
				"Yau Linda",
				"Feng Shibao",
				"Cremolini Chiara",
				"Zhang Wu",
				"Maus Martin K H",
				"Antoniotti Carlotta",
				"Langer Christiane",
				"Scherer Stefan J",
				"M\u00fcller Thomas",
				"Hurwitz Herbert I",
				"Saltz Leonard",
				"Falcone Alfredo",
				"Lenz Heinz-Josef"
			],
			"DOI": "10.1093/jnci/dju427",
			"date": "2015-04-06",
			"PMC": "",
			"citation": "",
			"abstract": "We sought to clarify the prognostic impact of primary tumor location in metastatic colorectal cancer (mCRC).",
			"category": 2,
			"name": "Loupakis Fotios,2015"
		},
		{
			"PMID": 25671252,
			"title": "Effect of mutation order on myeloproliferative neoplasms.",
			"journal": "The New England journal of medicine",
			"authorList": [
				"Ortmann Christina A",
				"Kent David G",
				"Nangalia Jyoti",
				"Silber Yvonne",
				"Wedge David C",
				"Grinfeld Jacob",
				"Baxter E Joanna",
				"Massie Charles E",
				"Papaemmanuil Elli",
				"Menon Suraj",
				"Godfrey Anna L",
				"Dimitropoulou Danai",
				"Guglielmelli Paola",
				"Bellosillo Beatriz",
				"Besses Carles",
				"D\u00f6hner Konstanze",
				"Harrison Claire N",
				"Vassiliou George S",
				"Vannucchi Alessandro",
				"Campbell Peter J",
				"Green Anthony R"
			],
			"DOI": "10.1056/NEJMoa1412098",
			"date": "2015-02-18",
			"PMC": "",
			"citation": "",
			"abstract": "Cancers result from the accumulation of somatic mutations, and their properties are thought to reflect the sum of these mutations. However, little is known about the effect of the order in which mutations are acquired.",
			"category": 2,
			"name": "Ortmann Christina A,2015"
		},
		{
			"PMID": 25650317,
			"title": "Adaptive mitochondrial reprogramming and resistance to PI3K therapy.",
			"journal": "Journal of the National Cancer Institute",
			"authorList": [
				"Ghosh Jagadish C",
				"Siegelin Markus D",
				"Vaira Valentina",
				"Faversani Alice",
				"Tavecchio Michele",
				"Chae Young Chan",
				"Lisanti Sofia",
				"Rampini Paolo",
				"Giroda Massimo",
				"Caino M Cecilia",
				"Seo Jae Ho",
				"Kossenkov Andrew V",
				"Michalek Ryan D",
				"Schultz David C",
				"Bosari Silvano",
				"Languino Lucia R",
				"Altieri Dario C"
			],
			"DOI": "10.1093/jnci/dju502",
			"date": "2015-04-06",
			"PMC": "",
			"citation": "",
			"abstract": "Small molecule inhibitors of phosphatidylinositol-3 kinase (PI3K) have been developed as molecular therapy for cancer, but their efficacy in the clinic is modest, hampered by resistance mechanisms.",
			"category": 2,
			"name": "Ghosh Jagadish C,2015"
		},
		{
			"PMID": 25650244,
			"title": "Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution.",
			"journal": "Genome research",
			"authorList": [
				"Kim Hoon",
				"Zheng Siyuan",
				"Amini Seyed S",
				"Virk Selene M",
				"Mikkelsen Tom",
				"Brat Daniel J",
				"Grimsby Jonna",
				"Sougnez Carrie",
				"Muller Florian",
				"Hu Jian",
				"Sloan Andrew E",
				"Cohen Mark L",
				"Van Meir Erwin G",
				"Scarpace Lisa",
				"Laird Peter W",
				"Weinstein John N",
				"Lander Eric S",
				"Gabriel Stacey",
				"Getz Gad",
				"Meyerson Matthew",
				"Chin Lynda",
				"Barnholtz-Sloan Jill S",
				"Verhaak Roel G W"
			],
			"DOI": "10.1101/gr.180612.114",
			"date": "2015-11-20",
			"PMC": "",
			"citation": "",
			"abstract": "Glioblastoma (GBM) is a prototypical heterogeneous brain tumor refractory to conventional therapy. A small residual population of cells escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence \u223c 7 mo after diagnosis. Understanding the molecular architecture of this residual population is critical for the development of successful therapies. We used whole-genome sequencing and whole-exome sequencing of multiple sectors from primary and paired recurrent GBM tumors to reconstruct the genomic profile of residual, therapy resistant tumor initiating cells. We found that genetic alteration of the p53 pathway is a primary molecular event predictive of a high number of subclonal mutations in glioblastoma. The genomic road leading to recurrence is highly idiosyncratic but can be broadly classified into linear recurrences that share extensive genetic similarity with the primary tumor and can be directly traced to one of its specific sectors, and divergent recurrences that share few genetic alterations with the primary tumor and originate from cells that branched off early during tumorigenesis. Our study provides mechanistic insights into how genetic alterations in primary tumors impact the ensuing evolution of tumor cells and the emergence of subclonal heterogeneity.",
			"category": 2,
			"name": "Kim Hoon,2015"
		},
		{
			"PMID": 25635677,
			"title": "Macrotene chromosomes provide insights to a new mechanism of high-order gene amplification in eukaryotes.",
			"journal": "Nature communications",
			"authorList": [
				"Thierry Agn\u00e8s",
				"Khanna Varun",
				"Cr\u00e9no Sophie",
				"Lafontaine Ingrid",
				"Ma Laurence",
				"Bouchier Christiane",
				"Dujon Bernard"
			],
			"DOI": "10.1038/ncomms7154",
			"date": "2015-10-26",
			"PMC": "",
			"citation": "",
			"abstract": "Copy number variation of chromosomal segments is now recognized as a major source of genetic polymorphism within natural populations of eukaryotes, as well as a possible cause of genetic diseases in humans, including cancer, but its molecular bases remain incompletely understood. In the baker's yeast Saccharomyces cerevisiae, a variety of low-order amplifications (segmental duplications) were observed after adaptation to limiting environmental conditions or recovery from gene dosage imbalance, and interpreted in terms of replication-based mechanisms associated or not with homologous recombination. Here we show the emergence of novel high-order amplification structures, with corresponding overexpression of embedded genes, during evolution under favourable growth conditions of severely unfit yeast cells bearing genetically disabled genomes. Such events form massively extended chromosomes, which we propose to call macrotene, whose characteristics suggest the products of intrachromosomal rolling-circle type of replication structures, probably initiated by increased accidental template switches under important cellular stress conditions.",
			"category": 2,
			"name": "Thierry Agn\u00e8s,2015"
		},
		{
			"PMID": 25600866,
			"title": "Cooperation between Noncanonical Ras Network Mutations.",
			"journal": "Cell reports",
			"authorList": [
				"Stites Edward C",
				"Trampont Paul C",
				"Haney Lisa B",
				"Walk Scott F",
				"Ravichandran Kodi S"
			],
			"DOI": "10.1016/j.celrep.2014.12.035",
			"date": "2022-08-17",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer develops after the acquisition of a collection of mutations that together create the cancer phenotype. How collections of mutations work together within a cell and whether there is selection for certain combinations of mutations are not well understood. We investigated this problem with a mathematical model of the Ras signaling network, including a computational random mutagenesis. Modeling and subsequent experiments revealed that mutations of the tumor suppressor gene NF1 can amplify the effects of other Ras pathway mutations, including weakly activating, noncanonical Ras mutants. Furthermore, analyzing recently available, large, cancer genomic data sets uncovered increased co-occurrence of NF1 mutations with mutations in other Ras network genes. Overall, these data suggest that combinations of Ras pathway mutations could serve the role of cancer \"driver.\" More generally, this work suggests that mutations that result in network instability may promote cancer in a manner analogous to genomic instability.",
			"category": 2,
			"name": "Stites Edward C,2022"
		},
		{
			"PMID": 25383969,
			"title": "Systematic analysis of noncoding somatic mutations and gene expression alterations across 14 tumor types.",
			"journal": "Nature genetics",
			"authorList": [
				"Fredriksson Nils J",
				"Ny Lars",
				"Nilsson Jonas A",
				"Larsson Erik"
			],
			"DOI": "10.1038/ng.3141",
			"date": "2015-01-23",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic mutations in noncoding sequences are poorly explored in cancer, a rare exception being the recent identification of activating mutations in TERT regulatory DNA. Although this finding is suggestive of a general mechanism for oncogene activation, this hypothesis remains untested. Here we map somatic mutations in 505 tumor genomes across 14 cancer types and systematically screen for associations between mutations in regulatory regions and RNA-level changes. We identify recurrent promoter mutations in several genes but find that TERT mutations are exceptional in showing a strong and genome-wide significant association with increased expression. Detailed analysis of TERT across cancers shows that the strength of this association is highly variable and is strongest in copy number-stable cancers such as thyroid carcinoma. We additionally propose that TERT promoter mutations control expression of the nearby gene CLPTM1L. Our analysis provides a detailed pan-cancer view of TERT transcriptional activation but finds no clear evidence for frequent oncogenic promoter mutations beyond TERT.",
			"category": 2,
			"name": "Fredriksson Nils J,2015"
		},
		{
			"PMID": 25288776,
			"title": "JAK2V617F promotes replication fork stalling with disease-restricted impairment of the intra-S checkpoint response.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Chen Edwin",
				"Ahn Jong Sook",
				"Massie Charlie E",
				"Clynes David",
				"Godfrey Anna L",
				"Li Juan",
				"Park Hyun Jung",
				"Nangalia Jyoti",
				"Silber Yvonne",
				"Mullally Ann",
				"Gibbons Richard J",
				"Green Anthony R"
			],
			"DOI": "10.1073/pnas.1401873111",
			"date": "2015-04-24",
			"PMC": "",
			"citation": "",
			"abstract": "Cancers result from the accumulation of genetic lesions, but the cellular consequences of driver mutations remain unclear, especially during the earliest stages of malignancy. The V617F mutation in the JAK2 non-receptor tyrosine kinase (JAK2V617F) is present as an early somatic event in most patients with myeloproliferative neoplasms (MPNs), and the study of these chronic myeloid malignancies provides an experimentally tractable approach to understanding early tumorigenesis. Introduction of exogenous JAK2V617F impairs replication fork progression and is associated with activation of the intra-S checkpoint, with both effects mediated by phosphatidylinositide 3-kinase (PI3K) signaling. Analysis of clonally derived JAK2V617F-positive erythroblasts from MPN patients also demonstrated impaired replication fork progression accompanied by increased levels of replication protein A (RPA)-containing foci. However, the associated intra-S checkpoint response was impaired in erythroblasts from polycythemia vera (PV) patients, but not in those from essential thrombocythemia (ET) patients. Moreover, inhibition of p53 in PV erythroblasts resulted in more gamma-H2Ax (\u03b3-H2Ax)-marked double-stranded breaks compared with in like-treated ET erythroblasts, suggesting the defective intra-S checkpoint function seen in PV increases DNA damage in the context of attenuated p53 signaling. These results demonstrate oncogene-induced impairment of replication fork progression in primary cells from MPN patients, reveal unexpected disease-restricted differences in activation of the intra-S checkpoint, and have potential implications for the clonal evolution of malignancies.",
			"category": 2,
			"name": "Chen Edwin,2015"
		},
		{
			"PMID": 25283145,
			"title": "The FHIT gene product: tumor suppressor and genome \"caretaker\".",
			"journal": "Cellular and molecular life sciences : CMLS",
			"authorList": [
				"Waters Catherine E",
				"Saldivar Joshua C",
				"Hosseini Seyed Ali",
				"Huebner Kay"
			],
			"DOI": "10.1007/s00018-014-1722-0",
			"date": "2015-01-12",
			"PMC": "",
			"citation": "",
			"abstract": "The FHIT gene at FRA3B is one of the earliest and most frequently altered genes in the majority of human cancers. It was recently discovered that the FHIT gene is not the most fragile locus in epithelial cells, the cell of origin for most Fhit-negative cancers, eroding support for past claims that deletions at this locus are simply passenger events that are carried along in expanding cancer clones, due to extreme vulnerability to DNA damage rather than to loss of FHIT function. Indeed, recent reports have reconfirmed FHIT as a tumor suppressor gene with roles in apoptosis and prevention of the epithelial-mesenchymal transition. Other recent works have identified a novel role for the FHIT gene product, Fhit, as a genome \"caretaker.\" Loss of this caretaker function leads to nucleotide imbalance, spontaneous replication stress, and DNA breaks. Because Fhit loss-induced DNA damage is \"checkpoint blind,\" cells accumulate further DNA damage during subsequent cell cycles, accruing global genome instability that could facilitate oncogenic mutation acquisition and expedite clonal expansion. Loss of Fhit activity therefore induces a mutator phenotype. Evidence for FHIT as a mutator gene is discussed in light of these recent investigations of Fhit loss and subsequent genome instability.",
			"category": 2,
			"name": "Waters Catherine E,2015"
		},
		{
			"PMID": 25253082,
			"title": "A general framework for analyzing tumor subclonality using SNP array and DNA sequencing data.",
			"journal": "Genome biology",
			"authorList": [
				"Li Bo",
				"Li Jun Z"
			],
			"DOI": "10.1186/s13059-014-0473-4",
			"date": "2015-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "Intra-tumor heterogeneity reflects cancer genome evolution and provides key information for diagnosis and treatment. When bulk tumor tissues are profiled for somatic copy number alterations (sCNA) and point mutations, it may be difficult to estimate their cellular fractions when a mutation falls within a sCNA. We present the Clonal Heterogeneity Analysis Tool, which estimates cellular fractions for both sCNAs and mutations, and uses their distributions to inform macroscopic clonal architecture. In a set of approximately 700 breast tumors, more than half appear to contain multiple recognizable aneuploid tumor clones, and many show subtype-specific differences in clonality for known cancer genes.",
			"category": 2,
			"name": "Li Bo,2015"
		},
		{
			"PMID": 25173447,
			"title": "Dihydropyrimidinase-like 3 is a putative hepatocellular carcinoma tumor suppressor.",
			"journal": "Journal of gastroenterology",
			"authorList": [
				"Oya Hisaharu",
				"Kanda Mitsuro",
				"Sugimoto Hiroyuki",
				"Shimizu Dai",
				"Takami Hideki",
				"Hibino Soki",
				"Hashimoto Ryoji",
				"Okamura Yukiyasu",
				"Yamada Suguru",
				"Fujii Tsutomu",
				"Nakayama Goro",
				"Koike Masahiko",
				"Nomoto Shuji",
				"Fujiwara Michitaka",
				"Kodera Yasuhiro"
			],
			"DOI": "10.1007/s00535-014-0993-4",
			"date": "2016-03-04",
			"PMC": "",
			"citation": "",
			"abstract": "Patients with hepatocellular carcinoma (HCC) may relapse after curative resection. Sensitive biomarkers for HCC are required to enhance disease management. Dihydropyrimidinase-like 3 (DPYSL3) suppresses cell proliferation and tumorigenicity of certain malignancies; however, its role in HCC is unknown.",
			"category": 2,
			"name": "Oya Hisaharu,2016"
		},
		{
			"PMID": 25155694,
			"title": "Cancer progression modeling using static sample data.",
			"journal": "Genome biology",
			"authorList": [
				"Sun Yijun",
				"Yao Jin",
				"Nowak Norma J",
				"Goodison Steve"
			],
			"DOI": "10.1186/s13059-014-0440-0",
			"date": "2015-06-24",
			"PMC": "",
			"citation": "",
			"abstract": "As molecular profiling data continues to accumulate, the design of integrative computational analyses that can provide insights into the dynamic aspects of cancer progression becomes feasible. Here, we present a novel computational method for the construction of cancer progression models based on the analysis of static tumor samples. We demonstrate the reliability of the method with simulated data, and describe the application to breast cancer data. Our findings support a linear, branching model for breast cancer progression. An interactive model facilitates the identification of key molecular events in the advance of disease to malignancy.",
			"category": 2,
			"name": "Sun Yijun,2015"
		},
		{
			"PMID": 25103687,
			"title": "Biased estimates of clonal evolution and subclonal heterogeneity can arise from PCR duplicates in deep sequencing experiments.",
			"journal": "Genome biology",
			"authorList": [
				"Smith Erin N",
				"Jepsen Kristen",
				"Khosroheidari Mahdieh",
				"Rassenti Laura Z",
				"D'Antonio Matteo",
				"Ghia Emanuela M",
				"Carson Dennis A",
				"Jamieson Catriona Hm",
				"Kipps Thomas J",
				"Frazer Kelly A"
			],
			"DOI": "10.1186/s13059-014-0420-4",
			"date": "2015-06-24",
			"PMC": "",
			"citation": "",
			"abstract": "Accurate allele frequencies are important for measuring subclonal heterogeneity and clonal evolution. Deep-targeted sequencing data can contain PCR duplicates, inflating perceived read depth. Here we adapted the Illumina TruSeq Custom Amplicon kit to include single molecule tagging (SMT) and show that SMT-identified duplicates arise from PCR. We demonstrate that retention of PCR duplicate reads can imply clonal evolution when none exists, while their removal effectively controls the false positive rate. Additionally, PCR duplicates alter estimates of subclonal heterogeneity in tumor samples. Our method simplifies PCR duplicate identification and emphasizes their removal in studies of tumor heterogeneity and clonal evolution.",
			"category": 2,
			"name": "Smith Erin N,2015"
		},
		{
			"PMID": 25101266,
			"title": "Implications of heterogeneity in multiple myeloma.",
			"journal": "BioMed research international",
			"authorList": [
				"de Mel Sanjay",
				"Lim Su Hong",
				"Tung Moon Ley",
				"Chng Wee-Joo"
			],
			"DOI": "10.1155/2014/232546",
			"date": "2015-04-14",
			"PMC": "",
			"citation": "",
			"abstract": "Multiple myeloma is the second most common hematologic malignancy in the world. Despite improvement in outcome, the disease is still incurable for most patients. However, not all myeloma are the same. With the same treatment, some patients can have very long survival whereas others can have very short survival. This suggests that there is underlying heterogeneity in myeloma. Studies over the years have revealed multiple layers of heterogeneity. First, clinical parameters such as age and tumor burden could significantly affect outcome. At the genetic level, there are also significant heterogeneity ranging for chromosome numbers, genetic translocations, and genetic mutations. At the clonal level, there appears to be significant clonal heterogeneity with multiple clones coexisting in the same patient. At the cell differentiation level, there appears to be a hierarchy of clonally related cells that have different clonogenic potential and sensitivity to therapies. These levels of complexities present challenges in terms of treatment and prognostication as well as monitoring of treatment. However, if we can clearly delineate and dissect this heterogeneity, we may also be presented with unique opportunities for precision and personalized treatment of myeloma. Some proof of concepts of such approaches has been demonstrated.",
			"category": 2,
			"name": "de Mel Sanjay,2015"
		},
		{
			"PMID": 25087573,
			"title": "Tumour heterogeneity and the evolution of polyclonal drug resistance.",
			"journal": "Molecular oncology",
			"authorList": [
				"Burrell Rebecca A",
				"Swanton Charles"
			],
			"DOI": "10.1016/j.molonc.2014.06.005",
			"date": "2015-10-30",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer drug resistance is a major problem, with the majority of patients with metastatic disease ultimately developing multidrug resistance and succumbing to their disease. Our understanding of molecular events underpinning treatment failure has been enhanced by new genomic technologies and pre-clinical studies. Intratumour genetic heterogeneity (ITH) is a prominent contributor to therapeutic failure, and it is becoming increasingly apparent that individual tumours may achieve resistance via multiple routes simultaneously - termed polyclonal resistance. Efforts to target single resistance mechanisms to overcome therapeutic failure may therefore yield only limited success. Clinical studies with sequential analysis of tumour material are needed to enhance our understanding of inter-clonal functional relationships and tumour evolution during therapy, and to improve drug development strategies in cancer medicine.",
			"category": 2,
			"name": "Burrell Rebecca A,2015"
		},
		{
			"PMID": 25003521,
			"title": "Tracking genomic cancer evolution for precision medicine: the lung TRACERx study.",
			"journal": "PLoS biology",
			"authorList": [
				"Jamal-Hanjani Mariam",
				"Hackshaw Alan",
				"Ngai Yenting",
				"Shaw Jacqueline",
				"Dive Caroline",
				"Quezada Sergio",
				"Middleton Gary",
				"de Bruin Elza",
				"Le Quesne John",
				"Shafi Seema",
				"Falzon Mary",
				"Horswell Stuart",
				"Blackhall Fiona",
				"Khan Iftekhar",
				"Janes Sam",
				"Nicolson Marianne",
				"Lawrence David",
				"Forster Martin",
				"Fennell Dean",
				"Lee Siow-Ming",
				"Lester Jason",
				"Kerr Keith",
				"Muller Salli",
				"Iles Natasha",
				"Smith Sean",
				"Murugaesu Nirupa",
				"Mitter Richard",
				"Salm Max",
				"Stuart Aengus",
				"Matthews Nik",
				"Adams Haydn",
				"Ahmad Tanya",
				"Attanoos Richard",
				"Bennett Jonathan",
				"Birkbak Nicolai Juul",
				"Booton Richard",
				"Brady Ged",
				"Buchan Keith",
				"Capitano Arrigo",
				"Chetty Mahendran",
				"Cobbold Mark",
				"Crosbie Philip",
				"Davies Helen",
				"Denison Alan",
				"Djearman Madhav",
				"Goldman Jacki",
				"Haswell Tom",
				"Joseph Leena",
				"Kornaszewska Malgorzata",
				"Krebs Matthew",
				"Langman Gerald",
				"MacKenzie Mairead",
				"Millar Joy",
				"Morgan Bruno",
				"Naidu Babu",
				"Nonaka Daisuke",
				"Peggs Karl",
				"Pritchard Catrin",
				"Remmen Hardy",
				"Rowan Andrew",
				"Shah Rajesh",
				"Smith Elaine",
				"Summers Yvonne",
				"Taylor Magali",
				"Veeriah Selvaraju",
				"Waller David",
				"Wilcox Ben",
				"Wilcox Maggie",
				"Woolhouse Ian",
				"McGranahan Nicholas",
				"Swanton Charles"
			],
			"DOI": "10.1371/journal.pbio.1001906",
			"date": "2015-02-24",
			"PMC": "",
			"citation": "",
			"abstract": "The importance of intratumour genetic and functional heterogeneity is increasingly recognised as a driver of cancer progression and survival outcome. Understanding how tumour clonal heterogeneity impacts upon therapeutic outcome, however, is still an area of unmet clinical and scientific need. TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy [Rx]), a prospective study of patients with primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through multiregion and longitudinal tumour sampling and genetic analysis. By following cancers from diagnosis to relapse, tracking the evolutionary trajectories of tumours in relation to therapeutic interventions, and determining the impact of clonal heterogeneity on clinical outcomes, TRACERx may help to identify novel therapeutic targets for NSCLC and may also serve as a model applicable to other cancer types.",
			"category": 2,
			"name": "Jamal-Hanjani Mariam,2015"
		},
		{
			"PMID": 24995162,
			"title": "Chromosomal instability, aneuploidy, and cancer.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Bakhoum Samuel F",
				"Swanton Charles"
			],
			"DOI": "10.3389/fonc.2014.00161",
			"date": "2014-07-04",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Bakhoum Samuel F,2014"
		},
		{
			"PMID": 24904834,
			"title": "Size Does Matter: Why Polyploid Tumor Cells are Critical Drug Targets in the War on Cancer.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Coward Jermaine",
				"Harding Angus"
			],
			"DOI": "10.3389/fonc.2014.00123",
			"date": "2014-06-24",
			"PMC": "",
			"citation": "",
			"abstract": "Tumor evolution presents a formidable obstacle that currently prevents the development of truly curative treatments for cancer. In this perspective, we advocate for the hypothesis that tumor cells with significantly elevated genomic content (polyploid tumor cells) facilitate rapid tumor evolution and the acquisition of therapy resistance in multiple incurable cancers. We appeal to studies conducted in yeast, cancer models, and cancer patients, which all converge on the hypothesis that polyploidy enables large phenotypic leaps, providing access to many different therapy-resistant phenotypes. We develop a flow-cytometry based method for quantifying the prevalence of polyploid tumor cells, and show the frequency of these cells in patient tumors may be higher than is generally appreciated. We then present recent studies identifying promising new therapeutic strategies that could be used to specifically target polyploid tumor cells in cancer patients. We argue that these therapeutic approaches should be incorporated into new treatment strategies aimed at blocking tumor evolution by killing the highly evolvable, therapy-resistant polyploid cell subpopulations, thus helping to maintain patient tumors in a drug sensitive state.",
			"category": 2,
			"name": "Coward Jermaine,2014"
		},
		{
			"PMID": 24893890,
			"title": "EGFR variant heterogeneity in glioblastoma resolved through single-nucleus sequencing.",
			"journal": "Cancer discovery",
			"authorList": [
				"Francis Joshua M",
				"Zhang Cheng-Zhong",
				"Maire Cecile L",
				"Jung Joonil",
				"Manzo Veronica E",
				"Adalsteinsson Viktor A",
				"Homer Heather",
				"Haidar Sam",
				"Blumenstiel Brendan",
				"Pedamallu Chandra Sekhar",
				"Ligon Azra H",
				"Love J Christopher",
				"Meyerson Matthew",
				"Ligon Keith L"
			],
			"DOI": "10.1158/2159-8290.CD-13-0879",
			"date": "2015-03-31",
			"PMC": "",
			"citation": "",
			"abstract": "Glioblastomas (GBM) with EGFR amplification represent approximately 50% of newly diagnosed cases, and recent studies have revealed frequent coexistence of multiple EGFR aberrations within the same tumor, which has implications for mutation cooperation and treatment resistance. However, bulk tumor sequencing studies cannot resolve the patterns of how the multiple EGFR aberrations coexist with other mutations within single tumor cells. Here, we applied a population-based single-cell whole-genome sequencing methodology to characterize genomic heterogeneity in EGFR-amplified glioblastomas. Our analysis effectively identified clonal events, including a novel translocation of a super enhancer to the TERT promoter, as well as subclonal LOH and multiple EGFR mutational variants within tumors. Correlating the EGFR mutations onto the cellular hierarchy revealed that EGFR truncation variants (EGFRvII and EGFR carboxyl-terminal deletions) identified in the bulk tumor segregate into nonoverlapping subclonal populations. In vitro and in vivo functional studies show that EGFRvII is oncogenic and sensitive to EGFR inhibitors currently in clinical trials. Thus, the association between diverse activating mutations in EGFR and other subclonal mutations within a single tumor supports an intrinsic mechanism for proliferative and clonal diversification with broad implications in resistance to treatment.",
			"category": 2,
			"name": "Francis Joshua M,2015"
		},
		{
			"PMID": 24686286,
			"title": "From genomes to societies: a holistic view of determinants of human health.",
			"journal": "Current opinion in biotechnology",
			"authorList": [
				"Shi Yuyan",
				"Zhong Sheng"
			],
			"DOI": "10.1016/j.copbio.2014.03.001",
			"date": "2014-10-03",
			"PMC": "",
			"citation": "",
			"abstract": "Both biological and social sciences have identified contributing factors to human health. However, health outcomes are unlikely to equal a simple sum of these identified factors. This article makes an attempt to put together the information, methods, and technologies that relate to health outcomes from biological, behavioral, and social disciplines. Much of this information was obtained by controlling for the variations of the factors in 'other' disciplines. For example, genetic factors were controlled for in identifying the behavioral determinants of health. Looking forward, better understandings of health outcomes may require exploiting the interactions of health determinants that were identified from different disciplines. We propose the concept of 'systems health' studies, which take health outcomes as the outputs of a system, where the inputs and their interactions from multiple disciplines are considered.",
			"category": 2,
			"name": "Shi Yuyan,2014"
		},
		{
			"PMID": 24668804,
			"title": "Biochemical, cellular, and biophysical characterization of a potent inhibitor of mutant isocitrate dehydrogenase IDH1.",
			"journal": "The Journal of biological chemistry",
			"authorList": [
				"Davis Mindy I",
				"Gross Stefan",
				"Shen Min",
				"Straley Kimberly S",
				"Pragani Rajan",
				"Lea Wendy A",
				"Popovici-Muller Janeta",
				"DeLaBarre Byron",
				"Artin Erin",
				"Thorne Natasha",
				"Auld Douglas S",
				"Li Zhuyin",
				"Dang Lenny",
				"Boxer Matthew B",
				"Simeonov Anton"
			],
			"DOI": "10.1074/jbc.M113.511030",
			"date": "2014-12-17",
			"PMC": "",
			"citation": "",
			"abstract": "Two mutant forms (R132H and R132C) of isocitrate dehydrogenase 1 (IDH1) have been associated with a number of cancers including glioblastoma and acute myeloid leukemia. These mutations confer a neomorphic activity of 2-hydroxyglutarate (2-HG) production, and 2-HG has previously been implicated as an oncometabolite. Inhibitors of mutant IDH1 can potentially be used to treat these diseases. In this study, we investigated the mechanism of action of a newly discovered inhibitor, ML309, using biochemical, cellular, and biophysical approaches. Substrate binding and product inhibition studies helped to further elucidate the IDH1 R132H catalytic cycle. This rapidly equilibrating inhibitor is active in both biochemical and cellular assays. The (+) isomer is active (IC50 = 68 nm), whereas the (-) isomer is over 400-fold less active (IC50 = 29 \u03bcm) for IDH1 R132H inhibition. IDH1 R132C was similarly inhibited by (+)-ML309. WT IDH1 was largely unaffected by (+)-ML309 (IC50 >36 \u03bcm). Kinetic analyses combined with microscale thermophoresis and surface plasmon resonance indicate that this reversible inhibitor binds to IDH1 R132H competitively with respect to \u03b1-ketoglutarate and uncompetitively with respect to NADPH. A reaction scheme for IDH1 R132H inhibition by ML309 is proposed in which ML309 binds to IDH1 R132H after formation of the IDH1 R132H NADPH complex. ML309 was also able to inhibit 2-HG production in a glioblastoma cell line (IC50 = 250 nm) and had minimal cytotoxicity. In the presence of racemic ML309, 2-HG levels drop rapidly. This drop was sustained until 48 h, at which point the compound was washed out and 2-HG levels recovered.",
			"category": 2,
			"name": "Davis Mindy I,2014"
		},
		{
			"PMID": 24589717,
			"title": "Antibody engineering and therapeutics, The Annual Meeting of the Antibody Society: December 8-12, 2013, Huntington Beach, CA.",
			"journal": "mAbs",
			"authorList": [
				"Almagro Juan Carlos",
				"Gilliland Gary L",
				"Breden Felix",
				"Scott Jamie K",
				"Sok Devin",
				"Pauthner Matthias",
				"Reichert Janice M",
				"Helguera Gustavo",
				"Andrabi Raiees",
				"Mabry Robert",
				"Bl\u00e9ry Mathieu",
				"Voss James E",
				"Laur\u00e9n Juha",
				"Abuqayyas Lubna",
				"Barghorn Stefan",
				"Ben-Jacob Eshel",
				"Crowe James E",
				"Huston James S",
				"Johnston Stephen Albert",
				"Krauland Eric",
				"Lund-Johansen Fridtjof",
				"Marasco Wayne A",
				"Parren Paul W H I",
				"Xu Kai Y"
			],
			"DOI": "10.4161/mabs.28421",
			"date": "2015-05-12",
			"PMC": "",
			"citation": "",
			"abstract": "The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates.",
			"category": 2,
			"name": "Almagro Juan Carlos,2015"
		},
		{
			"PMID": 24553385,
			"title": "Detection of circulating tumor DNA in early- and late-stage human malignancies.",
			"journal": "Science translational medicine",
			"authorList": [
				"Bettegowda Chetan",
				"Sausen Mark",
				"Leary Rebecca J",
				"Kinde Isaac",
				"Wang Yuxuan",
				"Agrawal Nishant",
				"Bartlett Bjarne R",
				"Wang Hao",
				"Luber Brandon",
				"Alani Rhoda M",
				"Antonarakis Emmanuel S",
				"Azad Nilofer S",
				"Bardelli Alberto",
				"Brem Henry",
				"Cameron John L",
				"Lee Clarence C",
				"Fecher Leslie A",
				"Gallia Gary L",
				"Gibbs Peter",
				"Le Dung",
				"Giuntoli Robert L",
				"Goggins Michael",
				"Hogarty Michael D",
				"Holdhoff Matthias",
				"Hong Seung-Mo",
				"Jiao Yuchen",
				"Juhl Hartmut H",
				"Kim Jenny J",
				"Siravegna Giulia",
				"Laheru Daniel A",
				"Lauricella Calogero",
				"Lim Michael",
				"Lipson Evan J",
				"Marie Suely Kazue Nagahashi",
				"Netto George J",
				"Oliner Kelly S",
				"Olivi Alessandro",
				"Olsson Louise",
				"Riggins Gregory J",
				"Sartore-Bianchi Andrea",
				"Schmidt Kerstin",
				"Shih le-Ming",
				"Oba-Shinjo Sueli Mieko",
				"Siena Salvatore",
				"Theodorescu Dan",
				"Tie Jeanne",
				"Harkins Timothy T",
				"Veronese Silvio",
				"Wang Tian-Li",
				"Weingart Jon D",
				"Wolfgang Christopher L",
				"Wood Laura D",
				"Xing Dongmei",
				"Hruban Ralph H",
				"Wu Jian",
				"Allen Peter J",
				"Schmidt C Max",
				"Choti Michael A",
				"Velculescu Victor E",
				"Kinzler Kenneth W",
				"Vogelstein Bert",
				"Papadopoulos Nickolas",
				"Diaz Luis A"
			],
			"DOI": "10.1126/scitranslmed.3007094",
			"date": "2014-10-21",
			"PMC": "",
			"citation": "",
			"abstract": "The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.",
			"category": 2,
			"name": "Bettegowda Chetan,2014"
		},
		{
			"PMID": 24522528,
			"title": "Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia.",
			"journal": "Nature",
			"authorList": [
				"Shlush Liran I",
				"Zandi Sasan",
				"Mitchell Amanda",
				"Chen Weihsu Claire",
				"Brandwein Joseph M",
				"Gupta Vikas",
				"Kennedy James A",
				"Schimmer Aaron D",
				"Schuh Andre C",
				"Yee Karen W",
				"McLeod Jessica L",
				"Doedens Monica",
				"Medeiros Jessie J F",
				"Marke Rene",
				"Kim Hyeoung Joon",
				"Lee Kwon",
				"McPherson John D",
				"Hudson Thomas J",
				"HALT Pan-Leukemia Gene Panel Consortium",
				"Brown Andrew M K",
				"Yousif Fouad",
				"Trinh Quang M",
				"Stein Lincoln D",
				"Minden Mark D",
				"Wang Jean C Y",
				"Dick John E"
			],
			"DOI": "10.1038/nature13038",
			"date": "2014-03-12",
			"PMC": "",
			"citation": "",
			"abstract": "In acute myeloid leukaemia (AML), the cell of origin, nature and biological consequences of initiating lesions, and order of subsequent mutations remain poorly understood, as AML is typically diagnosed without observation of a pre-leukaemic phase. Here, highly purified haematopoietic stem cells (HSCs), progenitor and mature cell fractions from the blood of AML patients were found to contain recurrent DNMT3A mutations (DNMT3A(mut)) at high allele frequency, but without coincident NPM1 mutations (NPM1c) present in AML blasts. DNMT3A(mut)-bearing HSCs showed a multilineage repopulation advantage over non-mutated HSCs in xenografts, establishing their identity as pre-leukaemic HSCs. Pre-leukaemic HSCs were found in remission samples, indicating that they survive chemotherapy. Therefore DNMT3A(mut) arises early in AML evolution, probably in HSCs, leading to a clonally expanded pool of pre-leukaemic HSCs from which AML evolves. Our findings provide a paradigm for the detection and treatment of pre-leukaemic clones before the acquisition of additional genetic lesions engenders greater therapeutic resistance.",
			"category": 2,
			"name": "Shlush Liran I,2014"
		},
		{
			"PMID": 24476156,
			"title": "Chromothripsis-like patterns are recurring but heterogeneously distributed features in a survey of 22,347 cancer genome screens.",
			"journal": "BMC genomics",
			"authorList": [
				"Cai Haoyang",
				"Kumar Nitin",
				"Bagheri Homayoun C",
				"von Mering Christian",
				"Robinson Mark D",
				"Baudis Michael"
			],
			"DOI": "10.1186/1471-2164-15-82",
			"date": "2014-08-29",
			"PMC": "",
			"citation": "",
			"abstract": "Chromothripsis is a recently discovered phenomenon of genomic rearrangement, possibly arising during a single genome-shattering event. This could provide an alternative paradigm in cancer development, replacing the gradual accumulation of genomic changes with a \"one-off\" catastrophic event. However, the term has been used with varying operational definitions, with the minimal consensus being a large number of locally clustered copy number aberrations. The mechanisms underlying these chromothripsis-like patterns (CTLP) and their specific impact on tumorigenesis are still poorly understood.",
			"category": 2,
			"name": "Cai Haoyang,2014"
		},
		{
			"PMID": 24453001,
			"title": "Chromosome 10, frequently lost in human melanoma, encodes multiple tumor-suppressive functions.",
			"journal": "Cancer research",
			"authorList": [
				"Kwong Lawrence N",
				"Chin Lynda"
			],
			"DOI": "10.1158/0008-5472.CAN-13-1446",
			"date": "2014-05-08",
			"PMC": "",
			"citation": "",
			"abstract": "Although many DNA aberrations in melanoma have been well characterized, including focal amplification and deletions of oncogenes and tumor suppressors, broad regions of chromosomal gain and loss are less well understood. One possibility is that these broad events are a consequence of collateral damage from targeting single loci. Another possibility is that the loss of large regions permits the simultaneous repression of multiple tumor suppressors by broadly decreasing the resident gene dosage and expression. Here, we test this hypothesis in a targeted fashion using RNA interference to suppress multiple candidate residents in broad regions of loss. We find that loss of chromosome regions 6q, 10, and 11q21-ter is correlated with broadly decreased expression of most resident genes and that multiple resident genes impacted by broad regional loss of chromosome 10 are tumor suppressors capable of affecting tumor growth and/or invasion. We also provide additional functional support for Ablim1 as a novel tumor suppressor. Our results support the hypothesis that multiple cancer genes are targeted by regional chromosome copy number aberrations.",
			"category": 2,
			"name": "Kwong Lawrence N,2014"
		},
		{
			"PMID": 24443148,
			"title": "Subclonal variant calling with multiple samples and prior knowledge.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Gerstung Moritz",
				"Papaemmanuil Elli",
				"Campbell Peter J"
			],
			"DOI": "10.1093/bioinformatics/btt750",
			"date": "2014-07-31",
			"PMC": "",
			"citation": "",
			"abstract": "Targeted resequencing of cancer genes in large cohorts of patients is important to understand the biological and clinical consequences of mutations. Cancers are often clonally heterogeneous, and the detection of subclonal mutations is important from a diagnostic point of view, but presents strong statistical challenges.",
			"category": 2,
			"name": "Gerstung Moritz,2014"
		},
		{
			"PMID": 24298051,
			"title": "Chromothripsis and beyond: rapid genome evolution from complex chromosomal rearrangements.",
			"journal": "Genes & development",
			"authorList": [
				"Zhang Cheng-Zhong",
				"Leibowitz Mitchell L",
				"Pellman David"
			],
			"DOI": "10.1101/gad.229559.113",
			"date": "2014-01-23",
			"PMC": "",
			"citation": "",
			"abstract": "Recent genome sequencing studies have identified several classes of complex genomic rearrangements that appear to be derived from a single catastrophic event. These discoveries identify ways that genomes can be altered in single large jumps rather than by many incremental steps. Here we compare and contrast these phenomena and examine the evidence that they arise \"all at once.\" We consider the impact of massive chromosomal change for the development of diseases such as cancer and for evolution more generally. Finally, we summarize current models for underlying mechanisms and discuss strategies for testing these models.",
			"category": 2,
			"name": "Zhang Cheng-Zhong,2014"
		},
		{
			"PMID": 24267946,
			"title": "Intra-tumor heterogeneity: lessons from microbial evolution and clinical implications.",
			"journal": "Genome medicine",
			"authorList": [
				"de Bruin Elza C",
				"Taylor Tiffany B",
				"Swanton Charles"
			],
			"DOI": "10.1186/gm505",
			"date": "2014-06-24",
			"PMC": "",
			"citation": "",
			"abstract": "Multiple subclonal populations of tumor cells can coexist within the same tumor. This intra-tumor heterogeneity will have clinical implications and it is therefore important to identify factors that drive or suppress such heterogeneous tumor progression. Evolutionary biology can provide important insights into this process. In particular, experimental evolution studies of microbial populations, which exist as clonal populations that can diversify into multiple subclones, have revealed important evolutionary processes driving heterogeneity within a population. There are transferrable lessons that can be learnt from these studies that will help us to understand the process of intra-tumor heterogeneity in the clinical setting. In this review, we summarize drivers of microbial diversity that have been identified, such as mutation rate and environmental influences, and discuss how knowledge gained from microbial experimental evolution studies may guide us to identify and understand important selective factors that promote intra-tumor heterogeneity. Furthermore, we discuss how these factors could be used to direct and optimize research efforts to improve patient care, focusing on therapeutic resistance. Finally, we emphasize the need for longitudinal studies to address the impact of these potential tumor heterogeneity-promoting factors on drug resistance, metastatic potential and clinical outcome.",
			"category": 2,
			"name": "de Bruin Elza C,2014"
		},
		{
			"PMID": 24254977,
			"title": "Tumour suppressor gene function in carcinoma-associated fibroblasts: from tumour cells via EMT and back again?",
			"journal": "The Journal of pathology",
			"authorList": [
				"Drake Lauren E",
				"Macleod Kay F"
			],
			"DOI": "10.1002/path.4298",
			"date": "2014-03-04",
			"PMC": "",
			"citation": "",
			"abstract": "Recent reports indicate that inactivation of the RB, TP53 or PTEN tumour suppressor genes is detected in tumour stroma of oropharyngeal, breast and other human cancers. Mouse models have validated the tumour-promoting effects of deleting Rb, Pten or p53 in fibroblasts that converts them from normal fibroblasts to carcinoma associated fibroblasts (CAFs). The tumour-promoting activity of CAFs in these contexts was associated with increased paracrine signaling to tumour cells through production of specific growth factors, chemokines and MMPs by CAFs. The conversion of NOFs into CAFs through acquisition of specific mutations, such as loss of tumour suppressors, or deregulated expression of microRNAs or key epigenetic events, can clearly occur independently of genetic and epigenetic changes in tumour cells but an alternative source of CAFs that is being reconsidered is that CAFs derive from the tumour cells by EMT. Recent mouse models employing lineage-tracing techniques have suggested that this can take place in vivo and the extent to which this is relevant more broadly is discussed.",
			"category": 2,
			"name": "Drake Lauren E,2014"
		},
		{
			"PMID": 24221193,
			"title": "Genomic and transcriptomic plasticity in treatment-naive ovarian cancer.",
			"journal": "Genome research",
			"authorList": [
				"Hoogstraat Marlous",
				"de Pagter Mirjam S",
				"Cirkel Geert A",
				"van Roosmalen Markus J",
				"Harkins Timothy T",
				"Duran Karen",
				"Kreeftmeijer Jennifer",
				"Renkens Ivo",
				"Witteveen Petronella O",
				"Lee Clarence C",
				"Nijman Isaac J",
				"Guy Tanisha",
				"van 't Slot Ruben",
				"Jonges Trudy N",
				"Lolkema Martijn P",
				"Koudijs Marco J",
				"Zweemer Ronald P",
				"Voest Emile E",
				"Cuppen Edwin",
				"Kloosterman Wigard P"
			],
			"DOI": "10.1101/gr.161026.113",
			"date": "2014-06-09",
			"PMC": "",
			"citation": "",
			"abstract": "Intra-tumor heterogeneity is a hallmark of many cancers and may lead to therapy resistance or interfere with personalized treatment strategies. Here, we combined topographic mapping of somatic breakpoints and transcriptional profiling to probe intra-tumor heterogeneity of treatment-na\u00efve stage IIIC/IV epithelial ovarian cancer. We observed that most substantial differences in genomic rearrangement landscapes occurred between metastases in the omentum and peritoneum versus tumor sites in the ovaries. Several cancer genes such as NF1, CDKN2A, and FANCD2 were affected by lesion-specific breakpoints. Furthermore, the intra-tumor variability involved different mutational hallmarks including lesion-specific kataegis (local mutation shower coinciding with genomic breakpoints), rearrangement classes, and coding mutations. In one extreme case, we identified two independent TP53 mutations in ovary tumors and omentum/peritoneum metastases, respectively. Examination of gene expression dynamics revealed up-regulation of key cancer pathways including WNT, integrin, chemokine, and Hedgehog signaling in only subsets of tumor samples from the same patient. Finally, we took advantage of the multilevel tumor analysis to understand the effects of genomic breakpoints on qualitative and quantitative gene expression changes. We show that intra-tumor gene expression differences are caused by site-specific genomic alterations, including formation of in-frame fusion genes. These data highlight the plasticity of ovarian cancer genomes, which may contribute to their strong capacity to adapt to changing environmental conditions and give rise to the high rate of recurrent disease following standard treatment regimes.",
			"category": 2,
			"name": "Hoogstraat Marlous,2014"
		},
		{
			"PMID": 24220311,
			"title": "Establishing the origin of metastatic deposits in the setting of multiple primary malignancies: the role of massively parallel sequencing.",
			"journal": "Molecular oncology",
			"authorList": [
				"De Mattos-Arruda Leticia",
				"Bidard Francois-Clement",
				"Won Helen H",
				"Cortes Javier",
				"Ng Charlotte K Y",
				"Peg Vicente",
				"Nuciforo Paolo",
				"Jungbluth Achim A",
				"Weigelt Britta",
				"Berger Michael F",
				"Seoane Joan",
				"Reis-Filho Jorge S"
			],
			"DOI": "10.1016/j.molonc.2013.10.006",
			"date": "2014-09-19",
			"PMC": "",
			"citation": "",
			"abstract": "In this proof-of-principle study, we sought to define whether targeted capture massively parallel sequencing can be employed to determine the origin of metastatic deposits in cases of synchronous primary malignancies and metastases in distinct anatomical sites. DNA samples extracted from synchronous tumor masses in the breast, adnexal, and pelvic-peritoneal regions from a 62-year-old BRCA1 germline mutation carrier were subjected to targeted massively parallel sequencing using a platform comprising 300 cancer genes known to harbor actionable mutations. In addition to BRCA1 germline mutations, all lesions harbored somatic loss of the BRCA1 wild-type allele and TP53 somatic mutations. The primary breast cancer displayed a TP53 frameshift (p.Q317fs) mutation, whereas and the adnexal lesion harbored a TP53 nonsense (p.R213*) mutation, consistent with a diagnosis of two independent primary tumors (i.e. breast and ovarian cancer). The adnexal tumor and all pelvic-peritoneal implants harbored identical TP53 (p.R213*) and NCOA2 (p.G952R) somatic mutations. Evidence of genetic heterogeneity within and between lesions was observed, both in terms of somatic mutations and copy number aberrations. The repertoires of somatic genetic aberrations found in the breast, ovarian, and pelvic-peritoneal lesions provided direct evidence in support of the distinct origin of the breast and ovarian cancers, and established that the pelvic-peritoneal implants were clonally related to the ovarian lesion. These observations were consistent with those obtained with immunohistochemical analyses employing markers to differentiate between carcinomas of the breast and ovary, including WT1 and PAX8. Our results on this case of a patient with BRCA1-mutant breast and ovarian cancer demonstrate that massively parallel sequencing may constitute a useful tool to define the relationship, clonality and intra-tumor genetic heterogeneity between primary tumor masses and their metastatic deposits in patients with multiple primary malignancies and synchronous metastases.",
			"category": 2,
			"name": "De Mattos-Arruda Leticia,2014"
		},
		{
			"PMID": 24189272,
			"title": "Lysosomal sorting receptors are essential for secretory granule biogenesis in Tetrahymena.",
			"journal": "The Journal of cell biology",
			"authorList": [
				"Briguglio Joseph S",
				"Kumar Santosh",
				"Turkewitz Aaron P"
			],
			"DOI": "10.1083/jcb.201305086",
			"date": "2014-01-08",
			"PMC": "",
			"citation": "",
			"abstract": "Secretory granules, such as neuronal dense core vesicles, are specialized for storing cargo at high concentration and releasing it via regulated exocytosis in response to extracellular stimuli. Here, we used expression profiling to identify new components of the machinery for sorting proteins into mucocysts, secretory granule-like vesicles in the ciliate Tetrahymena thermophila. We show that assembly of mucocysts depends on proteins classically associated with lysosome biogenesis. In particular, the delivery of nonaggregated, but not aggregated, cargo proteins requires classical receptors of the sortilin/VPS10 family, which indicates that dual mechanisms are involved in sorting to this secretory compartment. In addition, sortilins are required for delivery of a key protease involved in T. thermophila mucocyst maturation. Our results suggest potential similarities in the formation of regulated secretory organelles between even very distantly related eukaryotes.",
			"category": 2,
			"name": "Briguglio Joseph S,2014"
		},
		{
			"PMID": 24154670,
			"title": "Metabolic and protein interaction sub-networks controlling the proliferation rate of cancer cells and their impact on patient survival.",
			"journal": "Scientific reports",
			"authorList": [
				"Feizi Amir",
				"Bordel Sergio"
			],
			"DOI": "10.1038/srep03041",
			"date": "2014-07-06",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer cells can have a broad scope of proliferation rates. Here we aim to identify the molecular mechanisms that allow some cancer cell lines to grow up to 4 times faster than other cell lines. The correlation of gene expression profiles with the growth rate in 60 different cell lines has been analyzed using several genome-scale biological networks and new algorithms. New possible regulatory feedback loops have been suggested and the known roles of several cell cycle related transcription factors have been confirmed. Over 100 growth-correlated metabolic sub-networks have been identified, suggesting a key role of simultaneous lipid synthesis and degradation in the energy supply of the cancer cells growth. Many metabolic sub-networks involved in cell line proliferation appeared also to correlate negatively with the survival expectancy of colon cancer patients.",
			"category": 2,
			"name": "Feizi Amir,2014"
		},
		{
			"PMID": 24079872,
			"title": "Is cancer gene therapy an empty suit?",
			"journal": "The Lancet. Oncology",
			"authorList": [
				"Brenner Malcolm K",
				"Gottschalk Stephen",
				"Leen Ann M",
				"Vera Juan F"
			],
			"DOI": "10.1016/S1470-2045(13)70173-6",
			"date": "2013-11-26",
			"PMC": "",
			"citation": "",
			"abstract": "Gene therapy as a treatment for cancer is regarded as high in promise, but low in delivery, a deficiency that has become more obvious with ever-increasing reports of the successful correction of monogenic disorders by this approach. We review the commercial and scientific obstacles that have led to these delays and describe how they are progressively being overcome. Recent and striking successes and correspondingly increased commercial involvement suggest that gene transfer could finally become a powerful method for development of safe and effective cancer therapeutic drugs.",
			"category": 2,
			"name": "Brenner Malcolm K,2013"
		},
		{
			"PMID": 24056532,
			"title": "Single-cell mutational profiling and clonal phylogeny in cancer.",
			"journal": "Genome research",
			"authorList": [
				"Potter Nicola E",
				"Ermini Luca",
				"Papaemmanuil Elli",
				"Cazzaniga Giovanni",
				"Vijayaraghavan Gowri",
				"Titley Ian",
				"Ford Anthony",
				"Campbell Peter",
				"Kearney Lyndal",
				"Greaves Mel"
			],
			"DOI": "10.1101/gr.159913.113",
			"date": "2014-07-09",
			"PMC": "",
			"citation": "",
			"abstract": "The development of cancer is a dynamic evolutionary process in which intraclonal, genetic diversity provides a substrate for clonal selection and a source of therapeutic escape. The complexity and topography of intraclonal genetic architectures have major implications for biopsy-based prognosis and for targeted therapy. High-depth, next-generation sequencing (NGS) efficiently captures the mutational load of individual tumors or biopsies. But, being a snapshot portrait of total DNA, it disguises the fundamental features of subclonal variegation of genetic lesions and of clonal phylogeny. Single-cell genetic profiling provides a potential resolution to this problem, but methods developed to date all have limitations. We present a novel solution to this challenge using leukemic cells with known mutational spectra as a tractable model. DNA from flow-sorted single cells is screened using multiplex targeted Q-PCR within a microfluidic platform allowing unbiased single-cell selection, high-throughput, and comprehensive analysis for all main varieties of genetic abnormalities: chimeric gene fusions, copy number alterations, and single-nucleotide variants. We show, in this proof-of-principle study, that the method has a low error rate and can provide detailed subclonal genetic architectures and phylogenies.",
			"category": 2,
			"name": "Potter Nicola E,2014"
		},
		{
			"PMID": 24048066,
			"title": "The causes and consequences of genetic heterogeneity in cancer evolution.",
			"journal": "Nature",
			"authorList": [
				"Burrell Rebecca A",
				"McGranahan Nicholas",
				"Bartek Jiri",
				"Swanton Charles"
			],
			"DOI": "10.1038/nature12625",
			"date": "2013-11-05",
			"PMC": "",
			"citation": "",
			"abstract": "Recent studies have revealed extensive genetic diversity both between and within tumours. This heterogeneity affects key cancer pathways, driving phenotypic variation, and poses a significant challenge to personalized cancer medicine. A major cause of genetic heterogeneity in cancer is genomic instability. This instability leads to an increased mutation rate and can shape the evolution of the cancer genome through a plethora of mechanisms. By understanding these mechanisms we can gain insight into the common pathways of tumour evolution that could support the development of future therapeutic strategies.",
			"category": 2,
			"name": "Burrell Rebecca A,2013"
		},
		{
			"PMID": 24027532,
			"title": "The evolution of genome-scale models of cancer metabolism.",
			"journal": "Frontiers in physiology",
			"authorList": [
				"Lewis Nathan E",
				"Abdel-Haleem Alyaa M"
			],
			"DOI": "10.3389/fphys.2013.00237",
			"date": "2014-06-24",
			"PMC": "",
			"citation": "",
			"abstract": "The importance of metabolism in cancer is becoming increasingly apparent with the identification of metabolic enzyme mutations and the growing awareness of the influence of metabolism on signaling, epigenetic markers, and transcription. However, the complexity of these processes has challenged our ability to make sense of the metabolic changes in cancer. Fortunately, constraint-based modeling, a systems biology approach, now enables one to study the entirety of cancer metabolism and simulate basic phenotypes. With the newness of this field, there has been a rapid evolution of both the scope of these models and their applications. Here we review the various constraint-based models built for cancer metabolism and how their predictions are shedding new light on basic cancer phenotypes, elucidating pathway differences between tumors, and dicovering putative anti-cancer targets. As the field continues to evolve, the scope of these genome-scale cancer models must expand beyond central metabolism to address questions related to the diverse processes contributing to tumor development and metastasis.",
			"category": 2,
			"name": "Lewis Nathan E,2014"
		},
		{
			"PMID": 24022702,
			"title": "Emerging patterns of somatic mutations in cancer.",
			"journal": "Nature reviews. Genetics",
			"authorList": [
				"Watson Ian R",
				"Takahashi Koichi",
				"Futreal P Andrew",
				"Chin Lynda"
			],
			"DOI": "10.1038/nrg3539",
			"date": "2013-12-11",
			"PMC": "",
			"citation": "",
			"abstract": "Recent advances in technological tools for massively parallel, high-throughput sequencing of DNA have enabled the comprehensive characterization of somatic mutations in a large number of tumour samples. In this Review, we describe recent cancer genomic studies that have assembled emerging views of the landscapes of somatic mutations through deep-sequencing analyses of the coding exomes and whole genomes in various cancer types. We discuss the comparative genomics of different cancers, including mutation rates and spectra, as well as the roles of environmental insults that influence these processes. We highlight the developing statistical approaches that are used to identify significantly mutated genes, and discuss the emerging biological and clinical insights from such analyses, as well as the future challenges of translating these genomic data into clinical impacts.",
			"category": 2,
			"name": "Watson Ian R,2013"
		},
		{
			"PMID": 23907150,
			"title": "Intracystic papillary carcinoma of breast: interrelationship with in situ and invasive carcinoma and a proposal of pathogenesis: array comparative genomic hybridization study of 14 cases.",
			"journal": "Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc",
			"authorList": [
				"Khoury Thaer",
				"Hu Qiang",
				"Liu Song",
				"Wang Jianmin"
			],
			"DOI": "10.1038/modpathol.2013.136",
			"date": "2014-09-24",
			"PMC": "",
			"citation": "",
			"abstract": "Classifying intracystic papillary carcinoma under invasive or in situ ductal carcinoma is still a matter of debate. The purpose of this study was to explore the genomic relationship of this tumor to its concurrent invasive ductal carcinoma and ductal carcinoma in situ using array comparative genomic hybridization. Intracystic papillary carcinoma cases were classified into three categories: pure, with concurrent ductal carcinoma in situ or with concurrent invasive ductal carcinoma. Each component was dissected using laser capture microdissection. DNA was extracted and array comparative genomic hybridization was performed. The test of difference in copy number changes among the three tumors was carried out using CGHMultiArray. Intracystic papillary carcinoma clustered with four of five concurrent ductal carcinoma in situ cases and with two of two invasive ductal carcinoma cases. Intracystic papillary carcinoma showed the highest proportions of genome copy number aberration, followed by ductal carcinoma in situ, and then by invasive ductal carcinoma (P=0.06). Comparing intracystic papillary carcinoma with invasive ductal carcinoma vs without invasive ductal carcinoma, the former had 11q22.1-23.3 loss (P=0.031) and chr5 gain (P=0.085), and was enriched with matrix metalloproteinase genes. Comparing intracystic papillary carcinoma with ductal carcinoma in situ vs without ductal carcinoma in situ, the former had gain in 5q35.3 (P=0.041), 8q24.3 (P=0.041) and 21q13.2 to 21q13.31 (P=0.011). Comparing intracystic papillary carcinoma with ductal carcinoma in situ, the latter acquired a group of genes involved in cell adhesion and motility, whereas intracystic papillary carcinoma differentially expressed genes that are involved in papillary carcinomas of other organs (thyroid and kidney). We conclude that the overall molecular change in intracystic papillary carcinoma is closer to ductal carcinoma in situ than to invasive ductal carcinoma, which may explain the indolent behavior of this tumor. We offer herein a proposal of intracystic papillary carcinoma pathogenesis through its relation to invasive ductal carcinoma and ductal carcinoma in situ.",
			"category": 2,
			"name": "Khoury Thaer,2014"
		},
		{
			"PMID": 23897237,
			"title": "Single-cell sequencing-based technologies will revolutionize whole-organism science.",
			"journal": "Nature reviews. Genetics",
			"authorList": [
				"Shapiro Ehud",
				"Biezuner Tamir",
				"Linnarsson Sten"
			],
			"DOI": "10.1038/nrg3542",
			"date": "2013-12-11",
			"PMC": "",
			"citation": "",
			"abstract": "The unabated progress in next-generation sequencing technologies is fostering a wave of new genomics, epigenomics, transcriptomics and proteomics technologies. These sequencing-based technologies are increasingly being targeted to individual cells, which will allow many new and longstanding questions to be addressed. For example, single-cell genomics will help to uncover cell lineage relationships; single-cell transcriptomics will supplant the coarse notion of marker-based cell types; and single-cell epigenomics and proteomics will allow the functional states of individual cells to be analysed. These technologies will become integrated within a decade or so, enabling high-throughput, multi-dimensional analyses of individual cells that will produce detailed knowledge of the cell lineage trees of higher organisms, including humans. Such studies will have important implications for both basic biological research and medicine.",
			"category": 2,
			"name": "Shapiro Ehud,2013"
		},
		{
			"PMID": 23892400,
			"title": "TrAp: a tree approach for fingerprinting subclonal tumor composition.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Strino Francesco",
				"Parisi Fabio",
				"Micsinai Mariann",
				"Kluger Yuval"
			],
			"DOI": "10.1093/nar/gkt641",
			"date": "2013-11-13",
			"PMC": "",
			"citation": "",
			"abstract": "Revealing the clonal composition of a single tumor is essential for identifying cell subpopulations with metastatic potential in primary tumors or with resistance to therapies in metastatic tumors. Sequencing technologies provide only an overview of the aggregate of numerous cells. Computational approaches to de-mix a collective signal composed of the aberrations of a mixed cell population of a tumor sample into its individual components are not available. We propose an evolutionary framework for deconvolving data from a single genome-wide experiment to infer the composition, abundance and evolutionary paths of the underlying cell subpopulations of a tumor. We have developed an algorithm (TrAp) for solving this mixture problem. In silico analyses show that TrAp correctly deconvolves mixed subpopulations when the number of subpopulations and the measurement errors are moderate. We demonstrate the applicability of the method using tumor karyotypes and somatic hypermutation data sets. We applied TrAp to Exome-Seq experiment of a renal cell carcinoma tumor sample and compared the mutational profile of the inferred subpopulations to the mutational profiles of single cells of the same tumor. Finally, we deconvolve sequencing data from eight acute myeloid leukemia patients and three distinct metastases of one melanoma patient to exhibit the evolutionary relationships of their subpopulations.",
			"category": 2,
			"name": "Strino Francesco,2013"
		},
		{
			"PMID": 23881035,
			"title": "Luminal breast cancer: from biology to treatment.",
			"journal": "Nature reviews. Clinical oncology",
			"authorList": [
				"Ignatiadis Michail",
				"Sotiriou Christos"
			],
			"DOI": "10.1038/nrclinonc.2013.124",
			"date": "2014-03-25",
			"PMC": "",
			"citation": "",
			"abstract": "Oestrogen receptor (ER)-positive--or luminal--tumours represent around two-thirds of all breast cancers. Luminal breast cancer is a highly heterogeneous disease comprising different histologies, gene-expression profiles and mutational patterns, with very varied clinical courses and responses to systemic treatment. Despite adjuvant endocrine therapy and chemotherapy treatment for patients at high risk of relapse, both early and late relapses still occur, a fact that highlights the unmet medical needs of these patients. Ongoing research aims to identify those patients who can be spared adjuvant chemotherapy and who will benefit from extended adjuvant hormone therapy. This research also aims to explore the role of adjuvant bisphosphonates, to interrogate new agents for targeting minimal residual disease, and to address endocrine resistance. Data from next-generation sequencing studies have given us new insight into the biology of luminal breast cancer and, together with advances in preclinical models and the availability of newer targeted agents, have led to the testing of rationally chosen combination treatments in clinical trials. However, a major challenge will be to make sense of the large amount of patient genomic data that is becoming increasingly available. This analysis will be critical to our understanding how intertumour and intratumour heterogeneity can influence treatment response and resistance.",
			"category": 2,
			"name": "Ignatiadis Michail,2014"
		},
		{
			"PMID": 23852170,
			"title": "An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers.",
			"journal": "Nature genetics",
			"authorList": [
				"Roberts Steven A",
				"Lawrence Michael S",
				"Klimczak Leszek J",
				"Grimm Sara A",
				"Fargo David",
				"Stojanov Petar",
				"Kiezun Adam",
				"Kryukov Gregory V",
				"Carter Scott L",
				"Saksena Gordon",
				"Harris Shawn",
				"Shah Ruchir R",
				"Resnick Michael A",
				"Getz Gad",
				"Gordenin Dmitry A"
			],
			"DOI": "10.1038/ng.2702",
			"date": "2013-11-26",
			"PMC": "",
			"citation": "",
			"abstract": "Recent studies indicate that a subclass of APOBEC cytidine deaminases, which convert cytosine to uracil during RNA editing and retrovirus or retrotransposon restriction, may induce mutation clusters in human tumors. We show here that throughout cancer genomes APOBEC-mediated mutagenesis is pervasive and correlates with APOBEC mRNA levels. Mutation clusters in whole-genome and exome data sets conformed to the stringent criteria indicative of an APOBEC mutation pattern. Applying these criteria to 954,247 mutations in 2,680 exomes from 14 cancer types, mostly from The Cancer Genome Atlas (TCGA), showed a significant presence of the APOBEC mutation pattern in bladder, cervical, breast, head and neck, and lung cancers, reaching 68% of all mutations in some samples. Within breast cancer, the HER2-enriched subtype was clearly enriched for tumors with the APOBEC mutation pattern, suggesting that this type of mutagenesis is functionally linked with cancer development. The APOBEC mutation pattern also extended to cancer-associated genes, implying that ubiquitous APOBEC-mediated mutagenesis is carcinogenic.",
			"category": 2,
			"name": "Roberts Steven A,2013"
		},
		{
			"PMID": 23776569,
			"title": "Functional assessment of population and tumor-associated APE1 protein variants.",
			"journal": "PloS one",
			"authorList": [
				"Illuzzi Jennifer L",
				"Harris Nicole A",
				"Manvilla Brittney A",
				"Kim Daemyung",
				"Li Mengxia",
				"Drohat Alexander C",
				"Wilson David M"
			],
			"DOI": "10.1371/journal.pone.0065922",
			"date": "2014-01-16",
			"PMC": "",
			"citation": "",
			"abstract": "Apurinic/apyrimidinic endonuclease 1 (APE1) is the predominant AP site repair enzyme in mammals. APE1 also maintains 3'-5' exonuclease and 3'-repair activities, and regulates transcription factor DNA binding through its REF-1 function. Since complete or severe APE1 deficiency leads to embryonic lethality and cell death, it has been hypothesized that APE1 protein variants with slightly impaired function will contribute to disease etiology. Our data indicate that except for the endometrial cancer-associated APE1 variant R237C, the polymorphic variants Q51H, I64V and D148E, the rare population variants G241R, P311S and A317V, and the tumor-associated variant P112L exhibit normal thermodynamic stability of protein folding; abasic endonuclease, 3'-5' exonuclease and REF-1 activities; coordination during the early steps of base excision repair; and intracellular distribution when expressed exogenously in HeLa cells. The R237C mutant displayed reduced AP-DNA complex stability, 3'-5' exonuclease activity and 3'-damage processing. Re-sequencing of the exonic regions of APE1 uncovered no novel amino acid substitutions in the 60 cancer cell lines of the NCI-60 panel, or in HeLa or T98G cancer cell lines; only the common D148E and Q51H variants were observed. Our results indicate that APE1 missense mutations are seemingly rare and that the cancer-associated R237C variant may represent a reduced-function susceptibility allele.",
			"category": 2,
			"name": "Illuzzi Jennifer L,2014"
		},
		{
			"PMID": 23628380,
			"title": "EMu: probabilistic inference of mutational processes and their localization in the cancer genome.",
			"journal": "Genome biology",
			"authorList": [
				"Fischer Andrej",
				"Illingworth Christopher J R",
				"Campbell Peter J",
				"Mustonen Ville"
			],
			"DOI": "10.1186/gb-2013-14-4-r39",
			"date": "2015-04-07",
			"PMC": "",
			"citation": "",
			"abstract": "The spectrum of mutations discovered in cancer genomes can be explained by the activity of a few elementary mutational processes. We present a novel probabilistic method, EMu, to infer the mutational signatures of these processes from a collection of sequenced tumors. EMu naturally incorporates the tumor-specific opportunity for different mutation types according to sequence composition. Applying EMu to breast cancer data, we derive detailed maps of the activity of each process, both genome-wide and within specific local regions of the genome. Our work provides new opportunities to study the mutational processes underlying cancer development. EMu is available at http://www.sanger.ac.uk/resources/software/emu/.",
			"category": 2,
			"name": "Fischer Andrej,2015"
		},
		{
			"PMID": 23615877,
			"title": "Systems biology of cancer: entropy, disorder, and selection-driven evolution to independence, invasion and \"swarm intelligence\".",
			"journal": "Cancer metastasis reviews",
			"authorList": [
				"Tarabichi M",
				"Antoniou A",
				"Saiselet M",
				"Pita J M",
				"Andry G",
				"Dumont J E",
				"Detours V",
				"Maenhaut C"
			],
			"DOI": "10.1007/s10555-013-9431-y",
			"date": "2014-11-18",
			"PMC": "",
			"citation": "",
			"abstract": "Our knowledge of the biology of solid cancer has greatly progressed during the last few years, and many excellent reviews dealing with the various aspects of this biology have appeared. In the present review, we attempt to bring together these subjects in a general systems biology narrative. It starts from the roles of what we term entropy of signaling and noise in the initial oncogenic events, to the first major transition of tumorigenesis: the independence of the tumor cell and the switch in its physiology, i.e., from subservience to the organism to its own independent Darwinian evolution. The development after independence involves a constant dynamic reprogramming of the cells and the emergence of a sort of collective intelligence leading to invasion and metastasis and seldom to the ultimate acquisition of immortality through inter-individual infection. At each step, the probability of success is minimal to infinitesimal, but the number of cells possibly involved and the time scale account for the relatively high occurrence of tumorigenesis and metastasis in multicellular organisms.",
			"category": 2,
			"name": "Tarabichi M,2014"
		},
		{
			"PMID": 23592419,
			"title": "Do mutator mutations fuel tumorigenesis?",
			"journal": "Cancer metastasis reviews",
			"authorList": [
				"Fox Edward J",
				"Prindle Marc J",
				"Loeb Lawrence A"
			],
			"DOI": "10.1007/s10555-013-9426-8",
			"date": "2014-11-18",
			"PMC": "",
			"citation": "",
			"abstract": "The mutator phenotype hypothesis proposes that the mutation rate of normal cells is insufficient to account for the large number of mutations found in human cancers. Consequently, human tumors exhibit an elevated mutation rate that increases the likelihood of a tumor acquiring advantageous mutations. The hypothesis predicts that tumors are composed of cells harboring hundreds of thousands of mutations, as opposed to a small number of specific driver mutations, and that malignant cells within a tumor therefore constitute a highly heterogeneous population. As a result, drugs targeting specific mutated driver genes or even pathways of mutated driver genes will have only limited anticancer potential. In addition, because the tumor is composed of such a diverse cell population, tumor cells harboring drug-resistant mutations will exist prior to the administration of any chemotherapeutic agent. We present recent evidence in support of the mutator phenotype hypothesis, major arguments against this concept, and discuss the clinical consequences of tumor evolution fueled by an elevated mutation rate. We also consider the therapeutic possibility of altering the rate of mutation accumulation. Most significantly, we contend that there is a need to fundamentally reconsider current approaches to personalized cancer therapy. We propose that targeting cellular pathways that alter the rate of mutation accumulation in tumors will ultimately prove more effective than attempting to identify and target mutant driver genes or driver pathways.",
			"category": 2,
			"name": "Fox Edward J,2014"
		},
		{
			"PMID": 23589100,
			"title": "Targeting deregulated epigenetic control in cancer.",
			"journal": "Journal of cellular physiology",
			"authorList": [
				"Zaidi Sayyed K",
				"Van Wijnen Andre J",
				"Lian Jane B",
				"Stein Janet L",
				"Stein Gary S"
			],
			"DOI": "10.1002/jcp.24387",
			"date": "2013-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a multifaceted disease that involves acquisition of genetic mutations, deletions, and amplifications as well as deregulation of epigenetic mechanisms that fine-tune gene regulation. Key epigenetic mechanisms that include histone modifications, DNA methylation, and non-coding RNA-mediated gene silencing are often deregulated in a variety of cancers. Subnuclear localization of key proteins in the interphase nucleus and bookmarking of genes by lineage commitment factors in mitosis-a new dimension to epigenetic control of fundamental biological processes-is also modified in cancer. In this review, we discuss the various aspects of epigenetic control that are operative in a variety of cancers and their potential for risk assessment, early detection, targeted therapy, and personalized medicine.",
			"category": 2,
			"name": "Zaidi Sayyed K,2013"
		},
		{
			"PMID": 23493119,
			"title": "8(th) Annual European Antibody Congress 2012: November 27-28, 2012, Geneva, Switzerland.",
			"journal": "mAbs",
			"authorList": [
				"Beck Alain",
				"Carter Paul J",
				"Gerber Hans-Peter",
				"Lugovskoy Alexey A",
				"Wurch Thierry",
				"Junutula Jagath R",
				"Kontermann Roland E",
				"Mabry Robert"
			],
			"DOI": "10.4161/mabs.24105",
			"date": "2015-04-16",
			"PMC": "",
			"citation": "",
			"abstract": "The 8th European Antibody Congress (EAC), organized by Terrapin Ltd., was again held in Geneva, Switzerland, following on the tradition established with the 4th EAC. The new agenda format for 2012 included three parallel tracks on: (1) naked antibodies; (2) antibody drug conjugates (ADCs); and (3) bispecific antibodies and alternative scaffolds. The meeting started and closed with three plenary lectures to give common background and to share the final panel discussion and conclusions. The two day event included case studies and networking for nearly 250 delegates who learned of the latest advances and trends in the global development of antibody-based therapeutics. The monoclonal antibody track was focused on understanding the structure-function relationships, optimization of antibody design and developability, and processes that allow better therapeutic candidates to move through the clinic. Discussions on novel target identification and validation were also included. The ADC track was dedicated to evaluation of the ongoing success of the established ADC formats alongside the rise of the next generation drug-conjugates. The bispecific and alternative scaffold track was focused on taking stock of the multitude of bispecific formats being investigated and gaining insight into recent innovations and advancements. Mechanistic understanding, progression into the clinic and the exploration of multispecifics, redirected T cell killing and alternative scaffolds were extensively discussed. In total, nearly 50 speakers provided updates of programs related to antibody research and development on-going in the academic, government and commercial sectors.",
			"category": 2,
			"name": "Beck Alain,2015"
		},
		{
			"PMID": 23412337,
			"title": "Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Sottoriva Andrea",
				"Spiteri Inmaculada",
				"Piccirillo Sara G M",
				"Touloumis Anestis",
				"Collins V Peter",
				"Marioni John C",
				"Curtis Christina",
				"Watts Colin",
				"Tavar\u00e9 Simon"
			],
			"DOI": "10.1073/pnas.1219747110",
			"date": "2013-05-02",
			"PMC": "",
			"citation": "",
			"abstract": "Glioblastoma (GB) is the most common and aggressive primary brain malignancy, with poor prognosis and a lack of effective therapeutic options. Accumulating evidence suggests that intratumor heterogeneity likely is the key to understanding treatment failure. However, the extent of intratumor heterogeneity as a result of tumor evolution is still poorly understood. To address this, we developed a unique surgical multisampling scheme to collect spatially distinct tumor fragments from 11 GB patients. We present an integrated genomic analysis that uncovers extensive intratumor heterogeneity, with most patients displaying different GB subtypes within the same tumor. Moreover, we reconstructed the phylogeny of the fragments for each patient, identifying copy number alterations in EGFR and CDKN2A/B/p14ARF as early events, and aberrations in PDGFRA and PTEN as later events during cancer progression. We also characterized the clonal organization of each tumor fragment at the single-molecule level, detecting multiple coexisting cell lineages. Our results reveal the genome-wide architecture of intratumor variability in GB across multiple spatial scales and patient-specific patterns of cancer evolution, with consequences for treatment design.",
			"category": 2,
			"name": "Sottoriva Andrea,2013"
		},
		{
			"PMID": 23396760,
			"title": "Cancer stem cells as 'units of selection'.",
			"journal": "Evolutionary applications",
			"authorList": [
				"Greaves Mel"
			],
			"DOI": "10.1111/eva.12017",
			"date": "2013-02-12",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer development is widely recognized to be a somatic cell evolutionary process with complex dynamics and highly variable time frames. Variant cells and descendent subclones gain competitive advantage via their fitness in relation to micro-environmental selective pressures. In this context, the 'unit' of selection is the cell, but not any cell. The so-called 'cancer stem cells' have the essential properties required to function as the key units of selection, particularly with respect to their proliferative potential and longevity. These cells drive evolutionary progression of disease and provide reservoirs for relapse or recurrence and drug resistance. They represent the prime, but elusive and moving, targets for therapeutic control.",
			"category": 2,
			"name": "Greaves Mel,2013"
		},
		{
			"PMID": 23318448,
			"title": "Next-generation sequencing of endoscopic biopsies identifies ARID1A as a tumor-suppressor gene in Barrett's esophagus.",
			"journal": "Oncogene",
			"authorList": [
				"Streppel M M",
				"Lata S",
				"DelaBastide M",
				"Montgomery E A",
				"Wang J S",
				"Canto M I",
				"Macgregor-Das A M",
				"Pai S",
				"Morsink F H M",
				"Offerhaus G J",
				"Antoniou E",
				"Maitra A",
				"McCombie W R"
			],
			"DOI": "10.1038/onc.2012.586",
			"date": "2014-03-14",
			"PMC": "",
			"citation": "",
			"abstract": "The incidence of Barrett's esophagus (BE)-associated esophageal adenocarcinoma (EAC) is increasing. Next-generation sequencing (NGS) provides an unprecedented opportunity to uncover genomic alterations during BE pathogenesis and progression to EAC, but treatment-naive surgical specimens are scarce. The objective of this study was to establish the feasibility of using widely available endoscopic mucosal biopsies for successful NGS, using samples obtained from a BE 'progressor'. Paired-end whole-genome NGS was performed on the Illumina platform using libraries generated from mucosal biopsies of normal squamous epithelium (NSE), BE and EAC obtained from a patient who progressed to adenocarcinoma during endoscopic surveillance. Selective validation studies, including Sanger sequencing, immunohistochemistry and functional assays, were performed to confirm the NGS findings. NGS identified somatic nonsense mutations of AT-rich interactive domain 1A (SWI like) (ARID1A) and PPIE and an additional 37 missense mutations in BE and/or EAC, which were confirmed by Sanger sequencing. ARID1A mutations were detected in 15% (3/20) high-grade dysplasia (HGD)/EAC patients. Immunohistochemistry performed on an independent archival cohort demonstrated ARID1A protein loss in 0% (0/76), 4.9% (2/40), 14.3% (4/28), 16.0% (8/50) and 12.2% (12/98) of NSE, BE, low-grade dysplasia, HGD and EAC tissues, respectively, and was inversely associated with nuclear p53 accumulation (P=0.028). Enhanced cell growth, proliferation and invasion were observed on ARID1A knockdown in EAC cells. In addition, genes downstream of ARID1A that potentially contribute to the ARID1A knockdown phenotype were identified. Our studies establish the feasibility of using mucosal biopsies for NGS, which should enable the comparative analysis of larger 'progressor' versus 'non-progressor' cohorts. Further, we identify ARID1A as a novel tumor-suppressor gene in BE pathogenesis, reiterating the importance of aberrant chromatin in the metaplasia-dysplasia sequence.",
			"category": 2,
			"name": "Streppel M M,2014"
		},
		{
			"PMID": 23313965,
			"title": "Role of the microenvironment in the pathogenesis and treatment of hepatocellular carcinoma.",
			"journal": "Gastroenterology",
			"authorList": [
				"Hernandez-Gea Virginia",
				"Toffanin Sara",
				"Friedman Scott L",
				"Llovet Josep M"
			],
			"DOI": "10.1053/j.gastro.2013.01.002",
			"date": "2013-05-13",
			"PMC": "",
			"citation": "",
			"abstract": "Hepatocellular carcinoma (HCC) is the most common primary liver tumor and the third greatest cause of cancer-related death worldwide, and its incidence is increasing. Despite the significant improvement in management of HCC over the past 30 years, there are no effective chemoprevention strategies, and only one systemic therapy has been approved for patients with advanced tumors. This drug, sorafenib, acts on tumor cells and the stroma. HCC develops from chronically damaged tissue that contains large amounts of inflammation and fibrosis, which also promote tumor progression and resistance to therapy. Increasing our understanding of how stromal components interact with cancer cells and the signaling pathways involved could help identify new therapeutic and chemopreventive targets.",
			"category": 2,
			"name": "Hernandez-Gea Virginia,2013"
		},
		{
			"PMID": 38951641,
			"title": "Mitochondrial genetics through the lens of single-cell multi-omics.",
			"journal": "Nature genetics",
			"authorList": [
				"Nitsch Lena",
				"Lareau Caleb A",
				"Ludwig Leif S"
			],
			"DOI": "10.1038/s41588-024-01794-8",
			"date": "2024-07-15",
			"PMC": "",
			"citation": "",
			"abstract": "Mitochondria carry their own genetic information encoding for a subset of protein-coding genes and translational machinery essential for cellular respiration and metabolism. Despite its small size, the mitochondrial genome, its natural genetic variation and molecular phenotypes have been challenging to study using bulk sequencing approaches, due to its variation in cellular copy number, non-Mendelian modes of inheritance and propensity for mutations. Here we highlight emerging strategies designed to capture mitochondrial genetic variation across individual cells for lineage tracing and studying mitochondrial genetics in primary human cells and clinical specimens. We review recent advances surrounding single-cell mitochondrial genome sequencing and its integration with functional genomic readouts, including leveraging somatic mitochondrial DNA mutations as clonal markers that can resolve cellular population dynamics in complex human tissues. Finally, we discuss how single-cell whole mitochondrial genome sequencing approaches can be utilized to investigate mitochondrial genetics and its contribution to cellular heterogeneity and disease.",
			"category": 2,
			"name": "Nitsch Lena,2024"
		},
		{
			"PMID": 38831004,
			"title": "Strength of selection in lung tumors correlates with clinical features better than tumor mutation burden.",
			"journal": "Scientific reports",
			"authorList": [
				"Gorlov Ivan P",
				"Gorlova Olga Y",
				"Tsavachidis Spyridon",
				"Amos Christopher I"
			],
			"DOI": "10.1038/s41598-024-63468-z",
			"date": "2024-06-03",
			"PMC": "",
			"citation": "",
			"abstract": "Single nucleotide substitutions are the most common type of somatic mutations in cancer genome. The goal of this study was to use publicly available somatic mutation data to quantify negative and positive selection in individual lung tumors and test how strength of directional and absolute selection is associated with clinical features. The analysis found a significant variation in strength of selection (both negative and positive) among tumors, with median selection tending to be negative even though tumors with strong positive selection also exist. Strength of selection estimated as the density of missense mutations relative to the density of silent mutations showed only a weak correlation with tumor mutation burden. In the \"all histology together\" analysis we found that absolute strength of selection was strongly correlated with all clinically relevant features analyzed. In histology-stratified analysis selection was strongest in small cell lung cancer. Selection in adenocarcinoma was somewhat higher compared to squamous cell carcinoma. The study suggests that somatic mutation- based quantifying of directional and absolute selection in individual tumors can be a useful biomarker of tumor aggressiveness.",
			"category": 2,
			"name": "Gorlov Ivan P,2024"
		},
		{
			"PMID": 38806682,
			"title": "Genetic landscape of interval and screen detected breast cancer.",
			"journal": "NPJ precision oncology",
			"authorList": [
				"Mills Charlie",
				"Sud Amit",
				"Everall Andrew",
				"Chubb Daniel",
				"Lawrence Samuel E D",
				"Kinnersley Ben",
				"Cornish Alex J",
				"Bentham Robert",
				"Houlston Richard S"
			],
			"DOI": "10.1038/s41698-024-00618-6",
			"date": "2024-05-31",
			"PMC": "",
			"citation": "",
			"abstract": "Interval breast cancers (IBCs) are cancers diagnosed between screening episodes. Understanding the biological differences between IBCs and screen-detected breast-cancers (SDBCs) has the potential to improve mammographic screening and patient management. We analysed and compared the genomic landscape of 288 IBCs and 473 SDBCs by whole genome sequencing of paired tumour-normal patient samples collected as part of the UK 100,000 Genomes Project. Compared to SDBCs, IBCs were more likely to be lobular, higher grade, and triple negative. A more aggressive clinical phenotype was reflected in IBCs displaying features of genomic instability including a higher mutation rate and number of chromosomal structural abnormalities, defective homologous recombination and TP53 mutations. We did not however, find evidence to indicate that IBCs are associated with a significantly different immune response. While IBCs do not represent a unique molecular class of invasive breast cancer they exhibit a more aggressive phenotype, which is likely to be a consequence of the timing of tumour initiation. This information is relevant both with respect to treatment as well as informing the screening interval for mammography.",
			"category": 2,
			"name": "Mills Charlie,2024"
		},
		{
			"PMID": 38803565,
			"title": "Immune-tumor interaction dictates spatially directed evolution of esophageal squamous cell carcinoma.",
			"journal": "National science review",
			"authorList": [
				"Zhou Yong",
				"Mo Shanlan",
				"Cui Heyang",
				"Sun Ruifang",
				"Zhang Weimin",
				"Zhuang Xiaofei",
				"Xu Enwei",
				"Li Hongyi",
				"Cheng Yikun",
				"Meng Yongsheng",
				"Liu Meilin",
				"Yan Ting",
				"Liu Huijuan",
				"Zhang Ling",
				"Yang Bin",
				"Xi Yanfeng",
				"Wang Shubin",
				"Cheng Xiaolong",
				"Li ShuaiCheng",
				"Liu Zhihua",
				"Zhan Qimin",
				"Hu Zheng",
				"Cui Yongping"
			],
			"DOI": "10.1093/nsr/nwae150",
			"date": "2024-05-29",
			"PMC": "",
			"citation": "",
			"abstract": "Esophageal squamous cell carcinoma (ESCC) is a poor-prognostic cancer type with extensive intra- and inter-patient heterogeneity in both genomic variations and tumor microenvironment (TME). However, the patterns and drivers of spatial genomic and microenvironmental heterogeneity of ESCC remain largely unknown. Here, we generated a spatial multi-omic atlas by whole-exome, transcriptome, and methylome sequencing of 507 tumor samples from 103 patients. We identified a novel tumor suppressor ",
			"category": 2,
			"name": "Zhou Yong,2024"
		},
		{
			"PMID": 38783997,
			"title": "Pan-cancer analysis of the interplay between mutational signatures and cellular signaling.",
			"journal": "iScience",
			"authorList": [
				"Hakobyan Anna",
				"Meyenberg Mathilde",
				"Vardazaryan Nelli",
				"Hancock Joel",
				"Vulliard Loan",
				"Loizou Joanna I",
				"Menche J\u00f6rg"
			],
			"DOI": "10.1016/j.isci.2024.109873",
			"date": "2024-05-25",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a multi-faceted disease with intricate relationships between mutagenic processes, alterations in cellular signaling, and the tissue microenvironment. To date, these processes have been largely studied in isolation. A systematic understanding of how they interact and influence each other is lacking. Here, we present a framework for systematically characterizing the interaction between pairs of mutational signatures and between signatures and signaling pathway alterations. We applied this framework to large-scale data from TCGA and PCAWG and identified multiple positive and negative interactions, both cross\u058atissue and tissue\u058aspecific, that provide new insights into the molecular routes observed in tumorigenesis and their respective drivers. This framework allows for a more fine-grained dissection of common and distinct etiology of mutational signatures. We further identified several interactions with both positive and negative impacts on patient survival, demonstrating their clinical relevance and potential for improving personalized cancer care.",
			"category": 2,
			"name": "Hakobyan Anna,2024"
		},
		{
			"PMID": 38778164,
			"title": "Arginines of the CGN codon family are Achilles' heels of cancer genes.",
			"journal": "Scientific reports",
			"authorList": [
				"Trexler M\u00e1ria",
				"B\u00e1nyai L\u00e1szl\u00f3",
				"Kerekes Krisztina",
				"Patthy L\u00e1szl\u00f3"
			],
			"DOI": "10.1038/s41598-024-62553-7",
			"date": "2024-05-22",
			"PMC": "",
			"citation": "",
			"abstract": "Recent studies have revealed that arginine is the most favorable target of amino acid alteration in most cancer types and it has been suggested that the high preference for arginine mutations reflects the critical roles of this amino acid in the function of proteins. High rates of mutations of arginine residues in cancer, however, might also be due to increased mutability of arginine codons of the CGN family as the CpG dinucleotides of these codons may be methylated. In the present work we have analyzed spectra of single base substitutions of cancer genes (oncogenes, tumor suppressor genes) and passenger genes in cancer tissues to assess the contributions of CpG hypermutability and selection to arginine mutations. Our studies have shown that arginines encoded by the CGN codon family display higher rates of mutation in both cancer genes and passenger genes than arginine codons AGA and AGG that are devoid of CpG dinucleotide, suggesting that the predominance of arginine mutations in cancer is primarily due to CpG hypermutability, rather than selection for arginine replacement. Nevertheless, our results also suggest that CGN codons for arginines may serve as Achilles' heels of cancer genes. CpG hypermutability of key arginines of proto-oncogenes, leading to high rates of recurrence of driver mutations, contributes significantly to carcinogenesis. Similarly, our results indicate that hypermutability of the CpG dinucleotide of CGA codons (converting them to TGA stop codons) contributes significantly to recurrent truncation and inactivation of tumor suppressor genes.",
			"category": 2,
			"name": "Trexler M\u00e1ria,2024"
		},
		{
			"PMID": 38773520,
			"title": "HATCHet2: clone- and haplotype-specific copy number inference from bulk tumor sequencing data.",
			"journal": "Genome biology",
			"authorList": [
				"Myers Matthew A",
				"Arnold Brian J",
				"Bansal Vineet",
				"Balaban Metin",
				"Mullen Katelyn M",
				"Zaccaria Simone",
				"Raphael Benjamin J"
			],
			"DOI": "10.1186/s13059-024-03267-x",
			"date": "2024-05-22",
			"PMC": "",
			"citation": "",
			"abstract": "Bulk DNA sequencing of multiple samples from the same tumor is becoming common, yet most methods to infer copy-number aberrations (CNAs) from this data analyze individual samples independently. We introduce HATCHet2, an algorithm to identify haplotype- and clone-specific CNAs simultaneously from multiple bulk samples. HATCHet2 extends the earlier HATCHet method by improving identification of focal CNAs and introducing a novel statistic, the minor haplotype B-allele frequency (mhBAF), that enables identification of mirrored-subclonal CNAs. We demonstrate HATCHet2's improved accuracy using simulations and a single-cell sequencing dataset. HATCHet2 analysis of 10 prostate cancer patients reveals previously unreported mirrored-subclonal CNAs affecting cancer genes.",
			"category": 2,
			"name": "Myers Matthew A,2024"
		},
		{
			"PMID": 38760638,
			"title": "Spatial genomic, biochemical and cellular mechanisms underlying meningioma heterogeneity and evolution.",
			"journal": "Nature genetics",
			"authorList": [
				"Lucas Calixto-Hope G",
				"Mirchia Kanish",
				"Seo Kyounghee",
				"Najem Hinda",
				"Chen William C",
				"Zakimi Naomi",
				"Foster Kyla",
				"Eaton Charlotte D",
				"Cady Martha A",
				"Choudhury Abrar",
				"Liu S John",
				"Phillips Joanna J",
				"Magill Stephen T",
				"Horbinski Craig M",
				"Solomon David A",
				"Perry Arie",
				"Vasudevan Harish N",
				"Heimberger Amy B",
				"Raleigh David R"
			],
			"DOI": "10.1038/s41588-024-01747-1",
			"date": "2024-06-13",
			"PMC": "",
			"citation": "",
			"abstract": "Intratumor heterogeneity underlies cancer evolution and treatment resistance, but targetable mechanisms driving intratumor heterogeneity are poorly understood. Meningiomas are the most common primary intracranial tumors and are resistant to all medical therapies, and high-grade meningiomas have significant intratumor heterogeneity. Here we use spatial approaches to identify genomic, biochemical and cellular mechanisms linking intratumor heterogeneity to the molecular, temporal and spatial evolution of high-grade meningiomas. We show that divergent intratumor gene and protein expression programs distinguish high-grade meningiomas that are otherwise grouped together by current classification systems. Analyses of matched pairs of primary and recurrent meningiomas reveal spatial expansion of subclonal copy number variants associated with treatment resistance. Multiplexed sequential immunofluorescence and deconvolution of meningioma spatial transcriptomes using cell types from single-cell RNA sequencing show decreased immune infiltration, decreased MAPK signaling, increased PI3K-AKT signaling and increased cell proliferation, which are associated with meningioma recurrence. To translate these findings to preclinical models, we use CRISPR interference and lineage tracing approaches to identify combination therapies that target intratumor heterogeneity in meningioma cell co-cultures.",
			"category": 2,
			"name": "Lucas Calixto-Hope G,2024"
		},
		{
			"PMID": 38730722,
			"title": "Detection of Oncogene Hotspot Mutations in Female NSCLC Tumor DNA and Cell-Free DNA.",
			"journal": "Cancers",
			"authorList": [
				"Drejeriene Ieva",
				"Cicenas Saulius",
				"Stanciute Diana",
				"Krasauskas Arnoldas",
				"Gruode Jurate"
			],
			"DOI": "10.3390/cancers16091770",
			"date": "2024-05-13",
			"PMC": "",
			"citation": "",
			"abstract": "Non-small-cell lung cancer (NSCLC) is the most prevalent type of lung cancer, with extensively characterized mutational spectra. Several biomarkers (such as ",
			"category": 2,
			"name": "Drejeriene Ieva,2024"
		},
		{
			"PMID": 38724668,
			"title": "Tracking single-cell evolution using clock-like chromatin accessibility loci.",
			"journal": "Nature biotechnology",
			"authorList": [
				"Xiao Yu",
				"Jin Wan",
				"Ju Lingao",
				"Fu Jie",
				"Wang Gang",
				"Yu Mengxue",
				"Chen Fangjin",
				"Qian Kaiyu",
				"Wang Xinghuan",
				"Zhang Yi"
			],
			"DOI": "10.1038/s41587-024-02241-z",
			"date": "2024-05-09",
			"PMC": "",
			"citation": "",
			"abstract": "Single-cell chromatin accessibility sequencing (scATAC-seq) reconstructs developmental trajectory by phenotypic similarity. However, inferring the exact developmental trajectory is challenging. Previous studies showed age-associated DNA methylation (DNAm) changes in specific genomic regions, termed clock-like differential methylation loci (ClockDML). Age-associated DNAm could either result from or result in chromatin accessibility changes at ClockDML. As cells undergo mitosis, the heterogeneity of chromatin accessibility on clock-like loci is reduced, providing a measure of mitotic age. In this study, we developed a method, called EpiTrace, that counts the fraction of opened clock-like loci from scATAC-seq data to determine cell age and perform lineage tracing in various cell lineages and animal species. It shows concordance with known developmental hierarchies, correlates well with DNAm-based clocks and is complementary with mutation-based lineage tracing, RNA velocity and stemness predictions. Applying EpiTrace to scATAC-seq data reveals biological insights with clinically relevant implications, ranging from hematopoiesis, organ development, tumor biology and immunity to cortical gyrification.",
			"category": 2,
			"name": "Xiao Yu,2024"
		},
		{
			"PMID": 38714690,
			"title": "The genomic landscape of Vk*MYC myeloma highlights shared pathways of transformation between mice and humans.",
			"journal": "Nature communications",
			"authorList": [
				"Maura Francesco",
				"Coffey David G",
				"Stein Caleb K",
				"Braggio Esteban",
				"Ziccheddu Bachisio",
				"Sharik Meaghen E",
				"Du Megan T",
				"Tafoya Alvarado Yuliza",
				"Shi Chang-Xin",
				"Zhu Yuan Xiao",
				"Meermeier Erin W",
				"Morgan Gareth J",
				"Landgren Ola",
				"Bergsagel P Leif",
				"Chesi Marta"
			],
			"DOI": "10.1038/s41467-024-48091-w",
			"date": "2024-05-07",
			"PMC": "",
			"citation": "",
			"abstract": "Multiple myeloma (MM) is a heterogeneous disease characterized by frequent MYC translocations. Sporadic MYC activation in the germinal center of genetically engineered Vk*MYC mice is sufficient to induce plasma cell tumors in which a variety of secondary mutations are spontaneously acquired and selected over time. Analysis of 119 Vk*MYC myeloma reveals recurrent copy number alterations, structural variations, chromothripsis, driver mutations, apolipoprotein B mRNA-editing enzyme, catalytic polypeptide (APOBEC) mutational activity, and a progressive decrease in immunoglobulin transcription that inversely correlates with proliferation. Moreover, we identify frequent insertional mutagenesis by endogenous retro-elements as a murine specific mechanism to activate NF-kB and IL6 signaling pathways shared with human MM. Despite the increased genomic complexity associated with progression, advanced tumors remain dependent on MYC. In summary, here we credential the Vk*MYC mouse as a unique resource to explore MM genomic evolution and describe a fully annotated collection of diverse and immortalized murine MM tumors.",
			"category": 2,
			"name": "Maura Francesco,2024"
		},
		{
			"PMID": 38698126,
			"title": "Developmental origins shape the paediatric cancer genome.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Chen Xiaolong",
				"Yang Wentao",
				"Roberts Charles W M",
				"Zhang Jinghui"
			],
			"DOI": "10.1038/s41568-024-00684-9",
			"date": "2024-05-30",
			"PMC": "",
			"citation": "",
			"abstract": "In the past two decades, technological advances have brought unprecedented insights into the paediatric cancer genome revealing characteristics distinct from those of adult cancer. Originating from developing tissues, paediatric cancers generally have low mutation burden and are driven by variants that disrupt the transcriptional activity, chromatin state, non-coding cis-regulatory regions and other biological functions. Within each tumour, there are multiple populations of cells with varying states, and the lineages of some can be tracked to their fetal origins. Genome-wide genetic screening has identified vulnerabilities associated with both the cell of origin and transcription deregulation in paediatric cancer, which have become a valuable resource for designing new therapeutic approaches including those for small molecules, immunotherapy and targeted protein degradation. In this Review, we present recent findings on these facets of paediatric cancer from a pan-cancer perspective and provide an outlook on future investigations.",
			"category": 2,
			"name": "Chen Xiaolong,2024"
		},
		{
			"PMID": 38668357,
			"title": "Mitochondrial-Stem Cell Connection: Providing Additional Explanations for Understanding Cancer.",
			"journal": "Metabolites",
			"authorList": [
				"Martinez Pierrick",
				"Baghli Ilyes",
				"Gourjon G\u00e9raud",
				"Seyfried Thomas N"
			],
			"DOI": "10.3390/metabo14040229",
			"date": "2024-04-28",
			"PMC": "",
			"citation": "",
			"abstract": "The cancer paradigm is generally based on the somatic mutation model, asserting that cancer is a disease of genetic origin. The mitochondrial-stem cell connection (MSCC) proposes that tumorigenesis may result from an alteration of the mitochondria, specifically a chronic oxidative phosphorylation (OxPhos) insufficiency in stem cells, which forms cancer stem cells (CSCs) and leads to malignancy. Reviewed evidence suggests that the MSCC could provide a comprehensive understanding of all the different stages of cancer. The metabolism of cancer cells is altered (OxPhos insufficiency) and must be compensated by using the glycolysis and the glutaminolysis pathways, which are essential to their growth. The altered mitochondria regulate the tumor microenvironment, which is also necessary for cancer evolution. Therefore, the MSCC could help improve our understanding of tumorigenesis, metastases, the efficiency of standard treatments, and relapses.",
			"category": 2,
			"name": "Martinez Pierrick,2024"
		},
		{
			"PMID": 38617360,
			"title": "APOBEC shapes tumor evolution and age at onset of lung cancer in smokers.",
			"journal": "bioRxiv : the preprint server for biology",
			"authorList": [
				"Zhang Tongwu",
				"Sang Jian",
				"Hoang Phuc H",
				"Zhao Wei",
				"Rosenbaum Jennifer",
				"Johnson Kofi Ennu",
				"Klimczak Leszek J",
				"McElderry John",
				"Klein Alyssa",
				"Wirth Christopher",
				"Bergstrom Erik N",
				"D\u00edaz-Gay Marcos",
				"Vangara Raviteja",
				"Colon-Matos Frank",
				"Hutchinson Amy",
				"Lawrence Scott M",
				"Cole Nathan",
				"Zhu Bin",
				"Przytycka Teresa M",
				"Shi Jianxin",
				"Caporaso Neil E",
				"Homer Robert",
				"Pesatori Angela C",
				"Consonni Dario",
				"Imielinski Marcin",
				"Chanock Stephen J",
				"Wedge David C",
				"Gordenin Dmitry A",
				"Alexandrov Ludmil B",
				"Harris Reuben S",
				"Landi Maria Teresa"
			],
			"DOI": "10.1101/2024.04.02.587805",
			"date": "2024-04-25",
			"PMC": "",
			"citation": "",
			"abstract": "APOBEC enzymes are part of the innate immunity and are responsible for restricting viruses and retroelements by deaminating cytosine residues",
			"category": 2,
			"name": "Zhang Tongwu,2024"
		},
		{
			"PMID": 38617259,
			"title": "CINner: modeling and simulation of chromosomal instability in cancer at single-cell resolution.",
			"journal": "bioRxiv : the preprint server for biology",
			"authorList": [
				"Dinh Khanh N",
				"V\u00e1zquez-Garc\u00eda Ignacio",
				"Chan Andrew",
				"Malhotra Rhea",
				"Weiner Adam",
				"McPherson Andrew W",
				"Tavar\u00e9 Simon"
			],
			"DOI": "10.1101/2024.04.03.587939",
			"date": "2024-04-25",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer development is characterized by chromosomal instability, manifesting in frequent occurrences of different genomic alteration mechanisms ranging in extent and impact. Mathematical modeling can help evaluate the role of each mutational process during tumor progression, however existing frameworks can only capture certain aspects of chromosomal instability (CIN). We present CINner, a mathematical framework for modeling genomic diversity and selection during tumor evolution. The main advantage of CINner is its flexibility to incorporate many genomic events that directly impact cellular fitness, from driver gene mutations to copy number alterations (CNAs), including focal amplifications and deletions, missegregations and whole-genome duplication (WGD). We apply CINner to find chromosome-arm selection parameters that drive tumorigenesis in the absence of WGD in chromosomally stable cancer types. We found that the selection parameters predict WGD prevalence among different chromosomally unstable tumors, hinting that the selective advantage of WGD cells hinges on their tolerance for aneuploidy and escape from nullisomy. Direct application of CINner to model the WGD proportion and fraction of genome altered (FGA) further uncovers the increase in CNA probabilities associated with WGD in each cancer type. CINner can also be utilized to study chromosomally stable cancer types, by applying a selection model based on driver gene mutations and focal amplifications or deletions. Finally, we used CINner to analyze the impact of CNA probabilities, chromosome selection parameters, tumor growth dynamics and population size on cancer fitness and heterogeneity. We expect that CINner will provide a powerful modeling tool for the oncology community to quantify the impact of newly uncovered genomic alteration mechanisms on shaping tumor progression and adaptation.",
			"category": 2,
			"name": "Dinh Khanh N,2024"
		},
		{
			"PMID": 38517886,
			"title": "Evolution of chromosome-arm aberrations in breast cancer through genetic network rewiring.",
			"journal": "Cell reports",
			"authorList": [
				"Kuzmin Elena",
				"Baker Toby M",
				"Lesluyes Tom",
				"Monlong Jean",
				"Abe Kento T",
				"Coelho Paula P",
				"Schwartz Michael",
				"Del Corpo Joseph",
				"Zou Dongmei",
				"Morin Genevieve",
				"Pacis Alain",
				"Yang Yang",
				"Martinez Constanza",
				"Barber Jarrett",
				"Kuasne Hellen",
				"Li Rui",
				"Bourgey Mathieu",
				"Fortier Anne-Marie",
				"Davison Peter G",
				"Omeroglu Atilla",
				"Guiot Marie-Christine",
				"Morris Quaid",
				"Kleinman Claudia L",
				"Huang Sidong",
				"Gingras Anne-Claude",
				"Ragoussis Jiannis",
				"Bourque Guillaume",
				"Van Loo Peter",
				"Park Morag"
			],
			"DOI": "10.1016/j.celrep.2024.113988",
			"date": "2024-04-26",
			"PMC": "",
			"citation": "",
			"abstract": "The basal breast cancer subtype is enriched for triple-negative breast cancer (TNBC) and displays consistent large chromosomal deletions. Here, we characterize evolution and maintenance of chromosome 4p (chr4p) loss in basal breast cancer. Analysis of The Cancer Genome Atlas data shows recurrent deletion of chr4p in basal breast cancer. Phylogenetic analysis of a panel of 23 primary tumor/patient-derived xenograft basal breast cancers reveals early evolution of chr4p deletion. Mechanistically we show that chr4p loss is associated with enhanced proliferation. Gene function studies identify an unknown gene, C4orf19, within chr4p, which suppresses proliferation when overexpressed-a member of the PDCD10-GCKIII kinase module we name PGCKA1. Genome-wide pooled overexpression screens using a barcoded library of human open reading frames identify chromosomal regions, including chr4p, that suppress proliferation when overexpressed in a context-dependent manner, implicating network interactions. Together, these results shed light on the early emergence of complex aneuploid karyotypes involving chr4p and adaptive landscapes shaping breast cancer genomes.",
			"category": 2,
			"name": "Kuzmin Elena,2024"
		},
		{
			"PMID": 38503341,
			"title": "Latent evolutionary signatures: a general framework for analysing music and cultural evolution.",
			"journal": "Journal of the Royal Society, Interface",
			"authorList": [
				"Warrell Jonathan",
				"Salichos Leonidas",
				"Gancz Michael",
				"Gerstein Mark B"
			],
			"DOI": "10.1098/rsif.2023.0647",
			"date": "2024-03-21",
			"PMC": "",
			"citation": "",
			"abstract": "Cultural processes of change bear many resemblances to biological evolution. The underlying units of non-biological evolution have, however, remained elusive, especially in the domain of music. Here, we introduce a general framework to jointly identify underlying units and their associated evolutionary processes. We model musical styles and principles of organization in dimensions such as harmony and form as following an evolutionary process. Furthermore, we propose that such processes can be identified by extracting latent evolutionary signatures from musical corpora, analogously to identifying mutational signatures in genomics. These signatures provide a latent embedding for each song or musical piece. We develop a deep generative architecture for our model, which can be viewed as a type of variational autoencoder with an evolutionary prior constraining the latent space; specifically, the embeddings for each song are tied together via an energy-based prior, which encourages songs close in evolutionary space to share similar representations. As illustration, we analyse songs from the McGill Billboard dataset. We find frequent chord transitions and formal repetition schemes and identify latent evolutionary signatures related to these features. Finally, we show that the latent evolutionary representations learned by our model outperform non-evolutionary representations in such tasks as period and genre prediction.",
			"category": 2,
			"name": "Warrell Jonathan,2024"
		},
		{
			"PMID": 38485987,
			"title": "ERK pathway agonism for cancer therapy: evidence, insights, and a target discovery framework.",
			"journal": "NPJ precision oncology",
			"authorList": [
				"Timofeev Oleg",
				"Giron Philippe",
				"Lawo Steffen",
				"Pichler Martin",
				"Noeparast Maxim"
			],
			"DOI": "10.1038/s41698-024-00554-5",
			"date": "2024-03-17",
			"PMC": "",
			"citation": "",
			"abstract": "At least 40% of human cancers are associated with aberrant ERK pathway activity (ERKp). Inhibitors targeting various effectors within the ERKp have been developed and explored for over two decades. Conversely, a substantial body of evidence suggests that both normal human cells and, notably to a greater extent, cancer cells exhibit susceptibility to hyperactivation of ERKp. However, this vulnerability of cancer cells remains relatively unexplored. In this review, we reexamine the evidence on the selective lethality of highly elevated ERKp activity in human cancer cells of varying backgrounds. We synthesize the insights proposed for harnessing this vulnerability of ERK-associated cancers for therapeutical approaches and contextualize these insights within established pharmacological cancer-targeting models. Moreover, we compile the intriguing preclinical findings of ERK pathway agonism in diverse cancer models. Lastly, we present a conceptual framework for target discovery regarding ERKp agonism, emphasizing the utilization of mutual exclusivity among oncogenes to develop novel targeted therapies for precision oncology.",
			"category": 2,
			"name": "Timofeev Oleg,2024"
		},
		{
			"PMID": 38480884,
			"title": "Evolutionary trajectories of small cell lung cancer under therapy.",
			"journal": "Nature",
			"authorList": [
				"George Julie",
				"Maas Lukas",
				"Abedpour Nima",
				"Cartolano Maria",
				"Kaiser Laura",
				"Fischer Rieke N",
				"Scheel Andreas H",
				"Weber Jan-Philipp",
				"Hellmich Martin",
				"Bosco Graziella",
				"Volz Caroline",
				"Mueller Christian",
				"Dahmen Ilona",
				"John Felix",
				"Alves Cleidson Padua",
				"Werr Lisa",
				"Panse Jens Peter",
				"Kirschner Martin",
				"Engel-Riedel Walburga",
				"J\u00fcrgens Jessica",
				"Stoelben Erich",
				"Brockmann Michael",
				"Grau Stefan",
				"Sebastian Martin",
				"Stratmann Jan A",
				"Kern Jens",
				"Hummel Horst-Dieter",
				"Heged\u00fcs Balazs",
				"Schuler Martin",
				"Pl\u00f6nes Till",
				"Aigner Clemens",
				"Elter Thomas",
				"Toepelt Karin",
				"Ko Yon-Dschun",
				"Kurz Sylke",
				"Groh\u00e9 Christian",
				"Serke Monika",
				"H\u00f6pker Katja",
				"Hagmeyer Lars",
				"Doerr Fabian",
				"Hekmath Khosro",
				"Strapatsas Judith",
				"Kambartel Karl-Otto",
				"Chakupurakal Geothy",
				"Busch Annette",
				"Bauernfeind Franz-Georg",
				"Griesinger Frank",
				"Luers Anne",
				"Dirks Wiebke",
				"Wiewrodt Rainer",
				"Luecke Andrea",
				"Rodermann Ernst",
				"Diel Andreas",
				"Hagen Volker",
				"Severin Kai",
				"Ullrich Roland T",
				"Reinhardt Hans Christian",
				"Quaas Alexander",
				"Bogus Magdalena",
				"Courts Cornelius",
				"N\u00fcrnberg Peter",
				"Becker Kerstin",
				"Achter Viktor",
				"B\u00fcttner Reinhard",
				"Wolf J\u00fcrgen",
				"Peifer Martin",
				"Thomas Roman K"
			],
			"DOI": "10.1038/s41586-024-07177-7",
			"date": "2024-03-29",
			"PMC": "",
			"citation": "",
			"abstract": "The evolutionary processes that underlie the marked sensitivity of small cell lung cancer (SCLC) to chemotherapy and rapid relapse are unknown",
			"category": 2,
			"name": "George Julie,2024"
		},
		{
			"PMID": 38448455,
			"title": "Evolving copy number gains promote tumor expansion and bolster mutational diversification.",
			"journal": "Nature communications",
			"authorList": [
				"Wang Zicheng",
				"Xia Yunong",
				"Mills Lauren",
				"Nikolakopoulos Athanasios N",
				"Maeser Nicole",
				"Dehm Scott M",
				"Sheltzer Jason M",
				"Sun Ruping"
			],
			"DOI": "10.1038/s41467-024-46414-5",
			"date": "2024-03-08",
			"PMC": "",
			"citation": "",
			"abstract": "The timing and fitness effect of somatic copy number alterations (SCNA) in cancer evolution remains poorly understood. Here we present a framework to determine the timing of a clonal SCNA that encompasses multiple gains. This involves calculating the proportion of time from its last gain to the onset of population expansion (lead time) as well as the proportion of time prior to its first gain (initiation time). Our method capitalizes on the observation that a genomic segment, while in a specific copy number (CN) state, accumulates point mutations proportionally to its CN. Analyzing 184 whole genome sequenced samples from 75 patients across five tumor types, we commonly observe late gains following early initiating events, occurring just before the clonal expansion relevant to the sampling. These include gains acquired after genome doubling in more than 60% of cases. Notably, mathematical modeling suggests that late clonal gains may contain final-expansion drivers. Lastly, SCNAs bolster mutational diversification between subpopulations, exacerbating the circle of proliferation and increasing heterogeneity.",
			"category": 2,
			"name": "Wang Zicheng,2024"
		},
		{
			"PMID": 38428419,
			"title": "Genomic evolution shapes prostate cancer disease type.",
			"journal": "Cell genomics",
			"authorList": [
				"Woodcock Dan J",
				"Sahli Atef",
				"Teslo Ruxandra",
				"Bhandari Vinayak",
				"Gruber Andreas J",
				"Ziubroniewicz Aleksandra",
				"Gundem Gunes",
				"Xu Yaobo",
				"Butler Adam",
				"Anokian Ezequiel",
				"Pope Bernard J",
				"Jung Chol-Hee",
				"Tarabichi Maxime",
				"Dentro Stefan C",
				"Farmery J Henry R",
				"CRUK ICGC Prostate Group",
				"Van Loo Peter",
				"Warren Anne Y",
				"Gnanapragasam Vincent",
				"Hamdy Freddie C",
				"Bova G Steven",
				"Foster Christopher S",
				"Neal David E",
				"Lu Yong-Jie",
				"Kote-Jarai Zsofia",
				"Fraser Michael",
				"Bristow Robert G",
				"Boutros Paul C",
				"Costello Anthony J",
				"Corcoran Niall M",
				"Hovens Christopher M",
				"Massie Charlie E",
				"Lynch Andy G",
				"Brewer Daniel S",
				"Eeles Rosalind A",
				"Cooper Colin S",
				"Wedge David C"
			],
			"DOI": "10.1016/j.xgen.2024.100511",
			"date": "2024-03-18",
			"PMC": "",
			"citation": "",
			"abstract": "The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype tumors diverge from those of the Canonical-evotype through the stochastic accumulation of genetic alterations associated with disruptions to androgen receptor DNA binding. Our model unifies many previous molecular observations, providing a powerful new framework to investigate prostate cancer disease progression.",
			"category": 2,
			"name": "Woodcock Dan J,2024"
		},
		{
			"PMID": 38388697,
			"title": "Role of chromosomal cohesion and separation in aneuploidy and tumorigenesis.",
			"journal": "Cellular and molecular life sciences : CMLS",
			"authorList": [
				"Pati Debananda"
			],
			"DOI": "10.1007/s00018-024-05122-5",
			"date": "2024-02-26",
			"PMC": "",
			"citation": "",
			"abstract": "Cell division is a crucial process, and one of its essential steps involves copying the genetic material, which is organized into structures called chromosomes. Before a cell can divide into two, it needs to ensure that each newly copied chromosome is paired tightly with its identical twin. This pairing is maintained by a protein complex known as cohesin, which is conserved in various organisms, from single-celled ones to humans. Cohesin essentially encircles the DNA, creating a ring-like structure to handcuff, to keep the newly synthesized sister chromosomes together in pairs. Therefore, chromosomal cohesion and separation are fundamental processes governing the attachment and segregation of sister chromatids during cell division. Metaphase-to-anaphase transition requires dissolution of cohesins by the enzyme Separase. The tight regulation of these processes is vital for safeguarding genomic stability. Dysregulation in chromosomal cohesion and separation resulting in aneuploidy, a condition characterized by an abnormal chromosome count in a cell, is strongly associated with cancer. Aneuploidy is a recurring hallmark in many cancer types, and abnormalities in chromosomal cohesion and separation have been identified as significant contributors to various cancers, such as acute myeloid leukemia, myelodysplastic syndrome, colorectal, bladder, and other solid cancers. Mutations within the cohesin complex have been associated with these cancers, as they interfere with chromosomal segregation, genome organization, and gene expression, promoting aneuploidy and contributing to the initiation of malignancy. In summary, chromosomal cohesion and separation processes play a pivotal role in preserving genomic stability, and aberrations in these mechanisms can lead to aneuploidy and cancer. Gaining a deeper understanding of the molecular intricacies of chromosomal cohesion and separation offers promising prospects for the development of innovative therapeutic approaches in the battle against cancer.",
			"category": 2,
			"name": "Pati Debananda,2024"
		},
		{
			"PMID": 38383522,
			"title": "Converging and evolving immuno-genomic routes toward immune escape in breast cancer.",
			"journal": "Nature communications",
			"authorList": [
				"Blanco-Heredia Juan",
				"Souza Carla Anjos",
				"Trincado Juan L",
				"Gonzalez-Cao Maria",
				"Gon\u00e7alves-Ribeiro Samuel",
				"Gil Sara Ruiz",
				"Pravdyvets Dmytro",
				"Cede\u00f1o Samandhy",
				"Callari Maurizio",
				"Marra Antonio",
				"Gazzo Andrea M",
				"Weigelt Britta",
				"Pareja Fresia",
				"Vougiouklakis Theodore",
				"Jungbluth Achim A",
				"Rosell Rafael",
				"Brander Christian",
				"Tresserra Francesc",
				"Reis-Filho Jorge S",
				"Tiezzi Daniel Guimar\u00e3es",
				"de la Iglesia Nuria",
				"Heyn Holger",
				"De Mattos-Arruda Leticia"
			],
			"DOI": "10.1038/s41467-024-45292-1",
			"date": "2024-02-23",
			"PMC": "",
			"citation": "",
			"abstract": "The interactions between tumor and immune cells along the course of breast cancer progression remain largely unknown. Here, we extensively characterize multiple sequential and parallel multiregion tumor and blood specimens of an index patient and a cohort of metastatic triple-negative breast cancers. We demonstrate that a continuous increase in tumor genomic heterogeneity and distinct molecular clocks correlated with resistance to treatment, eventually allowing tumors to escape from immune control. TCR repertoire loses diversity over time, leading to convergent evolution as breast cancer progresses. Although mixed populations of effector memory and cytotoxic single T cells coexist in the peripheral blood, defects in the antigen presentation machinery coupled with subdued T cell recruitment into metastases are observed, indicating a potent immune avoidance microenvironment not compatible with an effective antitumor response in lethal metastatic disease. Our results demonstrate that the immune responses against cancer are not static, but rather follow dynamic processes that match cancer genomic progression, illustrating the complex nature of tumor and immune cell interactions.",
			"category": 2,
			"name": "Blanco-Heredia Juan,2024"
		},
		{
			"PMID": 38355797,
			"title": "Deep whole-genome analysis of 494 hepatocellular carcinomas.",
			"journal": "Nature",
			"authorList": [
				"Chen Lei",
				"Zhang Chong",
				"Xue Ruidong",
				"Liu Mo",
				"Bai Jian",
				"Bao Jinxia",
				"Wang Yin",
				"Jiang Nanhai",
				"Li Zhixuan",
				"Wang Wenwen",
				"Wang Ruiru",
				"Zheng Bo",
				"Yang Airong",
				"Hu Ji",
				"Liu Ke",
				"Shen Siyun",
				"Zhang Yangqianwen",
				"Bai Mixue",
				"Wang Yan",
				"Zhu Yanjing",
				"Yang Shuai",
				"Gao Qiang",
				"Gu Jin",
				"Gao Dong",
				"Wang Xin Wei",
				"Nakagawa Hidewaki",
				"Zhang Ning",
				"Wu Lin",
				"Rozen Steven G",
				"Bai Fan",
				"Wang Hongyang"
			],
			"DOI": "10.1038/s41586-024-07054-3",
			"date": "2024-03-22",
			"PMC": "",
			"citation": "",
			"abstract": "Over half of hepatocellular carcinoma (HCC) cases diagnosed worldwide are in China",
			"category": 2,
			"name": "Chen Lei,2024"
		},
		{
			"PMID": 38330461,
			"title": "Methylthioadenosine Phosphorylase Genomic Loss in Advanced Gastrointestinal Cancers.",
			"journal": "The oncologist",
			"authorList": [
				"Ngoi Natalie Y L",
				"Tang Tin-Yun",
				"Gaspar Catia F",
				"Pavlick Dean C",
				"Buchold Gregory M",
				"Scholefield Emma L",
				"Parimi Vamsi",
				"Huang Richard S P",
				"Janovitz Tyler",
				"Danziger Natalie",
				"Levy Mia A",
				"Pant Shubham",
				"De Armas Anaemy Danner",
				"Kumpula David",
				"Ross Jeffrey S",
				"Javle Milind",
				"Rodon Ahnert Jordi"
			],
			"DOI": "10.1093/oncolo/oyae011",
			"date": "2024-06-03",
			"PMC": "",
			"citation": "",
			"abstract": "One of the most common sporadic homozygous deletions in cancers is 9p21 loss, which includes the genes methylthioadenosine phosphorylase (MTAP), CDKN2A, and CDKN2B, and has been correlated with worsened outcomes and immunotherapy resistance. MTAP-loss is a developing drug target through synthetic lethality with MAT2A and PMRT5 inhibitors. The purpose of this study is to investigate the prevalence and genomic landscape of MTAP-loss in advanced gastrointestinal (GI) tumors and investigate its role as a prognostic biomarker.",
			"category": 2,
			"name": "Ngoi Natalie Y L,2024"
		},
		{
			"PMID": 38318814,
			"title": "Road of no return - loss of TP53 paves a defined evolution path from gastric preneoplasia-to-cancer.",
			"journal": "Cancer biology & medicine",
			"authorList": [
				"An Liwei",
				"Han Yi",
				"Jiao Shi",
				"Zhou Zhaocai"
			],
			"DOI": "10.20892/j.issn.2095-3941.2023.0435",
			"date": "2024-02-07",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "An Liwei,2024"
		},
		{
			"PMID": 38299304,
			"title": "Novel insights on genetics and epigenetics as clinical targets for paediatric astrocytoma.",
			"journal": "Clinical and translational medicine",
			"authorList": [
				"Johns Dona A",
				"Williams Richard J",
				"Smith Craig M",
				"Nadaminti Pavani P",
				"Samarasinghe Rasika M"
			],
			"DOI": "10.1002/ctm2.1560",
			"date": "2024-02-02",
			"PMC": "",
			"citation": "",
			"abstract": "Paediatric and adult astrocytomas are notably different, where clinical treatments used for adults are not as effective on children with the same form of cancer and these treatments lead to adverse long-term health concerns. Integrative omics-based studies have shown the pathology and fundamental molecular characteristics differ significantly and cannot be extrapolated from the more widely studied adult disease. Recent clinical advances in our understanding of paediatric astrocytomas, with the aid of next-generation sequencing and epigenome-wide profiling, have led to the identification of key canonical mutations that vary based on the tumour location and age of onset. These driver mutations, in particular the identification of the recurrent histone H3 mutations in high-grade tumours, have confirmed the important role epigenetic dysregulations play in cancer progression. This review summarises the current updates of the classification, epidemiology, pathogenesis and clinical management of paediatric astrocytoma based on their grades and the ongoing clinical trials. It also provides novel insights on genetic and epigenetic alterations as diagnostic biomarkers, highlighting the potential of targeting these pathways as therapeutics for this devastating childhood cancer.",
			"category": 2,
			"name": "Johns Dona A,2024"
		},
		{
			"PMID": 38297376,
			"title": "Computational validation of clonal and subclonal copy number alterations from bulk tumor sequencing using CNAqc.",
			"journal": "Genome biology",
			"authorList": [
				"Antonello Alice",
				"Bergamin Riccardo",
				"Calonaci Nicola",
				"Househam Jacob",
				"Milite Salvatore",
				"Williams Marc J",
				"Anselmi Fabio",
				"d'Onofrio Alberto",
				"Sundaram Vasavi",
				"Sosinsky Alona",
				"Cross William C H",
				"Caravagna Giulio"
			],
			"DOI": "10.1186/s13059-024-03170-5",
			"date": "2024-02-02",
			"PMC": "",
			"citation": "",
			"abstract": "Copy number alterations (CNAs) are among the most important genetic events in cancer, but their detection from sequencing data is challenging because of unknown sample purity, tumor ploidy, and general intra-tumor heterogeneity. Here, we present CNAqc, an evolution-inspired method to perform the computational validation of clonal and subclonal CNAs detected from bulk DNA sequencing. CNAqc is validated using single-cell data and simulations, is applied to over 4000 TCGA and PCAWG samples, and is incorporated into the validation process for the clinically accredited bioinformatics pipeline at Genomics England. CNAqc is designed to support automated quality control procedures for tumor somatic data validation.",
			"category": 2,
			"name": "Antonello Alice,2024"
		},
		{
			"PMID": 38286829,
			"title": "Aneuploidy and complex genomic rearrangements in cancer evolution.",
			"journal": "Nature cancer",
			"authorList": [
				"Baker Toby M",
				"Waise Sara",
				"Tarabichi Maxime",
				"Van Loo Peter"
			],
			"DOI": "10.1038/s43018-023-00711-y",
			"date": "2024-02-29",
			"PMC": "",
			"citation": "",
			"abstract": "Mutational processes that alter large genomic regions occur frequently in developing tumors. They range from simple copy number gains and losses to the shattering and reassembly of entire chromosomes. These catastrophic events, such as chromothripsis, chromoplexy and the formation of extrachromosomal DNA, affect the expression of many genes and therefore have a substantial effect on the fitness of the cells in which they arise. In this review, we cover large genomic alterations, the mechanisms that cause them and their effect on tumor development and evolution.",
			"category": 2,
			"name": "Baker Toby M,2024"
		},
		{
			"PMID": 38285005,
			"title": "Copy number gain of FAM131B-AS2 promotes the progression of glioblastoma by mitigating replication stress.",
			"journal": "Neuro-oncology",
			"authorList": [
				"Wang Shaobo",
				"Qi Yanhua",
				"Zhao Rongrong",
				"Pan Ziwen",
				"Li Boyan",
				"Qiu Wei",
				"Zhao Shulin",
				"Guo Xiaofan",
				"Ni Shilei",
				"Li Gang",
				"Xue Hao"
			],
			"DOI": "10.1093/neuonc/noae014",
			"date": "2024-06-03",
			"PMC": "",
			"citation": "",
			"abstract": "Glioblastoma (GBM) is characterized by chromosome 7 copy number gains, notably 7q34, potentially contributing to therapeutic resistance, yet the underlying oncogenes have not been fully characterized. Pertinently, the significance of long noncoding RNAs (lncRNAs) in this context has gained attention, necessitating further exploration.",
			"category": 2,
			"name": "Wang Shaobo,2024"
		},
		{
			"PMID": 38235376,
			"title": "Next generation of multispecific antibody engineering.",
			"journal": "Antibody therapeutics",
			"authorList": [
				"Keri Daniel",
				"Walker Matt",
				"Singh Isha",
				"Nishikawa Kyle",
				"Garces Fernando"
			],
			"DOI": "10.1093/abt/tbad027",
			"date": "2024-01-19",
			"PMC": "",
			"citation": "",
			"abstract": "Multispecific antibodies recognize two or more epitopes located on the same or distinct targets. This added capability through protein design allows these man-made molecules to address unmet medical needs that are no longer possible with single targeting such as with monoclonal antibodies or cytokines alone. However, the approach to the development of these multispecific molecules has been met with numerous road bumps, which suggests that a new workflow for multispecific molecules is required. The investigation of the molecular basis that mediates the successful assembly of the building blocks into non-native quaternary structures will lead to the writing of a playbook for multispecifics. This is a must do if we are to design workflows that we can control and in turn predict success. Here, we reflect on the current state-of-the-art of therapeutic biologics and look at the building blocks, in terms of proteins, and tools that can be used to build the foundations of such a next-generation workflow.",
			"category": 2,
			"name": "Keri Daniel,2024"
		},
		{
			"PMID": 38206124,
			"title": "Long-read single-cell sequencing reveals expressions of hypermutation clusters of isoforms in human liver cancer cells.",
			"journal": "eLife",
			"authorList": [
				"Liu Silvia",
				"Yu Yan-Ping",
				"Ren Bao-Guo",
				"Ben-Yehezkel Tuval",
				"Obert Caroline",
				"Smith Mat",
				"Wang Wenjia",
				"Ostrowska Alina",
				"Soto-Gutierrez Alejandro",
				"Luo Jian-Hua"
			],
			"DOI": "10.7554/eLife.87607",
			"date": "2024-01-12",
			"PMC": "",
			"citation": "",
			"abstract": "The protein diversity of mammalian cells is determined by arrays of isoforms from genes. Genetic mutation is essential in species evolution and cancer development. Accurate long-read transcriptome sequencing at single-cell level is required to decipher the spectrum of protein expressions in mammalian organisms. In this report, we developed a synthetic long-read single-cell sequencing technology based on LOOPSeq technique. We applied this technology to analyze 447 transcriptomes of hepatocellular carcinoma (HCC) and benign liver from an individual. Through Uniform Manifold Approximation and Projection analysis, we identified a panel of mutation mRNA isoforms highly specific to HCC cells. The evolution pathways that led to the hyper-mutation clusters in single human leukocyte antigen molecules were identified. Novel fusion transcripts were detected. The combination of gene expressions, fusion gene transcripts, and mutation gene expressions significantly improved the classification of liver cancer cells versus benign hepatocytes. In conclusion, LOOPSeq single-cell technology may hold promise to provide a new level of precision analysis on the mammalian transcriptome.",
			"category": 2,
			"name": "Liu Silvia,2024"
		},
		{
			"PMID": 38175731,
			"title": "Evolutionary mode and timing of dissemination of high-grade serous carcinomas.",
			"journal": "JCI insight",
			"authorList": [
				"Sveen Anita",
				"Johannessen Bjarne",
				"Klokkerud Solveig Mk",
				"Kraggerud Sigrid M",
				"Meza-Zepeda Leonardo A",
				"Bj\u00f8rnslett Merete",
				"Bischof Katharina",
				"Myklebost Ola",
				"Task\u00e9n Kjetil",
				"Skotheim Rolf I",
				"D\u00f8rum Anne",
				"Davidson Ben",
				"Lothe Ragnhild A"
			],
			"DOI": "10.1172/jci.insight.170423",
			"date": "2024-02-14",
			"PMC": "",
			"citation": "",
			"abstract": "Dissemination within the peritoneal cavity is a main determinant of poor patient outcomes from high-grade serous carcinomas (HGSCs). The dissemination process is poorly understood from a cancer evolutionary perspective. We reconstructed the evolutionary trajectories across a median of 5 tumor sites and regions from each of 23 patients based on deep whole-exome sequencing. Polyclonal cancer origin was detected in 1 patient. Ovarian tumors had more complex subclonal architectures than other intraperitoneal tumors in each patient, which indicated that tumors developed earlier in the ovaries. Three common modes of dissemination were identified, including monoclonal or polyclonal dissemination of monophyletic (linear) or polyphyletic (branched) subclones. Mutation profiles of initial or disseminated clones varied greatly among cancers, but recurrent mutations were found in 7 cancer-critical genes, including TP53, BRCA1, BRCA2, and DNMT3A, and in the PI3K/AKT1 pathway. Disseminated clones developed late in the evolutionary trajectory models of most cancers, in particular in cancers with DNA damage repair deficiency. Polyclonal dissemination was predicted to occur predominantly as a single and rapid wave, but chemotherapy exposure was associated with higher genomic diversity of disseminated clones. In conclusion, we described three common evolutionary dissemination modes across HGSCs and proposed factors associated with dissemination diversity.",
			"category": 2,
			"name": "Sveen Anita,2024"
		},
		{
			"PMID": 38167338,
			"title": "Mutant p53 gains oncogenic functions through a chromosomal instability-induced cytosolic DNA response.",
			"journal": "Nature communications",
			"authorList": [
				"Zhao Mei",
				"Wang Tianxiao",
				"Gleber-Netto Frederico O",
				"Chen Zhen",
				"McGrail Daniel J",
				"Gomez Javier A",
				"Ju Wutong",
				"Gadhikar Mayur A",
				"Ma Wencai",
				"Shen Li",
				"Wang Qi",
				"Tang Ximing",
				"Pathak Sen",
				"Raso Maria Gabriela",
				"Burks Jared K",
				"Lin Shiaw-Yih",
				"Wang Jing",
				"Multani Asha S",
				"Pickering Curtis R",
				"Chen Junjie",
				"Myers Jeffrey N",
				"Zhou Ge"
			],
			"DOI": "10.1038/s41467-023-44239-2",
			"date": "2024-01-05",
			"PMC": "",
			"citation": "",
			"abstract": "Inactivating TP53 mutations leads to a loss of function of p53, but can also often result in oncogenic gain-of-function (GOF) of mutant p53 (mutp53) proteins which promotes tumor development and progression. The GOF activities of TP53 mutations are well documented, but the mechanisms involved remain poorly understood. Here, we study the mutp53 interactome and find that by targeting minichromosome maintenance complex components (MCMs), GOF mutp53 predisposes cells to replication stress and chromosomal instability (CIN), leading to a tumor cell-autonomous and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-dependent cytosolic DNA response that activates downstream non-canonical nuclear factor kappa light chain enhancer of activated B cell (NC-NF-\u03baB) signaling. Consequently, GOF mutp53-MCMs-CIN-cytosolic DNA-cGAS-STING-NC-NF-\u03baB signaling promotes tumor cell metastasis and an immunosuppressive tumor microenvironment through antagonizing interferon signaling and regulating genes associated with pro-tumorigenic inflammation. Our findings have important implications for understanding not only the GOF activities of TP53 mutations but also the genome-guardian role of p53 and its inactivation during tumor development and progression.",
			"category": 2,
			"name": "Zhao Mei,2024"
		},
		{
			"PMID": 38163980,
			"title": "[Hypothesis of Genetic Diversity Selection in the Occurrence and Development of \u2029Lung Cancer: Molecular Evolution and Clinical Significance].",
			"journal": "Zhongguo fei ai za zhi = Chinese journal of lung cancer",
			"authorList": [
				"Liu Baodong"
			],
			"DOI": "10.3779/j.issn.1009-3419.2023.101.34",
			"date": "2024-01-03",
			"PMC": "",
			"citation": "",
			"abstract": "So far, the monoclonal hypothesis of tumor occurrence and development cannot be justified. The genetic diversity selection hypothesis for the occurrence and development of lung cancer links Mendelian genetics with Darwin's theory of evolution, suggesting that the genetic diversity of tumor cell populations with polyclonal origins-monoclonal selection-subclonal expansion is the result of selection pressure. Normal cells acquire mutations in oncogenic driver genes and have a selective advantage over other cells, becoming tumor initiating cells; In the interaction with the tumor microenvironment (TME), the vast majority of initiating cells are recognized and killed by the human immune system. If immune escape occurs, the incidence of malignant tumors will greatly increase, and subclonal expansion, intratumour heterogeneity, etc. will occur. This article proposed the hypothesis of genetic diversity selection and analyzed its clinical significance.\u2029.",
			"category": 2,
			"name": "Liu Baodong,2024"
		},
		{
			"PMID": 38106039,
			"title": "Whole genome sequencing refines stratification and therapy of patients with clear cell renal cell carcinoma.",
			"journal": "Research square",
			"authorList": [
				"Houlston Richard",
				"Culliford Richard",
				"Lawrence Sam",
				"Mills Charlie",
				"Tippu Zayd",
				"Chubb Daniel",
				"Cornish Alex",
				"Browining Lisa",
				"Kinnersley Ben",
				"Bentham Robert",
				"Sud Amit",
				"Pallikonda Husayn",
				"Frangou Anna",
				"Gruber Andreas",
				"Litchfield Kevin",
				"Wedge David",
				"Larkin James",
				"Turajlic Samra"
			],
			"DOI": "10.21203/rs.3.rs-3675752/v1",
			"date": "2024-05-15",
			"PMC": "",
			"citation": "",
			"abstract": "Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer, but a comprehensive description of its genomic landscape is lacking. We report the whole genome sequencing of 778 ccRCC patients enrolled in the 100,000 Genomes Project, providing the most detailed somatic mutational landscape to date. We identify new driver genes, which as well as emphasising the major role of epigenetic regulation in ccRCC highlight additional biological pathways extending opportunities for drug repurposing. Genomic characterisation identified patients with divergent clinical outcome; higher number of structural copy number alterations associated with poorer prognosis, whereas VHL mutations were independently associated with a better prognosis. The twin observations that higher T-cell infiltration is associated with better outcome and that genetically predicted immune evasion is not common supports the rationale for immunotherapy. These findings should inform personalised surveillance and treatment strategies for ccRCC patients.",
			"category": 2,
			"name": "Houlston Richard,2024"
		},
		{
			"PMID": 38096267,
			"title": "Time-resolved, integrated analysis of clonally evolving genomes.",
			"journal": "PLoS genetics",
			"authorList": [
				"Legrand Carine",
				"Andriantsoa Ranja",
				"Lichter Peter",
				"Raddatz G\u00fcnter",
				"Lyko Frank"
			],
			"DOI": "10.1371/journal.pgen.1011085",
			"date": "2023-12-29",
			"PMC": "",
			"citation": "",
			"abstract": "Clonal genome evolution is a key feature of asexually reproducing species and human cancer development. While many studies have described the landscapes of clonal genome evolution in cancer, few determine the underlying evolutionary parameters from molecular data, and even fewer integrate theory with data. We derived theoretical results linking mutation rate, time, expansion dynamics, and biological/clinical parameters. Subsequently, we inferred time-resolved estimates of evolutionary parameters from mutation accumulation, mutational signatures and selection. We then applied this framework to predict the time of speciation of the marbled crayfish, an enigmatic, globally invasive parthenogenetic freshwater crayfish. The results predict that speciation occurred between 1986 and 1990, which is consistent with biological records. We also used our framework to analyze whole-genome sequencing datasets from primary and relapsed glioblastoma, an aggressive brain tumor. The results identified evolutionary subgroups and showed that tumor cell survival could be inferred from genomic data that was generated during the resection of the primary tumor. In conclusion, our framework allowed a time-resolved, integrated analysis of key parameters in clonally evolving genomes, and provided novel insights into the evolutionary age of marbled crayfish and the progression of glioblastoma.",
			"category": 2,
			"name": "Legrand Carine,2023"
		},
		{
			"PMID": 38093010,
			"title": "Slide-tags enables single-nucleus barcoding for multimodal spatial genomics.",
			"journal": "Nature",
			"authorList": [
				"Russell Andrew J C",
				"Weir Jackson A",
				"Nadaf Naeem M",
				"Shabet Matthew",
				"Kumar Vipin",
				"Kambhampati Sandeep",
				"Raichur Ruth",
				"Marrero Giovanni J",
				"Liu Sophia",
				"Balderrama Karol S",
				"Vanderburg Charles R",
				"Shanmugam Vignesh",
				"Tian Luyi",
				"Iorgulescu J Bryan",
				"Yoon Charles H",
				"Wu Catherine J",
				"Macosko Evan Z",
				"Chen Fei"
			],
			"DOI": "10.1038/s41586-023-06837-4",
			"date": "2024-01-19",
			"PMC": "",
			"citation": "",
			"abstract": "Recent technological innovations have enabled the high-throughput quantification of gene expression and epigenetic regulation within individual cells, transforming our understanding of how complex tissues are constructed",
			"category": 2,
			"name": "Russell Andrew J C,2024"
		},
		{
			"PMID": 38045695,
			"title": "Structural basis for T cell recognition of cancer neoantigens and implications for predicting neoepitope immunogenicity.",
			"journal": "Frontiers in immunology",
			"authorList": [
				"Mariuzza Roy A",
				"Wu Daichao",
				"Pierce Brian G"
			],
			"DOI": "10.3389/fimmu.2023.1303304",
			"date": "2023-12-05",
			"PMC": "",
			"citation": "",
			"abstract": "Adoptive cell therapy (ACT) with tumor-specific T cells has been shown to mediate durable cancer regression. Tumor-specific T cells are also the basis of other therapies, notably cancer vaccines. The main target of tumor-specific T cells are neoantigens resulting from mutations in self-antigens over the course of malignant transformation. The detection of neoantigens presents a major challenge to T cells because of their high structural similarity to self-antigens, and the need to avoid autoimmunity. How different a neoantigen must be from its wild-type parent for it to induce a T cell response is poorly understood. Here we review recent structural and biophysical studies of T cell receptor (TCR) recognition of shared cancer neoantigens derived from oncogenes, including p53",
			"category": 2,
			"name": "Mariuzza Roy A,2023"
		},
		{
			"PMID": 38036971,
			"title": "Completing a genomic characterisation of microscopic tumour samples with copy number.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"Nulsen Joel",
				"Hussain Nosheen",
				"Al-Deka Aws",
				"Yap Jason",
				"Uddin Khalil",
				"Yau Christopher",
				"Ahmed Ahmed Ashour"
			],
			"DOI": "10.1186/s12859-023-05576-7",
			"date": "2023-12-04",
			"PMC": "",
			"citation": "",
			"abstract": "Genomic insights in settings where tumour sample sizes are limited to just hundreds or even tens of cells hold great clinical potential, but also present significant technical challenges. We previously developed the DigiPico sequencing platform to accurately identify somatic mutations from such samples.",
			"category": 2,
			"name": "Nulsen Joel,2023"
		},
		{
			"PMID": 38017136,
			"title": "CONIPHER: a computational framework for scalable phylogenetic reconstruction with error correction.",
			"journal": "Nature protocols",
			"authorList": [
				"Grigoriadis Kristiana",
				"Huebner Ariana",
				"Bunkum Abigail",
				"Colliver Emma",
				"Frankell Alexander M",
				"Hill Mark S",
				"Thol Kerstin",
				"Birkbak Nicolai J",
				"Swanton Charles",
				"Zaccaria Simone",
				"McGranahan Nicholas"
			],
			"DOI": "10.1038/s41596-023-00913-9",
			"date": "2024-01-12",
			"PMC": "",
			"citation": "",
			"abstract": "Intratumor heterogeneity provides the fuel for the evolution and selection of subclonal tumor cell populations. However, accurate inference of tumor subclonal architecture and reconstruction of tumor evolutionary histories from bulk DNA sequencing data remains challenging. Frequently, sequencing and alignment artifacts are not fully filtered out from cancer somatic mutations, and errors in the identification of copy number alterations or complex evolutionary events (e.g., mutation losses) affect the estimated cellular prevalence of mutations. Together, such errors propagate into the analysis of mutation clustering and phylogenetic reconstruction. In this Protocol, we present a new computational framework, CONIPHER (COrrecting Noise In PHylogenetic Evaluation and Reconstruction), that accurately infers subclonal structure and phylogenetic relationships from multisample tumor sequencing, accounting for both copy number alterations and mutation errors. CONIPHER has been used to reconstruct subclonal architecture and tumor phylogeny from multisample tumors with high-depth whole-exome sequencing from the TRACERx421 dataset, as well as matched primary-metastatic cases. CONIPHER outperforms similar methods on simulated datasets, and in particular scales to a large number of tumor samples and clones, while completing in under 1.5 h on average. CONIPHER enables automated phylogenetic analysis that can be effectively applied to large sequencing datasets generated with different technologies. CONIPHER can be run with a basic knowledge of bioinformatics and R and bash scripting languages.",
			"category": 2,
			"name": "Grigoriadis Kristiana,2024"
		},
		{
			"PMID": 38003387,
			"title": "Metastatic ER+ Breast Cancer: Mechanisms of Resistance and Future Therapeutic Approaches.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Raheem Farah",
				"Karikalan Suganya Arunachalam",
				"Batalini Felipe",
				"El Masry Aya",
				"Mina Lida"
			],
			"DOI": "10.3390/ijms242216198",
			"date": "2023-11-27",
			"PMC": "",
			"citation": "",
			"abstract": "Endocrine therapy is the main treatment for hormone receptor-positive (HR+) breast cancer. However, advanced tumors develop resistance to endocrine therapy, rendering it ineffective as the disease progresses. There are several molecular mechanisms of primary and secondary endocrine resistance. Resistance can develop due to either alteration of the estrogen receptor pathway (e.g., ESR1 mutations) or upstream growth factors signaling pathways (e.g., PI3K/Akt/mTOR pathway). Despite progress in the development of molecularly targeted anticancer therapies, the emergence of resistance remains a major limitation and an area of unmet need. In this article, we review the mechanisms of acquired endocrine resistance in HR+ advanced breast cancer and discuss current and future investigational therapeutic approaches.",
			"category": 2,
			"name": "Raheem Farah,2023"
		},
		{
			"PMID": 38003288,
			"title": "A Strategy Utilizing Protein-Protein Interaction Hubs for the Treatment of Cancer Diseases.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Carels Nicolas",
				"Sgariglia Domenico",
				"Junior Marcos Guilherme Vieira",
				"Lima Carlyle Ribeiro",
				"Carneiro Fl\u00e1via Raquel Gon\u00e7alves",
				"Silva Gilberto Ferreira da",
				"Silva Fabricio Alves Barbosa da",
				"Scardini Rafaela",
				"Tuszynski Jack Adam",
				"Andrade Cecilia Vianna de",
				"Monteiro Ana Carolina",
				"Martins Marcel Guimar\u00e3es",
				"Silva Talita Goulart da",
				"Ferraz Helen",
				"Finotelli Priscilla Vanessa",
				"Balbino Tiago Albertini",
				"Pinto Jos\u00e9 Carlos"
			],
			"DOI": "10.3390/ijms242216098",
			"date": "2023-11-30",
			"PMC": "",
			"citation": "",
			"abstract": "We describe a strategy for the development of a rational approach of neoplastic disease therapy based on the demonstration that scale-free networks are susceptible to specific attacks directed against its connective hubs. This strategy involves the (i) selection of up-regulated hubs of connectivity in the tumors interactome, (ii) drug repurposing of these hubs, (iii) RNA silencing of non-druggable hubs, (iv) in vitro hub validation, (v) tumor-on-a-chip, (vi) in vivo validation, and (vii) clinical trial. Hubs are protein targets that are assessed as targets for rational therapy of cancer in the context of personalized oncology. We confirmed the existence of a negative correlation between malignant cell aggressivity and the target number needed for specific drugs or RNA interference (RNAi) to maximize the benefit to the patient's overall survival. Interestingly, we found that some additional proteins not generally targeted by drug treatments might justify the addition of inhibitors designed against them in order to improve therapeutic outcomes. However, many proteins are not druggable, or the available pharmacopeia for these targets is limited, which justifies a therapy based on encapsulated RNAi.",
			"category": 2,
			"name": "Carels Nicolas,2023"
		},
		{
			"PMID": 38002970,
			"title": "Linking New Alleles at the Oscillator Loci to Flowering and Expansion of Asian Rice.",
			"journal": "Genes",
			"authorList": [
				"Gao Guangtong",
				"Chen Maoxian",
				"Mo Rong",
				"Li Nan",
				"Xu Yunzhang",
				"Lu Yingqing"
			],
			"DOI": "10.3390/genes14112027",
			"date": "2023-11-27",
			"PMC": "",
			"citation": "",
			"abstract": "The central oscillator is believed to be the key mechanism by which plants adapt to new environments. However, impacts from hybridization, the natural environment, and human selection have rarely been assessed on the oscillator of a crop. Here, from clearly identified alleles at oscillator loci (",
			"category": 2,
			"name": "Gao Guangtong,2023"
		},
		{
			"PMID": 37996064,
			"title": "Pairwise and higher-order epistatic effects among somatic cancer mutations across oncogenesis.",
			"journal": "Mathematical biosciences",
			"authorList": [
				"Alfaro-Murillo Jorge A",
				"Townsend Jeffrey P"
			],
			"DOI": "10.1016/j.mbs.2023.109091",
			"date": "2023-12-16",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer occurs as a consequence of multiple somatic mutations that lead to uncontrolled cell growth. Mutual exclusivity and co-occurrence of mutations imply-but do not prove-that mutations exert synergistic or antagonistic epistatic effects on oncogenesis. Knowledge of these interactions, and the consequent trajectories of mutation and selection that lead to cancer has been a longstanding goal within the cancer research community. Recent research has revealed mutation rates and scaled selection coefficients for specific recurrent variants across many cancer types. However, there are no current methods to quantify the strength of selection incorporating pairwise and higher-order epistatic effects on selection within the trajectory of likely cancer genotoypes. Therefore, we have developed a continuous-time Markov chain model that enables the estimation of mutation origination and fixation (flux), dependent on somatic cancer genotype. Coupling this continuous-time Markov chain model with a deconvolution approach provides estimates of underlying mutation rates and selection across the trajectory of oncogenesis. We demonstrate computation of fluxes and selection coefficients in a somatic evolutionary model for the four most frequently variant driver genes (TP53, LRP1B, KRAS and STK11) from 565 cases of lung adenocarcinoma. Our analysis reveals multiple antagonistic epistatic effects that reduce the possible routes of oncogenesis, and inform cancer research regarding viable trajectories of somatic evolution whose progression could be forestalled by precision medicine. Synergistic epistatic effects are also identified, most notably in the somatic genotype TP53 LRP1B for mutations in the KRAS gene, and in somatic genotypes containing KRAS or TP53 mutations for mutations in the STK11 gene. Large positive fluxes of KRAS variants were driven by large selection coefficients, whereas the flux toward LRP1B mutations was substantially aided by a large mutation rate for this gene. The approach enables inference of the most likely routes of site-specific variant evolution and estimation of the strength of selection operating on each step along the route, a key component of what we need to know to develop and implement personalized cancer therapies.",
			"category": 2,
			"name": "Alfaro-Murillo Jorge A,2023"
		},
		{
			"PMID": 37987212,
			"title": "Gene dosage compensation: Origins, criteria to identify compensated genes, and mechanisms including sensor loops as an emerging systems-level property in cancer.",
			"journal": "Cancer medicine",
			"authorList": [
				"Bravo-Estupi\u00f1an Diana M",
				"Aguilar-Guerrero Karol",
				"Quir\u00f3s Steve",
				"Ac\u00f3n Man-Sai",
				"Mar\u00edn-M\u00fcller Christian",
				"Ib\u00e1\u00f1ez-Hern\u00e1ndez Miguel",
				"Mora-Rodr\u00edguez Rodrigo A"
			],
			"DOI": "10.1002/cam4.6719",
			"date": "2024-01-01",
			"PMC": "",
			"citation": "",
			"abstract": "The gene dosage compensation hypothesis presents a mechanism through which the expression of certain genes is modulated to compensate for differences in the dose of genes when additional chromosomes are present. It is one of the means through which cancer cells actively cope with the potential damaging effects of aneuploidy, a hallmark of most cancers. Dosage compensation arises through several processes, including downregulation or overexpression of specific genes and the relocation of dosage-sensitive genes. In cancer, a majority of compensated genes are generally thought to be regulated at the translational or post-translational level, and include the basic components of a compensation loop, including sensors of gene dosage and modulators of gene expression. Post-translational regulation is mostly undertaken by a general degradation or aggregation of remaining protein subunits of macromolecular complexes. An increasingly important role has also been observed for transcriptional level regulation. This article reviews the process of targeted gene dosage compensation in cancer and other biological conditions, along with the mechanisms by which cells regulate specific genes to restore cellular homeostasis. These mechanisms represent potential targets for the inhibition of dosage compensation of specific genes in aneuploid cancers. This article critically examines the process of targeted gene dosage compensation in cancer and other biological contexts, alongside the criteria for identifying genes subject to dosage compensation and the intricate mechanisms by which cells orchestrate the regulation of specific genes to reinstate cellular homeostasis. Ultimately, our aim is to gain a comprehensive understanding of the intricate nature of a systems-level property. This property hinges upon the kinetic parameters of regulatory motifs, which we have termed \"gene dosage sensor loops.\" These loops have the potential to operate at both the transcriptional and translational levels, thus emerging as promising candidates for the inhibition of dosage compensation in specific genes. Additionally, they represent novel and highly specific therapeutic targets in the context of aneuploid cancer.",
			"category": 2,
			"name": "Bravo-Estupi\u00f1an Diana M,2024"
		},
		{
			"PMID": 37982847,
			"title": "Molecular diagnostics tailoring personalized cancer therapy-an oncologist's view.",
			"journal": "Virchows Archiv : an international journal of pathology",
			"authorList": [
				"Riedl Jakob M",
				"Moik Florian",
				"Esterl Tamara",
				"Kostmann Sarah M",
				"Gerger Armin",
				"Jost Philipp J"
			],
			"DOI": "10.1007/s00428-023-03702-7",
			"date": "2024-03-19",
			"PMC": "",
			"citation": "",
			"abstract": "Medical oncology is rapidly evolving with the implementation of personalized, targeted therapies. Advances in molecular diagnostics and the biologic understanding of cancer pathophysiology led to the identification of specific genetic alterations as drivers of cancer progression. Further, improvements in drug development enable the direct interference with these pathways, which allow tailoring personalized treatments based on a distinct molecular characterization of tumors. Thereby, we are currently experiencing a paradigm-shift in the treatment of cancers towards cancer-type agnostic, molecularly targeted, personalized therapies. However, this concept has several important hurdles and limitations to overcome to ultimately increase the proportion of patients benefitting from the precision oncology approach. These include the assessment of clinical relevancy of identified alterations, capturing and interpreting levels of heterogeneity based on intra-tumoral or time-dependent molecular evolution, and challenges in the practical implementation of precision oncology in routine clinical care. In the present review, we summarize the current state of cancer-agnostic precision oncology, discuss the concept of molecular tumor boards, and consider current limitations of personalized cancer therapy. Further, we provide an outlook towards potential future developments including the implementation of functionality assessments of identified genetic alterations and the broader use of liquid biopsies in order to obtain more comprehensive and longitudinal genetic information that might guide personalized cancer therapy in the future.",
			"category": 2,
			"name": "Riedl Jakob M,2024"
		},
		{
			"PMID": 37930255,
			"title": "ORAOV1, CCND1, and MIR548K Are the Driver Oncogenes of the 11q13 Amplicon in Squamous Cell Carcinoma.",
			"journal": "Molecular cancer research : MCR",
			"authorList": [
				"Mahieu C\u00e9line I",
				"Mancini Andrew G",
				"Vikram Ellee P",
				"Planells-Palop Vicente",
				"Joseph Nancy M",
				"Tward Aaron D"
			],
			"DOI": "10.1158/1541-7786.MCR-23-0746",
			"date": "2024-02-06",
			"PMC": "",
			"citation": "",
			"abstract": "11q13 amplification is a frequent event in human cancer and in particular in squamous cell carcinomas (SCC). Despite almost invariably spanning 10 genes, it is unclear which genetic components of the amplicon are the key driver events in SCC. A combination of computational, in vitro, ex vivo, and in vivo models leveraging efficient primary human keratinocyte genome editing by Cas9-RNP electroporation, identified ORAOV1, CCND1, and MIR548K as the critical drivers of the amplicon in head and neck SCC. CCND1 amplification drives the cell cycle in a CDK4/6/RB1-independent fashion and may confer a novel dependency on RRM2. MIR548K contributes to epithelial-mesenchymal transition. Finally, we identify ORAOV1 as an oncogene that acts likely via its ability to modulate reactive oxygen species. Thus, the 11q13 amplicon drives SCC through at least three independent genetic elements and suggests therapeutic targets for this morbid and lethal disease.",
			"category": 2,
			"name": "Mahieu C\u00e9line I,2024"
		},
		{
			"PMID": 37918402,
			"title": "Accessible high-throughput single-cell whole-genome sequencing with paired chromatin accessibility.",
			"journal": "Cell reports methods",
			"authorList": [
				"Queitsch Konstantin",
				"Moore Travis W",
				"O'Connell Brendan L",
				"Nichols Ruth V",
				"Muschler John L",
				"Keith Dove",
				"Lopez Charles",
				"Sears Rosalie C",
				"Mills Gordon B",
				"Yard\u0131mc\u0131 Galip G\u00fcrkan",
				"Adey Andrew C"
			],
			"DOI": "10.1016/j.crmeth.2023.100625",
			"date": "2023-11-23",
			"PMC": "",
			"citation": "",
			"abstract": "Single-cell whole-genome sequencing (scWGS) enables the assessment of genome-level molecular differences between individual cells with particular relevance to genetically diverse systems like solid tumors. The application of scWGS was limited due to a dearth of accessible platforms capable of producing high-throughput profiles. We present a technique that leverages nucleosome disruption methodologies with the\u00a0widely adopted 10\u00d7 Genomics ATAC-seq workflow to produce scWGS profiles for high-throughput copy-number analysis without new equipment or custom reagents. We further demonstrate the use of commercially available indexed transposase complexes from ScaleBio for sample multiplexing, reducing the per-sample preparation costs. Finally, we demonstrate that sequential indexed tagmentation with an intervening nucleosome disruption step allows for the generation of both ATAC and WGS data from the same cell, producing comparable data to the unimodal assays. By exclusively utilizing accessible commercial reagents, we anticipate that these scWGS and scWGS+ATAC methods can be broadly adopted by the research community.",
			"category": 2,
			"name": "Queitsch Konstantin,2023"
		},
		{
			"PMID": 37884500,
			"title": "Molecular mechanisms in colitis-associated colorectal cancer.",
			"journal": "Oncogenesis",
			"authorList": [
				"Zhou Royce W",
				"Harpaz Noam",
				"Itzkowitz Steven H",
				"Parsons Ramon E"
			],
			"DOI": "10.1038/s41389-023-00492-0",
			"date": "2024-02-10",
			"PMC": "",
			"citation": "",
			"abstract": "Sustained chronic inflammation of the large intestine leads to tissue damage and repair, which is associated with an increased incidence of colitis-associated colorectal cancer (CAC). The genetic makeup of CAC is somewhat similar to sporadic colorectal carcinoma (sCRC), but there are differences in the sequence and timing of alterations in the carcinogenesis process. Several models have been developed to explain the development of CAC, particularly the \"field cancerization\" model, which proposes that chronic inflammation accelerates mutagenesis and selects for the clonal expansion of phenotypically normal, pro-tumorigenic cells. In contrast, the \"Big Bang\" model posits that tumorigenic clones with multiple driver gene mutations emerge spontaneously. The details of CAC tumorigenesis-and how they differ from sCRC-are not yet fully understood. In this Review, we discuss recent genetic, epigenetic, and environmental findings related to CAC pathogenesis in the past five years, with a focus on unbiased, high-resolution genetic profiling of non-dysplastic field cancerization in the context of inflammatory bowel disease (IBD).",
			"category": 2,
			"name": "Zhou Royce W,2024"
		},
		{
			"PMID": 37868040,
			"title": "Mutational topography reflects clinical neuroblastoma heterogeneity.",
			"journal": "Cell genomics",
			"authorList": [
				"Rodriguez-Fos Elias",
				"Planas-F\u00e8lix Merc\u00e8",
				"Burkert Martin",
				"Puiggr\u00f2s Montserrat",
				"Toedling Joern",
				"Thiessen Nina",
				"Blanc Eric",
				"Szymansky Annabell",
				"Hertwig Falk",
				"Ishaque Naveed",
				"Beule Dieter",
				"Torrents David",
				"Eggert Angelika",
				"Koche Richard P",
				"Schwarz Roland F",
				"Haase Kerstin",
				"Schulte Johannes H",
				"Henssen Anton G"
			],
			"DOI": "10.1016/j.xgen.2023.100402",
			"date": "2024-02-14",
			"PMC": "",
			"citation": "",
			"abstract": "Neuroblastoma is a pediatric solid tumor characterized by strong clinical heterogeneity. Although clinical risk-defining genomic alterations exist in neuroblastomas, the mutational processes involved in their generation remain largely unclear. By examining the topography and mutational signatures derived from all variant classes, we identified co-occurring mutational footprints, which we termed mutational scenarios. We demonstrate that clinical neuroblastoma heterogeneity is associated with differences in the mutational processes driving these scenarios, linking risk-defining pathognomonic variants to distinct molecular processes. Whereas high-risk ",
			"category": 2,
			"name": "Rodriguez-Fos Elias,2024"
		},
		{
			"PMID": 37864038,
			"title": "Permission to pass: on the role of p53 as a gatekeeper for aneuploidy.",
			"journal": "Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology",
			"authorList": [
				"Marques Joana F",
				"Kops Geert J P L"
			],
			"DOI": "10.1007/s10577-023-09741-9",
			"date": "2023-11-08",
			"PMC": "",
			"citation": "",
			"abstract": "Aneuploidy-the karyotype state in which the number of chromosomes deviates from a multiple of the haploid chromosome set-is common in cancer, where it is thought to facilitate tumor initiation and progression. However, it is poorly tolerated in healthy cells: during development and tissue homeostasis, aneuploid cells are efficiently cleared from the population. It is still largely unknown how cancer cells become, and adapt to being, aneuploid. P53, the gatekeeper of the genome, has been proposed to guard against aneuploidy. Aneuploidy in cancer genomes strongly correlates with mutations in TP53, and p53 is thought to prevent the propagation of aneuploid cells. Whether p53 also participates in preventing the mistakes in cell division that lead to aneuploidy is still under debate. In this review, we summarize the current understanding of the role of p53 in protecting cells from aneuploidy, and we explore the consequences of functional p53 loss for the propagation of aneuploidy in cancer.",
			"category": 2,
			"name": "Marques Joana F,2023"
		},
		{
			"PMID": 37828555,
			"title": "Cancer origin tracing and timing in two high-risk prostate cancers using multisample whole genome analysis: prospects for personalized medicine.",
			"journal": "Genome medicine",
			"authorList": [
				"Nurminen Anssi",
				"Jaatinen Serafiina",
				"Taavitsainen Sinja",
				"H\u00f6gn\u00e4s Gunilla",
				"Lesluyes Tom",
				"Ansari-Pour Naser",
				"Tolonen Teemu",
				"Haase Kerstin",
				"Koskenalho Antti",
				"Kankainen Matti",
				"Jasu Juho",
				"Rauhala Hanna",
				"Kes\u00e4niemi Jenni",
				"Nikupaavola Tiia",
				"Kujala Paula",
				"Rinta-Kiikka Irina",
				"Riikonen Jarno",
				"Kaipia Antti",
				"Murtola Teemu",
				"Tammela Teuvo L",
				"Visakorpi Tapio",
				"Nykter Matti",
				"Wedge David C",
				"Van Loo Peter",
				"Bova G Steven"
			],
			"DOI": "10.1186/s13073-023-01242-y",
			"date": "2023-11-02",
			"PMC": "",
			"citation": "",
			"abstract": "Prostate cancer (PrCa) genomic heterogeneity causes resistance to therapies such as androgen deprivation. Such heterogeneity can be deciphered in the context of evolutionary principles, but current clinical trials do not include evolution as an essential feature. Whether or not analysis of genomic data in an evolutionary context in primary prostate cancer can provide unique added value in the research and clinical domains remains an open question.",
			"category": 2,
			"name": "Nurminen Anssi,2023"
		},
		{
			"PMID": 37812025,
			"title": "Subclonal Somatic Copy-Number Alterations Emerge and Dominate in Recurrent Osteosarcoma.",
			"journal": "Cancer research",
			"authorList": [
				"Kinnaman Michael D",
				"Zaccaria Simone",
				"Makohon-Moore Alvin",
				"Arnold Brian",
				"Levine Max F",
				"Gundem Gunes",
				"Arango Ossa Juan E",
				"Glodzik Dominik",
				"Rodr\u00edguez-S\u00e1nchez M Irene",
				"Bouvier Nancy",
				"Li Shanita",
				"Stockfisch Emily",
				"Dunigan Marisa",
				"Cobbs Cassidy",
				"Bhanot Umesh K",
				"You Daoqi",
				"Mullen Katelyn",
				"Melchor Jerry P",
				"Ortiz Michael V",
				"O'Donohue Tara J",
				"Slotkin Emily K",
				"Wexler Leonard H",
				"Dela Cruz Filemon S",
				"Hameed Meera R",
				"Glade Bender Julia L",
				"Tap William D",
				"Meyers Paul A",
				"Papaemmanuil Elli",
				"Kung Andrew L",
				"Iacobuzio-Donahue Christine A"
			],
			"DOI": "10.1158/0008-5472.CAN-23-0385",
			"date": "2023-11-30",
			"PMC": "",
			"citation": "",
			"abstract": "Multiple large-scale genomic profiling efforts have been undertaken in osteosarcoma to define the genomic drivers of tumorigenesis, therapeutic response, and disease recurrence. The spatial and temporal intratumor heterogeneity could also play a role in promoting tumor growth and treatment resistance. We conducted longitudinal whole-genome sequencing of 37 tumor samples from 8 patients with relapsed or refractory osteosarcoma. Each patient had at least one sample from a primary site and a metastatic or relapse site. Subclonal copy-number alterations were identified in all patients except one. In 5 patients, subclones from the primary tumor emerged and dominated at subsequent relapses. MYC gain/amplification was enriched in the treatment-resistant clones in 6 of 7 patients with multiple clones. Amplifications in other potential driver genes, such as CCNE1, RAD21, VEGFA, and IGF1R, were also observed in the resistant copy-number clones. A chromosomal duplication timing analysis revealed that complex genomic rearrangements typically occurred prior to diagnosis, supporting a macroevolutionary model of evolution, where a large number of genomic aberrations are acquired over a short period of time followed by clonal selection, as opposed to ongoing evolution. A mutational signature analysis of recurrent tumors revealed that homologous repair deficiency (HRD)-related SBS3 increases at each time point in patients with recurrent disease, suggesting that HRD continues to be an active mutagenic process after diagnosis. Overall, by examining the clonal relationships between temporally and spatially separated samples from patients with relapsed/refractory osteosarcoma, this study sheds light on the intratumor heterogeneity and potential drivers of treatment resistance in this disease.",
			"category": 2,
			"name": "Kinnaman Michael D,2023"
		},
		{
			"PMID": 37795443,
			"title": "The potential and challenges of targeting ",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Bray Chandler",
				"Balcells Cristina",
				"McNeish Iain A",
				"Keun Hector C"
			],
			"DOI": "10.3389/fonc.2023.1264785",
			"date": "2023-10-30",
			"PMC": "",
			"citation": "",
			"abstract": "Approximately 15% of cancers exhibit loss of the chromosomal locus 9p21.3 - the genomic location of the tumour suppressor gene ",
			"category": 2,
			"name": "Bray Chandler,2023"
		},
		{
			"PMID": 37778926,
			"title": "Aneuploidy in human cancer: new tools and perspectives.",
			"journal": "Trends in genetics : TIG",
			"authorList": [
				"Lakhani Asad A",
				"Thompson Sarah L",
				"Sheltzer Jason M"
			],
			"DOI": "10.1016/j.tig.2023.09.002",
			"date": "2023-11-16",
			"PMC": "",
			"citation": "",
			"abstract": "Chromosome copy number imbalances, otherwise known as aneuploidies, are a common but poorly understood feature of cancer. Here, we describe recent advances in both detecting and manipulating aneuploidies that have greatly advanced our ability to study their role in tumorigenesis. In particular, new clustered regularly interspaced short palindromic repeats (CRISPR)-based techniques have been developed that allow the creation of isogenic cell lines with specific chromosomal changes, thereby facilitating experiments in genetically controlled backgrounds to uncover the consequences of aneuploidy. These approaches provide increasing evidence that aneuploidy is a key driver of cancer development and enable the identification of multiple dosage-sensitive genes encoded on aneuploid chromosomes. Consequently, measuring aneuploidy may inform clinical prognosis, while treatment strategies that target aneuploidy could represent a novel method to counter malignant growth.",
			"category": 2,
			"name": "Lakhani Asad A,2023"
		},
		{
			"PMID": 37743495,
			"title": "Convergent TP53 loss and evolvability in cancer.",
			"journal": "BMC ecology and evolution",
			"authorList": [
				"Mansur Marcela Braga",
				"Greaves Mel"
			],
			"DOI": "10.1186/s12862-023-02146-6",
			"date": "2023-10-23",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer cell populations evolve by a stepwise process involving natural selection of the fittest variants within a tissue ecosystem context and as modified by therapy. Genomic scrutiny of patient samples reveals an extraordinary diversity of mutational profiles both between patients with similar cancers and within the cancer cell population of individual patients. Does this signify highly divergent evolutionary trajectories or are there repetitive and predictable patterns?Major evolutionary innovations or adaptations in different species are frequently repeated, or convergent, reflecting both common selective pressures and constraints on optimal solutions. We argue this is true of evolving cancer cells, especially with respect to the TP53 gene. Functional loss variants in TP53 are the most common genetic change in cancer. We discuss the likely microenvironmental selective pressures involved and the profound impact this has on cell fitness, evolvability and probability of subsequent drug resistance.",
			"category": 2,
			"name": "Mansur Marcela Braga,2023"
		},
		{
			"PMID": 37724294,
			"title": "Chromosomal Copy Number Variation Predicts EGFR-TKI Response and Prognosis for Patients with Non-Small Cell Lung Cancer.",
			"journal": "Pharmacogenomics and personalized medicine",
			"authorList": [
				"He Haiyan",
				"Ma Hang",
				"Chen Zhuo",
				"Chen Jingliang",
				"Wu Dandan",
				"Lv Xuedong",
				"Zhu Jie"
			],
			"DOI": "10.2147/PGPM.S418320",
			"date": "2023-09-20",
			"PMC": "",
			"citation": "",
			"abstract": "Chromosomal abnormalities represent genomic signatures linked to cancer prognosis and responses to chemotherapy, immunotherapy, and drug resistance. This study aimed to investigate the impact of chromosome copy number variants (CNVs) on the efficacy of tyrosine kinase inhibitors (TKIs) in EGFR-mutated non-small cell lung cancer (NSCLC) patients, as well as its prognostic implications for progression-free survival (PFS) and overall survival (OS) in EGFR wild-type patients.",
			"category": 2,
			"name": "He Haiyan,2023"
		},
		{
			"PMID": 37719146,
			"title": "Single-cell phylogenies reveal changes in the evolutionary rate within cancer and healthy tissues.",
			"journal": "Cell genomics",
			"authorList": [
				"Borgsm\u00fcller Nico",
				"Valecha Monica",
				"Kuipers Jack",
				"Beerenwinkel Niko",
				"Posada David"
			],
			"DOI": "10.1016/j.xgen.2023.100380",
			"date": "2023-09-20",
			"PMC": "",
			"citation": "",
			"abstract": "Cell lineages accumulate somatic mutations during organismal development, potentially leading to pathological states. The rate of somatic evolution within a cell population can vary due to multiple factors, including selection, a change in the mutation rate, or differences in the microenvironment. Here, we developed a statistical test called the Poisson Tree (PT) test to detect varying evolutionary rates among cell lineages, leveraging the phylogenetic signal of single-cell DNA sequencing (scDNA-seq) data. We applied the PT test to 24 healthy and cancer samples, rejecting a constant evolutionary rate in 11 out of 15 cancer and five out of nine healthy scDNA-seq datasets. In six cancer datasets, we identified subclonal mutations in known driver genes that could explain the rate accelerations of particular cancer lineages. Our findings demonstrate the efficacy of scDNA-seq for studying somatic evolution and suggest that cell lineages often evolve at different rates within cancer and healthy tissues.",
			"category": 2,
			"name": "Borgsm\u00fcller Nico,2023"
		},
		{
			"PMID": 37715023,
			"title": "Histological diagnosis of polyploidy discriminates an aggressive subset of hepatocellular carcinomas with poor prognosis.",
			"journal": "British journal of cancer",
			"authorList": [
				"Matsuura Takanori",
				"Ueda Yoshihide",
				"Harada Yoshiyuki",
				"Hayashi Kazuki",
				"Horisaka Kisara",
				"Yano Yoshihiko",
				"So Shinichi",
				"Kido Masahiro",
				"Fukumoto Takumi",
				"Kodama Yuzo",
				"Hara Eiji",
				"Matsumoto Tomonori"
			],
			"DOI": "10.1038/s41416-023-02408-6",
			"date": "2023-10-23",
			"PMC": "",
			"citation": "",
			"abstract": "Although genome duplication, or polyploidization, is believed to drive cancer evolution and affect tumor features, its significance in hepatocellular carcinoma (HCC) is unclear. We aimed to determine the characteristics of polyploid HCCs by evaluating chromosome duplication and to discover surrogate markers to discriminate polyploid HCCs.",
			"category": 2,
			"name": "Matsuura Takanori,2023"
		},
		{
			"PMID": 37704749,
			"title": "Evolution of structural rearrangements in prostate cancer intracranial metastases.",
			"journal": "NPJ precision oncology",
			"authorList": [
				"Khani Francesca",
				"Hooper William F",
				"Wang Xiaofei",
				"Chu Timothy R",
				"Shah Minita",
				"Winterkorn Lara",
				"Sigouros Michael",
				"Conteduca Vincenza",
				"Pisapia David",
				"Wobker Sara",
				"Walker Sydney",
				"Graff Julie N",
				"Robinson Brian",
				"Mosquera Juan Miguel",
				"Sboner Andrea",
				"Elemento Olivier",
				"Robine Nicolas",
				"Beltran Himisha"
			],
			"DOI": "10.1038/s41698-023-00435-3",
			"date": "2023-11-21",
			"PMC": "",
			"citation": "",
			"abstract": "Intracranial metastases in prostate cancer are uncommon but clinically aggressive. A detailed molecular characterization of prostate cancer intracranial metastases would improve our understanding of their pathogenesis and the search for new treatment strategies. We evaluated the clinical and molecular characteristics of 36 patients with metastatic prostate cancer to either the dura or brain parenchyma. We performed whole genome sequencing (WGS) of 10 intracranial prostate cancer metastases, as well as WGS of primary prostate tumors from men who later developed metastatic disease (n\u2009=\u20096) and nonbrain prostate cancer metastases (n\u2009=\u200936). This first whole genome sequencing study of prostate intracranial metastases led to several new insights. First, there was a higher diversity of complex structural alterations in prostate cancer intracranial metastases compared to primary tumor tissues. Chromothripsis and chromoplexy events seemed to dominate, yet there were few enrichments of specific categories of structural variants compared with non-brain metastases. Second, aberrations involving the AR gene, including AR enhancer gain were observed in 7/10 (70%) of intracranial metastases, as well as recurrent loss of function aberrations involving TP53 in 8/10 (80%), RB1 in 2/10 (20%), BRCA2 in 2/10 (20%), and activation of the PI3K/AKT/PTEN pathway in 8/10 (80%). These alterations were frequently present in tumor tissues from other sites of disease obtained concurrently or sequentially from the same individuals. Third, clonality analysis points to genomic factors and evolutionary bottlenecks that contribute to metastatic spread in patients with prostate cancer. These results describe the aggressive molecular features underlying intracranial metastasis that may inform future diagnostic and treatment approaches.",
			"category": 2,
			"name": "Khani Francesca,2023"
		},
		{
			"PMID": 37704602,
			"title": "Global impact of somatic structural variation on the cancer proteome.",
			"journal": "Nature communications",
			"authorList": [
				"Chen Fengju",
				"Zhang Yiqun",
				"Chandrashekar Darshan S",
				"Varambally Sooryanarayana",
				"Creighton Chad J"
			],
			"DOI": "10.1038/s41467-023-41374-8",
			"date": "2023-09-15",
			"PMC": "",
			"citation": "",
			"abstract": "Both proteome and transcriptome data can help assess the relevance of non-coding somatic mutations in cancer. Here, we combine mass spectrometry-based proteomics data with whole genome sequencing data across 1307 human tumors spanning various tissues to determine the extent somatic structural variant (SV) breakpoint patterns impact protein expression of nearby genes. We find that about 25% of the hundreds of genes with SV-associated cis-regulatory alterations at the mRNA level are similarly associated at the protein level. SVs associated with enhancer hijacking, retrotransposon translocation, altered DNA methylation, or fusion transcripts are implicated in protein over-expression. SVs combined with altered protein levels considerably extend the numbers of patients with tumors somatically altered for critical pathways. We catalog both SV breakpoint patterns involving patient survival and genes with nearby SV breakpoints associated with increased cell dependency in cancer cell lines. Pan-cancer proteogenomics identifies targetable non-coding alterations, by virtue of the associated deregulated genes.",
			"category": 2,
			"name": "Chen Fengju,2023"
		},
		{
			"PMID": 37699006,
			"title": "cloneRate: fast estimation of single-cell clonal dynamics using coalescent theory.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Johnson Brian",
				"Shuai Yubo",
				"Schweinsberg Jason",
				"Curtius Kit"
			],
			"DOI": "10.1093/bioinformatics/btad561",
			"date": "2023-10-23",
			"PMC": "",
			"citation": "",
			"abstract": "While evolutionary approaches to medicine show promise, measuring evolution itself is difficult due to experimental constraints and the dynamic nature of body systems. In cancer evolution, continuous observation of clonal architecture is impossible, and longitudinal samples from multiple timepoints are rare. Increasingly available DNA sequencing datasets at single-cell resolution enable the reconstruction of past evolution using mutational history, allowing for a better understanding of dynamics prior to detectable disease. There is an unmet need for an accurate, fast, and easy-to-use method to quantify clone growth dynamics from these datasets.",
			"category": 2,
			"name": "Johnson Brian,2023"
		},
		{
			"PMID": 37660330,
			"title": "Epidemiology and Control of Opisthorchis viverrini Infection: Implications for Cholangiocarcinoma Prevention.",
			"journal": "Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer",
			"authorList": [
				"Khuntikeo Narong",
				"Thinkhamrop Bandit",
				"Crellen Thomas",
				"Eamudomkarn Chatanun",
				"Petney Trevor N",
				"Andrews Ross H",
				"Sithithaworn Paiboon"
			],
			"DOI": "10.1007/978-3-031-35166-2_3",
			"date": "2023-09-05",
			"PMC": "",
			"citation": "",
			"abstract": "It is known that Opisthorchis viverrini (OV) is the most significant risk factor for the development of cholangiocarcinoma (CCA); hence, it is also known as carcinogenic parasite. Effective control and elimination of OV infection should significantly reduce O. viverrini-related CCA. This chapter includes details of the three recently developed innovative tools, namely the Isan cohort database software, an OV-RDT for screening of O. viverrini, and an ultrasound telecommunication system. Past and current control programs, i.e., education, medication, and sanitation were discussed and stressed the need for a comprehensive control program which encompasses primary, secondary, and tertiary patient care programs for confirmation and management of suspected CCA cases. The approach of mathematical modeling for control of OV and CCA was also briefly described. Additionally, we highlighted the current progress toward control of OV and CCA in Thailand and potential for expansion into nearby countries in Southeast Asia.",
			"category": 2,
			"name": "Khuntikeo Narong,2023"
		},
		{
			"PMID": 37620409,
			"title": "Synthetic viability induces resistance to immune checkpoint inhibitors in cancer cells.",
			"journal": "British journal of cancer",
			"authorList": [
				"Liu Mingyue",
				"Dong Qi",
				"Chen Bo",
				"Liu Kaidong",
				"Zhao Zhangxiang",
				"Wang Yuquan",
				"Zhuang Shuping",
				"Han Huiming",
				"Shi Xingyang",
				"Jin Zixin",
				"Hui Yang",
				"Gu Yunyan"
			],
			"DOI": "10.1038/s41416-023-02404-w",
			"date": "2023-10-23",
			"PMC": "",
			"citation": "",
			"abstract": "Immune checkpoint inhibitors (ICI) have revolutionized the treatment for multiple cancers. However, most of patients encounter resistance. Synthetic viability (SV) between genes could induce resistance. In this study, we established SV signature to predict the efficacy of ICI treatment for melanoma.",
			"category": 2,
			"name": "Liu Mingyue,2023"
		},
		{
			"PMID": 37608017,
			"title": "Convergent somatic evolution commences in utero in a germline ribosomopathy.",
			"journal": "Nature communications",
			"authorList": [
				"Machado Heather E",
				"\u00d8bro Nina F",
				"Williams Nicholas",
				"Tan Shengjiang",
				"Boukerrou Ahmed Z",
				"Davies Megan",
				"Belmonte Miriam",
				"Mitchell Emily",
				"Baxter E Joanna",
				"Mende Nicole",
				"Clay Anna",
				"Ancliff Philip",
				"K\u00f6glmeier Jutta",
				"Killick Sally B",
				"Kulasekararaj Austin",
				"Meyer Stefan",
				"Laurenti Elisa",
				"Campbell Peter J",
				"Kent David G",
				"Nangalia Jyoti",
				"Warren Alan J"
			],
			"DOI": "10.1038/s41467-023-40896-5",
			"date": "2023-08-24",
			"PMC": "",
			"citation": "",
			"abstract": "Clonal tracking of cells using somatic mutations permits exploration of clonal dynamics in human disease. Here, we perform whole genome sequencing of 323 haematopoietic colonies from 10 individuals with the inherited ribosomopathy Shwachman-Diamond syndrome to reconstruct haematopoietic phylogenies. In ~30% of colonies, we identify mutually exclusive mutations in TP53, EIF6, RPL5, RPL22, PRPF8, plus chromosome 7 and 15 aberrations that increase SBDS and EFL1 gene dosage, respectively. Target gene mutations commence in utero, resulting in a profusion of clonal expansions, with only a few haematopoietic stem cell lineages (mean 8, range 1-24) contributing ~50% of haematopoietic colonies across 8 individuals (range 4-100% clonality) by young adulthood. Rapid clonal expansion during disease transformation is associated with biallelic TP53 mutations and increased mutation burden. Our study highlights how convergent somatic mutation of the p53-dependent nucleolar surveillance pathway offsets the deleterious effects of germline ribosomopathy but increases opportunity for TP53-mutated cancer evolution.",
			"category": 2,
			"name": "Machado Heather E,2023"
		},
		{
			"PMID": 37598702,
			"title": "Modelling morbidity for neglected tropical diseases: the long and winding road from cumulative exposure to long-term pathology.",
			"journal": "Philosophical transactions of the Royal Society of London. Series B, Biological sciences",
			"authorList": [
				"Borlase Anna",
				"Prada Joaquin M",
				"Crellen Thomas"
			],
			"DOI": "10.1098/rstb.2022.0279",
			"date": "2023-08-22",
			"PMC": "",
			"citation": "",
			"abstract": "Reducing the morbidities caused by neglected tropical diseases (NTDs) is a central aim of ongoing disease control programmes. The broad spectrum of pathogens under the umbrella of NTDs lead to a range of negative health outcomes, from malnutrition and anaemia to organ failure, blindness and carcinogenesis. For some NTDs, the most severe clinical manifestations develop over many years of chronic or repeated infection. For these diseases, the association between infection and risk of long-term pathology is generally complex, and the impact of multiple interacting factors, such as age, co-morbidities and host immune response, is often poorly quantified. Mathematical modelling has been used for many years to gain insights into the complex processes underlying the transmission dynamics of infectious diseases; however, long-term morbidities associated with chronic or cumulative exposure are generally not incorporated into dynamic models for NTDs. Here we consider the complexities and challenges for determining the relationship between cumulative pathogen exposure and morbidity at the individual and population levels, drawing on case studies for trachoma, schistosomiasis and foodborne trematodiasis. We explore potential frameworks for explicitly incorporating long-term morbidity into NTD transmission models, and consider the insights such frameworks may bring in terms of policy-relevant projections for the elimination era. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.",
			"category": 2,
			"name": "Borlase Anna,2023"
		},
		{
			"PMID": 37579145,
			"title": "Triple-negative breast tumors are dependent on mutant p53 for growth and survival.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Dibra Denada",
				"Moyer Sydney M",
				"El-Naggar Adel K",
				"Qi Yuan",
				"Su Xiaoping",
				"Lozano Guillermina"
			],
			"DOI": "10.1073/pnas.2308807120",
			"date": "2023-08-16",
			"PMC": "",
			"citation": "",
			"abstract": "The ",
			"category": 2,
			"name": "Dibra Denada,2023"
		},
		{
			"PMID": 37539322,
			"title": "Gene expression networks involved in multiple cellular programs coexist in individual hepatocellular cancer cells.",
			"journal": "Heliyon",
			"authorList": [
				"Zhao Jin",
				"Lu Ran",
				"Jin Chen",
				"Li Siying",
				"Chen Yulin",
				"Huang Qiaorong",
				"Li Xue",
				"Meng Wentong",
				"Wu Hong",
				"Wen Tianfu",
				"Mo Xianming"
			],
			"DOI": "10.1016/j.heliyon.2023.e18305",
			"date": "2023-08-05",
			"PMC": "",
			"citation": "",
			"abstract": "The gene expression networks of a single cell can be used to reveal cell type- and condition-specific patterns that account for cell states, cell identity, and its responses to environmental changes. We applied single cell sequencing datasets to define mRNA patterns and visualized potential cellular capacities among hepatocellular cancer cells. The expressing numbers and levels of genes were highly heterogenous among the cancer cells. The cellular characteristics were dependent strongly on the expressing numbers and levels of genes, especially oncogenes and anti-oncogenes, in an individual cancer cell. The transcriptional activations of oncogenes and anti-oncogenes were strongly linked to inherent multiple cellular programs, some of which oppose and contend against other processes, in a cancer cell. The gene expression networks of multiple cellular programs proliferation, differentiation, apoptosis, autophagy, epithelial-mesenchymal transition, ATP production, and neurogenesis coexisted in an individual cancer cell. The findings give rise a hypothesis that a cancer cell expresses balanced combinations of genes and undergoes a given biological process by rapidly transmuting gene expressing networks.",
			"category": 2,
			"name": "Zhao Jin,2023"
		},
		{
			"PMID": 37502835,
			"title": "HATCHet2: clone- and haplotype-specific copy number inference from bulk tumor sequencing data.",
			"journal": "bioRxiv : the preprint server for biology",
			"authorList": [
				"Myers Matthew A",
				"Arnold Brian J",
				"Bansal Vineet",
				"Mullen Katelyn M",
				"Zaccaria Simone",
				"Raphael Benjamin J"
			],
			"DOI": "10.1101/2023.07.13.548855",
			"date": "2024-07-02",
			"PMC": "",
			"citation": "",
			"abstract": "Multi-region DNA sequencing of primary tumors and metastases from individual patients helps identify somatic aberrations driving cancer development. However, most methods to infer copy-number aberrations (CNAs) analyze individual samples. We introduce HATCHet2 to identify haplotype- and clone-specific CNAs simultaneously from multiple bulk samples. HATCHet2 introduces a novel statistic, the mirrored haplotype B-allele frequency (mhBAF), to identify mirrored-subclonal CNAs having different numbers of copies of parental haplotypes in different tumor clones. HATCHet2 also has high accuracy in identifying focal CNAs and extends the earlier HATCHet method in several directions. We demonstrate HATCHet2's improved accuracy using simulations and a single-cell sequencing dataset. HATCHet2 analysis of 50 prostate cancer samples from 10 patients reveals previously-unreported mirrored-subclonal CNAs affecting cancer genes.",
			"category": 2,
			"name": "Myers Matthew A,2024"
		},
		{
			"PMID": 37491836,
			"title": "Identifying the personalized driver gene sets maximally contributing to abnormality of transcriptome phenotype in glioblastoma multiforme individuals.",
			"journal": "Molecular oncology",
			"authorList": [
				"Xu Jinyuan",
				"Pang Bo",
				"Lan Yujia",
				"Dou Renjie",
				"Wang Shuai",
				"Kang Shaobo",
				"Zhang Wanmei",
				"Liu Yuanyuan",
				"Zhang Yijing",
				"Ping Yanyan"
			],
			"DOI": "10.1002/1878-0261.13499",
			"date": "2023-11-03",
			"PMC": "",
			"citation": "",
			"abstract": "High heterogeneity in genome and phenotype of cancer populations made it difficult to apply population-based common driver genes to the diagnosis and treatment of cancer individuals. Characterizing and identifying the personalized driver mechanism for glioblastoma multiforme (GBM) individuals were pivotal for the realization of precision medicine. We proposed an integrative method to identify the personalized driver gene sets by integrating the profiles of gene expression and genetic alterations in cancer individuals. This method coupled genetic algorithm and random walk to identify the optimal gene sets that could explain abnormality of transcriptome phenotype to the maximum extent. The personalized driver gene sets were identified for 99 GBM individuals using our method. We found that genomic alterations in between one and seven driver genes could maximally and cumulatively explain the dysfunction of cancer hallmarks across GBM individuals. The driver gene sets were distinct even in GBM individuals with significantly similar transcriptomic phenotypes. Our method identified MCM4 with rare genetic alterations as previously unknown oncogenic genes, the high expression of which were significantly associated with poor GBM prognosis. The functional experiments confirmed that knockdown of MCM4 could significantly inhibit proliferation, invasion, migration, and clone formation of the GBM cell lines U251 and U118MG, and overexpression of MCM4 significantly promoted the proliferation, invasion, migration, and clone formation of the GBM cell line U87MG. Our method could dissect the personalized driver genetic alteration sets that are pivotal for developing targeted therapy strategies and precision medicine. Our method could be extended to identify key drivers from other levels and could be applied to more cancer types.",
			"category": 2,
			"name": "Xu Jinyuan,2023"
		},
		{
			"PMID": 37490642,
			"title": "Multi-Omic Integration of Blood-Based Tumor-Associated Genomic and Lipidomic Profiles Using Machine Learning Models in Metastatic Prostate Cancer.",
			"journal": "JCO clinical cancer informatics",
			"authorList": [
				"Fang Shikai",
				"Zhe Shandian",
				"Lin Hui-Ming",
				"Azad Arun A",
				"Fettke Heidi",
				"Kwan Edmond M",
				"Horvath Lisa",
				"Mak Blossom",
				"Zheng Tiantian",
				"Du Pan",
				"Jia Shidong",
				"Kirby Robert M",
				"Kohli Manish"
			],
			"DOI": "10.1200/CCI.23.00057",
			"date": "2023-07-27",
			"PMC": "",
			"citation": "",
			"abstract": "To determine prognostic and predictive clinical outcomes in metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castrate-resistant prostate cancer (mCRPC) on the basis of a combination of plasma-derived genomic alterations and lipid features in a longitudinal cohort of patients with advanced prostate cancer.",
			"category": 2,
			"name": "Fang Shikai,2023"
		},
		{
			"PMID": 37454136,
			"title": "Mutational signature dynamics shaping the evolution of oesophageal adenocarcinoma.",
			"journal": "Nature communications",
			"authorList": [
				"Abbas Sujath",
				"Pich Oriol",
				"Devonshire Ginny",
				"Zamani Shahriar A",
				"Katz-Summercorn Annalise",
				"Killcoyne Sarah",
				"Cheah Calvin",
				"Nutzinger Barbara",
				"Grehan Nicola",
				"Lopez-Bigas Nuria",
				"OCCAMS Consortium",
				"Fitzgerald Rebecca C",
				"Secrier Maria"
			],
			"DOI": "10.1038/s41467-023-39957-6",
			"date": "2023-07-17",
			"PMC": "",
			"citation": "",
			"abstract": "A variety of mutational processes drive cancer development, but their dynamics across the entire disease spectrum from pre-cancerous to advanced neoplasia are poorly understood. We explore the mutagenic processes shaping oesophageal adenocarcinoma tumorigenesis in 997 instances comprising distinct stages of this malignancy, from Barrett Oesophagus to primary tumours and advanced metastatic disease. The mutational landscape is dominated by the C[T\u2009>\u2009C/G]T substitution enriched signatures SBS17a/b, which are linked with TP53 mutations, increased proliferation, genomic instability and disease progression. The APOBEC mutagenesis signature is a weak but persistent signal amplified in primary tumours. We also identify prevalent alterations in DNA damage repair pathways, with homologous recombination, base and nucleotide excision repair and translesion synthesis mutated in up to 50% of the cohort, and surprisingly uncoupled from transcriptional activity. Among these, the presence of base excision repair deficiencies show remarkably poor prognosis in the cohort. In this work, we provide insights on the mutational aetiology and changes enabling the transition from pre-neoplastic to advanced oesophageal adenocarcinoma.",
			"category": 2,
			"name": "Abbas Sujath,2023"
		},
		{
			"PMID": 37434117,
			"title": "Characteristics of DNA macro-alterations in breast cancer with liver metastasis before treatment.",
			"journal": "BMC genomics",
			"authorList": [
				"Fan Yu",
				"Zou Linglin",
				"Zhong Xiaorong",
				"Wang Zhu",
				"Wang Yu",
				"Luo Chuanxu",
				"Zheng Hong",
				"Wang Yanping"
			],
			"DOI": "10.1186/s12864-023-09497-w",
			"date": "2023-07-13",
			"PMC": "",
			"citation": "",
			"abstract": "Whole-genome doubling (WGD) has been observed in 30% of cancers, followed by a highly complex rearranged karyotype unfavourable to breast cancer's outcome. However, the macro-alterations that characterise liver metastasis in breast cancer(BC) are poorly understood. Here, we conducted a whole-genome sequencing analysis of liver metastases to explore the status and the time frame model of these macro-alterations in pre-treatment patients with metastatic breast cancer.",
			"category": 2,
			"name": "Fan Yu,2023"
		},
		{
			"PMID": 37420249,
			"title": "Mutation-Attention (MuAt): deep representation learning of somatic mutations for tumour typing and subtyping.",
			"journal": "Genome medicine",
			"authorList": [
				"Sanjaya Prima",
				"Maljanen Katri",
				"Katainen Riku",
				"Waszak Sebastian M",
				"Genomics England Research Consortium",
				"Aaltonen Lauri A",
				"Stegle Oliver",
				"Korbel Jan O",
				"Pitk\u00e4nen Esa"
			],
			"DOI": "10.1186/s13073-023-01204-4",
			"date": "2023-07-21",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer genome sequencing enables accurate classification of tumours and tumour subtypes. However, prediction performance is still limited using exome-only sequencing and for tumour types with low somatic mutation burden such as many paediatric tumours. Moreover, the ability to leverage deep representation learning in discovery of tumour entities remains unknown.",
			"category": 2,
			"name": "Sanjaya Prima,2023"
		},
		{
			"PMID": 37400777,
			"title": "Pan-cancer analysis of whole-genome doubling and its association with patient prognosis.",
			"journal": "BMC cancer",
			"authorList": [
				"Kikutake Chie",
				"Suyama Mikita"
			],
			"DOI": "10.1186/s12885-023-11132-6",
			"date": "2023-07-05",
			"PMC": "",
			"citation": "",
			"abstract": "Whole-genome doubling (WGD) is a common mutation in cancer. Various studies have suggested that WGD is associated with a poor prognosis in cancer. However, the detailed association between WGD occurrence and prognosis remains unclear. In this study, we aimed to elucidate the mechanism by which WGD affects prognosis using sequencing data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) and The Cancer Genome Atlas.",
			"category": 2,
			"name": "Kikutake Chie,2023"
		},
		{
			"PMID": 37384143,
			"title": "Understanding human aging and the fundamental cell signaling link in age-related diseases: the middle-aging hypovascularity hypoxia hypothesis.",
			"journal": "Frontiers in aging",
			"authorList": [
				"Phua Teow J"
			],
			"DOI": "10.3389/fragi.2023.1196648",
			"date": "2023-10-04",
			"PMC": "",
			"citation": "",
			"abstract": "Aging-related hypoxia, oxidative stress, and inflammation pathophysiology are closely associated with human age-related carcinogenesis and chronic diseases. However, the connection between hypoxia and hormonal cell signaling pathways is unclear, but such human age-related comorbid diseases do coincide with the middle-aging period of declining sex hormonal signaling. This scoping review evaluates the relevant interdisciplinary evidence to assess the systems biology of function, regulation, and homeostasis in order to discern and decipher the etiology of the connection between hypoxia and hormonal signaling in human age-related comorbid diseases. The hypothesis charts the accumulating evidence to support the development of a hypoxic milieu and oxidative stress-inflammation pathophysiology in middle-aged individuals, as well as the induction of amyloidosis, autophagy, and epithelial-to-mesenchymal transition in aging-related degeneration. Taken together, this new approach and strategy can provide the clarity of concepts and patterns to determine the causes of declining vascularity hemodynamics (blood flow) and physiological oxygenation perfusion (oxygen bioavailability) in relation to oxygen homeostasis and vascularity that cause hypoxia (hypovascularity hypoxia). The middle-aging hypovascularity hypoxia hypothesis could provide the mechanistic interface connecting the endocrine, nitric oxide, and oxygen homeostasis signaling that is closely linked to the progressive conditions of degenerative hypertrophy, atrophy, fibrosis, and neoplasm. An in-depth understanding of these intrinsic biological processes of the developing middle-aged hypoxia could provide potential new strategies for time-dependent therapies in maintaining healthspan for healthy lifestyle aging, medical cost savings, and health system sustainability.",
			"category": 2,
			"name": "Phua Teow J,2023"
		},
		{
			"PMID": 37344522,
			"title": "Joint inference of exclusivity patterns and recurrent trajectories from tumor mutation trees.",
			"journal": "Nature communications",
			"authorList": [
				"Luo Xiang Ge",
				"Kuipers Jack",
				"Beerenwinkel Niko"
			],
			"DOI": "10.1038/s41467-023-39400-w",
			"date": "2023-06-23",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer progression is an evolutionary process shaped by both deterministic and stochastic forces. Multi-region and single-cell sequencing of tumors enable high-resolution reconstruction of the mutational history of each tumor and highlight the extensive diversity across tumors and patients. Resolving the interactions among mutations and recovering recurrent evolutionary processes may offer greater opportunities for successful therapeutic strategies. To this end, we present a novel probabilistic framework, called TreeMHN, for the joint inference of exclusivity patterns and recurrent trajectories from a cohort of intra-tumor phylogenetic trees. Through simulations, we show that TreeMHN outperforms existing alternatives that can only focus on one aspect of the task. By analyzing datasets of blood, lung, and breast cancers, we find the most likely evolutionary trajectories and mutational patterns, consistent with and enriching our current understanding of tumorigenesis. Moreover, TreeMHN facilitates the prediction of tumor evolution and provides probabilistic measures on the next mutational events given a tumor tree, a prerequisite for evolution-guided treatment strategies.",
			"category": 2,
			"name": "Luo Xiang Ge,2023"
		},
		{
			"PMID": 37342233,
			"title": "Whole-Genome Doubling as a source of cancer: how, when, where, and why?",
			"journal": "Frontiers in cell and developmental biology",
			"authorList": [
				"Sanz-G\u00f3mez Natalia",
				"Gonz\u00e1lez-\u00c1lvarez Mar\u00eda",
				"De Las Rivas Javier",
				"de C\u00e1rcer Guillermo"
			],
			"DOI": "10.3389/fcell.2023.1209136",
			"date": "2023-07-01",
			"PMC": "",
			"citation": "",
			"abstract": "Chromosome instability is a well-known hallmark of cancer, leading to increased genetic plasticity of tumoral cells, which favors cancer aggressiveness, and poor prognosis. One of the main sources of chromosomal instability are events that lead to a Whole-Genome Duplication (WGD) and the subsequently generated cell polyploidy. In recent years, several studies showed that WGD occurs at the early stages of cell transformation, which allows cells to later become aneuploid, thus leading to cancer progression. On the other hand, other studies convey that polyploidy plays a tumor suppressor role, by inducing cell cycle arrest, cell senescence, apoptosis, and even prompting cell differentiation, depending on the tissue cell type. There is still a gap in understanding how cells that underwent WGD can overcome the deleterious effect on cell fitness and evolve to become tumoral. Some laboratories in the chromosomal instability field recently explored this paradox, finding biomarkers that modulate polyploid cells to become oncogenic. This review brings a historical view of how WGD and polyploidy impact cell fitness and cancer progression, and bring together the last studies that describe the genes helping cells to adapt to polyploidy.",
			"category": 2,
			"name": "Sanz-G\u00f3mez Natalia,2023"
		},
		{
			"PMID": 37339630,
			"title": "Autoimmune alleles at the major histocompatibility locus modify melanoma susceptibility.",
			"journal": "American journal of human genetics",
			"authorList": [
				"Talwar James V",
				"Laub David",
				"Pagadala Meghana S",
				"Castro Andrea",
				"Lewis McKenna",
				"Luebeck Georg E",
				"Gorman Bryan R",
				"Pan Cuiping",
				"Dong Frederick N",
				"Markianos Kyriacos",
				"Teerlink Craig C",
				"Lynch Julie",
				"Hauger Richard",
				"Pyarajan Saiju",
				"Tsao Philip S",
				"Morris Gerald P",
				"Salem Rany M",
				"Thompson Wesley K",
				"Curtius Kit",
				"Zanetti Maurizio",
				"Carter Hannah"
			],
			"DOI": "10.1016/j.ajhg.2023.05.013",
			"date": "2023-07-10",
			"PMC": "",
			"citation": "",
			"abstract": "Autoimmunity and cancer represent two different aspects of immune dysfunction. Autoimmunity is characterized by breakdowns in immune self-tolerance, while impaired immune surveillance can allow for tumorigenesis. The class I major histocompatibility complex (MHC-I), which displays derivatives of the cellular peptidome for immune surveillance by CD8",
			"category": 2,
			"name": "Talwar James V,2023"
		},
		{
			"PMID": 37327081,
			"title": "Clonal Patterns Between Pouch Neoplasia and Prior Colorectal Neoplasia in Inflammatory Bowel Disease Patients: An Exploratory Cohort Study.",
			"journal": "Inflammatory bowel diseases",
			"authorList": [
				"Te Groen Maarten",
				"Derikx Lauranne A A P",
				"van Lierop Lisa",
				"Ylstra Bauke",
				"Hoentjen Frank",
				"Nagtegaal Iris D",
				"Simmer Femke"
			],
			"DOI": "10.1093/ibd/izad112",
			"date": "2023-08-03",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Te Groen Maarten,2023"
		},
		{
			"PMID": 37323575,
			"title": "Targeted ",
			"journal": "Cell reports methods",
			"authorList": [
				"Haas Brian J",
				"Dobin Alexander",
				"Ghandi Mahmoud",
				"Van Arsdale Anne",
				"Tickle Timothy",
				"Robinson James T",
				"Gillani Riaz",
				"Kasif Simon",
				"Regev Aviv"
			],
			"DOI": "10.1016/j.crmeth.2023.100467",
			"date": "2023-06-19",
			"PMC": "",
			"citation": "",
			"abstract": "Here, we present FusionInspector for ",
			"category": 2,
			"name": "Haas Brian J,2023"
		},
		{
			"PMID": 37273168,
			"title": "Molecular evolution in different subtypes of\u00a0multifocal hepatocellular carcinoma.",
			"journal": "Hepatology international",
			"authorList": [
				"Tang Xia",
				"Xiang Lei",
				"Li Qingshu",
				"Shao Yue",
				"Wan Li",
				"Zhao Dachun",
				"Li Xiaoyuan",
				"Wu Songfeng",
				"Wang Haijian",
				"Li Dewei",
				"Ding Keyue"
			],
			"DOI": "10.1007/s12072-023-10551-8",
			"date": "2023-11-22",
			"PMC": "",
			"citation": "",
			"abstract": "Multifocal hepatocellular carcinoma (MF-HCC) accounts for\u2009>\u200940% of HCCs, exhibiting a poor prognosis than single primary HCCs. Characterizing molecular features including dynamic changes of mutational signature along with clonal evolution, intrahepatic metastatic timing, and genetic footprint in the preneoplastic stage underlying different subtypes of MF-HCC are important for understanding their molecular evolution and developing a precision management strategy.",
			"category": 2,
			"name": "Tang Xia,2023"
		},
		{
			"PMID": 37258665,
			"title": "Deterministic evolution and stringent selection during preneoplasia.",
			"journal": "Nature",
			"authorList": [
				"Karlsson Kasper",
				"Przybilla Moritz J",
				"Kotler Eran",
				"Khan Aziz",
				"Xu Hang",
				"Karagyozova Kremena",
				"Sockell Alexandra",
				"Wong Wing H",
				"Liu Katherine",
				"Mah Amanda",
				"Lo Yuan-Hung",
				"Lu Bingxin",
				"Houlahan Kathleen E",
				"Ma Zhicheng",
				"Suarez Carlos J",
				"Barnes Chris P",
				"Kuo Calvin J",
				"Curtis Christina"
			],
			"DOI": "10.1038/s41586-023-06102-8",
			"date": "2023-06-09",
			"PMC": "",
			"citation": "",
			"abstract": "The earliest events during human tumour initiation, although poorly characterized, may hold clues to malignancy detection and prevention",
			"category": 2,
			"name": "Karlsson Kasper,2023"
		},
		{
			"PMID": 37254150,
			"title": "Progesterone from ovulatory menstrual cycles is an important cause of breast cancer.",
			"journal": "Breast cancer research : BCR",
			"authorList": [
				"Coelingh Bennink Herjan J T",
				"Schultz Iman J",
				"Schmidt Marcus",
				"Jordan V Craig",
				"Briggs Paula",
				"Egberts Jan F M",
				"Gemzell-Danielsson Kristina",
				"Kiesel Ludwig",
				"Kluivers Kirsten",
				"Krijgh Jan",
				"Simoncini Tommaso",
				"Stanczyk Frank Z",
				"Langer Robert D"
			],
			"DOI": "10.1186/s13058-023-01661-0",
			"date": "2023-06-01",
			"PMC": "",
			"citation": "",
			"abstract": "Many factors, including reproductive hormones, have been linked to a woman's risk of developing breast cancer (BC). We reviewed the literature regarding the relationship between ovulatory menstrual cycles (MCs) and BC risk. Physiological variations in the frequency of MCs and interference with MCs through genetic variations, pathological conditions and or pharmaceutical interventions revealed a strong link between BC risk and the lifetime number of MCs. A substantial reduction in BC risk is observed in situations without MCs. In genetic or transgender situations with normal female breasts and estrogens, but no progesterone (P4), the incidence of BC is very low, suggesting an essential role of P4. During the MC, P4 has a strong proliferative effect on normal breast epithelium, whereas estradiol (E2) has only a minimal effect. The origin of BC has been strongly linked to proliferation associated DNA replication errors, and the repeated stimulation of the breast epithelium by P4 with each MC is likely to impact the epithelial mutational burden. Long-lived cells, such as stem cells, present in the breast epithelium, can carry mutations forward for an extended period of time, and studies show that breast tumors tend to take decades to develop before detection. We therefore postulate that P4 is an important factor in a woman's lifetime risk of developing BC, and that breast tumors arising during hormonal contraception or after menopause, with or without menopausal hormone therapy, are the consequence of the outgrowth of pre-existing neoplastic lesions, eventually stimulated by estrogens and some progestins.",
			"category": 2,
			"name": "Coelingh Bennink Herjan J T,2023"
		},
		{
			"PMID": 37228770,
			"title": "PD-L1: expression regulation.",
			"journal": "Blood science (Baltimore, Md.)",
			"authorList": [
				"Zhou Yu-Jie",
				"Li Guoli",
				"Wang Jiyin",
				"Liu Mengyuan",
				"Wang Zihan",
				"Song Yu",
				"Zhang Xulong",
				"Wang Xi"
			],
			"DOI": "10.1097/BS9.0000000000000149",
			"date": "2023-05-28",
			"PMC": "",
			"citation": "",
			"abstract": "Programmed death-ligand 1 (PD-L1), expressed on the surface of tumor cells, can bind to programmed cell death-1 (PD-1) on T cells. The interaction of PD-1 and PD-L1 can inhibit T-cell responses by decreasing T-cell activity and accelerating their apoptosis. Various cancers express high levels of PD-L1 and exploit PD-L1/PD-1 signaling to evade T-cell immunity, and immunotherapies targeting the PD-1/PD-L1 axis have been shown to exert remarkable anti-tumor effects; however, not all tumor patients benefit from these therapies. Therefore, study of the mechanisms regulating PD-L1 expression are imperative. In this review, we explore regulation of PD-L1 expression in the contexts of gene transcription, signaling pathways, histone modification and remodeling, microRNAs, long noncoding RNAs, and post-translational modification. Current developments in studies of agents that block PD-L1 and correlations between immunotherapies targeting PD-1/PD-L1 and PD-L1 expression are also summarized. Our review will assist in understanding of PD-L1 expression regulation and discusses the implications of reported findings in cancer diagnosis and immunotherapy.",
			"category": 2,
			"name": "Zhou Yu-Jie,2023"
		},
		{
			"PMID": 37216686,
			"title": "The genomic landscape of acute lymphoblastic leukemia with intrachromosomal amplification of chromosome 21.",
			"journal": "Blood",
			"authorList": [
				"Gao Qingsong",
				"Ryan Sarra L",
				"Iacobucci Ilaria",
				"Ghate Pankaj S",
				"Cranston Ruth E",
				"Schwab Claire",
				"Elsayed Abdelrahman H",
				"Shi Lei",
				"Pounds Stanley",
				"Lei Shaohua",
				"Baviskar Pradyuamna",
				"Pei Deqing",
				"Cheng Cheng",
				"Bashton Matthew",
				"Sinclair Paul",
				"Bentley David R",
				"Ross Mark T",
				"Kingsbury Zoya",
				"James Terena",
				"Roberts Kathryn G",
				"Devidas Meenakshi",
				"Fan Yiping",
				"Chen Wenan",
				"Chang Ti-Cheng",
				"Wu Gang",
				"Carroll Andrew",
				"Heerema Nyla",
				"Valentine Virginia",
				"Valentine Marcus",
				"Yang Wenjian",
				"Yang Jun J",
				"Moorman Anthony V",
				"Harrison Christine J",
				"Mullighan Charles G"
			],
			"DOI": "10.1182/blood.2022019094",
			"date": "2023-08-25",
			"PMC": "",
			"citation": "",
			"abstract": "Intrachromosomal amplification of chromosome 21 defines a subtype of high-risk childhood acute lymphoblastic leukemia (iAMP21-ALL) characterized by copy number changes and complex rearrangements of chromosome 21. The genomic basis of iAMP21-ALL and the pathogenic role of the region of amplification of chromosome 21 to leukemogenesis remains incompletely understood. In this study, using integrated whole genome and transcriptome sequencing of 124 patients with iAMP21-ALL, including rare cases arising in the context of constitutional chromosomal aberrations, we identified subgroups of iAMP21-ALL based on the patterns of copy number alteration and structural variation. This large data set enabled formal delineation of a 7.8 Mb common region of amplification harboring 71 genes, 43 of which were differentially expressed compared with non-iAMP21-ALL ones, including multiple genes implicated in the pathogenesis of acute leukemia (CHAF1B, DYRK1A, ERG, HMGN1, and RUNX1). Using multimodal single-cell genomic profiling, including single-cell whole genome sequencing of 2 cases, we documented clonal heterogeneity and genomic evolution, demonstrating that the acquisition of the iAMP21 chromosome is an early event that may undergo progressive amplification during disease ontogeny. We show that UV-mutational signatures and high mutation load are characteristic secondary genetic features. Although the genomic alterations of chromosome 21 are variable, these integrated genomic analyses and demonstration of an extended common minimal region of amplification broaden the definition of iAMP21-ALL for more precise diagnosis using cytogenetic or genomic methods to inform clinical management.",
			"category": 2,
			"name": "Gao Qingsong,2023"
		},
		{
			"PMID": 37198482,
			"title": "ER\u03b1-associated translocations underlie oncogene amplifications in breast cancer.",
			"journal": "Nature",
			"authorList": [
				"Lee Jake June-Koo",
				"Jung Youngsook Lucy",
				"Cheong Taek-Chin",
				"Espejo Valle-Inclan Jose",
				"Chu Chong",
				"Gulhan Doga C",
				"Ljungstr\u00f6m Viktor",
				"Jin Hu",
				"Viswanadham Vinayak V",
				"Watson Emma V",
				"Cort\u00e9s-Ciriano Isidro",
				"Elledge Stephen J",
				"Chiarle Roberto",
				"Pellman David",
				"Park Peter J"
			],
			"DOI": "10.1038/s41586-023-06057-w",
			"date": "2023-07-05",
			"PMC": "",
			"citation": "",
			"abstract": "Focal copy-number amplification is an oncogenic event. Although recent studies have revealed the complex structure",
			"category": 2,
			"name": "Lee Jake June-Koo,2023"
		},
		{
			"PMID": 37169874,
			"title": "Clonal evolution during metastatic spread in high-risk neuroblastoma.",
			"journal": "Nature genetics",
			"authorList": [
				"Gundem Gunes",
				"Levine Max F",
				"Roberts Stephen S",
				"Cheung Irene Y",
				"Medina-Mart\u00ednez Juan S",
				"Feng Yi",
				"Arango-Ossa Juan E",
				"Chadoutaud Loic",
				"Rita Mathieu",
				"Asimomitis Georgios",
				"Zhou Joe",
				"You Daoqi",
				"Bouvier Nancy",
				"Spitzer Barbara",
				"Solit David B",
				"Dela Cruz Filemon",
				"LaQuaglia Michael P",
				"Kushner Brian H",
				"Modak Shakeel",
				"Shukla Neerav",
				"Iacobuzio-Donahue Christine A",
				"Kung Andrew L",
				"Cheung Nai-Kong V",
				"Papaemmanuil Elli"
			],
			"DOI": "10.1038/s41588-023-01395-x",
			"date": "2023-06-14",
			"PMC": "",
			"citation": "",
			"abstract": "Patients with high-risk neuroblastoma generally present with widely metastatic disease and often relapse despite intensive therapy. As most studies to date focused on diagnosis-relapse pairs, our understanding of the genetic and clonal dynamics of metastatic spread and disease progression remain limited. Here, using genomic profiling of 470 sequential and spatially separated samples from 283 patients, we characterize subtype-specific genetic evolutionary trajectories from diagnosis through progression and end-stage metastatic disease. Clonal tracing timed disease initiation to embryogenesis. Continuous acquisition of structural variants at disease-defining loci (MYCN, TERT, MDM2-CDK4) followed by convergent evolution of mutations targeting shared pathways emerged as the predominant feature of progression. At diagnosis metastatic clones were already established at distant sites where they could stay dormant, only to cause relapses years later and spread via metastasis-to-metastasis and polyclonal seeding after therapy.",
			"category": 2,
			"name": "Gundem Gunes,2023"
		},
		{
			"PMID": 37167978,
			"title": "Advances in Mapping Tumor Progression from Precancer Atlases.",
			"journal": "Cancer prevention research (Philadelphia, Pa.)",
			"authorList": [
				"Chen Zhengyi",
				"Lau Ken S"
			],
			"DOI": "10.1158/1940-6207.CAPR-22-0473",
			"date": "2023-09-18",
			"PMC": "",
			"citation": "",
			"abstract": "Tissue profiling technologies present opportunities for understanding transition from precancerous lesions to malignancy, which may impact risk stratification, prevention, and even cancer treatment. A human precancer atlas building effort is ongoing to tackle the significant challenge of decoding the heterogeneity among cells, specimens, and patients. Here, we discuss the findings resulting from atlases built across precancer types, including those found in colon, breast, lung, stomach, cervix, and skin, using bulk, single-cell, and spatial profiling strategies. We highlight two main themes that emerge across precancer types: the ordering of molecular events that occur during tumor progression and the fluctuation of microenvironmental response during precancer progression. We further highlight the key challenges of data integration across large cohorts of patients, and the need for computational tools to reliably annotate and quality control high-volume, high-dimensional data.",
			"category": 2,
			"name": "Chen Zhengyi,2023"
		},
		{
			"PMID": 37166279,
			"title": "High-grade serous ovarian carcinoma organoids as models of chromosomal instability.",
			"journal": "eLife",
			"authorList": [
				"Vias Maria",
				"Morrill Gavarr\u00f3 Lena",
				"Sauer Carolin M",
				"Sanders Deborah A",
				"Piskorz Anna M",
				"Couturier Dominique-Laurent",
				"Ballereau St\u00e9phane",
				"Hernando B\u00e1rbara",
				"Schneider Michael P",
				"Hall James",
				"Correia-Martins Filipe",
				"Markowetz Florian",
				"Macintyre Geoff",
				"Brenton James D"
			],
			"DOI": "10.7554/eLife.83867",
			"date": "2023-05-15",
			"PMC": "",
			"citation": "",
			"abstract": "High-grade serous ovarian carcinoma (HGSOC) is the most genomically complex cancer, characterized by ubiquitous ",
			"category": 2,
			"name": "Vias Maria,2023"
		},
		{
			"PMID": 37166062,
			"title": "Deletions of DNA in cancer and their possible uses for therapy.",
			"journal": "BioEssays : news and reviews in molecular, cellular and developmental biology",
			"authorList": [
				"Varshavsky Alexander",
				"Lewis Kim",
				"Chen Shun-Jia"
			],
			"DOI": "10.1002/bies.202300051",
			"date": "2023-06-22",
			"PMC": "",
			"citation": "",
			"abstract": "Despite advances in treatments over the last decades, a uniformly reliable and free of side effects therapy of human cancers remains to be achieved. During chromosome replication, a premature halt of two converging DNA replication forks would cause incomplete replication and a cytotoxic chromosome nondisjunction during mitosis. In contrast to normal cells, most cancer cells bear numerous DNA deletions. A homozygous deletion permanently marks a cell and its descendants. Here, we propose an approach to cancer therapy in which a pair of sequence-specific roadblocks is placed solely at two cancer-confined deletion sites that are located ahead of two converging replication forks. We describe this method, termed \"replication blocks specific for deletions\" (RBSD), and another deletions-based approach as well. RBSD can be expanded by placing pairs of replication roadblocks on several different chromosomes. The resulting simultaneous nondisjunctions of these chromosomes in cancer cells would further increase the cancer-specific toxicity of RBSD.",
			"category": 2,
			"name": "Varshavsky Alexander,2023"
		},
		{
			"PMID": 37165200,
			"title": "Maternal and childhood medical history and the risk of childhood brain tumours: a case-control study in Ontario, Canada.",
			"journal": "British journal of cancer",
			"authorList": [
				"Cheng Sierra",
				"McLaughlin John R",
				"Brown M Catherine",
				"Al-Sawaihey Hamad",
				"Rutka James",
				"Bouffet Eric",
				"Hawkins Cynthia",
				"Cairney A Elizabeth",
				"Ranger Adrianna",
				"Fleming Adam J",
				"Johnston Donna",
				"Greenberg Mark",
				"Malkin David",
				"Hung Rayjean J"
			],
			"DOI": "10.1038/s41416-023-02281-3",
			"date": "2023-07-14",
			"PMC": "",
			"citation": "",
			"abstract": "Studies to date have yielded inconclusive results as to whether maternal medical history during pregnancy, and a child's early-life medical history contribute to the development of childhood brain tumours (CBTs). This study examined associations between maternal and childhood medical history and the risk of CBTs.",
			"category": 2,
			"name": "Cheng Sierra,2023"
		},
		{
			"PMID": 37165194,
			"title": "Pan-cancer whole-genome comparison of primary and metastatic solid tumours.",
			"journal": "Nature",
			"authorList": [
				"Mart\u00ednez-Jim\u00e9nez Francisco",
				"Movasati Ali",
				"Brunner Sascha Remy",
				"Nguyen Luan",
				"Priestley Peter",
				"Cuppen Edwin",
				"Van Hoeck Arne"
			],
			"DOI": "10.1038/s41586-023-06054-z",
			"date": "2023-06-13",
			"PMC": "",
			"citation": "",
			"abstract": "Metastatic cancer remains an almost inevitably lethal disease",
			"category": 2,
			"name": "Mart\u00ednez-Jim\u00e9nez Francisco,2023"
		},
		{
			"PMID": 37165041,
			"title": "Possible involvement of silent mutations in cancer pathogenesis and evolution.",
			"journal": "Scientific reports",
			"authorList": [
				"Kikutake Chie",
				"Suyama Mikita"
			],
			"DOI": "10.1038/s41598-023-34452-w",
			"date": "2023-05-12",
			"PMC": "",
			"citation": "",
			"abstract": "Recent studies have shown that some silent mutations can be harmful to various processes. In this study, we performed a comprehensive in silico analysis to elucidate the effects of silent mutations on cancer pathogenesis using exome sequencing data derived from the Cancer Genome Atlas. We focused on the codon optimality scores of silent mutations, which were defined as the difference between the optimality of synonymous codons, calculated using the codon usage table. The relationship between cancer evolution and silent mutations showed that the codon optimality score of the mutations that occurred later in carcinogenesis was significantly higher than of those that occurred earlier. In addition, mutations with higher scores were enriched in genes involved in the cell cycle and cell division, while those with lower scores were enriched in genes involved in apoptosis and cellular senescence. Our results demonstrate that some silent mutations can be involved in cancer pathogenesis.",
			"category": 2,
			"name": "Kikutake Chie,2023"
		},
		{
			"PMID": 37152984,
			"title": "Multi-omics analysis reveals a molecular landscape of the early recurrence and early metastasis in pan-cancer.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"He Dan-Ni",
				"Wang Na",
				"Wen Xiao-Ling",
				"Li Xu-Hua",
				"Guo Yu",
				"Fu Shu-Heng",
				"Xiong Fei-Fan",
				"Wu Zhe-Yu",
				"Zhu Xu",
				"Gao Xiao-Ling",
				"Wang Zhen-Zhen",
				"Wang Hong-Jiu"
			],
			"DOI": "10.3389/fgene.2023.1061364",
			"date": "2023-05-09",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer remains a formidable challenge in medicine due to its propensity for recurrence and metastasis, which can result in unfavorable treatment outcomes. This challenge is particularly acute for early-stage patients, who may experience recurrence and metastasis without timely detection. Here, we first analyzed the differences in clinical characteristics among the primary tumor, recurrent tumor, and metastatic tumor in different stages of cancer, which may be caused by the molecular level. Moreover, the importance of predicting early cancer recurrence and metastasis is emphasized by survival analyses. Next, we used a multi-omics approach to identify key molecular changes associated with early cancer recurrence and metastasis and discovered that early metastasis in cancer demonstrated a high degree of genomic and cellular heterogeneity. We performed statistical comparisons for each level of omics data including gene expression, mutation, copy number variation, immune cell infiltration, and cell status. Then, various analytical techniques, such as proportional hazard model and Fisher's exact test, were used to identify specific genes or immune characteristics associated with early cancer recurrence and metastasis. For example, we observed that the overexpression of BPIFB1 and high initial B-cell infiltration levels are linked to early cancer recurrence, while the overexpression or amplification of ANKRD22 and LIPM, mutation of IGHA1 and MUC16, high fibroblast infiltration level, M1 polarization of macrophages, cellular status of DNA repair are all linked to early cancer metastasis. These findings have led us to construct classifiers, and the average area under the curve (AUC) of these classifiers was greater than 0.75 in The Cancer Genome Atlas (TCGA) cancer patients, confirming that the features we identified could be biomarkers for predicting recurrence and metastasis of early cancer. Finally, we identified specific early sensitive targets for targeted therapy and immune checkpoint inhibitor therapy. Once the biomarkers we identified changed, treatment-sensitive targets can be treated accordingly. Our study has comprehensively characterized the multi-omics characteristics and identified a panel of biomarkers of early cancer recurrence and metastasis. Overall, it provides a valuable resource for cancer recurrence and metastasis research and improves our understanding of the underlying mechanisms driving early cancer recurrence and metastasis.",
			"category": 2,
			"name": "He Dan-Ni,2023"
		},
		{
			"PMID": 37121998,
			"title": "DREAMS: deep read-level error model for sequencing data applied to low-frequency variant calling and circulating tumor DNA detection.",
			"journal": "Genome biology",
			"authorList": [
				"Christensen Mikkel H",
				"Drue Simon O",
				"Rasmussen Mads H",
				"Frydendahl Amanda",
				"Lyskj\u00e6r Iben",
				"Demuth Christina",
				"Nors Jesper",
				"Gotschalck K\u00e5re A",
				"Iversen Lene H",
				"Andersen Claus L",
				"Pedersen Jakob Skou"
			],
			"DOI": "10.1186/s13059-023-02920-1",
			"date": "2023-05-02",
			"PMC": "",
			"citation": "",
			"abstract": "Circulating tumor DNA detection using next-generation sequencing (NGS) data of plasma DNA is promising for cancer identification and characterization. However, the tumor signal in the blood is often low and difficult to distinguish from errors. We present DREAMS (Deep Read-level Modelling of Sequencing-errors) for estimating error rates of individual read positions. Using DREAMS, we develop statistical methods for variant calling (DREAMS-vc) and cancer detection (DREAMS-cc). For evaluation, we generate deep targeted NGS data of matching tumor and plasma DNA from 85 colorectal cancer patients. The DREAMS approach performs better than state-of-the-art methods for variant calling and cancer detection.",
			"category": 2,
			"name": "Christensen Mikkel H,2023"
		},
		{
			"PMID": 37106072,
			"title": "Single duplex DNA sequencing with CODEC detects mutations with high sensitivity.",
			"journal": "Nature genetics",
			"authorList": [
				"Bae Jin H",
				"Liu Ruolin",
				"Roberts Eugenia",
				"Nguyen Erica",
				"Tabrizi Shervin",
				"Rhoades Justin",
				"Blewett Timothy",
				"Xiong Kan",
				"Gydush Gregory",
				"Shea Douglas",
				"An Zhenyi",
				"Patel Sahil",
				"Cheng Ju",
				"Sridhar Sainetra",
				"Liu Mei Hong",
				"Lassen Emilie",
				"Skytte Anne-Bine",
				"Gro\u0144ska-P\u0119ski Marta",
				"Shoag Jonathan E",
				"Evrony Gilad D",
				"Parsons Heather A",
				"Mayer Erica L",
				"Makrigiorgos G Mike",
				"Golub Todd R",
				"Adalsteinsson Viktor A"
			],
			"DOI": "10.1038/s41588-023-01376-0",
			"date": "2023-05-15",
			"PMC": "",
			"citation": "",
			"abstract": "Detecting mutations from single DNA molecules is crucial in many fields but challenging. Next-generation sequencing (NGS) affords tremendous throughput but cannot directly sequence double-stranded DNA molecules ('single duplexes') to discern the true mutations on both strands. Here we present Concatenating Original Duplex for Error Correction (CODEC), which confers single duplex resolution to NGS. CODEC affords 1,000-fold higher accuracy than NGS, using up to 100-fold fewer reads than duplex sequencing. CODEC revealed mutation frequencies of 2.72\u2009\u00d7\u200910",
			"category": 2,
			"name": "Bae Jin H,2023"
		},
		{
			"PMID": 37081260,
			"title": "Inferring early genetic progression in cancers with unobtainable premalignant disease.",
			"journal": "Nature cancer",
			"authorList": [
				"Leshchiner Ignaty",
				"Mroz Edmund A",
				"Cha Justin",
				"Rosebrock Daniel",
				"Spiro Oliver",
				"Bonilla-Velez Juliana",
				"Faquin William C",
				"Lefranc-Torres Armida",
				"Lin Derrick T",
				"Michaud William A",
				"Getz Gad",
				"Rocco James W"
			],
			"DOI": "10.1038/s43018-023-00533-y",
			"date": "2023-04-28",
			"PMC": "",
			"citation": "",
			"abstract": "Analysis of premalignant tissue has identified the typical order of somatic events leading to invasive tumors in several cancer types. For other cancers, premalignant tissue is unobtainable, leaving genetic progression unknown. Here, we demonstrate how to infer progression from exome sequencing of primary tumors. Our computational method, PhylogicNDT, recapitulated the previous experimentally determined genetic progression of human papillomavirus-negative (HPV",
			"category": 2,
			"name": "Leshchiner Ignaty,2023"
		},
		{
			"PMID": 37046619,
			"title": "Computational Methods Summarizing Mutational Patterns in Cancer: Promise and Limitations for Clinical Applications.",
			"journal": "Cancers",
			"authorList": [
				"Patterson Andrew",
				"Elbasir Abdurrahman",
				"Tian Bin",
				"Auslander Noam"
			],
			"DOI": "10.3390/cancers15071958",
			"date": "2023-12-14",
			"PMC": "",
			"citation": "",
			"abstract": "Since the rise of next-generation sequencing technologies, the catalogue of mutations in cancer has been continuously expanding. To address the complexity of the cancer-genomic landscape and extract meaningful insights, numerous computational approaches have been developed over the last two decades. In this review, we survey the current leading computational methods to derive intricate mutational patterns in the context of clinical relevance. We begin with mutation signatures, explaining first how mutation signatures were developed and then examining the utility of studies using mutation signatures to correlate environmental effects on the cancer genome. Next, we examine current clinical research that employs mutation signatures and discuss the potential use cases and challenges of mutation signatures in clinical decision-making. We then examine computational studies developing tools to investigate complex patterns of mutations beyond the context of mutational signatures. We survey methods to identify cancer-driver genes, from single-driver studies to pathway and network analyses. In addition, we review methods inferring complex combinations of mutations for clinical tasks and using mutations integrated with multi-omics data to better predict cancer phenotypes. We examine the use of these tools for either discovery or prediction, including prediction of tumor origin, treatment outcomes, prognosis, and cancer typing. We further discuss the main limitations preventing widespread clinical integration of computational tools for the diagnosis and treatment of cancer. We end by proposing solutions to address these challenges using recent advances in machine learning.",
			"category": 2,
			"name": "Patterson Andrew,2023"
		},
		{
			"PMID": 37046096,
			"title": "The evolution of lung cancer and impact of subclonal selection in TRACERx.",
			"journal": "Nature",
			"authorList": [
				"Frankell Alexander M",
				"Dietzen Michelle",
				"Al Bakir Maise",
				"Lim Emilia L",
				"Karasaki Takahiro",
				"Ward Sophia",
				"Veeriah Selvaraju",
				"Colliver Emma",
				"Huebner Ariana",
				"Bunkum Abigail",
				"Hill Mark S",
				"Grigoriadis Kristiana",
				"Moore David A",
				"Black James R M",
				"Liu Wing Kin",
				"Thol Kerstin",
				"Pich Oriol",
				"Watkins Thomas B K",
				"Naceur-Lombardelli Cristina",
				"Cook Daniel E",
				"Salgado Roberto",
				"Wilson Gareth A",
				"Bailey Chris",
				"Angelova Mihaela",
				"Bentham Robert",
				"Mart\u00ednez-Ruiz Carlos",
				"Abbosh Christopher",
				"Nicholson Andrew G",
				"Le Quesne John",
				"Biswas Dhruva",
				"Rosenthal Rachel",
				"Puttick Clare",
				"Hessey Sonya",
				"Lee Claudia",
				"Prymas Paulina",
				"Toncheva Antonia",
				"Smith Jon",
				"Xing Wei",
				"Nicod Jerome",
				"Price Gillian",
				"Kerr Keith M",
				"Naidu Babu",
				"Middleton Gary",
				"Blyth Kevin G",
				"Fennell Dean A",
				"Forster Martin D",
				"Lee Siow Ming",
				"Falzon Mary",
				"Hewish Madeleine",
				"Shackcloth Michael J",
				"Lim Eric",
				"Benafif Sarah",
				"Russell Peter",
				"Boleti Ekaterini",
				"Krebs Matthew G",
				"Lester Jason F",
				"Papadatos-Pastos Dionysis",
				"Ahmad Tanya",
				"Thakrar Ricky M",
				"Lawrence David",
				"Navani Neal",
				"Janes Sam M",
				"Dive Caroline",
				"Blackhall Fiona H",
				"Summers Yvonne",
				"Cave Judith",
				"Marafioti Teresa",
				"Herrero Javier",
				"Quezada Sergio A",
				"Peggs Karl S",
				"Schwarz Roland F",
				"Van Loo Peter",
				"Miedema Dani\u00ebl M",
				"Birkbak Nicolai J",
				"Hiley Crispin T",
				"Hackshaw Allan",
				"Zaccaria Simone",
				"TRACERx Consortium",
				"Jamal-Hanjani Mariam",
				"McGranahan Nicholas",
				"Swanton Charles"
			],
			"DOI": "10.1038/s41586-023-05783-5",
			"date": "2023-05-12",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer is the leading cause of cancer-associated mortality worldwide",
			"category": 2,
			"name": "Frankell Alexander M,2023"
		},
		{
			"PMID": 37038978,
			"title": "A kinesin-based approach for inducing chromosome-specific mis-segregation in human cells.",
			"journal": "The EMBO journal",
			"authorList": [
				"Truong My Anh",
				"Can\u00e9-Gasull Paula",
				"de Vries Sippe G",
				"Nijenhuis Wilco",
				"Wardenaar Ren\u00e9",
				"Kapitein Lukas C",
				"Foijer Floris",
				"Lens Susanne Ma"
			],
			"DOI": "10.15252/embj.2022111559",
			"date": "2023-05-16",
			"PMC": "",
			"citation": "",
			"abstract": "Various cancer types exhibit characteristic and recurrent aneuploidy patterns. The origins of these cancer type-specific karyotypes are still unknown, partly because introducing or eliminating specific chromosomes in human cells still poses a challenge. Here, we describe a novel strategy to induce mis-segregation of specific chromosomes in different human cell types. We employed Tet repressor or nuclease-dead Cas9 to link a microtubule minus-end-directed kinesin (Kinesin14VIb) from Physcomitrella patens to integrated Tet operon repeats and chromosome-specific endogenous repeats, respectively. By live- and fixed-cell imaging, we observed poleward movement of the targeted loci during (pro)metaphase. Kinesin14VIb-mediated pulling forces on the targeted chromosome were counteracted by forces from kinetochore-attached microtubules. This tug-of-war resulted in chromosome-specific segregation errors during anaphase and revealed that spindle forces can heavily stretch chromosomal arms. By single-cell whole-genome sequencing, we established that kinesin-induced targeted mis-segregations predominantly result in chromosomal arm aneuploidies after a single cell division. Our kinesin-based strategy opens the possibility to investigate the immediate cellular responses to specific aneuploidies in different cell types; an important step toward understanding how tissue-specific aneuploidy patterns evolve.",
			"category": 2,
			"name": "Truong My Anh,2023"
		},
		{
			"PMID": 36992846,
			"title": "Molecular origins of mutational spectra produced by the environmental carcinogen ",
			"journal": "NAR cancer",
			"authorList": [
				"Armijo Amanda L",
				"Thongararm Pennapa",
				"Fedeles Bogdan I",
				"Yau Judy",
				"Kay Jennifer E",
				"Corrigan Joshua J",
				"Chancharoen Marisa",
				"Chawanthayatham Supawadee",
				"Samson Leona D",
				"Carrasco Sebastian E",
				"Engelward Bevin P",
				"Fox James G",
				"Croy Robert G",
				"Essigmann John M"
			],
			"DOI": "10.1093/narcan/zcad015",
			"date": "2024-03-25",
			"PMC": "",
			"citation": "",
			"abstract": "DNA-methylating environmental carcinogens such as ",
			"category": 2,
			"name": "Armijo Amanda L,2024"
		},
		{
			"PMID": 36973454,
			"title": "Neuroblastoma arises in early fetal development and its evolutionary duration predicts outcome.",
			"journal": "Nature genetics",
			"authorList": [
				"K\u00f6rber Verena",
				"Stainczyk Sabine A",
				"Kurilov Roma",
				"Henrich Kai-Oliver",
				"Hero Barbara",
				"Brors Benedikt",
				"Westermann Frank",
				"H\u00f6fer Thomas"
			],
			"DOI": "10.1038/s41588-023-01332-y",
			"date": "2023-04-17",
			"PMC": "",
			"citation": "",
			"abstract": "Neuroblastoma, the most frequent solid tumor in infants, shows very diverse outcomes from spontaneous regression to fatal disease. When these different tumors originate and how they evolve are not known. Here we quantify the somatic evolution of neuroblastoma by deep whole-genome sequencing, molecular clock analysis and population-genetic modeling in a comprehensive cohort covering all subtypes. We find that tumors across the entire clinical spectrum begin to develop via aberrant mitoses as early as the first trimester of pregnancy. Neuroblastomas with favorable prognosis expand clonally after short evolution, whereas aggressive neuroblastomas show prolonged evolution during which they acquire telomere maintenance mechanisms. The initial aneuploidization events condition subsequent evolution, with aggressive neuroblastoma exhibiting early genomic instability. We find in the discovery cohort (n\u2009=\u2009100), and validate in an independent cohort (n\u2009=\u200986), that the duration of evolution is an accurate predictor of outcome. Thus, insight into neuroblastoma evolution may prospectively guide treatment decisions.",
			"category": 2,
			"name": "K\u00f6rber Verena,2023"
		},
		{
			"PMID": 36932241,
			"title": "Diagnostic classification of childhood cancer using multiscale transcriptomics.",
			"journal": "Nature medicine",
			"authorList": [
				"Comitani Federico",
				"Nash Joshua O",
				"Cohen-Gogo Sarah",
				"Chang Astra I",
				"Wen Timmy T",
				"Maheshwari Anant",
				"Goyal Bipasha",
				"Tio Earvin S",
				"Tabatabaei Kevin",
				"Mayoh Chelsea",
				"Zhao Regis",
				"Ho Ben",
				"Brunga Ledia",
				"Lawrence John E G",
				"Balogh Petra",
				"Flanagan Adrienne M",
				"Teichmann Sarah",
				"Huang Annie",
				"Ramaswamy Vijay",
				"Hitzler Johann",
				"Wasserman Jonathan D",
				"Gladdy Rebecca A",
				"Dickson Brendan C",
				"Tabori Uri",
				"Cowley Mark J",
				"Behjati Sam",
				"Malkin David",
				"Villani Anita",
				"Irwin Meredith S",
				"Shlien Adam"
			],
			"DOI": "10.1038/s41591-023-02221-x",
			"date": "2023-03-24",
			"PMC": "",
			"citation": "",
			"abstract": "The causes of pediatric cancers' distinctiveness compared to adult-onset tumors of the same type are not completely clear and not fully explained by their genomes. In this study, we used an optimized multilevel RNA clustering approach to derive molecular definitions for most childhood cancers. Applying this method to 13,313 transcriptomes, we constructed a pediatric cancer atlas to explore age-associated changes. Tumor entities were sometimes unexpectedly grouped due to common lineages, drivers or stemness profiles. Some established entities were divided into subgroups that predicted outcome better than current diagnostic approaches. These definitions account for inter-tumoral and intra-tumoral heterogeneity and have the potential of enabling reproducible, quantifiable diagnostics. As a whole, childhood tumors had more transcriptional diversity than adult tumors, maintaining greater expression flexibility. To apply these insights, we designed an ensemble convolutional neural network classifier. We show that this tool was able to match or clarify the diagnosis for 85% of childhood tumors in a prospective cohort. If further validated, this framework could be extended to derive molecular definitions for all cancer types.",
			"category": 2,
			"name": "Comitani Federico,2023"
		},
		{
			"PMID": 36930945,
			"title": "Clonal Evolution in Healthy and Premalignant Tissues: Implications for Early Cancer Interception Strategies.",
			"journal": "Cancer prevention research (Philadelphia, Pa.)",
			"authorList": [
				"Rane Jayant K",
				"Frankell Alexander M",
				"Weeden Clare E",
				"Swanton Charles"
			],
			"DOI": "10.1158/1940-6207.CAPR-22-0469",
			"date": "2023-07-06",
			"PMC": "",
			"citation": "",
			"abstract": "Histologically normal human tissues accumulate significant mutational burden with age. The extent and spectra of mutagenesis are comparable both in rapidly proliferating and post-mitotic tissues and in stem cells compared with their differentiated progeny. Some of these mutations provide increased fitness, giving rise to clones which, at times, can replace the entire surface area of tissues. Compared with cancer, somatic mutations in histologically normal tissues are primarily single-nucleotide variations. Interestingly though, the presence of these mutations and positive clonal selection in isolation remains a poor indicator of potential future cancer transformation in solid tissues. Common clonally expanded mutations in histologically normal tissues also do not always represent the most frequent early mutations in cancers of corresponding tissues, indicating differences in selection pressures. Preliminary evidence implies that stroma and immune system co-evolve with age, which may impact selection dynamics. In this review, we will explore the mutational landscape of histologically normal and premalignant human somatic tissues in detail and discuss cell-intrinsic and environmental factors that can determine the fate of positively selected mutations within them. Precisely pinpointing these determinants of cancer transformation would aid development of early cancer interventional and prevention strategies.",
			"category": 2,
			"name": "Rane Jayant K,2023"
		},
		{
			"PMID": 36928603,
			"title": "Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity.",
			"journal": "Nature genetics",
			"authorList": [
				"Mangiante Lise",
				"Alcala Nicolas",
				"Sexton-Oates Alexandra",
				"Di Genova Alex",
				"Gonzalez-Perez Abel",
				"Khandekar Azhar",
				"Bergstrom Erik N",
				"Kim Jaehee",
				"Liu Xiran",
				"Blazquez-Encinas Ricardo",
				"Giacobi Colin",
				"Le Stang Nolwenn",
				"Boyault Sandrine",
				"Cuenin Cyrille",
				"Tabone-Eglinger Severine",
				"Damiola Francesca",
				"Voegele Catherine",
				"Ardin Maude",
				"Michallet Marie-Cecile",
				"Soudade Lorraine",
				"Delhomme Tiffany M",
				"Poret Arnaud",
				"Brevet Marie",
				"Copin Marie-Christine",
				"Giusiano-Courcambeck Sophie",
				"Damotte Diane",
				"Girard Cecile",
				"Hofman Veronique",
				"Hofman Paul",
				"Mouroux J\u00e9r\u00f4me",
				"Cohen Charlotte",
				"Lacomme Stephanie",
				"Mazieres Julien",
				"de Montpreville Vincent Thomas",
				"Perrin Corinne",
				"Planchard Gaetane",
				"Rousseau Nathalie",
				"Rouquette Isabelle",
				"Sagan Christine",
				"Scherpereel Arnaud",
				"Thivolet Francoise",
				"Vignaud Jean-Michel",
				"Jean Didier",
				"Ilg Anabelle Gilg Soit",
				"Olaso Robert",
				"Meyer Vincent",
				"Boland-Auge Anne",
				"Deleuze Jean-Francois",
				"Altmuller Janine",
				"Nuernberg Peter",
				"Ib\u00e1\u00f1ez-Costa Alejandro",
				"Casta\u00f1o Justo P",
				"Lantuejoul Sylvie",
				"Ghantous Akram",
				"Maussion Charles",
				"Courtiol Pierre",
				"Hernandez-Vargas Hector",
				"Caux Christophe",
				"Girard Nicolas",
				"Lopez-Bigas Nuria",
				"Alexandrov Ludmil B",
				"Galateau-Salle Fran\u00e7oise",
				"Foll Matthieu",
				"Fernandez-Cuesta Lynnette"
			],
			"DOI": "10.1038/s41588-023-01321-1",
			"date": "2023-04-17",
			"PMC": "",
			"citation": "",
			"abstract": "Malignant pleural mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Through a large series of whole-genome sequencing data, integrated with transcriptomic and epigenomic data using multiomics factor analysis, we demonstrate that the current World Health Organization classification only accounts for up to 10% of interpatient molecular differences. Instead, the MESOMICS project paves the way for a morphomolecular classification of MPM based on four dimensions: ploidy, tumor cell morphology, adaptive immune response and CpG island methylator profile. We show that these four dimensions are complementary, capture major interpatient molecular differences and are delimited by extreme phenotypes that-in the case of the interdependent tumor cell morphology and adapted immune response-reflect tumor specialization. These findings unearth the interplay between MPM functional biology and its genomic history, and provide insights into the variations observed in the clinical behavior of patients with MPM.",
			"category": 2,
			"name": "Mangiante Lise,2023"
		},
		{
			"PMID": 36915069,
			"title": "Fragment length profiles of cancer mutations enhance detection of circulating tumor DNA in patients with early-stage hepatocellular carcinoma.",
			"journal": "BMC cancer",
			"authorList": [
				"Nguyen Van-Chu",
				"Nguyen Trong Hieu",
				"Phan Thanh Hai",
				"Tran Thanh-Huong Thi",
				"Pham Thu Thuy Thi",
				"Ho Tan Dat",
				"Nguyen Hue Hanh Thi",
				"Duong Minh-Long",
				"Nguyen Cao Minh",
				"Nguyen Que-Tran Bui",
				"Bach Hoai-Phuong Thi",
				"Kim Van-Vu",
				"Pham The-Anh",
				"Nguyen Bao Toan",
				"Nguyen Thanh Nhan Vo",
				"Huynh Le Anh Khoa",
				"Tran Vu Uyen",
				"Tran Thuy Thi Thu",
				"Nguyen Thanh Dang",
				"Phu Dung Thai Bieu",
				"Phan Boi Hoan Huu",
				"Nguyen Quynh-Tho Thi",
				"Truong Dinh-Kiet",
				"Do Thanh-Thuy Thi",
				"Nguyen Hoai-Nghia",
				"Phan Minh-Duy",
				"Giang Hoa",
				"Tran Le Son"
			],
			"DOI": "10.1186/s12885-023-10681-0",
			"date": "2023-03-15",
			"PMC": "",
			"citation": "",
			"abstract": "Late detection of hepatocellular carcinoma (HCC) results in an overall 5-year survival rate of less than 16%. Liquid biopsy (LB) assays based on detecting circulating tumor DNA (ctDNA) might provide an opportunity to detect HCC early noninvasively. Increasing evidence indicates that ctDNA detection using mutation-based assays is significantly challenged by the abundance of white blood cell-derived mutations, non-tumor tissue-derived somatic mutations in plasma, and the mutational tumor heterogeneity.",
			"category": 2,
			"name": "Nguyen Van-Chu,2023"
		},
		{
			"PMID": 36914722,
			"title": "The emerging role of PI3K inhibitors for solid tumour treatment and beyond.",
			"journal": "British journal of cancer",
			"authorList": [
				"Belli Carmen",
				"Repetto Matteo",
				"Anand Santosh",
				"Porta Camillo",
				"Subbiah Vivek",
				"Curigliano Giuseppe"
			],
			"DOI": "10.1038/s41416-023-02221-1",
			"date": "2023-06-07",
			"PMC": "",
			"citation": "",
			"abstract": "Phosphoinositide 3-kinases (PI3Ks) play a central role in tumourigenesis with recurrent activating mutations of its p110\u03b1 subunit (PIK3CA) identified in several tumours. Although several PI3K inhibitors are approved for haematological malignancies, only alpelisib was approved in solid tumours and for the treatment of PIK3CA-related overgrowth spectrum (PROS) syndrome. Traditional PI3K inhibitors inhibit both wild-type and mutant PI3K with almost equal potency, thus limiting their efficacy due to on-target toxicity. Since the initiation of phase I clinical trials investigating next generation allosteric mutant and isoform selective PIK3CA inhibitors, there has been a surge in interest in PIK3CA targeting in solid tumours. Preclinical characterisation of these compounds showed that maximal mutant protein inhibition fails to elicit metabolic and glucose homoeostasis dysregulation, one of the dose limiting toxicities of both selective and pan PI3K inhibitors. While extreme selectivity can be hypothesised to grant activity and safety advantage to these novel agents, on the other hand reduced benefit can be speculated for patients harbouring multiple or rare PIK3CA mutations. This review summarises the current understanding of PI3K alterations and the state-of-the-art treatment strategies in PI3K driven solid tumours, while also exploring the potential intrinsic and acquired resistance mechanisms to these agents, and the emerging role of mutant selective PIK3CA inhibitors.",
			"category": 2,
			"name": "Belli Carmen,2023"
		},
		{
			"PMID": 36894662,
			"title": "State-dependent evolutionary models reveal modes of solid tumour growth.",
			"journal": "Nature ecology & evolution",
			"authorList": [
				"Lewinsohn Maya A",
				"Bedford Trevor",
				"M\u00fcller Nicola F",
				"Feder Alison F"
			],
			"DOI": "10.1038/s41559-023-02000-4",
			"date": "2023-04-13",
			"PMC": "",
			"citation": "",
			"abstract": "Spatial properties of tumour growth have profound implications for cancer progression, therapeutic resistance and metastasis. Yet, how spatial position governs tumour cell division remains difficult to evaluate in clinical tumours. Here, we demonstrate that faster division on the tumour periphery leaves characteristic genetic patterns, which become evident when a phylogenetic tree is reconstructed from spatially sampled cells. Namely, rapidly dividing peripheral lineages branch more extensively and acquire more mutations than slower-dividing centre lineages. We develop a Bayesian state-dependent evolutionary phylodynamic model (SDevo) that quantifies these patterns to infer the differential division rates between peripheral and central cells. We demonstrate that this approach accurately infers spatially varying birth rates of simulated tumours across a range of growth conditions and sampling strategies. We then show that SDevo outperforms state-of-the-art, non-cancer multi-state phylodynamic methods that ignore differential sequence evolution. Finally, we apply SDevo to single-time-point, multi-region sequencing data from clinical hepatocellular carcinomas and find evidence of a three- to six-times-higher division rate on the tumour edge. With the increasing availability of high-resolution, multi-region sequencing, we anticipate that SDevo will be useful in interrogating spatial growth restrictions and could be extended to model non-spatial factors that influence tumour progression.",
			"category": 2,
			"name": "Lewinsohn Maya A,2023"
		},
		{
			"PMID": 36892717,
			"title": "The evolutionary cancer gene network theory versus embryogenic hypotheses.",
			"journal": "Medical oncology (Northwood, London, England)",
			"authorList": [
				"Niculescu Vladimir Florin"
			],
			"DOI": "10.1007/s12032-023-01983-1",
			"date": "2023-03-13",
			"PMC": "",
			"citation": "",
			"abstract": "The present paper compares the statements of the evolutionary cancer gene-network theory (cancer genome theory) with the statements of embryogenic hypotheses like the embryonic rest hypothesis, the very small embryonic-like stem cells hypothesis, (VSEL), the para-embryonic p-ESC hypothesis, and the PGCC-life cycle hypothesis, including the life code theory. In my opinion, the evolutionary gene network theory is the only theory that can satisfactorily explain the homologies between carcinogenesis, tumorigenesis, metastasis, gametogenesis, and early embryogenesis. From an evolutionary point of view, there is no reason to see the origin of cancer in cells of early embryonic life.",
			"category": 2,
			"name": "Niculescu Vladimir Florin,2023"
		},
		{
			"PMID": 36889927,
			"title": "Defining clonal hematopoiesis of indeterminate potential: evolutionary dynamics and detection under aging and inflammation.",
			"journal": "Cold Spring Harbor molecular case studies",
			"authorList": [
				"Goldman Elisabeth A",
				"Spellman Paul T",
				"Agarwal Anupriya"
			],
			"DOI": "10.1101/mcs.a006251",
			"date": "2023-05-11",
			"PMC": "",
			"citation": "",
			"abstract": "Clonal hematopoiesis (CH), in which hematopoietic stem and progenitor cell (HSPC) clones and their progeny expand in the circulating blood cell population, occurs following the acquisition of somatic driver mutations. Individuals diagnosed with clonal hematopoiesis of indeterminate potential (CHIP) carry somatic mutations in hematological malignancy-associated driver genes, historically at or above a variant allele frequency of 2%, but do not exhibit abnormal blood cell counts or any other symptoms of hematologic disease. However, CHIP is associated with moderately increased risk of hematological cancer and a greater likelihood of cardiovascular and pulmonary disease. Recent advances in the resolution of high-throughput sequencing experiments suggest CHIP is much more prevalent in the population than once thought, particularly among those aged 60 and over. Although CHIP does elevate the risk of eventual hematological malignancy, only one in 10 individuals with CHIP will receive such a diagnosis; the problem lies in the continued difficulty in accurately separating the 10% of CHIP patients who are most likely to be in a premalignant state from those who are not, given the heterogeneity of this condition and the etiology of the associated hematological cancers. Concerns over the risk of eventual malignancies must be balanced with growing recognition of CH as a common age-dependent occurrence, and efforts to better characterize and differentiate oncogenic clonal expansion from that which is much more benign. In this review, we discuss evolutionary dynamics of CH and CHIP, the relationship of CH to aging and inflammation, and the role of the epigenome in promoting potentially pathogenic or benign cellular trajectories. We outline molecular mechanisms that may contribute to heterogeneity in the etiology of CHIP and the incidence of malignant disease among individuals. Finally, we discuss epigenetic markers and modifications for CHIP detection and monitoring with the potential for translational applications and clinical utility in the near future.",
			"category": 2,
			"name": "Goldman Elisabeth A,2023"
		},
		{
			"PMID": 36860424,
			"title": "Cell Adaptive Fitness and Cancer Evolutionary Dynamics.",
			"journal": "Cancer informatics",
			"authorList": [
				"Derbal Youcef"
			],
			"DOI": "10.1177/11769351231154679",
			"date": "2023-03-03",
			"PMC": "",
			"citation": "",
			"abstract": "Genome instability of cancer cells translates into increased entropy and lower information processing capacity, leading to metabolic reprograming toward higher energy states, presumed to be aligned with a cancer growth imperative. Dubbed as the cell adaptive fitness, the proposition postulates that the coupling between cell signaling and metabolism constrains cancer evolutionary dynamics along trajectories privileged by the maintenance of metabolic sufficiency for survival. In particular, the conjecture postulates that clonal expansion becomes restricted when genetic alterations induce a sufficiently high level of disorder, that is, high entropy, in the regulatory signaling network, abrogating as a result the ability of cancer cells to successfully replicate, leading to a stage of clonal stagnation. The proposition is analyzed in the context of an in-silico model of tumor evolutionary dynamics to illustrate how cell-inherent adaptive fitness may predictably constrain clonal evolution of tumors, which would have significant implications for the design of adaptive cancer therapies.",
			"category": 2,
			"name": "Derbal Youcef,2023"
		},
		{
			"PMID": 36812605,
			"title": "An integrated analysis of the cancer genome atlas data discovers a hierarchical association structure across thirty three cancer types.",
			"journal": "PLOS digital health",
			"authorList": [
				"Tiong Khong-Loon",
				"Sintupisut Nardnisa",
				"Lin Min-Chin",
				"Cheng Chih-Hung",
				"Woolston Andrew",
				"Lin Chih-Hsu",
				"Ho Mirrian",
				"Lin Yu-Wei",
				"Padakanti Sridevi",
				"Yeang Chen-Hsiang"
			],
			"DOI": "10.1371/journal.pdig.0000151",
			"date": "2023-02-24",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer cells harbor molecular alterations at all levels of information processing. Genomic/epigenomic and transcriptomic alterations are inter-related between genes, within and across cancer types and may affect clinical phenotypes. Despite the abundant prior studies of integrating cancer multi-omics data, none of them organizes these associations in a hierarchical structure and validates the discoveries in extensive external data. We infer this Integrated Hierarchical Association Structure (IHAS) from the complete data of The Cancer Genome Atlas (TCGA) and compile a compendium of cancer multi-omics associations. Intriguingly, diverse alterations on genomes/epigenomes from multiple cancer types impact transcriptions of 18 Gene Groups. Half of them are further reduced to three Meta Gene Groups enriched with (1) immune and inflammatory responses, (2) embryonic development and neurogenesis, (3) cell cycle process and DNA repair. Over 80% of the clinical/molecular phenotypes reported in TCGA are aligned with the combinatorial expressions of Meta Gene Groups, Gene Groups, and other IHAS subunits. Furthermore, IHAS derived from TCGA is validated in more than 300 external datasets including multi-omics measurements and cellular responses upon drug treatments and gene perturbations in tumors, cancer cell lines, and normal tissues. To sum up, IHAS stratifies patients in terms of molecular signatures of its subunits, selects targeted genes or drugs for precision cancer therapy, and demonstrates that associations between survival times and transcriptional biomarkers may vary with cancer types. These rich information is critical for diagnosis and treatments of cancers.",
			"category": 2,
			"name": "Tiong Khong-Loon,2023"
		},
		{
			"PMID": 36802377,
			"title": "On the gene expression landscape of cancer.",
			"journal": "PloS one",
			"authorList": [
				"Gonzalez Augusto",
				"Leon Dario A",
				"Perera Yasser",
				"Perez Rolando"
			],
			"DOI": "10.1371/journal.pone.0277786",
			"date": "2023-02-23",
			"PMC": "",
			"citation": "",
			"abstract": "Kauffman picture of normal and tumor states as attractors in an abstract state space is used in order to interpret gene expression data for 15 cancer localizations obtained from The Cancer Genome Atlas. A principal component analysis of this data unveils the following qualitative aspects about tumors: 1) The state of a tissue in gene expression space can be described by a few variables. In particular, there is a single variable describing the progression from a normal tissue to a tumor. 2) Each cancer localization is characterized by a gene expression profile, in which genes have specific weights in the definition of the cancer state. There are no less than 2500 differentially-expressed genes, which lead to power-like tails in the expression distribution functions. 3) Tumors in different localizations share hundreds or even thousands of differentially expressed genes. There are 6 genes common to the 15 studied tumor localizations. 4) The tumor region is a kind of attractor. Tumors in advanced stages converge to this region independently of patient age or genetic characteristics. 5) There is a landscape of cancer in gene expression space with an approximate border separating normal tissues from tumors.",
			"category": 2,
			"name": "Gonzalez Augusto,2023"
		},
		{
			"PMID": 36792751,
			"title": "A timeline of tumour-associated macrophage biology.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Cassetta Luca",
				"Pollard Jeffrey W"
			],
			"DOI": "10.1038/s41568-022-00547-1",
			"date": "2023-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "Tumour progression is modulated by the local microenvironment. This environment is populated by many immune cells, of which macrophages are among the most abundant. Clinical correlative data and a plethora of preclinical studies in mouse models of cancers have shown that tumour-associated macrophages (TAMs) play a cancer-promoting role. Within the primary tumour, TAMs promote tumour cell invasion and intravasation and tumour stem cell viability and induce angiogenesis. At the metastatic site, metastasis-associated macrophages promote extravasation, tumour cell survival and persistent growth, as well as maintain tumour cell dormancy in some contexts. In both the primary and metastatic sites, TAMs are suppressive to the activities of cytotoxic T and natural killer cells that have the potential to eradicate tumours. Such activities suggest that TAMs will be a major target for therapeutic intervention. In this Perspective article, we chronologically explore the evolution of our understanding of TAM biology put into the context of major enabling advances in macrophage biology.",
			"category": 2,
			"name": "Cassetta Luca,2023"
		},
		{
			"PMID": 36780550,
			"title": "Copy number footprints of platinum-based anticancer therapies.",
			"journal": "PLoS genetics",
			"authorList": [
				"Gonzalez Santiago",
				"Lopez-Bigas Nuria",
				"Gonzalez-Perez Abel"
			],
			"DOI": "10.1371/journal.pgen.1010634",
			"date": "2023-02-28",
			"PMC": "",
			"citation": "",
			"abstract": "Recently, distinct mutational footprints observed in metastatic tumors, secondary malignancies and normal human tissues have been demonstrated to be caused by the exposure to several chemotherapeutic drugs. These characteristic mutations originate from specific lesions caused by these chemicals to the DNA of exposed cells. However, it is unknown whether the exposure to these chemotherapies leads to a specific footprint of larger chromosomal aberrations. Here, we address this question exploiting whole genome sequencing data of metastatic tumors obtained from patients exposed to different chemotherapeutic drugs. As a result, we discovered a specific copy number footprint across tumors from patients previously exposed to platinum-based therapies. This footprint is characterized by a significant increase in the number of chromosomal fragments of copy number 1-4 and size smaller than 10 Mb in exposed tumors with respect to their unexposed counterparts (median 14-387% greater across tumor types). The number of chromosomal fragments characteristic of the platinum-associated CN footprint increases significantly with the activity of the well known platinum-related footprint of single nucleotide variants across exposed tumors.",
			"category": 2,
			"name": "Gonzalez Santiago,2023"
		},
		{
			"PMID": 36778659,
			"title": "The eternal quest for self-improvement of somatic cells.",
			"journal": "Cell genomics",
			"authorList": [
				"Campbell Peter J"
			],
			"DOI": "10.1016/j.xgen.2022.100094",
			"date": "2023-02-14",
			"PMC": "",
			"citation": "",
			"abstract": "Multiple somatic mutations drive cancer cell transformation, but the sequence of events is poorly understood. In this issue of ",
			"category": 2,
			"name": "Campbell Peter J,2023"
		},
		{
			"PMID": 36765661,
			"title": "Current State and Future Challenges for PI3K Inhibitors in Cancer Therapy.",
			"journal": "Cancers",
			"authorList": [
				"Sirico Marianna",
				"D'Angelo Alberto",
				"Gianni Caterina",
				"Casadei Chiara",
				"Merloni Filippo",
				"De Giorgi Ugo"
			],
			"DOI": "10.3390/cancers15030703",
			"date": "2023-09-18",
			"PMC": "",
			"citation": "",
			"abstract": "The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB/AKT)-mammalian target of the rapamycin (mTOR) axis is a key signal transduction system that links oncogenes and multiple receptor classes which are involved in many essential cellular functions. Aberrant PI3K signalling is one of the most commonly mutated pathways in cancer. Consequently, more than 40 compounds targeting key components of this signalling network have been tested in clinical trials among various types of cancer. As the oncogenic activation of the PI3K/AKT/mTOR pathway often occurs alongside mutations in other signalling networks, combination therapy should be considered. In this review, we highlight recent advances in the knowledge of the PI3K pathway and discuss the current state and future challenges of targeting this pathway in clinical practice.",
			"category": 2,
			"name": "Sirico Marianna,2023"
		},
		{
			"PMID": 36762803,
			"title": "Molecular Biology of Brain Metastases.",
			"journal": "Brain tumor research and treatment",
			"authorList": [
				"Gwak Ho-Shin"
			],
			"DOI": "10.14791/btrt.2022.0045",
			"date": "2023-02-17",
			"PMC": "",
			"citation": "",
			"abstract": "Brain metastases (BMs) often occur in patients with lung cancer, breast cancer, and melanoma and are the leading cause of morbidity and mortality. The incidence of BM has increased with advanced neuroimaging and prolonged overall survival of cancer patients. With the advancement of local treatment modalities, including stereotactic radiosurgery and navigation-guided microsurgery, BM can be controlled long-term, even in cases with multiple lesions. However, radiation/chemotherapeutic agents are also toxic to the brain, usually irreversibly and cumulatively, and it remains difficult to completely cure BM. Thus, we must understand the molecular events that begin and sustain BM to develop effective targeted therapies and tools to prevent local and distant treatment failure. BM most often spreads hematogenously, and the blood-brain barrier (BBB) presents the first hurdle for disseminated tumor cells (DTCs) entering the brain parenchyma. Nevertheless, how the DTCs cross the BBB and settle on relatively infertile central nervous system tissue remains unknown. Even after successfully taking up residence in the brain, the unique tumor microenvironment is marked by restricted aerobic glycolysis metabolism and limited lymphocyte infiltration. Brain organotropism, certain phenotype of primary cancers that favors brain metastasis, may result from somatic mutation or epigenetic modulation. Recent studies revealed that exosome secretion from primary cancer or over-expression of proteolytic enzymes can \"pre-condition\" brain vasculoendothelial cells. The concept of the \"metastatic niche,\" where resident DTCs remain dormant and protected from systemic chemotherapy and antigen exposure before proliferation, is supported by clinical observation of BM in patients clearing systemic cancer and experimental evidence of the interaction between cancer cells and tumor-infiltrating lymphocytes. This review examines extant research on the metastatic cascade of BM through the molecular events that create and sustain BM to reveal clues that can assist the development of effective targeted therapies that treat established BMs and prevent BM recurrence.",
			"category": 2,
			"name": "Gwak Ho-Shin,2023"
		},
		{
			"PMID": 36755104,
			"title": "Johann Gregor Mendel: the victory of statistics over human imagination.",
			"journal": "European journal of human genetics : EJHG",
			"authorList": [
				"Raudenska Martina",
				"Vicar Tomas",
				"Gumulec Jaromir",
				"Masarik Michal"
			],
			"DOI": "10.1038/s41431-023-01303-1",
			"date": "2023-07-10",
			"PMC": "",
			"citation": "",
			"abstract": "In 2022, we celebrated 200 years since the birth of Johann Gregor Mendel. Although his contributions to science went unrecognized during his lifetime, Mendel not only described the principles of monogenic inheritance but also pioneered the modern way of doing science based on precise experimental data acquisition and evaluation. Novel statistical and algorithmic approaches are now at the center of scientific work, showing that work that is considered marginal in one era can become a mainstream research approach in the next era. The onset of data-driven science caused a shift from hypothesis-testing to hypothesis-generating approaches in science. Mendel is remembered here as a promoter of this approach, and the benefits of big data and statistical approaches are discussed.",
			"category": 2,
			"name": "Raudenska Martina,2023"
		},
		{
			"PMID": 36726722,
			"title": "Candidate targets of copy number deletion events across 17 cancer types.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Huang Qingyao",
				"Baudis Michael"
			],
			"DOI": "10.3389/fgene.2022.1017657",
			"date": "2023-02-03",
			"PMC": "",
			"citation": "",
			"abstract": "Genome variation is the direct cause of cancer and driver of its clonal evolution. While the impact of many point mutations can be evaluated through their modification of individual genomic elements, even a single copy number aberration (CNA) may encompass hundreds of genes and therefore pose challenges to untangle potentially complex functional effects. However, consistent, recurring and disease-specific patterns in the genome-wide CNA landscape imply that particular CNA may promote cancer-type-specific characteristics. Discerning essential cancer-promoting alterations from the inherent co-dependency in CNA would improve the understanding of mechanisms of CNA and provide new insights into cancer biology and potential therapeutic targets. Here we implement a model using segmental breakpoints to discover non-random gene coverage by copy number deletion (CND). With a diverse set of cancer types from multiple resources, this model identified common and cancer-type-specific oncogenes and tumor suppressor genes as well as cancer-promoting functional pathways. Confirmed by differential expression analysis of data from corresponding cancer types, the results show that for most cancer types, despite dissimilarity of their CND landscapes, similar canonical pathways are affected. In 25 analyses of 17 cancer types, we have identified 19 to 169 significant genes by copy deletion, including RB1, PTEN and CDKN2A as the most significantly deleted genes among all cancer types. We have also shown a shared dependence on core pathways for cancer progression in different cancers as well as cancer type separation by genome-wide significance scores. While this work provides a reference for gene specific significance in many cancers, it chiefly contributes a general framework to derive genome-wide significance and molecular insights in CND profiles with a potential for the analysis of rare cancer types as well as non-coding regions.",
			"category": 2,
			"name": "Huang Qingyao,2023"
		},
		{
			"PMID": 36724177,
			"title": "Age at cancer diagnosis by breed, weight, sex, and cancer type in a cohort of more than 3,000 dogs: Determining the optimal age to initiate cancer screening in canine patients.",
			"journal": "PloS one",
			"authorList": [
				"Rafalko Jill M",
				"Kruglyak Kristina M",
				"McCleary-Wheeler Angela L",
				"Goyal Vidit",
				"Phelps-Dunn Ashley",
				"Wong Lilian K",
				"Warren Chelsea D",
				"Brandstetter Gina",
				"Rosentel Michelle C",
				"DiMarzio Lauren",
				"McLennan Lisa M",
				"O'Kell Allison L",
				"Cohen Todd A",
				"Grosu Daniel S",
				"Chibuk Jason",
				"Tsui Dana W Y",
				"Chorny Ilya",
				"Flory Andi"
			],
			"DOI": "10.1371/journal.pone.0280795",
			"date": "2023-02-03",
			"PMC": "",
			"citation": "",
			"abstract": "The goal of cancer screening is to detect disease at an early stage when treatment may be more effective. Cancer screening in dogs has relied upon annual physical examinations and routine laboratory tests, which are largely inadequate for detecting preclinical disease. With the introduction of non-invasive liquid biopsy cancer detection methods, the discussion is shifting from how to screen dogs for cancer to when to screen dogs for cancer. To address this question, we analyzed data from 3,452 cancer-diagnosed dogs to determine the age at which dogs of certain breeds and weights are typically diagnosed with cancer. In our study population, the median age at cancer diagnosis was 8.8 years, with males diagnosed at younger ages than females, and neutered dogs diagnosed at significantly later ages than intact dogs. Overall, weight was inversely correlated with age at cancer diagnosis, and purebred dogs were diagnosed at significantly younger ages than mixed-breed dogs. For breeds represented by \u226510 dogs, a breed-based median age at diagnosis was calculated. A weight-based linear regression model was developed to predict the median age at diagnosis for breeds represented by \u226410 dogs and for mixed-breed dogs. Our findings, combined with findings from previous studies which established a long duration of the preclinical phase of cancer development in dogs, suggest that it might be reasonable to consider annual cancer screening starting 2 years prior to the median age at cancer diagnosis for dogs of similar breed or weight. This logic would support a general recommendation to start cancer screening for all dogs at the age of 7, and as early as age 4 for breeds with a lower median age at cancer diagnosis, in order to increase the likelihood of early detection and treatment.",
			"category": 2,
			"name": "Rafalko Jill M,2023"
		},
		{
			"PMID": 36723991,
			"title": "Molecular Evolution of Classic Hodgkin Lymphoma Revealed Through Whole-Genome Sequencing of Hodgkin and Reed Sternberg Cells.",
			"journal": "Blood cancer discovery",
			"authorList": [
				"Maura Francesco",
				"Ziccheddu Bachisio",
				"Xiang Jenny Z",
				"Bhinder Bhavneet",
				"Rosiene Joel",
				"Abascal Federico",
				"Maclachlan Kylee H",
				"Eng Kenneth Wha",
				"Uppal Manik",
				"He Feng",
				"Zhang Wei",
				"Gao Qi",
				"Yellapantula Venkata D",
				"Trujillo-Alonso Vicenta",
				"Park Sunita I",
				"Oberley Matthew J",
				"Ruckdeschel Elizabeth",
				"Lim Megan S",
				"Wertheim Gerald B",
				"Barth Matthew J",
				"Horton Terzah M",
				"Derkach Andriy",
				"Kovach Alexandra E",
				"Forlenza Christopher J",
				"Zhang Yanming",
				"Landgren Ola",
				"Moskowitz Craig H",
				"Cesarman Ethel",
				"Imielinski Marcin",
				"Elemento Olivier",
				"Roshal Mikhail",
				"Giulino-Roth Lisa"
			],
			"DOI": "10.1158/2643-3230.BCD-22-0128",
			"date": "2023-05-02",
			"PMC": "",
			"citation": "",
			"abstract": "The rarity of malignant Hodgkin and Reed Sternberg (HRS) cells in classic Hodgkin lymphoma (cHL) limits the ability to study the genomics of cHL. To circumvent this, our group has previously optimized fluorescence-activated cell sorting to purify HRS cells. Using this approach, we now report the whole-genome sequencing landscape of HRS cells and reconstruct the chronology and likely etiology of pathogenic events leading to cHL. We identified alterations in driver genes not previously described in cHL, APOBEC mutational activity, and the presence of complex structural variants including chromothripsis. We found that high ploidy in cHL is often acquired through multiple, independent chromosomal gains events including whole-genome duplication. Evolutionary timing analyses revealed that structural variants enriched for RAG motifs, driver mutations in B2M, BCL7A, GNA13, and PTPN1, and the onset of AID-driven mutagenesis usually preceded large chromosomal gains. This study provides a temporal reconstruction of cHL pathogenesis.",
			"category": 2,
			"name": "Maura Francesco,2023"
		},
		{
			"PMID": 36671795,
			"title": "Escape from Cellular Senescence Is Associated with Chromosomal Instability in Oral Pre-Malignancy.",
			"journal": "Biology",
			"authorList": [
				"Prime Stephen S",
				"Cirillo Nicola",
				"Parkinson E Kenneth"
			],
			"DOI": "10.3390/biology12010103",
			"date": "2023-02-01",
			"PMC": "",
			"citation": "",
			"abstract": "An escape from cellular senescence through the development of unlimited growth potential is one of the hallmarks of cancer, which is thought to be an early event in carcinogenesis. In this review, we propose that the molecular effectors of senescence, particularly the inactivation of TP53 and CDKN2A, together with telomere attrition and telomerase activation, all lead to aneuploidy in the keratinocytes from oral potentially malignant disorders (OPMD). Premalignant keratinocytes, therefore, not only become immortal but also develop genotypic and phenotypic cellular diversity. As a result of these changes, certain clonal cell populations likely gain the capacity to invade the underlying connective tissue. We review the clinical implications of these changes and highlight a new PCR-based assay to identify aneuploid cell in fluids such as saliva, a technique that is extremely sensitive and could facilitate the regular monitoring of OPMD without the need for surgical biopsies and may avoid potential biopsy sampling errors. We also draw attention to recent studies designed to eliminate aneuploid tumour cell populations that, potentially, is a new therapeutic approach to prevent malignant transformations in OPMD.",
			"category": 2,
			"name": "Prime Stephen S,2023"
		},
		{
			"PMID": 36656749,
			"title": "Ras/MAPK signalling intensity defines subclonal fitness in a mouse model of hepatocellular carcinoma.",
			"journal": "eLife",
			"authorList": [
				"Lozano Anthony",
				"Souche Francois-R\u00e9gis",
				"Chavey Carine",
				"Dardalhon Val\u00e9rie",
				"Ramirez Christel",
				"Vegna Serena",
				"Desandre Guillaume",
				"Riviere Ana\u00efs",
				"Zine El Aabidine Amal",
				"Fort Philippe",
				"Akkari Leila",
				"Hibner Urszula",
				"Gr\u00e9goire Damien"
			],
			"DOI": "10.7554/eLife.76294",
			"date": "2023-02-08",
			"PMC": "",
			"citation": "",
			"abstract": "Quantitative differences in signal transduction are to date an understudied feature of tumour heterogeneity. The MAPK Erk pathway, which is activated in a large proportion of human tumours, is a prototypic example of distinct cell fates being driven by signal intensity. We have used primary hepatocyte precursors transformed with different dosages of an oncogenic form of Ras to model subclonal variations in MAPK signalling. Orthotopic allografts of Ras-transformed cells in immunocompromised mice gave rise to fast-growing aggressive tumours, both at the primary location and in the peritoneal cavity. Fluorescent labelling of cells expressing different oncogene levels, and consequently varying levels of MAPK Erk activation, highlighted the selection processes operating at the two sites of tumour growth. Indeed, significantly higher Ras expression was observed in primary as compared to secondary, metastatic sites, despite the apparent evolutionary trade-off of increased apoptotic death in the liver that correlated with high Ras dosage. Analysis of the immune tumour microenvironment at the two locations suggests that fast peritoneal tumour growth in the immunocompromised setting is abrogated in immunocompetent animals due to efficient antigen presentation by peritoneal dendritic cells. Furthermore, our data indicate that, in contrast to the metastatic-like outgrowth, strong MAPK signalling is required in the primary liver tumours to resist elimination by NK (natural killer) cells. Overall, this study describes a quantitative aspect of tumour heterogeneity and points to a potential vulnerability of a subtype of hepatocellular carcinoma as a function of MAPK Erk signalling intensity.",
			"category": 2,
			"name": "Lozano Anthony,2023"
		},
		{
			"PMID": 36626250,
			"title": "Tracking the evolution of therapy-related myeloid neoplasms using chemotherapy signatures.",
			"journal": "Blood",
			"authorList": [
				"Diamond Benjamin",
				"Ziccheddu Bachisio",
				"Maclachlan Kylee",
				"Taylor Justin",
				"Boyle Eileen",
				"Ossa Juan Arango",
				"Jahn Jacob",
				"Affer Maurizio",
				"Totiger Tulasigeri M",
				"Coffey David",
				"Chandhok Namrata",
				"Watts Justin",
				"Cimmino Luisa",
				"Lu Sydney X",
				"Bolli Niccol\u00f2",
				"Bolton Kelly",
				"Landau Heather",
				"Park Jae H",
				"Ganesh Karuna",
				"McPherson Andrew",
				"Sekeres Mikkael A",
				"Lesokhin Alexander",
				"Chung David J",
				"Zhang Yanming",
				"Ho Caleb",
				"Roshal Mikhail",
				"Tyner Jeffrey",
				"Nimer Stephen",
				"Papaemmanuil Elli",
				"Usmani Saad",
				"Morgan Gareth",
				"Landgren Ola",
				"Maura Francesco"
			],
			"DOI": "10.1182/blood.2022018244",
			"date": "2023-05-15",
			"PMC": "",
			"citation": "",
			"abstract": "Patients treated with cytotoxic therapies, including autologous stem cell transplantation, are at risk for developing therapy-related myeloid neoplasms (tMN). Preleukemic clones (ie, clonal hematopoiesis [CH]) are detectable years before the development of these aggressive malignancies, although the genomic events leading to transformation and expansion are not well defined. Here, by leveraging distinctive chemotherapy-associated mutational signatures from whole-genome sequencing data and targeted sequencing of prechemotherapy samples, we reconstructed the evolutionary life-history of 39 therapy-related myeloid malignancies. A dichotomy was revealed, in which neoplasms with evidence of chemotherapy-induced mutagenesis from platinum and melphalan were hypermutated and enriched for complex structural variants (ie, chromothripsis), whereas neoplasms with nonmutagenic chemotherapy exposures were genomically similar to de novo acute myeloid leukemia. Using chemotherapy-associated mutational signatures as temporal barcodes linked to discrete clinical exposure in each patient's life, we estimated that several complex events and genomic drivers were acquired after chemotherapy was administered. For patients with prior multiple myeloma who were treated with high-dose melphalan and autologous stem cell transplantation, we demonstrate that tMN can develop from either a reinfused CH clone that escapes melphalan exposure and is selected after reinfusion, or from TP53-mutant CH that survives direct myeloablative conditioning and acquires melphalan-induced DNA damage. Overall, we revealed a novel mode of tMN progression that is not reliant on direct mutagenesis or even exposure to chemotherapy. Conversely, for tMN that evolve under the influence of chemotherapy-induced mutagenesis, distinct chemotherapies not only select preexisting CH but also promote the acquisition of recurrent genomic drivers.",
			"category": 2,
			"name": "Diamond Benjamin,2023"
		},
		{
			"PMID": 36604421,
			"title": "Germline TP53 mutations undergo copy number gain years prior to tumor diagnosis.",
			"journal": "Nature communications",
			"authorList": [
				"Light Nicholas",
				"Layeghifard Mehdi",
				"Attery Ayush",
				"Subasri Vallijah",
				"Zatzman Matthew",
				"Anderson Nathaniel D",
				"Hatkar Rupal",
				"Blay Sasha",
				"Chen David",
				"Novokmet Ana",
				"Fuligni Fabio",
				"Tran James",
				"de Borja Richard",
				"Agarwal Himanshi",
				"Waldman Larissa",
				"Abegglen Lisa M",
				"Albertson Daniel",
				"Finlay Jonathan L",
				"Hansford Jordan R",
				"Behjati Sam",
				"Villani Anita",
				"Gerstung Moritz",
				"Alexandrov Ludmil B",
				"Somers Gino R",
				"Schiffman Joshua D",
				"Rotter Varda",
				"Malkin David",
				"Shlien Adam"
			],
			"DOI": "10.1038/s41467-022-35727-y",
			"date": "2023-01-09",
			"PMC": "",
			"citation": "",
			"abstract": "Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome associated with germline TP53 pathogenic variants. Here, we perform whole-genome sequence (WGS) analysis of tumors from 22 patients with TP53 germline pathogenic variants. We observe somatic mutations affecting Wnt, PI3K/AKT signaling, epigenetic modifiers and homologous recombination genes as well as mutational signatures associated with prior chemotherapy. We identify near-ubiquitous early loss of heterozygosity of TP53, with gain of the mutant allele. This occurs earlier in these tumors compared to tumors with somatic TP53 mutations, suggesting the timing of this mark may distinguish germline from somatic TP53 mutations. Phylogenetic trees of tumor evolution, reconstructed from bulk and multi-region WGS, reveal that LFS tumors exhibit comparatively limited heterogeneity. Overall, our study delineates early copy number gains of mutant TP53 as a characteristic mutational process in LFS tumorigenesis, likely arising years prior to tumor diagnosis.",
			"category": 2,
			"name": "Light Nicholas,2023"
		},
		{
			"PMID": 36601633,
			"title": "Clinically relevant fusion oncogenes: detection and practical implications.",
			"journal": "Therapeutic advances in medical oncology",
			"authorList": [
				"Sorokin Maksim",
				"Rabushko Elizaveta",
				"Rozenberg Julian Markovich",
				"Mohammad Tharaa",
				"Seryakov Aleksander",
				"Sekacheva Marina",
				"Buzdin Anton"
			],
			"DOI": "10.1177/17588359221144108",
			"date": "2023-01-11",
			"PMC": "",
			"citation": "",
			"abstract": "Mechanistically, chimeric genes result from DNA rearrangements and include parts of preexisting normal genes combined at the genomic junction site. Some rearranged genes encode pathological proteins with altered molecular functions. Those which can aberrantly promote carcinogenesis are called fusion oncogenes. Their formation is not a rare event in human cancers, and many of them were documented in numerous study reports and in specific databases. They may have various molecular peculiarities like increased stability of an oncogenic part, self-activation of tyrosine kinase receptor moiety, and altered transcriptional regulation activities. Currently, tens of low molecular mass inhibitors are approved in cancers as the drugs targeting receptor tyrosine kinase (RTK) oncogenic fusion proteins, that is, including ",
			"category": 2,
			"name": "Sorokin Maksim,2023"
		},
		{
			"PMID": 36551871,
			"title": "Liquid Biopsy in Diagnosis and Prognosis of Non-Metastatic Prostate Cancer.",
			"journal": "Biomedicines",
			"authorList": [
				"Rzhevskiy Alexey S",
				"Kapitannikova Alina Y",
				"Butnaru Denis V",
				"Shpot Evgeniy V",
				"Joosse Simon A",
				"Zvyagin Andrei V",
				"Ebrahimi Warkiani Majid"
			],
			"DOI": "10.3390/biomedicines10123115",
			"date": "2022-12-25",
			"PMC": "",
			"citation": "",
			"abstract": "Currently, sensitive and specific methods for the detection and prognosis of early stage PCa are lacking. To establish the diagnosis and further identify an appropriate treatment strategy, prostate specific antigen (PSA) blood test followed by tissue biopsy have to be performed. The combination of tests is justified by the lack of a highly sensitive, specific, and safe single test. Tissue biopsy is specific but invasive and may have severe side effects, and therefore is inappropriate for screening of the disease. At the same time, the PSA blood test, which is conventionally used for PCa screening, has low specificity and may be elevated in the case of noncancerous prostate tumors and inflammatory conditions, including benign prostatic hyperplasia and prostatitis. Thus, diverse techniques of liquid biopsy have been investigated to supplement or replace the existing tests of prostate cancer early diagnosis and prognostics. Here, we provide a review on the advances in diagnosis and prognostics of non-metastatic prostate cancer by means of various biomarkers extracted via liquid biopsy, including circulating tumor cells, exosomal miRNAs, and circulating DNAs.",
			"category": 2,
			"name": "Rzhevskiy Alexey S,2022"
		},
		{
			"PMID": 36494509,
			"title": "Spatial biology of cancer evolution.",
			"journal": "Nature reviews. Genetics",
			"authorList": [
				"Seferbekova Zaira",
				"Lomakin Artem",
				"Yates Lucy R",
				"Gerstung Moritz"
			],
			"DOI": "10.1038/s41576-022-00553-x",
			"date": "2023-04-21",
			"PMC": "",
			"citation": "",
			"abstract": "The natural history of cancers can be understood through the lens of evolution given that the driving forces of cancer development are mutation and selection of fitter clones. Cancer growth and progression are spatial processes that involve the breakdown of normal tissue organization, invasion and metastasis. For these reasons, spatial patterns are an integral part of histological tumour grading and staging as they measure the progression from normal to malignant disease. Furthermore, tumour cells are part of an ecosystem of tumour cells and their surrounding tumour microenvironment. A range of new spatial genomic, transcriptomic and proteomic technologies offers new avenues for the study of cancer evolution with great molecular and spatial detail. These methods enable precise characterizations of the tumour microenvironment, cellular interactions therein and micro-anatomical structures. In conjunction with spatial genomics, it emerges that tumours and microenvironments co-evolve, which helps explain observable patterns of heterogeneity and offers new routes for therapeutic interventions.",
			"category": 2,
			"name": "Seferbekova Zaira,2023"
		},
		{
			"PMID": 36477027,
			"title": "Phosphoproteomic analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A.",
			"journal": "Nature communications",
			"authorList": [
				"Mouron S",
				"Bueno M J",
				"Lluch A",
				"Manso L",
				"Calvo I",
				"Cortes J",
				"Garcia-Saenz J A",
				"Gil-Gil M",
				"Martinez-Janez N",
				"Apala J V",
				"Caleiras E",
				"Xim\u00e9nez-Emb\u00fan Pilar",
				"Mu\u00f1oz J",
				"Gonzalez-Cortijo L",
				"Murillo R",
				"S\u00e1nchez-Bayona R",
				"Cejalvo J M",
				"G\u00f3mez-L\u00f3pez G",
				"Fustero-Torre C",
				"Sabroso-Lasa S",
				"Malats N",
				"Martinez M",
				"Moreno A",
				"Megias D",
				"Malumbres M",
				"Colomer R",
				"Quintela-Fandino M"
			],
			"DOI": "10.1038/s41467-022-35065-z",
			"date": "2023-08-10",
			"PMC": "",
			"citation": "",
			"abstract": "Precision oncology research is challenging outside the contexts of oncogenic addiction and/or targeted therapies. We previously showed that phosphoproteomics is a powerful approach to reveal patient subsets of interest characterized by the activity of a few kinases where the underlying genomics is complex. Here, we conduct a phosphoproteomic screening of samples from HER2-negative female breast cancer receiving neoadjuvant paclitaxel (N\u2009=\u2009130), aiming to find candidate biomarkers of paclitaxel sensitivity. Filtering 11 candidate biomarkers through 2 independent patient sets (N\u2009=\u2009218) allowed the identification of a subgroup of patients characterized by high levels of CDK4 and filamin-A who had a 90% chance of achieving a pCR in response to paclitaxel. Mechanistically, CDK4 regulates filamin-A transcription, which in turn forms a complex with tubulin and CLIP-170, which elicits increased binding of paclitaxel to microtubules, microtubule acetylation and stabilization, and mitotic catastrophe. Thus, phosphoproteomics allows the identification of explainable factors for predicting response to paclitaxel.",
			"category": 2,
			"name": "Mouron S,2023"
		},
		{
			"PMID": 36476325,
			"title": "Therapy sculpts the complex interplay between cancer and the immune system during tumour evolution.",
			"journal": "Genome medicine",
			"authorList": [
				"Thol Kerstin",
				"Pawlik Piotr",
				"McGranahan Nicholas"
			],
			"DOI": "10.1186/s13073-022-01138-3",
			"date": "2022-12-15",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer development is an evolutionary process. A key selection pressure is exerted by therapy, one of the few players in cancer evolution that can be controlled. As such, an understanding of how treatment acts to sculpt the tumour and its microenvironment and how this influences a tumour's subsequent evolutionary trajectory is critical. In this review, we examine cancer evolution and intra-tumour heterogeneity in the context of therapy. We focus on how radiotherapy, chemotherapy and immunotherapy shape both tumour development and the environment in which tumours evolve and how resistance can develop or be selected for during treatment.",
			"category": 2,
			"name": "Thol Kerstin,2022"
		},
		{
			"PMID": 36474143,
			"title": "Identification of multiplicatively acting modulatory mutational signatures in cancer.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"Ki\u010diatovas Dovydas",
				"Guo Qingli",
				"Kailas Miika",
				"Pesonen Henri",
				"Corander Jukka",
				"Kaski Samuel",
				"Pitk\u00e4nen Esa",
				"Mustonen Ville"
			],
			"DOI": "10.1186/s12859-022-05060-8",
			"date": "2022-12-15",
			"PMC": "",
			"citation": "",
			"abstract": "A deep understanding of carcinogenesis at the DNA level underpins many advances in cancer prevention and treatment. Mutational signatures provide a breakthrough conceptualisation, as well as an analysis framework, that can be used to build such understanding. They capture somatic mutation patterns and at best identify their causes. Most studies in this context have focused on an inherently additive analysis, e.g. by non-negative matrix factorization, where the mutations within a cancer sample are explained by a linear combination of independent mutational signatures. However, other recent studies show that the mutational signatures exhibit non-additive interactions.",
			"category": 2,
			"name": "Ki\u010diatovas Dovydas,2022"
		},
		{
			"PMID": 36469540,
			"title": "ToMExO: A probabilistic tree-structured model for cancer progression.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Mohaghegh Neyshabouri Mohammadreza",
				"Lagergren Jens"
			],
			"DOI": "10.1371/journal.pcbi.1010732",
			"date": "2022-12-19",
			"PMC": "",
			"citation": "",
			"abstract": "Identifying the interrelations among cancer driver genes and the patterns in which the driver genes get mutated is critical for understanding cancer. In this paper, we study cross-sectional data from cohorts of tumors to identify the cancer-type (or subtype) specific process in which the cancer driver genes accumulate critical mutations. We model this mutation accumulation process using a tree, where each node includes a driver gene or a set of driver genes. A mutation in each node enables its children to have a chance of mutating. This model simultaneously explains the mutual exclusivity patterns observed in mutations in specific cancer genes (by its nodes) and the temporal order of events (by its edges). We introduce a computationally efficient dynamic programming procedure for calculating the likelihood of our noisy datasets and use it to build our Markov Chain Monte Carlo (MCMC) inference algorithm, ToMExO. Together with a set of engineered MCMC moves, our fast likelihood calculations enable us to work with datasets with hundreds of genes and thousands of tumors, which cannot be dealt with using available cancer progression analysis methods. We demonstrate our method's performance on several synthetic datasets covering various scenarios for cancer progression dynamics. Then, a comparison against two state-of-the-art methods on a moderate-size biological dataset shows the merits of our algorithm in identifying significant and valid patterns. Finally, we present our analyses of several large biological datasets, including colorectal cancer, glioblastoma, and pancreatic cancer. In all the analyses, we validate the results using a set of method-independent metrics testing the causality and significance of the relations identified by ToMExO or competing methods.",
			"category": 2,
			"name": "Mohaghegh Neyshabouri Mohammadreza,2022"
		},
		{
			"PMID": 36469539,
			"title": "Regional mutational signature activities in cancer genomes.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Timmons Caitlin",
				"Morris Quaid",
				"Harrigan Caitlin F"
			],
			"DOI": "10.1371/journal.pcbi.1010733",
			"date": "2022-12-19",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer genomes harbor a catalog of somatic mutations. The type and genomic context of these mutations depend on their causes and allow their attribution to particular mutational signatures. Previous work has shown that mutational signature activities change over the course of tumor development, but investigations of genomic region variability in mutational signatures have been limited. Here, we expand upon this work by constructing regional profiles of mutational signature activities over 2,203 whole genomes across 25 tumor types, using data aggregated by the Pan-Cancer Analysis of Whole Genomes (PCAWG) consortium. We present GenomeTrackSig as an extension to the TrackSig R package to construct regional signature profiles using optimal segmentation and the expectation-maximization (EM) algorithm. We find that 426 genomes from 20 tumor types display at least one change in mutational signature activities (changepoint), and 306 genomes contain at least one of 54 recurrent changepoints shared by seven or more genomes of the same tumor type. Five recurrent changepoint locations are shared by multiple tumor types. Within these regions, the particular signature changes are often consistent across samples of the same type and some, but not all, are characterized by signatures associated with subclonal expansion. The changepoints we found cannot strictly be explained by gene density, mutation density, or cell-of-origin chromatin state. We hypothesize that they reflect a confluence of factors including evolutionary timing of mutational processes, regional differences in somatic mutation rate, large-scale changes in chromatin state that may be tissue type-specific, and changes in chromatin accessibility during subclonal expansion. These results provide insight into the regional effects of DNA damage and repair processes, and may help us localize genomic and epigenomic changes that occur during cancer development.",
			"category": 2,
			"name": "Timmons Caitlin,2022"
		},
		{
			"PMID": 36406672,
			"title": "Occurrence and risk assessment of fullerene colloidal nanoparticles by ultrasonic-assisted dispersive liquid-liquid extraction and high-performance liquid chromatography in surface waters.",
			"journal": "Heliyon",
			"authorList": [
				"Hendricks Nokwanda",
				"Olatunji Olatunde S",
				"Gumbi Bhekumuzi P"
			],
			"DOI": "10.1016/j.heliyon.2022.e11454",
			"date": "2022-11-22",
			"PMC": "",
			"citation": "",
			"abstract": "This paper presents a developed analytical technique for risk assessment of colloidal fullerene in surface waters by ultrasonic-assisted dispersive liquid-liquid extraction (UADLLE) and high-performance liquid chromatography ultraviolet-visible detector (HPLC-UV). Fullerene colloidal nanoparticles were synthesised and characterized by high-resolution transmission electron microscopy (HRTEM) and ultraviolet-visible spectroscopy (UV-Vis). Ultrasonication step, disperser solvent, and sodium chloride salt enhance the surface area of fullerene derivative aggregates for better contact and lowers the solubility of fullerene derivative to the aqueous solution, respectively promoting mass transfer of fullerene from aqueous into the organic phase. Several extraction parameters were optimized, and the optimal conditions were established: 5 mL toluene as extraction solvent (2 cycles); 200 mL water sample; 1% sodium chloride salt; 15 min ultrasonication, and 400 \u03bcL methanol as disperser solvent. The mean absolute recoveries established in drinking water, wastewater, and river water were 117%, 103%, and 93%, respectively. The proposed analytical technique was linear in the ranges between 0.25 \u03bcg L",
			"category": 2,
			"name": "Hendricks Nokwanda,2022"
		},
		{
			"PMID": 36352222,
			"title": "Spatial genomics maps the structure, nature and evolution of cancer clones.",
			"journal": "Nature",
			"authorList": [
				"Lomakin Artem",
				"Svedlund Jessica",
				"Strell Carina",
				"Gataric Milana",
				"Shmatko Artem",
				"Rukhovich Gleb",
				"Park Jun Sung",
				"Ju Young Seok",
				"Dentro Stefan",
				"Kleshchevnikov Vitalii",
				"Vaskivskyi Vasyl",
				"Li Tong",
				"Bayraktar Omer Ali",
				"Pinder Sarah",
				"Richardson Andrea L",
				"Santagata Sandro",
				"Campbell Peter J",
				"Russnes Hege",
				"Gerstung Moritz",
				"Nilsson Mats",
				"Yates Lucy R"
			],
			"DOI": "10.1038/s41586-022-05425-2",
			"date": "2022-11-29",
			"PMC": "",
			"citation": "",
			"abstract": "Genome sequencing of cancers often reveals mosaics of different subclones present in the same tumour",
			"category": 2,
			"name": "Lomakin Artem,2022"
		},
		{
			"PMID": 36332058,
			"title": "Waldenstr\u00f6m macroglobulinemia whole genome reveals prolonged germinal center activity and late copy number aberrations.",
			"journal": "Blood advances",
			"authorList": [
				"Maclachlan Kylee H",
				"Bagratuni Tina",
				"Kastritis Efstathios",
				"Ziccheddu Bachisio",
				"Lu Sydney",
				"Yellapantula Venkata",
				"Famulare Chris",
				"Argyropoulos Kimon",
				"Derkach Andriy",
				"Papaemmanuil Elli",
				"Dogan Ahmet",
				"Lesokhin Alexander",
				"Usmani Saad Z",
				"Landgren C Ola",
				"Palomba Lia M",
				"Maura Francesco",
				"Dimopoulos Meletios A"
			],
			"DOI": "10.1182/bloodadvances.2022008876",
			"date": "2023-03-21",
			"PMC": "",
			"citation": "",
			"abstract": "The genomic landscape of Waldenstr\u00f6m macroglobulinemia (WM) is characterized by somatic mutations in MYD88, present from the precursor stages. Using the comprehensive resolution of whole genome sequencing (WGS) in 14 CD19-selected primary WM samples; comparing clonal and subclonal mutations revealed that germinal center (GC) mutational signatures SBS9 (poly-eta) and SBS84 (AID) have sustained activity, suggesting that the interaction between WM and the GC continues over time. Expanding our cohort size with 33 targeted sequencing samples, we interrogated the WM copy number aberration (CNA) landscape and chronology. Of interest, CNA prevalence progressively increased in symptomatic WM and relapsed disease when compared with stable precursor stages, with stable precursors lacking genomic complexity. Two MYD88 wild-type WGS contained a clonal gain affecting chromosome 12, which is typically an early event in chronic lymphocytic leukemia. Molecular time analysis demonstrated that both chromosomal 12 gain events occurred early in cancer development whereas other CNA changes tend to occur later in the disease course and are often subclonal. In summary, WGS analysis in WM allows the demonstration of sustained GC activity over time and allows the reconstruction of the temporal evolution of specific genomic features. In addition, our data suggest that, although MYD88-mutations are central to WM clone establishment and can be observed in precursor disease, CNA may contribute to later phases, and may be used as a biomarker for progression risk from precursor conditions to symptomatic disease.",
			"category": 2,
			"name": "Maclachlan Kylee H,2023"
		},
		{
			"PMID": 36331987,
			"title": "Inferring parameters of cancer evolution in chronic lymphocytic leukemia.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Lee Nathan D",
				"Bozic Ivana"
			],
			"DOI": "10.1371/journal.pcbi.1010677",
			"date": "2022-11-18",
			"PMC": "",
			"citation": "",
			"abstract": "As a cancer develops, its cells accrue new mutations, resulting in a heterogeneous, complex genomic profile. We make use of this heterogeneity to derive simple, analytic estimates of parameters driving carcinogenesis and reconstruct the timeline of selective events following initiation of an individual cancer, where two longitudinal samples are available for sequencing. Using stochastic computer simulations of cancer growth, we show that we can accurately estimate mutation rate, time before and after a driver event occurred, and growth rates of both initiated cancer cells and subsequently appearing subclones. We demonstrate that in order to obtain accurate estimates of mutation rate and timing of events, observed mutation counts should be corrected to account for clonal mutations that occurred after the founding of the tumor, as well as sequencing coverage. Chronic lymphocytic leukemia (CLL), which often does not require treatment for years after diagnosis, presents an optimal system to study the untreated, natural evolution of cancer cell populations. When we apply our methodology to reconstruct the individual evolutionary histories of CLL patients, we find that the parental leukemic clone typically appears within the first fifteen years of life.",
			"category": 2,
			"name": "Lee Nathan D,2022"
		},
		{
			"PMID": 36291621,
			"title": "Searching for the Metabolic Signature of Cancer: A Review from Warburg's Time to Now.",
			"journal": "Biomolecules",
			"authorList": [
				"Jacquet Pierre",
				"St\u00e9phanou Ang\u00e9lique"
			],
			"DOI": "10.3390/biom12101412",
			"date": "2022-10-28",
			"PMC": "",
			"citation": "",
			"abstract": "This review focuses on the evolving understanding that we have of tumor cell metabolism, particularly glycolytic and oxidative metabolism, and traces back its evolution through time. This understanding has developed since the pioneering work of Otto Warburg, but the understanding of tumor cell metabolism continues to be hampered by misinterpretation of his work. This has contributed to the use of the new concepts of ",
			"category": 2,
			"name": "Jacquet Pierre,2022"
		},
		{
			"PMID": 36291592,
			"title": "Mutational Signatures as Sensors of Environmental Exposures: Analysis of Smoking-Induced Lung Tissue Remodeling.",
			"journal": "Biomolecules",
			"authorList": [
				"Kim Yoo-Ah",
				"Hodzic Ermin",
				"Amgalan Bayarbaatar",
				"Saslafsky Ariella",
				"Wojtowicz Damian",
				"Przytycka Teresa M"
			],
			"DOI": "10.3390/biom12101384",
			"date": "2022-10-28",
			"PMC": "",
			"citation": "",
			"abstract": "Smoking is a widely recognized risk factor in the emergence of cancers and other lung diseases. Studies of non-cancer lung diseases typically investigate the role that smoking has in chronic changes in lungs that might predispose patients to the diseases, whereas most cancer studies focus on the mutagenic properties of smoking. Large-scale cancer analysis efforts have collected expression data from both tumor and control lung tissues, and studies have used control samples to estimate the impact of smoking on gene expression. However, such analyses may be confounded by tumor-related micro-environments as well as patient-specific exposure to smoking. Thus, in this paper, we explore the utilization of mutational signatures to study environment-induced changes of gene expression in control lung tissues from lung adenocarcinoma samples. We show that a joint computational analysis of mutational signatures derived from sequenced tumor samples, and the gene expression obtained from control samples, can shed light on the combined impact that smoking and tumor-related micro-environments have on gene expression and cell-type composition in non-neoplastic (control) lung tissue. The results obtained through such analysis are both supported by experimental studies, including studies utilizing single-cell technology, and also suggest additional novel insights. We argue that the study provides a proof of principle of the utility of mutational signatures to be used as sensors of environmental exposures not only in the context of the mutational landscape of cancer, but also as a reference for changes in non-cancer lung tissues. It also provides an example of how a database collected with the purpose of understanding cancer can provide valuable information for studies not directly related to the disease.",
			"category": 2,
			"name": "Kim Yoo-Ah,2022"
		},
		{
			"PMID": 36286845,
			"title": "Common Germline Risk Variants Impact Somatic Alterations and Clinical Features across Cancers.",
			"journal": "Cancer research",
			"authorList": [
				"Namba Shinichi",
				"Saito Yuki",
				"Kogure Yasunori",
				"Masuda Tatsuo",
				"Bondy Melissa L",
				"Gharahkhani Puya",
				"Gockel Ines",
				"Heider Dominik",
				"Hillmer Axel",
				"Jankowski Janusz",
				"MacGregor Stuart",
				"Maj Carlo",
				"Melin Beatrice",
				"Ostrom Quinn T",
				"Palles Claire",
				"Schumacher Johannes",
				"Tomlinson Ian",
				"Whiteman David C",
				"Okada Yukinori",
				"Kataoka Keisuke"
			],
			"DOI": "10.1158/0008-5472.CAN-22-1492",
			"date": "2023-01-05",
			"PMC": "",
			"citation": "",
			"abstract": "Aggregation of genome-wide common risk variants, such as polygenic risk score (PRS), can measure genetic susceptibility to cancer. A better understanding of how common germline variants associate with somatic alterations and clinical features could facilitate personalized cancer prevention and early detection. We constructed PRSs from 14 genome-wide association studies (median n = 64,905) for 12 cancer types by multiple methods and calibrated them using the UK Biobank resources (n = 335,048). Meta-analyses across cancer types in The Cancer Genome Atlas (n = 7,965) revealed that higher PRS values were associated with earlier cancer onset and lower burden of somatic alterations, including total mutations, chromosome/arm somatic copy-number alterations (SCNA), and focal SCNAs. This contrasts with rare germline pathogenic variants (e.g., BRCA1/2 variants), showing heterogeneous associations with somatic alterations. Our results suggest that common germline cancer risk variants allow early tumor development before the accumulation of many somatic alterations characteristic of later stages of carcinogenesis.",
			"category": 2,
			"name": "Namba Shinichi,2023"
		},
		{
			"PMID": 36280735,
			"title": "Addressing the benefits of inhibiting APOBEC3-dependent mutagenesis in cancer.",
			"journal": "Nature genetics",
			"authorList": [
				"Petljak Mia",
				"Green Abby M",
				"Maciejowski John",
				"Weitzman Matthew D"
			],
			"DOI": "10.1038/s41588-022-01196-8",
			"date": "2022-11-14",
			"PMC": "",
			"citation": "",
			"abstract": "Mutational signatures associated with apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC)3 cytosine deaminase activity have been found in over half of cancer types, including some therapy-resistant and metastatic tumors. Driver mutations can occur in APOBEC3-favored sequence contexts, suggesting that mutagenesis by APOBEC3 enzymes may drive cancer evolution. The APOBEC3-mediated signatures are often detected in subclonal branches of tumor phylogenies and are acquired in cancer cell lines over long periods of time, indicating that APOBEC3 mutagenesis can be ongoing in cancer. Collectively, these and other observations have led to the proposal that APOBEC3 mutagenesis represents a disease-modifying process that could be inhibited to limit tumor heterogeneity, metastasis and drug resistance. However, critical aspects of APOBEC3 biology in cancer and in healthy tissues have not been clearly defined, limiting well-grounded predictions regarding the benefits of inhibiting APOBEC3 mutagenesis in different settings in cancer. We discuss the relevant mechanistic gaps and strategies to address them to investigate whether inhibiting APOBEC3 mutagenesis may confer clinical benefits in cancer.",
			"category": 2,
			"name": "Petljak Mia,2022"
		},
		{
			"PMID": 36233691,
			"title": "Urinary Comprehensive Genomic Profiling Correlates Urothelial Carcinoma Mutations with Clinical Risk and Efficacy of Intervention.",
			"journal": "Journal of clinical medicine",
			"authorList": [
				"Bicocca Vincent T",
				"Phillips Kevin G",
				"Fischer Daniel S",
				"Caruso Vincent M",
				"Goudarzi Mahdi",
				"Garcia-Ransom Monica",
				"Lentz Peter S",
				"MacBride Andrew R",
				"Jensen Brad W",
				"Mazzarella Brian C",
				"Koppie Theresa",
				"Korkola James E",
				"Gray Joe W",
				"Levin Trevor G"
			],
			"DOI": "10.3390/jcm11195827",
			"date": "2022-10-19",
			"PMC": "",
			"citation": "",
			"abstract": "The clinical standard of care for urothelial carcinoma (UC) relies on invasive procedures with suboptimal performance. To enhance UC treatment, we developed a urinary comprehensive genomic profiling (uCGP) test, UroAmplitude, that measures mutations from tumor DNA present in urine. In this study, we performed a blinded, prospective validation of technical sensitivity and positive predictive value (PPV) using reference standards, and found at 1% allele frequency, mutation detection performs at 97.4% sensitivity and 80.4% PPV. We then prospectively compared the mutation profiles of urine-extracted DNA to those of matched tumor tissue to validate clinical performance. Here, we found tumor single-nucleotide variants were observed in the urine with a median concordance of 91.7% and uCGP revealed distinct patterns of genomic lesions enriched in low- and high-grade disease. Finally, we retrospectively explored longitudinal case studies to quantify residual disease following bladder-sparing treatments, and found uCGP detected residual disease in patients receiving bladder-sparing treatment and predicted recurrence and disease progression. These findings demonstrate the potential of the UroAmplitude platform to reliably identify and track mutations associated with UC at each stage of disease: diagnosis, treatment, and surveillance. Multiple case studies demonstrate utility for patient risk classification to guide both surgical and therapeutic interventions.",
			"category": 2,
			"name": "Bicocca Vincent T,2022"
		},
		{
			"PMID": 36227997,
			"title": "Cellular barcoding to decipher clonal dynamics in disease.",
			"journal": "Science (New York, N.Y.)",
			"authorList": [
				"Sankaran Vijay G",
				"Weissman Jonathan S",
				"Zon Leonard I"
			],
			"DOI": "10.1126/science.abm5874",
			"date": "2022-10-21",
			"PMC": "",
			"citation": "",
			"abstract": "Cellular barcodes are distinct DNA sequences that enable one to track specific cells across time or space. Recent advances in our ability to detect natural or synthetic cellular barcodes, paired with single-cell readouts of cell state, have markedly increased our knowledge of clonal dynamics and genealogies of the cells that compose a variety of tissues and organs. These advances hold promise to redefine our view of human disease. Here, we provide an overview of cellular barcoding approaches, discuss applications to gain new insights into disease mechanisms, and provide an outlook on future applications. We discuss unanticipated insights gained through barcoding in studies of cancer and blood cell production and describe how barcoding can be applied to a growing array of medical fields, particularly with the increasing recognition of clonal contributions in human diseases.",
			"category": 2,
			"name": "Sankaran Vijay G,2022"
		},
		{
			"PMID": 36198671,
			"title": "Single-cell dissection of remodeled inflammatory ecosystem in primary and metastatic gallbladder carcinoma.",
			"journal": "Cell discovery",
			"authorList": [
				"Wang Xiang",
				"Liu Chunliang",
				"Chen Jianan",
				"Chen Lei",
				"Ren Xianwen",
				"Hou Minghui",
				"Cui Xiuliang",
				"Jiang Youhai",
				"Liu Erdong",
				"Zong Yali",
				"Duan Anqi",
				"Fu Xiaohui",
				"Yu Wenlong",
				"Zhao Xiaofang",
				"Yang Zhao",
				"Zhang Yongjie",
				"Fu Jing",
				"Wang Hongyang"
			],
			"DOI": "10.1038/s41421-022-00445-8",
			"date": "2022-10-09",
			"PMC": "",
			"citation": "",
			"abstract": "Gallbladder carcinoma (GBC) is the most common biliary tract malignancy with the lowest survival rate, primarily arising from chronic inflammation. To better characterize the progression from inflammation to cancer to metastasis, we performed single-cell RNA sequencing across samples of 6 chronic cholecystitis, 12 treatment-naive GBCs, and 6 matched metastases. Benign epithelial cells from inflamed gallbladders displayed resting, immune-regulating, and gastrointestinal metaplastic phenotypes. A small amount of PLA2G2A",
			"category": 2,
			"name": "Wang Xiang,2022"
		},
		{
			"PMID": 36186123,
			"title": "UPP1 Promotes Lung Adenocarcinoma Progression through Epigenetic Regulation of Glycolysis.",
			"journal": "Aging and disease",
			"authorList": [
				"Wang Xuan",
				"Wang Zheng",
				"Huang Renhong",
				"Lu Zhouyi",
				"Chen Xiaofeng",
				"Huang Dayu"
			],
			"DOI": "10.14336/AD.2022.0218",
			"date": "2022-10-04",
			"PMC": "",
			"citation": "",
			"abstract": "Uridine phosphorylase 1 (UPP1) is a dimeric enzyme that plays an indispensable role in pyrimidine salvage as well as uridine homeostasis and is upregulated in various cancers, including LUAD. However, the function and underlying mechanisms of UPP1 in mediating LUAD cell progression are still largely unknown. Single-cell RNA transcription analysis was applied to compare the expression of UPP1 in tumor tissues and adjacent tissue. In vitro gain- and loss-of-function experiments with LUAD cells were performed to elucidate the functions of UPP1. Western blotting, qRT-PCR, cell apoptosis, IHC staining, Seahorse XF24 Extracellular Flux analysis, chromatin immunoprecipitation (ChIP) assay, and bioinformatics analysis were performed to reveal the underlying mechanisms. In this study, UPP1 was found to be the top metabolism-related gene that was upregulated by single-cell transcriptomic profiling of LUAD. Next, we confirmed that UPP1 was highly expressed in LUAD tissues and cell lines and was correlated with poor overall survival in LUAD patients. UPP1 drove glycolytic metabolism and significantly regulated the sensitivity of tumors to glycolytic inhibitors in vitro and in vivo. UPP1 is subject to epigenetic regulation through histone acetylation. The CBP/p300 inhibitor SGC-CBP30 reduced the protein levels of UPP1, H3K27ac, and H3K9ac. ChIP assays revealed that acetyl-histone H3 and RNA polymerase II bind to the UPP1 promoter. UPP1 overexpression restored lactic acid production and glucose uptake compared to the SGC-CBP30 group. Our findings confirm UPP1 as a novel oncogene in LUAD, thus providing a potential novel diagnostic and therapeutic target for LUAD.",
			"category": 2,
			"name": "Wang Xuan,2022"
		},
		{
			"PMID": 36163358,
			"title": "Modeling tissue-specific breakpoint proximity of structural variations from whole-genomes to identify cancer drivers.",
			"journal": "Nature communications",
			"authorList": [
				"Martinez-Fundichely Alexander",
				"Dixon Austin",
				"Khurana Ekta"
			],
			"DOI": "10.1038/s41467-022-32945-2",
			"date": "2022-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Structural variations (SVs) in cancer cells often impact large genomic regions with functional consequences. However, identification of SVs under positive selection is a challenging task because little is known about the genomic features related to the background breakpoint distribution in different cancers. We report a method that uses a generalized additive model to investigate the breakpoint proximity curves from 2,382 whole-genomes of 32 cancer types. We find that a multivariate model, which includes linear and nonlinear partial contributions of various tissue-specific features and their interaction terms, can explain up to 57% of the observed deviance of breakpoint proximity. In particular, three-dimensional genomic features such as topologically associating domains (TADs), TAD-boundaries and their interaction with other features show significant contributions. The model is validated by identification of known cancer genes and revealed putative drivers in cancers different than those with previous evidence of positive selection.",
			"category": 2,
			"name": "Martinez-Fundichely Alexander,2022"
		},
		{
			"PMID": 36139658,
			"title": "Targeting Mutant p53 for Cancer Treatment: Moving Closer to Clinical Use?",
			"journal": "Cancers",
			"authorList": [
				"Duffy Michael J",
				"Tang Minhong",
				"Rajaram Subhasree",
				"O'Grady Shane",
				"Crown John"
			],
			"DOI": "10.3390/cancers14184499",
			"date": "2023-04-26",
			"PMC": "",
			"citation": "",
			"abstract": "Mutant p53 is one of the most attractive targets for new anti-cancer drugs. Although traditionally regarded as difficult to drug, several new strategies have recently become available for targeting the mutant protein. One of the most promising of these involves the use of low molecular weight compounds that promote refolding and reactivation of mutant p53 to its wild-type form. Several such reactivating drugs are currently undergoing evaluation in clinical trials, including eprenetapopt (APR-246), COTI-2, arsenic trioxide and PC14586. Of these, the most clinically advanced for targeting mutant p53 is eprenetapopt which has completed phase I, II and III clinical trials, the latter in patients with mutant ",
			"category": 2,
			"name": "Duffy Michael J,2023"
		},
		{
			"PMID": 36139626,
			"title": "Unraveling the Structural Variations of Early-Stage Mycosis Fungoides-CD3 Based Purification and Third Generation Sequencing as Novel Tools for the Genomic Landscape in CTCL.",
			"journal": "Cancers",
			"authorList": [
				"Hain Carsten",
				"Stadler Rudolf",
				"Kalinowski J\u00f6rn"
			],
			"DOI": "10.3390/cancers14184466",
			"date": "2022-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL). At present, knowledge of genetic changes in early-stage MF is insufficient. Additionally, low tumor cell fraction renders calling of copy-number variations as the predominant mutations in MF challenging, thereby impeding further investigations. We show that enrichment of T cells from a biopsy of a stage I MF patient greatly increases tumor fraction. This improvement enables accurate calling of recurrent MF copy-number variants such as ",
			"category": 2,
			"name": "Hain Carsten,2022"
		},
		{
			"PMID": 36122307,
			"title": "Natural Coevolution of Tumor and Immunoenvironment in Glioblastoma.",
			"journal": "Cancer discovery",
			"authorList": [
				"Wu Lingxiang",
				"Wu Wei",
				"Zhang Junxia",
				"Zhao Zheng",
				"Li Liangyu",
				"Zhu Mengyan",
				"Wu Min",
				"Wu Fan",
				"Zhou Fengqi",
				"Du Yuxin",
				"Chai Rui-Chao",
				"Zhang Wei",
				"Qiu Xiaoguang",
				"Liu Quanzhong",
				"Wang Ziyu",
				"Li Jie",
				"Li Kening",
				"Chen Apeng",
				"Jiang Yinan",
				"Xiao Xiangwei",
				"Zou Han",
				"Srivastava Rashmi",
				"Zhang Tingting",
				"Cai Yun",
				"Liang Yuan",
				"Huang Bin",
				"Zhang Ruohan",
				"Lin Fan",
				"Hu Lang",
				"Wang Xiuxing",
				"Qian Xu",
				"Lv Sali",
				"Hu Baoli",
				"Zheng Siyuan",
				"Hu Zhibin",
				"Shen Hongbing",
				"You Yongping",
				"Verhaak Roel G W",
				"Jiang Tao",
				"Wang Qianghu"
			],
			"DOI": "10.1158/2159-8290.CD-22-0196",
			"date": "2022-12-05",
			"PMC": "",
			"citation": "",
			"abstract": "Isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) has a dismal prognosis. A better understanding of tumor evolution holds the key to developing more effective treatment. Here we study GBM's natural evolutionary trajectory by using rare multifocal samples. We sequenced 61,062 single cells from eight multifocal IDH wild-type primary GBMs and defined a natural evolution signature (NES) of the tumor. We show that the NES significantly associates with the activation of transcription factors that regulate brain development, including MYBL2 and FOSL2. Hypoxia is involved in inducing NES transition potentially via activation of the HIF1A-FOSL2 axis. High-NES tumor cells could recruit and polarize bone marrow-derived macrophages through activation of the FOSL2-ANXA1-FPR1/3 axis. These polarized macrophages can efficiently suppress T-cell activity and accelerate NES transition in tumor cells. Moreover, the polarized macrophages could upregulate CCL2 to induce tumor cell migration.",
			"category": 2,
			"name": "Wu Lingxiang,2022"
		},
		{
			"PMID": 36098958,
			"title": "Comparative Genomics Provides Etiologic and Biological Insight into Melanoma Subtypes.",
			"journal": "Cancer discovery",
			"authorList": [
				"Newell Felicity",
				"Johansson Peter A",
				"Wilmott James S",
				"Nones Katia",
				"Lakis Vanessa",
				"Pritchard Antonia L",
				"Lo Serigne N",
				"Rawson Robert V",
				"Kazakoff Stephen H",
				"Colebatch Andrew J",
				"Koufariotis Lambros T",
				"Ferguson Peter M",
				"Wood Scott",
				"Leonard Conrad",
				"Law Matthew H",
				"Brooks Kelly M",
				"Broit Natasa",
				"Palmer Jane M",
				"Couts Kasey L",
				"Vergara Ismael A",
				"Long Georgina V",
				"Barbour Andrew P",
				"Nieweg Omgo E",
				"Shivalingam Brindha",
				"Robinson William A",
				"Stretch Jonathan R",
				"Spillane Andrew J",
				"Saw Robyn P M",
				"Shannon Kerwin F",
				"Thompson John F",
				"Mann Graham J",
				"Pearson John V",
				"Scolyer Richard A",
				"Waddell Nicola",
				"Hayward Nicholas K"
			],
			"DOI": "10.1158/2159-8290.CD-22-0603",
			"date": "2022-12-05",
			"PMC": "",
			"citation": "",
			"abstract": "Melanoma is a cancer of melanocytes, with multiple subtypes based on body site location. Cutaneous melanoma is associated with skin exposed to ultraviolet radiation; uveal melanoma occurs in the eyes; mucosal melanoma occurs in internal mucous membranes; and acral melanoma occurs on the palms, soles, and nail beds. Here, we present the largest whole-genome sequencing study of melanoma to date, with 570 tumors profiled, as well as methylation and RNA sequencing for subsets of tumors. Uveal melanoma is genomically distinct from other melanoma subtypes, harboring the lowest tumor mutation burden and with significantly mutated genes in the G-protein signaling pathway. Most cutaneous, acral, and mucosal melanomas share alterations in components of the MAPK, PI3K, p53, p16, and telomere pathways. However, the mechanism by which these pathways are activated or inactivated varies between melanoma subtypes. Additionally, we identify potential novel germline predisposition genes for some of the less common melanoma subtypes.",
			"category": 2,
			"name": "Newell Felicity,2022"
		},
		{
			"PMID": 36097176,
			"title": "A mechanistic mathematical model of initiation and malignant transformation in sporadic vestibular schwannoma.",
			"journal": "British journal of cancer",
			"authorList": [
				"Paterson Chay",
				"Bozic Ivana",
				"Smith Miriam J",
				"Hoad Xanthe",
				"Evans D Gareth R"
			],
			"DOI": "10.1038/s41416-022-01955-8",
			"date": "2022-11-10",
			"PMC": "",
			"citation": "",
			"abstract": "A vestibular schwannoma (VS) is a relatively rare, benign tumour of the eighth cranial nerve, often involving alterations to the gene NF2. Previous mathematical models of schwannoma incidence have not attempted to account for alterations in specific genes, and could not distinguish between nonsense mutations and loss of heterozygosity (LOH).",
			"category": 2,
			"name": "Paterson Chay,2022"
		},
		{
			"PMID": 36089134,
			"title": "APOBEC mutagenesis, kataegis, chromothripsis in EGFR-mutant osimertinib-resistant lung adenocarcinomas.",
			"journal": "Annals of oncology : official journal of the European Society for Medical Oncology",
			"authorList": [
				"Selenica P",
				"Marra A",
				"Choudhury N J",
				"Gazzo A",
				"Falcon C J",
				"Patel J",
				"Pei X",
				"Zhu Y",
				"Ng C K Y",
				"Curry M",
				"Heller G",
				"Zhang Y-K",
				"Berger M F",
				"Ladanyi M",
				"Rudin C M",
				"Chandarlapaty S",
				"Lovly C M",
				"Reis-Filho J S",
				"Yu H A"
			],
			"DOI": "10.1016/j.annonc.2022.09.151",
			"date": "2022-12-05",
			"PMC": "",
			"citation": "",
			"abstract": "Studies of targeted therapy resistance in lung cancer have primarily focused on single-gene alterations. Based on prior work implicating apolipoprotein b mRNA-editing enzyme, catalytic polypeptide-like (APOBEC) mutagenesis in histological transformation of epidermal growth factor receptor (EGFR)-mutant lung cancers, we hypothesized that mutational signature analysis may help elucidate acquired resistance to targeted therapies.",
			"category": 2,
			"name": "Selenica P,2022"
		},
		{
			"PMID": 36045292,
			"title": "African-specific molecular taxonomy of prostate cancer.",
			"journal": "Nature",
			"authorList": [
				"Jaratlerdsiri Weerachai",
				"Jiang Jue",
				"Gong Tingting",
				"Patrick Sean M",
				"Willet Cali",
				"Chew Tracy",
				"Lyons Ruth J",
				"Haynes Anne-Maree",
				"Pasqualim Gabriela",
				"Louw Melanie",
				"Kench James G",
				"Campbell Raymond",
				"Horvath Lisa G",
				"Chan Eva K F",
				"Wedge David C",
				"Sadsad Rosemarie",
				"Brum Ilma Simoni",
				"Mutambirwa Shingai B A",
				"Stricker Phillip D",
				"Bornman M S Riana",
				"Hayes Vanessa M"
			],
			"DOI": "10.1038/s41586-022-05154-6",
			"date": "2022-09-19",
			"PMC": "",
			"citation": "",
			"abstract": "Prostate cancer is characterized by considerable geo-ethnic disparity. African ancestry is a significant risk factor, with mortality rates across sub-Saharan Africa of 2.7-fold higher than global averages",
			"category": 2,
			"name": "Jaratlerdsiri Weerachai,2022"
		},
		{
			"PMID": 36012671,
			"title": "Implications of Polyploidy and Ploidy Alterations in Hepatocytes in Liver Injuries and Cancers.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Matsumoto Tomonori"
			],
			"DOI": "10.3390/ijms23169409",
			"date": "2022-08-29",
			"PMC": "",
			"citation": "",
			"abstract": "Polyploidy, a condition in which more than two sets of chromosomes are present in a cell, is a characteristic feature of hepatocytes. A significant number of hepatocytes physiologically undergo polyploidization at a young age. Polyploidization of hepatocytes is enhanced with age and in a diseased liver. It is worth noting that polyploid hepatocytes can proliferate, in marked contrast to other types of polyploid cells, such as megakaryocytes and cardiac myocytes. Polyploid hepatocytes divide to maintain normal liver homeostasis and play a role in the regeneration of the damaged liver. Furthermore, polyploid hepatocytes have been shown to dynamically reduce ploidy during liver regeneration. Although it is still unclear why hepatocytes undergo polyploidization, accumulating evidence has revealed that alterations in the ploidy in hepatocytes are involved in the pathophysiology of liver cirrhosis and carcinogenesis. This review discusses the significance of hepatocyte ploidy in physiological liver function, liver injury, and liver cancer.",
			"category": 2,
			"name": "Matsumoto Tomonori,2022"
		},
		{
			"PMID": 35993362,
			"title": "Inactivation of Hippo pathway characterizes a poor-prognosis subtype of esophageal cancer.",
			"journal": "JCI insight",
			"authorList": [
				"Mai Zihang",
				"Yuan Jianye",
				"Yang Hong",
				"Fang Shuogui",
				"Xie Xiuying",
				"Wang Xinye",
				"Xie Jiaxin",
				"Wen Jing",
				"Fu Jianhua"
			],
			"DOI": "10.1172/jci.insight.155218",
			"date": "2022-08-23",
			"PMC": "",
			"citation": "",
			"abstract": "Identification of molecular subtypes that reflect different prognoses and treatment responses, especially immune checkpoint inhibitors (ICIs) in esophageal squamous cell carcinoma (ESCC), is essential for treatment decisions. We performed targeted sequencing in 201 patients with ESCC to discover genetic subtypes and validate our findings via multiple data sets. We identified 3 driver genes (FCGBP, GRIN2B, and FRY), and recurrent truncating mutations in FRY impaired its tumor-suppressive function and promoted tumor proliferation. A 3-gene mutation signature (FAT1, FAT3, and FRY) recognized a molecular subtype named \"FAT/FRY\" with frequent Hippo pathway-related mutations. In multiple ESCC cohorts, the patients with the FAT/FRY subtype had poorer prognosis than did patients in the WT group. Transcriptome analysis indicated that the FAT/FRY subtype was characterized by inactivation of the Hippo pathway, hypoxia, chemoresistance, higher infiltration of CD8+ T cells and activated DCs, and a transcriptome similar to that of cancer responders. Furthermore, the 3-gene signature predicted better survival for patients treated with ICIs, partially explained by its positive correlation with the tumor mutation burden and neoantigen burden. The 3-gene signature is a biomarker to recognize the FAT/FRY molecular subtype, evaluate prognosis, and select potential beneficiaries of ICIs in ESCC.",
			"category": 2,
			"name": "Mai Zihang,2022"
		},
		{
			"PMID": 35986254,
			"title": "SCONCE2: jointly inferring single cell copy number profiles and tumor evolutionary distances.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"Hui Sandra",
				"Nielsen Rasmus"
			],
			"DOI": "10.1186/s12859-022-04890-w",
			"date": "2022-08-23",
			"PMC": "",
			"citation": "",
			"abstract": "Single cell whole genome tumor sequencing can yield novel insights into the evolutionary history of somatic copy number alterations. Existing single cell copy number calling methods do not explicitly model the shared evolutionary process of multiple cells, and generally analyze cells independently. Additionally, existing methods for estimating tumor cell phylogenies using copy number profiles are sensitive to profile estimation errors.",
			"category": 2,
			"name": "Hui Sandra,2022"
		},
		{
			"PMID": 35978189,
			"title": "Ordered and deterministic cancer genome evolution after p53 loss.",
			"journal": "Nature",
			"authorList": [
				"Baslan Timour",
				"Morris John P",
				"Zhao Zhen",
				"Reyes Jose",
				"Ho Yu-Jui",
				"Tsanov Kaloyan M",
				"Bermeo Jonathan",
				"Tian Sha",
				"Zhang Sean",
				"Askan Gokce",
				"Yavas Aslihan",
				"Lecomte Nicolas",
				"Erakky Amanda",
				"Varghese Anna M",
				"Zhang Amy",
				"Kendall Jude",
				"Ghiban Elena",
				"Chorbadjiev Lubomir",
				"Wu Jie",
				"Dimitrova Nevenka",
				"Chadalavada Kalyani",
				"Nanjangud Gouri J",
				"Bandlamudi Chaitanya",
				"Gong Yixiao",
				"Donoghue Mark T A",
				"Socci Nicholas D",
				"Krasnitz Alex",
				"Notta Faiyaz",
				"Leach Steve D",
				"Iacobuzio-Donahue Christine A",
				"Lowe Scott W"
			],
			"DOI": "10.1038/s41586-022-05082-5",
			"date": "2022-08-26",
			"PMC": "",
			"citation": "",
			"abstract": "Although p53 inactivation promotes genomic instability",
			"category": 2,
			"name": "Baslan Timour,2022"
		},
		{
			"PMID": 35975562,
			"title": "The role of evolutionary game theory in spatial and non-spatial models of the survival of cooperation in cancer: a review.",
			"journal": "Journal of the Royal Society, Interface",
			"authorList": [
				"Coggan Helena",
				"Page Karen M"
			],
			"DOI": "10.1098/rsif.2022.0346",
			"date": "2022-08-18",
			"PMC": "",
			"citation": "",
			"abstract": "Evolutionary game theory (EGT) is a branch of mathematics which considers populations of individuals interacting with each other to receive pay-offs. An individual's pay-off is dependent on the strategy of its opponent(s) as well as on its own, and the higher its pay-off, the higher its reproductive fitness. Its offspring generally inherit its interaction strategy, subject to random mutation. Over time, the composition of the population shifts as different strategies spread or are driven extinct. In the last 25 years there has been a flood of interest in applying EGT to cancer modelling, with the aim of explaining how cancerous mutations spread through healthy tissue and how intercellular cooperation persists in tumour-cell populations. This review traces this body of work from theoretical analyses of well-mixed infinite populations through to more realistic spatial models of the development of cooperation between epithelial cells. We also consider work in which EGT has been used to make experimental predictions about the evolution of cancer, and discuss work that remains to be done before EGT can make large-scale contributions to clinical treatment and patient outcomes.",
			"category": 2,
			"name": "Coggan Helena,2022"
		},
		{
			"PMID": 35975235,
			"title": "Novel Driver Strength Index highlights important cancer genes in TCGA PanCanAtlas patients.",
			"journal": "PeerJ",
			"authorList": [
				"Belikov Aleksey V",
				"Vyatkin Alexey D",
				"Leonov Sergey V"
			],
			"DOI": "10.7717/peerj.13860",
			"date": "2023-01-17",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer driver genes are usually ranked by mutation frequency, which does not necessarily reflect their driver strength. We hypothesize that driver strength is higher for genes preferentially mutated in patients with few driver mutations overall, because these few mutations should be strong enough to initiate cancer.",
			"category": 2,
			"name": "Belikov Aleksey V,2023"
		},
		{
			"PMID": 35960311,
			"title": "[New insights into the pathogenesis and molecular understanding of cutaneous T-cell lymphomas].",
			"journal": "Dermatologie (Heidelberg, Germany)",
			"authorList": [
				"Stadler Rudolf",
				"Hain Carsten"
			],
			"DOI": "10.1007/s00105-022-05047-9",
			"date": "2022-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "The pathogenesis of cutaneous T\u2011cell lymphomas (CTCL) is still an enigma. Therefore, extensive translational research efforts have been undertaken in recent years to gain further clinical and molecular insights. There is increasing evidence that the different clinical appearance of the CTCL subtypes derives from the assumption that they develop from different skin subpopulations of T\u00a0cells. Detection and quantification of the malignant T\u2011cell clones is crucial for the diagnosis and prognosis of CTCL. Numerous recurrent mutant cellular signalling pathways have been found in recent years. This includes the JAK-STAT, NF\u03baB, T\u2011cell receptor and MAP kinase signalling pathways, as well as cell cycle control and epigenetics. The most recent analyses imply a\u00a0tumour evolution model with initial copy number variation, like amplification or deletions of specific DNA fragments (CNVs) and only subsequent later single nucleotide variations (SNVs). The crucial question, however, is which CNVs are sufficient to initiate general tumourigenesis? The challenge is to identify possible driver genes. Increasing molecular understanding in CTCL will include new breakthrough therapeutic options in the near future.",
			"category": 2,
			"name": "Stadler Rudolf,2022"
		},
		{
			"PMID": 35953722,
			"title": "The clonal evolution of Richter transformation cells uncovers therapeutic vulnerabilities.",
			"journal": "Nature medicine",
			"authorList": [],
			"DOI": "10.1038/s41591-022-01928-7",
			"date": "2022-08-22",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "PMID:35953722;title:The clonal evolution of Richter transformation cells uncovers therapeutic vulnerabilities.;journal:Nature medicine;DOI:10.1038/s41591-022-01928-7;date:2022-08-22;"
		},
		{
			"PMID": 35953718,
			"title": "Detection of early seeding of Richter transformation in chronic lymphocytic leukemia.",
			"journal": "Nature medicine",
			"authorList": [
				"Nadeu Ferran",
				"Royo Romina",
				"Massoni-Badosa Ramon",
				"Playa-Albinyana Heribert",
				"Garcia-Torre Beatriz",
				"Duran-Ferrer Mart\u00ed",
				"Dawson Kevin J",
				"Kulis Marta",
				"Diaz-Navarro Ander",
				"Villamor Neus",
				"Melero Juan L",
				"Chapaprieta Vicente",
				"Dueso-Barroso Ana",
				"Delgado Julio",
				"Moia Riccardo",
				"Ruiz-Gil Sara",
				"Marchese Domenica",
				"Gir\u00f3 Ariadna",
				"Verdaguer-Dot N\u00faria",
				"Romo M\u00f3nica",
				"Clot Guillem",
				"Rozman Maria",
				"Frigola Gerard",
				"Rivas-Delgado Alfredo",
				"Baumann Tycho",
				"Alcoceba Miguel",
				"Gonz\u00e1lez Marcos",
				"Climent Fina",
				"Abrisqueta Pau",
				"Castellv\u00ed Josep",
				"Bosch Francesc",
				"Aymerich Marta",
				"Enjuanes Anna",
				"Ruiz-Gasp\u00e0 S\u00edlvia",
				"L\u00f3pez-Guillermo Armando",
				"Jares Pedro",
				"Be\u00e0 S\u00edlvia",
				"Capella-Gutierrez Salvador",
				"Gelp\u00ed Josep Ll",
				"L\u00f3pez-Bigas N\u00faria",
				"Torrents David",
				"Campbell Peter J",
				"Gut Ivo",
				"Rossi Davide",
				"Gaidano Gianluca",
				"Puente Xose S",
				"Garcia-Roves Pablo M",
				"Colomer Dolors",
				"Heyn Holger",
				"Maura Francesco",
				"Mart\u00edn-Subero Jos\u00e9 I",
				"Campo El\u00edas"
			],
			"DOI": "10.1038/s41591-022-01927-8",
			"date": "2022-08-22",
			"PMC": "",
			"citation": "",
			"abstract": "Richter transformation (RT) is a paradigmatic evolution of chronic lymphocytic leukemia (CLL) into a very aggressive large B cell lymphoma conferring a dismal prognosis. The mechanisms driving RT remain largely unknown. We characterized the whole genome, epigenome and transcriptome, combined with single-cell DNA/RNA-sequencing analyses and functional experiments, of 19 cases of CLL developing RT. Studying 54 longitudinal samples covering up to 19 years of disease course, we uncovered minute subclones carrying genomic, immunogenetic and transcriptomic features of RT cells already at CLL diagnosis, which were dormant for up to 19 years before transformation. We also identified new driver alterations, discovered a new mutational signature (SBS-RT), recognized an oxidative phosphorylation (OXPHOS)",
			"category": 2,
			"name": "Nadeu Ferran,2022"
		},
		{
			"PMID": 35953478,
			"title": "Clonal diversification and histogenesis of malignant germ cell tumours.",
			"journal": "Nature communications",
			"authorList": [
				"Oliver Thomas R W",
				"Chappell Lia",
				"Sanghvi Rashesh",
				"Deighton Lauren",
				"Ansari-Pour Naser",
				"Dentro Stefan C",
				"Young Matthew D",
				"Coorens Tim H H",
				"Jung Hyunchul",
				"Butler Tim",
				"Neville Matthew D C",
				"Leongamornlert Daniel",
				"Sanders Mathijs A",
				"Hooks Yvette",
				"Cagan Alex",
				"Mitchell Thomas J",
				"Cortes-Ciriano Isidro",
				"Warren Anne Y",
				"Wedge David C",
				"Heer Rakesh",
				"Coleman Nicholas",
				"Murray Matthew J",
				"Campbell Peter J",
				"Rahbari Raheleh",
				"Behjati Sam"
			],
			"DOI": "10.1038/s41467-022-31375-4",
			"date": "2022-08-15",
			"PMC": "",
			"citation": "",
			"abstract": "Germ cell tumours (GCTs) are a collection of benign and malignant neoplasms derived from primordial germ cells. They are uniquely able to recapitulate embryonic and extraembryonic tissues, which carries prognostic and therapeutic significance. The developmental pathways underpinning GCT initiation and histogenesis are incompletely understood. Here, we study the relationship of histogenesis and clonal diversification in GCTs by analysing the genomes and transcriptomes of 547 microdissected histological units. We find no correlation between genomic and histological heterogeneity. However, we identify unifying features including the retention of fetal developmental transcripts across tissues, expression changes on chromosome 12p, and a conserved somatic evolutionary sequence of whole genome duplication followed by clonal diversification. While this pattern is preserved across all GCTs, the developmental timing of the duplication varies between prepubertal and postpubertal cases. In addition, tumours of younger children exhibit distinct substitution signatures which may lend themselves as potential biomarkers for risk stratification. Our findings portray the extensive diversification of GCT tissues and genetic subclones as randomly distributed, while identifying overarching transcriptional and genomic features.",
			"category": 2,
			"name": "Oliver Thomas R W,2022"
		},
		{
			"PMID": 35947558,
			"title": "Chromatin accessibility of primary human cancers ties regional mutational processes and signatures with tissues of origin.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Ocsenas Oliver",
				"Reimand J\u00fcri"
			],
			"DOI": "10.1371/journal.pcbi.1010393",
			"date": "2022-08-12",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic mutations in cancer genomes are associated with DNA replication timing (RT) and chromatin accessibility (CA), however these observations are based on normal tissues and cell lines while primary cancer epigenomes remain uncharacterised. Here we use machine learning to model megabase-scale mutation burden in 2,500 whole cancer genomes and 17 cancer types via a compendium of 900 CA and RT profiles covering primary cancers, normal tissues, and cell lines. CA profiles of primary cancers, rather than those of normal tissues, are most predictive of regional mutagenesis in most cancer types. Feature prioritisation shows that the epigenomes of matching cancer types and organ systems are often the strongest predictors of regional mutation burden, highlighting disease-specific associations of mutational processes. The genomic distributions of mutational signatures are also shaped by the epigenomes of matched cancer and tissue types, with SBS5/40, carcinogenic and unknown signatures most accurately predicted by our models. In contrast, fewer associations of RT and regional mutagenesis are found. Lastly, the models highlight genomic regions with overrepresented mutations that dramatically exceed epigenome-derived expectations and show a pan-cancer convergence to genes and pathways involved in development and oncogenesis, indicating the potential of this approach for coding and non-coding driver discovery. The association of regional mutational processes with the epigenomes of primary cancers suggests that the landscape of passenger mutations is predominantly shaped by the epigenomes of cancer cells after oncogenic transformation.",
			"category": 2,
			"name": "Ocsenas Oliver,2022"
		},
		{
			"PMID": 35935840,
			"title": "A Novel Anti-Cancer Therapy: CRISPR/Cas9 Gene Editing.",
			"journal": "Frontiers in pharmacology",
			"authorList": [
				"Chen Xin-Zhu",
				"Guo Rong",
				"Zhao Cong",
				"Xu Jing",
				"Song Hang",
				"Yu Hua",
				"Pilarsky Christian",
				"Nainu Firzan",
				"Li Jing-Quan",
				"Zhou Xin-Ke",
				"Zhang Jian-Ye"
			],
			"DOI": "10.3389/fphar.2022.939090",
			"date": "2022-08-09",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer becomes one of the main causes of human deaths in the world due to the high incidence and mortality rate and produces serious economic burdens. With more and more attention is paid on cancer, its therapies are getting more of a concern. Previous research has shown that the occurrence, progression, and treatment prognosis of malignant tumors are closely related to genetic and gene mutation. CRISPR/Cas9 has emerged as a powerful method for making changes to the genome, which has extensively been applied in various cell lines. Establishing the cell and animal models by CRISPR/Cas9 laid the foundation for the clinical trials which possibly treated the tumor. CRISPR-Cas9-mediated genome editing technology brings a great promise for inhibiting migration, invasion, and even treatment of tumor. However, the potential off-target effect limits its clinical application, and the effective ethical review is necessary. The article reviews the molecular mechanisms of CRISPR/Cas9 and discusses the research and the limitation related to cancer clinical trials.",
			"category": 2,
			"name": "Chen Xin-Zhu,2022"
		},
		{
			"PMID": 35902848,
			"title": "Increased blood-based intratumor heterogeneity (bITH) is associated with unfavorable outcomes of immune checkpoint inhibitors plus chemotherapy in non-small cell lung cancer.",
			"journal": "BMC medicine",
			"authorList": [
				"Zhou Juan",
				"Bao Minwei",
				"Gao Guanghui",
				"Cai Yiran",
				"Wu Lihong",
				"Lei Lei",
				"Zhao Jing",
				"Ji Xianxiu",
				"Huang Ying",
				"Su Chunxia"
			],
			"DOI": "10.1186/s12916-022-02444-8",
			"date": "2022-08-01",
			"PMC": "",
			"citation": "",
			"abstract": "The combination of immune checkpoint inhibitors (ICIs) and chemotherapy has been the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with driver-gene negative. However, efficacy biomarkers for ICIs-based combination therapy are lacking. We aimed to identify potential factors associated with outcomes of ICIs plus chemotherapy at baseline and dynamic changes in peripheral blood.",
			"category": 2,
			"name": "Zhou Juan,2022"
		},
		{
			"PMID": 35901164,
			"title": "Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability.",
			"journal": "Science (New York, N.Y.)",
			"authorList": [
				"Bae Taejeong",
				"Fasching Liana",
				"Wang Yifan",
				"Shin Joo Heon",
				"Suvakov Milovan",
				"Jang Yeongjun",
				"Norton Scott",
				"Dias Caroline",
				"Mariani Jessica",
				"Jourdon Alexandre",
				"Wu Feinan",
				"Panda Arijit",
				"Pattni Reenal",
				"Chahine Yasmine",
				"Yeh Rebecca",
				"Roberts Rosalinda C",
				"Huttner Anita",
				"Kleinman Joel E",
				"Hyde Thomas M",
				"Straub Richard E",
				"Walsh Christopher A",
				"Brain Somatic Mosaicism Network\u00a7",
				"Urban Alexander E",
				"Leckman James F",
				"Weinberger Daniel R",
				"Vaccarino Flora M",
				"Abyzov Alexej"
			],
			"DOI": "10.1126/science.abm6222",
			"date": "2022-08-01",
			"PMC": "",
			"citation": "",
			"abstract": "We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 with schizophrenia, and 59 with autism) for somatic mutations after whole genome sequencing to a depth of more than 200\u00d7. Typically, brains had 20 to 60 detectable single-nucleotide mutations, but ~6% of brains harbored hundreds of somatic mutations. Hypermutability was associated with age and damaging mutations in genes implicated in cancers and, in some brains, reflected in vivo clonal expansions. Somatic duplications, likely arising during development, were found in ~5% of normal and diseased brains, reflecting background mutagenesis. Brains with autism were associated with mutations creating putative transcription factor binding motifs in enhancer-like regions in the developing brain. The top-ranked affected motifs corresponded to MEIS (myeloid ectopic viral integration site) transcription factors, suggesting a potential link between their involvement in gene regulation and autism.",
			"category": 2,
			"name": "Bae Taejeong,2022"
		},
		{
			"PMID": 35887203,
			"title": "Integrated Workflow for the Label-Free Isolation and Genomic Analysis of Single Circulating Tumor Cells in Pancreatic Cancer.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Rupp Brittany",
				"Owen Sarah",
				"Ball Harrison",
				"Smith Kaylee Judith",
				"Gunchick Valerie",
				"Keller Evan T",
				"Sahai Vaibhav",
				"Nagrath Sunitha"
			],
			"DOI": "10.3390/ijms23147852",
			"date": "2022-07-28",
			"PMC": "",
			"citation": "",
			"abstract": "As pancreatic cancer is the third deadliest cancer in the U.S., the ability to study genetic alterations is necessary to provide further insight into potentially targetable regions for cancer treatment. Circulating tumor cells (CTCs) represent an especially aggressive subset of cancer cells, capable of causing metastasis and progressing the disease. Here, we present the Labyrinth-DEPArray pipeline for the isolation and analysis of single CTCs. Established cell lines, patient-derived CTC cell lines and freshly isolated CTCs were recovered and sequenced to reveal single-cell copy number variations (CNVs). The resulting CNV profiles of established cell lines showed concordance with previously reported data and highlight several gains and losses of cancer-related genes such as FGFR3 and GNAS. The novel sequencing of patient-derived CTC cell lines showed gains in chromosome 8q, 10q and 17q across both CTC cell lines. The pipeline was used to process and isolate single cells from a metastatic pancreatic cancer patient revealing a gain of chromosome 1q and a loss of chromosome 5q. Overall, the Labyrinth-DEPArray pipeline offers a validated workflow combining the benefits of antigen-free CTC isolation with single cell genomic analysis.",
			"category": 2,
			"name": "Rupp Brittany,2022"
		},
		{
			"PMID": 35884424,
			"title": "Isolation of Circulating Tumor Cells from Seminal Fluid of Patients with Prostate Cancer Using Inertial Microfluidics.",
			"journal": "Cancers",
			"authorList": [
				"Rzhevskiy Alexey S",
				"Kapitannikova Alina Y",
				"Vasilescu Steven A",
				"Karashaeva Tamilla A",
				"Razavi Bazaz Sajad",
				"Taratkin Mark S",
				"Enikeev Dmitry V",
				"Lekarev Vladimir Y",
				"Shpot Evgeniy V",
				"Butnaru Denis V",
				"Deyev Sergey M",
				"Thiery Jean Paul",
				"Zvyagin Andrei V",
				"Ebrahimi Warkiani Majid"
			],
			"DOI": "10.3390/cancers14143364",
			"date": "2022-07-31",
			"PMC": "",
			"citation": "",
			"abstract": "Prostate cancer (PCa) diagnosis is primarily based on prostate-specific antigen (PSA) testing and prostate tissue biopsies. However, PSA testing has relatively low specificity, while tissue biopsies are highly invasive and have relatively low sensitivity at early stages of PCa. As an alternative, we developed a technique of liquid biopsy, based on isolation of circulating tumor cells (CTCs) from seminal fluid (SF). The recovery of PCa cells from SF was demonstrated using PCa cell lines, achieving an efficiency and throughput as high as 89% (\u00b13.8%) and 1.7 mL min",
			"category": 2,
			"name": "Rzhevskiy Alexey S,2022"
		},
		{
			"PMID": 35877212,
			"title": "Upfront Next Generation Sequencing in Non-Small Cell Lung Cancer.",
			"journal": "Current oncology (Toronto, Ont.)",
			"authorList": [
				"Kuang Shelley",
				"Fung Andrea S",
				"Perdrizet Kirstin A",
				"Chen Kaitlin",
				"Li Janice J N",
				"Le Lisa W",
				"Cabanero Michael",
				"Karsaneh Ola Abu Al",
				"Tsao Ming S",
				"Morganstein Josh",
				"Ranich Laura",
				"Smith Adam C",
				"Wei Cuihong",
				"Cheung Carol",
				"Shepherd Frances A",
				"Liu Geoffrey",
				"Bradbury Penelope",
				"Pal Prodipto",
				"Schwock Joerg",
				"Sacher Adrian G",
				"Law Jennifer H",
				"Stockley Tracy L",
				"Leighl Natasha B"
			],
			"DOI": "10.3390/curroncol29070352",
			"date": "2022-07-27",
			"PMC": "",
			"citation": "",
			"abstract": "In advanced non-small cell lung cancer (NSCLC), patients with actionable genomic alterations may derive additional clinical benefit from targeted treatment compared to cytotoxic chemotherapy. Current guidelines recommend extensive testing with next generation sequencing (NGS) panels. We investigated the impact of using a targeted NGS panel (TruSight Tumor 15, Illumina) as reflex testing for NSCLC samples at a single institution. Molecular analysis examined 15 genes for hotspot mutation variants, including ",
			"category": 2,
			"name": "Kuang Shelley,2022"
		},
		{
			"PMID": 35853870,
			"title": "A brain precursor atlas reveals the acquisition of developmental-like states in adult cerebral tumours.",
			"journal": "Nature communications",
			"authorList": [
				"Hamed Akram A",
				"Kunz Daniel J",
				"El-Hamamy Ibrahim",
				"Trinh Quang M",
				"Subedar Omar D",
				"Richards Laura M",
				"Foltz Warren",
				"Bullivant Garrett",
				"Ware Matthaeus",
				"Vladoiu Maria C",
				"Zhang Jiao",
				"Raj Antony M",
				"Pugh Trevor J",
				"Taylor Michael D",
				"Teichmann Sarah A",
				"Stein Lincoln D",
				"Simons Benjamin D",
				"Dirks Peter B"
			],
			"DOI": "10.1038/s41467-022-31408-y",
			"date": "2022-07-21",
			"PMC": "",
			"citation": "",
			"abstract": "Human cerebral cancers are known to contain cell types resembling the varying stages of neural development. However, the basis of this association remains unclear. Here, we map the development of mouse cerebrum across the developmental time-course, from embryonic day 12.5 to postnatal day 365, performing single-cell transcriptomics on\u2009>100,000 cells. By comparing this reference atlas to single-cell data from\u2009>100 glial tumours of the adult and paediatric human cerebrum, we find that tumour cells have an expression signature that overlaps with temporally restricted, embryonic radial glial precursors (RGPs) and their immediate sublineages. Further, we demonstrate that prenatal\u00a0transformation of RGPs in a genetic mouse model gives rise to adult cerebral tumours that show an embryonic/juvenile RGP identity. Together, these findings implicate the acquisition of embryonic-like states in the genesis of adult glioma, providing insight into the origins of human glioma, and identifying specific developmental cell types for therapeutic targeting.",
			"category": 2,
			"name": "Hamed Akram A,2022"
		},
		{
			"PMID": 35837331,
			"title": "Cancer Risk and Mutational Patterns Following Organ Transplantation.",
			"journal": "Frontiers in cell and developmental biology",
			"authorList": [
				"Shen Yangyang",
				"Lian Di",
				"Shi Kai",
				"Gao Yuefeng",
				"Hu Xiaoxiang",
				"Yu Kun",
				"Zhao Qian",
				"Feng Chungang"
			],
			"DOI": "10.3389/fcell.2022.956334",
			"date": "2022-07-16",
			"PMC": "",
			"citation": "",
			"abstract": "The rapid development of medical technology and widespread application of immunosuppressive drugs have improved the success rate of organ transplantation significantly. However, the use of immunosuppressive agents increases the frequency of malignancy greatly. With the prospect of \"precision medicine\" for tumors and development of next-generation sequencing technology, more attention has been paid to the application of high-throughput sequencing technology in clinical oncology research, which is mainly applied to the early diagnosis of tumors and analysis of tumor-related genes. All generations of cancers carry somatic mutations, meanwhile, significant differences were observed in mutational signatures across tumors. Systematic sequencing of cancer genomes from patients after organ transplantation can reveal DNA damage and repair processes in exposed cancer cells and their precursors. In this review, we summarize the application of high-throughput sequencing and organoids in the field of organ transplantation, the mutational patterns of cancer genomes, and propose a new research strategy for understanding the mechanism of cancer following organ transplantation.",
			"category": 2,
			"name": "Shen Yangyang,2022"
		},
		{
			"PMID": 35822044,
			"title": "The Dynamics of Somatic Mutagenesis During Life in Humans.",
			"journal": "Frontiers in aging",
			"authorList": [
				"Manders Freek",
				"van Boxtel Ruben",
				"Middelkamp Sjors"
			],
			"DOI": "10.3389/fragi.2021.802407",
			"date": "2022-07-16",
			"PMC": "",
			"citation": "",
			"abstract": "From conception to death, human cells accumulate somatic mutations in their genomes. These mutations can contribute to the development of cancer and non-malignant diseases and have also been associated with aging. Rapid technological developments in sequencing approaches in the last few years and their application to normal tissues have greatly advanced our knowledge about the accumulation of these mutations during healthy aging. Whole genome sequencing studies have revealed that there are significant differences in mutation burden and patterns across tissues, but also that the mutation rates within tissues are surprisingly constant during adult life. In contrast, recent lineage-tracing studies based on whole-genome sequencing have shown that the rate of mutation accumulation is strongly increased early in life before birth. These early mutations, which can be shared by many cells in the body, may have a large impact on development and the origin of somatic diseases. For example, cancer driver mutations can arise early in life, decades before the detection of the malignancy. Here, we review the recent insights in mutation accumulation and mutagenic processes in normal tissues. We compare mutagenesis early and later in life and discuss how mutation rates and patterns evolve during aging. Additionally, we outline the potential impact of these mutations on development, aging and disease.",
			"category": 2,
			"name": "Manders Freek,2022"
		},
		{
			"PMID": 35817764,
			"title": "Machine learning-based tissue of origin classification for cancer of unknown primary diagnostics using genome-wide mutation features.",
			"journal": "Nature communications",
			"authorList": [
				"Nguyen Luan",
				"Van Hoeck Arne",
				"Cuppen Edwin"
			],
			"DOI": "10.1038/s41467-022-31666-w",
			"date": "2022-07-13",
			"PMC": "",
			"citation": "",
			"abstract": "Cancers of unknown primary (CUP) origin account for \u223c3% of all cancer diagnoses, whereby the tumor tissue of origin (TOO) cannot be determined. Using a uniformly processed dataset encompassing 6756 whole-genome sequenced primary and metastatic tumors, we develop Cancer of Unknown Primary Location Resolver (CUPLR), a random forest TOO classifier that employs 511 features based on simple and complex somatic driver and passenger mutations. CUPLR distinguishes 35 cancer (sub)types with \u223c90% recall and \u223c90% precision based on cross-validation and test set predictions. We find that structural variant derived features increase the performance and utility for classifying specific cancer types. With CUPLR, we could determine the TOO for 82/141 (58%) of CUP patients. Although CUPLR is based on machine learning, it provides a human interpretable graphical report with detailed feature explanations. The comprehensive output of CUPLR complements existing histopathological procedures and can enable improved diagnostics for CUP patients.",
			"category": 2,
			"name": "Nguyen Luan,2022"
		},
		{
			"PMID": 35788723,
			"title": "Structural variants shape driver combinations and outcomes in pediatric high-grade glioma.",
			"journal": "Nature cancer",
			"authorList": [
				"Dubois Frank P B",
				"Shapira Ofer",
				"Greenwald Noah F",
				"Zack Travis",
				"Wala Jeremiah",
				"Tsai Jessica W",
				"Crane Alexander",
				"Baguette Audrey",
				"Hadjadj Djihad",
				"Harutyunyan Ashot S",
				"Kumar Kiran H",
				"Blattner-Johnson Mirjam",
				"Vogelzang Jayne",
				"Sousa Cecilia",
				"Kang Kyung Shin",
				"Sinai Claire",
				"Wang Dayle K",
				"Khadka Prasidda",
				"Lewis Kathleen",
				"Nguyen Lan",
				"Malkin Hayley",
				"Ho Patricia",
				"O'Rourke Ryan",
				"Zhang Shu",
				"Gold Rose",
				"Deng Davy",
				"Serrano Jonathan",
				"Snuderl Matija",
				"Jones Chris",
				"Wright Karen D",
				"Chi Susan N",
				"Grill Jacques",
				"Kleinman Claudia L",
				"Goumnerova Liliana C",
				"Jabado Nada",
				"Jones David T W",
				"Kieran Mark W",
				"Ligon Keith L",
				"Beroukhim Rameen",
				"Bandopadhayay Pratiti"
			],
			"DOI": "10.1038/s43018-022-00403-z",
			"date": "2022-08-26",
			"PMC": "",
			"citation": "",
			"abstract": "We analyzed the contributions of structural variants (SVs) to gliomagenesis across 179 pediatric high-grade gliomas (pHGGs). The most recurrent SVs targeted MYC isoforms and receptor tyrosine kinases (RTKs), including an SV amplifying a MYC enhancer in 12% of diffuse midline gliomas (DMG), indicating an underappreciated role for MYC in pHGG. SV signature analysis revealed that tumors with simple signatures were TP53 wild type (TP53",
			"category": 2,
			"name": "Dubois Frank P B,2022"
		},
		{
			"PMID": 35732905,
			"title": "A phylogenetic approach to study the evolution of somatic mutational processes in cancer.",
			"journal": "Communications biology",
			"authorList": [
				"Miura Sayaka",
				"Vu Tracy",
				"Choi Jiyeong",
				"Townsend Jeffrey P",
				"Karim Sajjad",
				"Kumar Sudhir"
			],
			"DOI": "10.1038/s42003-022-03560-0",
			"date": "2022-06-24",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer cell genomes change continuously due to mutations, and mutational processes change over time in patients, leaving dynamic signatures in the accumulated genomic variation in tumors. Many computational methods detect the relative activities of known mutation signatures. However, these methods may produce erroneous signatures when applied to individual branches in cancer cell phylogenies. Here, we show that the inference of branch-specific mutational signatures can be improved through a joint analysis of the collections of mutations mapped on proximal branches of the cancer cell phylogeny. This approach reduces the false-positive discovery rate of branch-specific signatures and can sometimes detect faint signatures. An analysis of empirical data from 61 lung cancer patients supports trends based on computer-simulated datasets for which the correct signatures are known. In lung cancer somatic variation, we detect a decreasing trend of smoking-related mutational processes over time and an increasing influence of APOBEC mutational processes as the tumor evolution progresses. These analyses also reveal patterns of conservation and divergence of mutational processes in cell lineages within patients.",
			"category": 2,
			"name": "Miura Sayaka,2022"
		},
		{
			"PMID": 35725896,
			"title": "A clinically annotated post-mortem approach to study multi-organ somatic mutational clonality in normal tissues.",
			"journal": "Scientific reports",
			"authorList": [
				"Luijts Tom",
				"Elliott Kerryn",
				"Siaw Joachim Tetteh",
				"Van de Velde Joris",
				"Beyls Elien",
				"Claeys Arne",
				"Lammens Tim",
				"Larsson Erik",
				"Willaert Wouter",
				"Vral Anne",
				"Van den Eynden Jimmy"
			],
			"DOI": "10.1038/s41598-022-14240-8",
			"date": "2022-06-22",
			"PMC": "",
			"citation": "",
			"abstract": "Recent research on normal human tissues identified omnipresent clones of cells, driven by somatic mutations known to be responsible for carcinogenesis (e.g., in TP53 or NOTCH1). These new insights are fundamentally changing current tumor evolution models, with broad oncological implications. Most studies are based on surgical remnant tissues, which are not available for many organs and rarely in a pan-organ setting (multiple organs from the same individual). Here, we describe an approach based on clinically annotated post-mortem tissues, derived from whole-body donors that are routinely used for educational purposes at human anatomy units. We validated this post-mortem approach using UV-exposed and unexposed epidermal skin tissues and confirm the presence of positively selected NOTCH1/2-, TP53- and FAT1-driven clones. No selection signals were detected in a set of immune genes or housekeeping genes. Additionally, we provide the first evidence for smoking-induced clonal changes in oral epithelia, likely underlying the origin of head and neck carcinogenesis. In conclusion, the whole-body donor-based approach provides a nearly unlimited healthy tissue resource to study mutational clonality and gain fundamental mutagenic insights in the presumed earliest stages of tumor evolution.",
			"category": 2,
			"name": "Luijts Tom,2022"
		},
		{
			"PMID": 35723313,
			"title": "Multigene Panel Sequencing Reveals Cancer-Specific and Common Somatic Mutations in Colorectal Cancer Patients: An Egyptian Experience.",
			"journal": "Current issues in molecular biology",
			"authorList": [
				"Youssef Amira Salah El-Din",
				"Abdel-Fattah Mohamed A",
				"Lotfy Mai M",
				"Nassar Auhood",
				"Abouelhoda Mohamed",
				"Touny Ahmed O",
				"Hassan Zeinab K",
				"Mohey Eldin Mohammed",
				"Bahnassy Abeer A",
				"Khaled Hussein",
				"Zekri Abdel Rahman N"
			],
			"DOI": "10.3390/cimb44030090",
			"date": "2023-09-17",
			"PMC": "",
			"citation": "",
			"abstract": "This study aims at identifying common pathogenic somatic mutations at different stages of colorectal carcinogenesis in Egyptian patients. Our cohort included colonoscopic biopsies collected from 120 patients: 20 biopsies from patients with inflammatory bowel disease, 38 from colonic polyp patients, and 62 from patients with colorectal cancer. On top of this, the cohort included 20 biopsies from patients with non-specific mild to moderated colitis. Targeted DNA sequencing using a customized gene panel of 96 colorectal related genes running on the Ion Torrent NGS technology was used to process the samples. Our results revealed that 69% of all cases harbored at least one somatic mutation. Fifty-seven genes were found to carry 232 somatic non-synonymous variants. The most frequently pathogenic somatic mutations were localized in ",
			"category": 2,
			"name": "Youssef Amira Salah El-Din,2023"
		},
		{
			"PMID": 35697807,
			"title": "Estimation of tumor cell total mRNA expression in 15 cancer types predicts disease progression.",
			"journal": "Nature biotechnology",
			"authorList": [
				"Cao Shaolong",
				"Wang Jennifer R",
				"Ji Shuangxi",
				"Yang Peng",
				"Dai Yaoyi",
				"Guo Shuai",
				"Montierth Matthew D",
				"Shen John Paul",
				"Zhao Xiao",
				"Chen Jingxiao",
				"Lee Jaewon James",
				"Guerrero Paola A",
				"Spetsieris Nicholas",
				"Engedal Nikolai",
				"Taavitsainen Sinja",
				"Yu Kaixian",
				"Livingstone Julie",
				"Bhandari Vinayak",
				"Hubert Shawna M",
				"Daw Najat C",
				"Futreal P Andrew",
				"Efstathiou Eleni",
				"Lim Bora",
				"Viale Andrea",
				"Zhang Jianjun",
				"Nykter Matti",
				"Czerniak Bogdan A",
				"Brown Powel H",
				"Swanton Charles",
				"Msaouel Pavlos",
				"Maitra Anirban",
				"Kopetz Scott",
				"Campbell Peter",
				"Speed Terence P",
				"Boutros Paul C",
				"Zhu Hongtu",
				"Urbanucci Alfonso",
				"Demeulemeester Jonas",
				"Van Loo Peter",
				"Wang Wenyi"
			],
			"DOI": "10.1038/s41587-022-01342-x",
			"date": "2022-11-11",
			"PMC": "",
			"citation": "",
			"abstract": "Single-cell RNA sequencing studies have suggested that total mRNA content correlates with tumor phenotypes. Technical and analytical challenges, however, have so far impeded at-scale pan-cancer examination of total mRNA content. Here we present a method to quantify tumor-specific total mRNA expression (TmS) from bulk sequencing data, taking into account tumor transcript proportion, purity and ploidy, which are estimated through transcriptomic/genomic deconvolution. We estimate and validate TmS in 6,590 patient tumors across 15 cancer types, identifying significant inter-tumor variability. Across cancers, high TmS is associated with increased risk of disease progression and death. TmS is influenced by cancer-specific patterns of gene alteration and intra-tumor genetic heterogeneity as well as by pan-cancer trends in metabolic dysregulation. Taken together, our results indicate that measuring cell-type-specific total mRNA expression in tumor cells predicts tumor phenotypes and clinical outcomes.",
			"category": 2,
			"name": "Cao Shaolong,2022"
		},
		{
			"PMID": 35686268,
			"title": "An Update to Hallmarks of Cancer.",
			"journal": "Cureus",
			"authorList": [
				"Ravi Swapna",
				"Alencar Antonio M",
				"Arakelyan Jemma",
				"Xu Weihao",
				"Stauber Roberta",
				"Wang Cheng-Chi I",
				"Papyan Ruzanna",
				"Ghazaryan Narine",
				"Pereira Rosalina M"
			],
			"DOI": "10.7759/cureus.24803",
			"date": "2022-07-16",
			"PMC": "",
			"citation": "",
			"abstract": "In the last decade, there has been remarkable progress in research toward understanding and refining the hallmarks of cancer. In this review, we propose a new hallmark - \"pro-survival autophagy.\"\u00a0The importance of pro-survival autophagy is well established in tumorigenesis, as it is related to multiple steps in cancer progression and vital for some cancers. Autophagy is a potential anti-cancer therapeutic target. For this reason, autophagy is a good candidate as a new hallmark of cancer. We describe two enabling characteristics that play a major role in enabling cells to acquire the hallmarks of cancer - \"tumor-promoting microenvironment and macroenvironment\" and \"cancer epigenetics, genome instability and mutation.\"\u00a0We also discuss the recent updates, therapeutic and prognostic implications of the eight hallmarks of cancer described by Hanahan et al. in 2011. Understanding these hallmarks and enabling characteristics is key not only to developing new ways to treat cancer efficiently but also to exploring options to overcome cancer resistance to treatment.",
			"category": 2,
			"name": "Ravi Swapna,2022"
		},
		{
			"PMID": 35651714,
			"title": "The Promise of Single-cell Technology in Providing New Insights Into the Molecular Heterogeneity and Management of Acute Lymphoblastic Leukemia.",
			"journal": "HemaSphere",
			"authorList": [
				"Pearson Holly C L",
				"Hunt Kooper V",
				"Trahair Toby N",
				"Lock Richard B",
				"Lee Heather J",
				"de Bock Charles E"
			],
			"DOI": "10.1097/HS9.0000000000000734",
			"date": "2022-07-16",
			"PMC": "",
			"citation": "",
			"abstract": "Drug resistance and treatment failure in pediatric acute lymphoblastic leukemia (ALL) are in part driven by tumor heterogeneity and clonal evolution. Although bulk tumor genomic analyses have provided some insight into these processes, single-cell sequencing has emerged as a powerful technique to profile individual cells in unprecedented detail. Since the introduction of single-cell RNA sequencing, we now have the capability to capture not only transcriptomic, but also genomic, epigenetic, and proteomic variation between single cells separately and in combination. This rapidly evolving field has the potential to transform our understanding of the fundamental biology of pediatric ALL and guide the management of ALL patients to improve their clinical outcome. Here, we discuss the impact single-cell sequencing has had on our understanding of tumor heterogeneity and clonal evolution in ALL and provide examples of how single-cell technology can be integrated into the clinic to inform treatment decisions for children with high-risk disease.",
			"category": 2,
			"name": "Pearson Holly C L,2022"
		},
		{
			"PMID": 35637336,
			"title": "In utero origin of myelofibrosis presenting in adult monozygotic twins.",
			"journal": "Nature medicine",
			"authorList": [
				"Sousos Nikolaos",
				"N\u00ed Leathlobhair M\u00e1ire",
				"Simoglou Karali Christina",
				"Louka Eleni",
				"Bienz Nicola",
				"Royston Daniel",
				"Clark Sally-Ann",
				"Hamblin Angela",
				"Howard Kieran",
				"Mathews Vikram",
				"George Biju",
				"Roy Anindita",
				"Psaila Bethan",
				"Wedge David C",
				"Mead Adam J"
			],
			"DOI": "10.1038/s41591-022-01793-4",
			"date": "2022-06-21",
			"PMC": "",
			"citation": "",
			"abstract": "The latency between acquisition of an initiating somatic driver mutation by a single-cell and clinical presentation with cancer is largely unknown. We describe a remarkable case of monozygotic twins presenting with CALR mutation-positive myeloproliferative neoplasms (MPNs) (aged 37 and 38 years), with a clinical phenotype of primary myelofibrosis. The CALR mutation was absent in T cells and dermal fibroblasts, confirming somatic acquisition. Whole-genome sequencing lineage tracing revealed a common clonal origin of the CALR-mutant MPN clone, which occurred in utero followed by twin-to-twin transplacental transmission and subsequent similar disease latency. Index sorting and single-colony genotyping revealed phenotypic hematopoietic stem cells (HSCs) as the likely MPN-propagating cell. Furthermore, neonatal blood spot analysis confirmed in utero origin of the JAK2V617F mutation in a patient presenting with polycythemia vera (aged 34 years). These findings provide a unique window into the prolonged evolutionary dynamics of MPNs and fitness advantage exerted by MPN-associated driver mutations in HSCs.",
			"category": 2,
			"name": "Sousos Nikolaos,2022"
		},
		{
			"PMID": 35586565,
			"title": "Pan-Cancer Analyses Reveal Oncogenic and Immunological Role of PLOD2.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Xu Qiqi",
				"Kong Na",
				"Zhao Yiguo",
				"Wu Quan",
				"Wang Xin",
				"Xun Xiaodong",
				"Gao Pengji"
			],
			"DOI": "10.3389/fgene.2022.864655",
			"date": "2022-07-16",
			"PMC": "",
			"citation": "",
			"abstract": "Some previous studies have shown that ",
			"category": 2,
			"name": "Xu Qiqi,2022"
		},
		{
			"PMID": 35526333,
			"title": "Chromosomal instability as a source of genomic plasticity.",
			"journal": "Current opinion in genetics & development",
			"authorList": [
				"Al-Rawi Duaa H",
				"Bakhoum Samuel F"
			],
			"DOI": "10.1016/j.gde.2022.101913",
			"date": "2022-06-02",
			"PMC": "",
			"citation": "",
			"abstract": "Chromosomal instability (CIN) is a hallmark of the most aggressive malignancies. Features of these tumors include complex genomic rearrangements, the presence of mis-segregated chromosomes in micronuclei, and extrachromosomal DNA (ecDNA) formation. Here, we review the development of CIN, and examine CIN in the context of cancer evolution, tumor genomic evolution, and therapeutic resistance. We also discuss the role of whole-genome duplications, breakage-fusion-bridge cycles, ecDNA or double minutes in gene amplification promoting tumor evolution.",
			"category": 2,
			"name": "Al-Rawi Duaa H,2022"
		},
		{
			"PMID": 35523183,
			"title": "Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution.",
			"journal": "Cell",
			"authorList": [
				"Yang Dian",
				"Jones Matthew G",
				"Naranjo Santiago",
				"Rideout William M",
				"Min Kyung Hoi Joseph",
				"Ho Raymond",
				"Wu Wei",
				"Replogle Joseph M",
				"Page Jennifer L",
				"Quinn Jeffrey J",
				"Horns Felix",
				"Qiu Xiaojie",
				"Chen Michael Z",
				"Freed-Pastor William A",
				"McGinnis Christopher S",
				"Patterson David M",
				"Gartner Zev J",
				"Chow Eric D",
				"Bivona Trever G",
				"Chan Michelle M",
				"Yosef Nir",
				"Jacks Tyler",
				"Weissman Jonathan S"
			],
			"DOI": "10.1016/j.cell.2022.04.015",
			"date": "2022-05-31",
			"PMC": "",
			"citation": "",
			"abstract": "Tumor evolution is driven by the progressive acquisition of genetic and epigenetic alterations that enable uncontrolled growth and expansion to neighboring and distal tissues. The study of phylogenetic relationships between cancer cells provides key insights into these processes. Here, we introduced an evolving lineage-tracing system with a single-cell RNA-seq readout into a mouse model of Kras;Trp53(KP)-driven lung adenocarcinoma and tracked tumor evolution from single-transformed cells to metastatic tumors at unprecedented resolution. We found that the loss of the initial, stable alveolar-type2-like state was accompanied by a transient increase in plasticity. This was followed by the adoption of distinct transcriptional programs that enable rapid expansion and, ultimately, clonal sweep of stable subclones capable of metastasizing. Finally, tumors develop through stereotypical evolutionary trajectories, and perturbing additional tumor suppressors accelerates progression by creating novel trajectories. Our study elucidates the hierarchical nature of tumor evolution and, more broadly, enables in-depth studies of tumor progression.",
			"category": 2,
			"name": "Yang Dian,2022"
		},
		{
			"PMID": 35482653,
			"title": "Inferring ongoing cancer evolution from single tumour biopsies using synthetic supervised learning.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Ouellette Tom W",
				"Awadalla Philip"
			],
			"DOI": "10.1371/journal.pcbi.1010007",
			"date": "2022-05-02",
			"PMC": "",
			"citation": "",
			"abstract": "Variant allele frequencies (VAF) encode ongoing evolution and subclonal selection in growing tumours. However, existing methods that utilize VAF information for cancer evolutionary inference are compressive, slow, or incorrectly specify the underlying cancer evolutionary dynamics. Here, we provide a proof-of-principle synthetic supervised learning method, TumE, that integrates simulated models of cancer evolution with Bayesian neural networks, to infer ongoing selection in bulk-sequenced single tumour biopsies. Analyses in synthetic and patient tumours show that TumE significantly improves both accuracy and inference time per sample when detecting positive selection, deconvoluting selected subclonal populations, and estimating subclone frequency. Importantly, we show how transfer learning can leverage stored knowledge within TumE models for related evolutionary inference tasks-substantially reducing data and computational time for further model development and providing a library of recyclable deep learning models for the cancer evolution community. This extensible framework provides a foundation and future directions for harnessing progressive computational methods for the benefit of cancer genomics and, in turn, the cancer patient.",
			"category": 2,
			"name": "Ouellette Tom W,2022"
		},
		{
			"PMID": 35425963,
			"title": "Colorectal Cancer Is Associated with the Presence of Cancer Driver Mutations in Normal Colon.",
			"journal": "Cancer research",
			"authorList": [
				"Matas Julia",
				"Kohrn Brendan",
				"Fredrickson Jeanne",
				"Carter Kelly",
				"Yu Ming",
				"Wang Ting",
				"Gui Xianyong",
				"Soussi Thierry",
				"Moreno Victor",
				"Grady William M",
				"Peinado Miguel A",
				"Risques Rosa Ana"
			],
			"DOI": "10.1158/0008-5472.CAN-21-3607",
			"date": "2022-04-18",
			"PMC": "",
			"citation": "",
			"abstract": "Although somatic mutations in colorectal cancer are well characterized, little is known about the accumulation of cancer mutations in the normal colon before cancer. Here, we have developed and applied an ultrasensitive, single-molecule mutational test based on CRISPR-DS technology, which enables mutation detection at extremely low frequency (<0.001) in normal colon from patients with and without colorectal cancer. This testing platform revealed that normal colon from patients with and without colorectal cancer carries mutations in common colorectal cancer genes, but these mutations are more abundant in patients with cancer. Oncogenic KRAS mutations were observed in the normal colon of about one third of patients with colorectal cancer but in none of the patients without colorectal cancer. Patients with colorectal cancer also carried more TP53 mutations than patients without cancer and these mutations were more pathogenic and formed larger clones, especially in patients with early-onset colorectal cancer. Most mutations in the normal colon were different from the driver mutations in tumors, suggesting that the occurrence of independent clones with pathogenic KRAS and TP53 mutations is a common event in the colon of individuals who develop colorectal cancer. These results indicate that somatic evolution contributes to clonal expansions in the normal colon and that this process is enhanced in individuals with cancer, particularly in those with early-onset colorectal cancer.",
			"category": 2,
			"name": "Matas Julia,2022"
		},
		{
			"PMID": 35420163,
			"title": "An overview of mutational and copy number signatures in human cancer.",
			"journal": "The Journal of pathology",
			"authorList": [
				"Steele Christopher D",
				"Pillay Nischalan",
				"Alexandrov Ludmil B"
			],
			"DOI": "10.1002/path.5912",
			"date": "2022-07-06",
			"PMC": "",
			"citation": "",
			"abstract": "The genome of each cell in the human body is constantly under assault from a plethora of exogenous and endogenous processes that can damage DNA. If not successfully repaired, DNA damage generally becomes permanently imprinted in cells, and all their progenies, as somatic mutations. In most cases, the patterns of these somatic mutations contain the tell-tale signs of the mutagenic processes that have imprinted and are termed mutational signatures. Recent pan-cancer genomic analyses have elucidated the compendium of mutational signatures for all types of small mutational events, including (1) single base substitutions, (2) doublet base substitutions, and (3) small insertions/deletions. In contrast to small mutational events, where, in most cases, DNA damage is a prerequisite, aneuploidy, which refers to the abnormal number of chromosomes in a cell, usually develops from mistakes during DNA replication. Such mistakes include DNA replication stress, mitotic errors caused by faulty microtubule dynamics, or cohesion defects that contribute to chromosomal breakage and can lead to copy number (CN) alterations (CNAs) or even to structural rearrangements. These aberrations also leave behind genomic scars which can be inferred from sequencing as CN signatures and rearrangement signatures. The analyses of mutational signatures of small mutational events have been extensively reviewed, so we will not comprehensively re-examine them here. Rather, our focus will be on summarising the existing knowledge for mutational signatures of CNAs. As studying CN signatures is an emerging field, we briefly summarise the utility that mutational signatures of small mutational events have provided in basic science, cancer treatment, and cancer prevention, and we emphasise the future role that CN signatures may play in each of these fields. \u00a9 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.",
			"category": 2,
			"name": "Steele Christopher D,2022"
		},
		{
			"PMID": 35401654,
			"title": "Esophageal Cancer Genomics in Africa: Recommendations for Future Research.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Simba Hannah",
				"Tromp Gerard",
				"Sewram Vikash",
				"Mathew Christopher G",
				"Chen Wenlong C",
				"Kuivaniemi Helena"
			],
			"DOI": "10.3389/fgene.2022.864575",
			"date": "2024-03-24",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Simba Hannah,2024"
		},
		{
			"PMID": 35397477,
			"title": "Somatic Mutation: What Shapes the Mutational Landscape of Normal Epithelia?",
			"journal": "Cancer discovery",
			"authorList": [
				"Fowler Joanna C",
				"Jones Philip H"
			],
			"DOI": "10.1158/2159-8290.CD-22-0145",
			"date": "2022-07-08",
			"PMC": "",
			"citation": "",
			"abstract": "Epithelial stem cells accumulate mutations throughout life. Some of these mutants increase competitive fitness and may form clones that colonize the stem cell niche and persist to acquire further genome alterations. After a transient expansion, mutant stem cells must revert to homeostatic behavior so normal tissue architecture is maintained. Some positively selected mutants may promote cancer development, whereas others inhibit carcinogenesis. Factors that shape the mutational landscape include wild-type and mutant stem cell dynamics, competition for the niche, and environmental exposures. Understanding these processes may give new insight into the basis of cancer risk and opportunities for cancer prevention.",
			"category": 2,
			"name": "Fowler Joanna C,2022"
		},
		{
			"PMID": 35380536,
			"title": "Quantifying chromosomal instability from intratumoral karyotype diversity using agent-based modeling and Bayesian inference.",
			"journal": "eLife",
			"authorList": [
				"Lynch Andrew R",
				"Arp Nicholas L",
				"Zhou Amber S",
				"Weaver Beth A",
				"Burkard Mark E"
			],
			"DOI": "10.7554/eLife.69799",
			"date": "2022-05-03",
			"PMC": "",
			"citation": "",
			"abstract": "Chromosomal instability (CIN)-persistent chromosome gain or loss through abnormal mitotic segregation-is a hallmark of cancer that drives aneuploidy. Intrinsic chromosome mis-segregation rate, a measure of CIN, can inform prognosis and is a promising biomarker for response to anti-microtubule agents. However, existing methodologies to measure this rate are labor intensive, indirect, and confounded by selection against aneuploid cells, which reduces observable diversity. We developed a framework to measure CIN, accounting for karyotype selection, using simulations with various levels of CIN and models of selection. To identify the model parameters that best fit karyotype data from single-cell sequencing, we used approximate Bayesian computation to infer mis-segregation rates and karyotype selection. Experimental validation confirmed the extensive chromosome mis-segregation rates caused by the chemotherapy paclitaxel (18.5 \u00b1 0.5/division). Extending this approach to clinical samples revealed that inferred rates fell within direct observations of cancer cell lines. This work provides the necessary framework to quantify CIN in human tumors and develop it as a predictive biomarker.",
			"category": 2,
			"name": "Lynch Andrew R,2022"
		},
		{
			"PMID": 35355264,
			"title": "Unravelling the tumour genome: The evolutionary and clinical impacts of structural variants in tumourigenesis.",
			"journal": "The Journal of pathology",
			"authorList": [
				"Hamdan Alhafidz",
				"Ewing Ailith"
			],
			"DOI": "10.1002/path.5901",
			"date": "2022-07-07",
			"PMC": "",
			"citation": "",
			"abstract": "Structural variants (SVs) represent a major source of aberration in tumour genomes. Given the diversity in the size and type of SVs present in tumours, the accurate detection and interpretation of SVs in tumours is challenging. New classes of complex structural events in tumours are discovered frequently, and the definitions of the genomic consequences of complex events are constantly being refined. Detailed analyses of short-read whole-genome sequencing (WGS) data from large tumour cohorts facilitate the interrogation of SVs at orders of magnitude greater scale and depth. However, the inherent technical limitations of short-read WGS prevent us from accurately detecting and investigating the impact of all the SVs present in tumours. The expanded use of long-read WGS will be critical for improving the accuracy of SV detection, and in fully resolving complex SV events, both of which are crucial for determining the impact of SVs on tumour progression and clinical outcome. Despite the present limitations, we demonstrate that SVs play an important role in tumourigenesis. In particular, SVs contribute significantly to late-stage tumour development and to intratumoural heterogeneity. The evolutionary trajectories of SVs represent a window into the clonal dynamics in tumours, a comprehensive understanding of which will be vital for influencing patient outcomes in the future. Recent findings have highlighted many clinical applications of SVs in cancer, from early detection to biomarkers for treatment response and prognosis. As the methods to detect and interpret SVs improve, elucidating the full breadth of the complex SV landscape and determining how these events modulate tumour evolution will improve our understanding of cancer biology and our ability to capitalise on the utility of SVs in the clinical management of cancer patients. \u00a9 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.",
			"category": 2,
			"name": "Hamdan Alhafidz,2022"
		},
		{
			"PMID": 35326660,
			"title": "Distinct Genomic Profiles Are Associated with Treatment Response and Survival in Ovarian Cancer.",
			"journal": "Cancers",
			"authorList": [
				"de Witte Chris J",
				"Kutzera Joachim",
				"van Hoeck Arne",
				"Nguyen Luan",
				"Boere Ingrid A",
				"Jalving Mathilde",
				"Ottevanger Petronella B",
				"van Schaik-van de Mheen Christa",
				"Stevense Marion",
				"Kloosterman Wigard P",
				"Zweemer Ronald P",
				"Cuppen Edwin",
				"Witteveen Petronella O"
			],
			"DOI": "10.3390/cancers14061511",
			"date": "2022-03-29",
			"PMC": "",
			"citation": "",
			"abstract": "The majority of patients with ovarian cancer ultimately develop recurrent chemotherapy-resistant disease. Treatment stratification is mainly based on histological subtype and stage, prior response to platinum-based chemotherapy, and time to recurrent disease. Here, we integrated clinical treatment, treatment response, and survival data with whole-genome sequencing profiles of 132 solid tumor biopsies of metastatic epithelial ovarian cancer to explore genome-informed stratification opportunities. Samples from primary and recurrent disease harbored comparable numbers of single nucleotide variants and structural variants. Mutational signatures represented platinum exposure, homologous recombination deficiency, and aging. Unsupervised hierarchical clustering based on genomic input data identified specific ovarian cancer subgroups, characterized by homologous recombination deficiency, genome stability, and duplications. The clusters exhibited distinct response rates and survival probabilities which could thus potentially be used for genome-informed therapy stratification for more personalized ovarian cancer treatment.",
			"category": 2,
			"name": "de Witte Chris J,2022"
		},
		{
			"PMID": 35290628,
			"title": "Robust Computational Approaches to Defining Insights on the Interface of DNA Repair with Replication and Transcription in Cancer.",
			"journal": "Methods in molecular biology (Clifton, N.J.)",
			"authorList": [
				"Bacolla Albino",
				"Tainer John A"
			],
			"DOI": "10.1007/978-1-0716-2063-2_1",
			"date": "2022-03-17",
			"PMC": "",
			"citation": "",
			"abstract": "The massive amount of experimental DNA and RNA sequence information provides an encyclopedia for cell biology that requires computational tools for efficient interpretation. The ability to write and apply simple computing scripts propels the investigator beyond the boundaries of online analysis tools to more broadly interrogate laboratory experimental data and to integrate them with all available datasets to test and challenge hypotheses. Here we describe robust prototypic bash and C++ scripts with metrics and methods for validation that we have made publicly available to address the roles of non-B DNA-forming motifs in eliciting genetic instability and to query The Cancer Genome Atlas. Importantly, the methods presented provide practical data interpretation tools to examine fundamental relationships and to enable insights and correlations between alterations in gene expression patterns and patient outcome. The exemplary source codes described are simple and can be efficiently modified, elaborated, and applied to other relationships and areas of investigation.",
			"category": 2,
			"name": "Bacolla Albino,2022"
		},
		{
			"PMID": 35253958,
			"title": "Intra-epithelial non-canonical Activin A signaling safeguards prostate progenitor quiescence.",
			"journal": "EMBO reports",
			"authorList": [
				"Cambuli Francesco",
				"Foletto Veronica",
				"Alaimo Alessandro",
				"De Felice Dario",
				"Gandolfi Francesco",
				"Palumbieri Maria Dilia",
				"Zaffagni Michela",
				"Genovesi Sacha",
				"Lorenzoni Marco",
				"Celotti Martina",
				"Bertossio Emiliana",
				"Mazzero Giosu\u00e8",
				"Bertossi Arianna",
				"Bisio Alessandra",
				"Berardinelli Francesco",
				"Antoccia Antonio",
				"Gaspari Marco",
				"Barbareschi Mattia",
				"Fiorentino Michelangelo",
				"Shen Michael M",
				"Loda Massimo",
				"Romanel Alessandro",
				"Lunardi Andrea"
			],
			"DOI": "10.15252/embr.202154049",
			"date": "2022-05-05",
			"PMC": "",
			"citation": "",
			"abstract": "The healthy prostate is a relatively quiescent tissue. Yet, prostate epithelium overgrowth is a common condition during aging, associated with urinary dysfunction and tumorigenesis. For over thirty years, TGF-\u03b2 ligands have been known to induce cytostasis in a variety of epithelia, but the intracellular pathway mediating this signal in the prostate, and its relevance for quiescence, have remained elusive. Here, using mouse prostate organoids to model epithelial progenitors, we find that intra-epithelial non-canonical Activin A signaling inhibits cell proliferation in a Smad-independent manner. Mechanistically, Activin A triggers Tak1 and p38 \u039cAPK activity, leading to p16 and p21 nuclear import. Spontaneous evasion from this quiescent state occurs upon prolonged culture, due to reduced Activin A secretion, a condition associated with DNA replication stress and aneuploidy. Organoids capable to escape quiescence in vitro are also able to implant with increased frequency into immunocompetent mice. This study demonstrates that non-canonical Activin A signaling safeguards epithelial quiescence in the healthy prostate, with potential implications for the understanding of cancer initiation, and the development of therapies targeting quiescent tumor progenitors.",
			"category": 2,
			"name": "Cambuli Francesco,2022"
		},
		{
			"PMID": 35252434,
			"title": "Early Breast Cancer Evolution by Autosomal Broad Copy Number Alterations.",
			"journal": "International journal of genomics",
			"authorList": [
				"Larsen Joseph R",
				"Kuhn Peter",
				"Hicks James B"
			],
			"DOI": "10.1155/2022/9332922",
			"date": "2022-03-09",
			"PMC": "",
			"citation": "",
			"abstract": "The availability of comprehensive genomic datasets across patient populations enables the application of novel methods for reconstructing tumor evolution within individual patients. To this end, we propose studying autosomal broad copy number alterations (CNAs) as a framework to better understand early tumor evolution. We compared the broad CNAs and somatic mutations of patients with 1 to 10 autosomal broad CNAs against the full set of patients, using data from The Cancer Genome Atlas breast cancer project. We reveal here that the frequency of a chromosome arm obtaining a broad CNA and a genome acquiring somatic mutations changes as autosomal broad CNAs accumulate. Therefore, we propose that the number of autosomal broad CNAs is an important characteristic of breast tumors that needs to be taken into consideration when studying breast tumors. To investigate this idea more in-depth, we next studied the frequency that specific chromosome arms acquire broad CNAs in patients with 1 to 10 broad CNAs. With this process, we identified the broad CNAs that exhibit the fastest rates of accumulation across all patients. This finding suggests a likely order of occurrence of these alterations in patients, which is apparent when we consider a subset of patients with few broad CNAs. Here, we lay the foundation for future studies to build upon our findings and use autosomal broad CNAs as a method to monitor breast tumor progression in vivo to further our understanding of how early tumor evolution unfolds.",
			"category": 2,
			"name": "Larsen Joseph R,2022"
		},
		{
			"PMID": 35247876,
			"title": "Reconstructing Complex Cancer Evolutionary Histories from Multiple Bulk DNA Samples Using Pairtree.",
			"journal": "Blood cancer discovery",
			"authorList": [
				"Wintersinger Jeff A",
				"Dobson Stephanie M",
				"Kulman Ethan",
				"Stein Lincoln D",
				"Dick John E",
				"Morris Quaid"
			],
			"DOI": "10.1158/2643-3230.BCD-21-0092",
			"date": "2022-05-06",
			"PMC": "",
			"citation": "",
			"abstract": "Cancers are composed of genetically distinct subpopulations of malignant cells. DNA-sequencing data can be used to determine the somatic point mutations specific to each population and build clone trees describing the evolutionary relationships between them. These clone trees can reveal critical points in disease development and inform treatment. Pairtree is a new method that constructs more accurate and detailed clone trees than previously possible using variant allele frequency data from one or more bulk cancer samples. It does so by first building a Pairs Tensor that captures the evolutionary relationships between pairs of subpopulations, and then it uses these relations to constrain clone trees and infer violations of the infinite sites assumption. Pairtree can accurately build clone trees using up to 100 samples per cancer that contain 30 or more subclonal populations. On 14 B-progenitor acute lymphoblastic leukemias, Pairtree replicates or improves upon expert-derived clone tree reconstructions.",
			"category": 2,
			"name": "Wintersinger Jeff A,2022"
		},
		{
			"PMID": 35186006,
			"title": "A Tumor Suppressor Gene-Based Prognostic Classifier Predicts Prognosis, Tumor Immune Infiltration, and Small Molecule Compounds in Breast Cancer.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Jiang Suxiao",
				"Bu Xiangjing",
				"Tang Desheng",
				"Yan Changsheng",
				"Huang Yan",
				"Fang Kun"
			],
			"DOI": "10.3389/fgene.2021.783026",
			"date": "2022-02-23",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "Jiang Suxiao,2022"
		},
		{
			"PMID": 35174643,
			"title": "Hepatocellular carcinoma after a sustained virological response by direct-acting antivirals harbors TP53 inactivation.",
			"journal": "Cancer medicine",
			"authorList": [
				"Imamura Taisuke",
				"Okamura Yukiyasu",
				"Ohshima Keiichi",
				"Uesaka Katsuhiko",
				"Sugiura Teiichi",
				"Ito Takaaki",
				"Yamamoto Yusuke",
				"Ashida Ryo",
				"Ohgi Katsuhisa",
				"Otsuka Shimpei",
				"Ohnami Sumiko",
				"Nagashima Takeshi",
				"Hatakeyama Keiichi",
				"Kakuda Yuko",
				"Sugino Takashi",
				"Urakami Kenichi",
				"Akiyama Yasuto",
				"Yamaguchi Ken"
			],
			"DOI": "10.1002/cam4.4571",
			"date": "2022-04-28",
			"PMC": "",
			"citation": "",
			"abstract": "The genomic characteristics of hepatocellular carcinoma (HCC) after a sustained virological response (SVR) and its differences according to whether an SVR was achieved by treatment with direct-acting antivirals (DAA) or interferon (IFN) are still not fully understood.",
			"category": 2,
			"name": "Imamura Taisuke,2022"
		},
		{
			"PMID": 35154165,
			"title": "Genetic Changes Driving Immunosuppressive Microenvironments in Oral Premalignancy.",
			"journal": "Frontiers in immunology",
			"authorList": [
				"Rangel Roberto",
				"Pickering Curtis R",
				"Sikora Andrew G",
				"Spiotto Michael T"
			],
			"DOI": "10.3389/fimmu.2022.840923",
			"date": "2022-03-14",
			"PMC": "",
			"citation": "",
			"abstract": "Oral premalignant lesions (OPLs) are the precursors to oral cavity cancers, and have variable rates of progression to invasive disease. As an intermediate state, OPLs have acquired a subset of the genomic alterations while arising in an oral inflammatory environment. These specific genomic changes may facilitate the transition to an immune microenvironment that permits malignant transformation. Here, we will discuss mechanisms by which OPLs develop an immunosuppressive microenvironment that facilitates progression to invasive cancer. We will describe how genomic alterations and immune microenvironmental changes co-evolve and cooperate to promote OSCC progression. Finally, we will describe how these immune microenvironmental changes provide specific and unique evolutionary vulnerabilities for targeted therapies. Therefore, understanding the genomic changes that drive immunosuppressive microenvironments may eventually translate into novel biomarker and/or therapeutic approaches to limit the progression of OPLs to potential lethal oral cancers.",
			"category": 2,
			"name": "Rangel Roberto,2022"
		},
		{
			"PMID": 35122049,
			"title": "Pan-cancer computational histopathology reveals mutations, tumor composition and prognosis.",
			"journal": "Nature cancer",
			"authorList": [
				"Fu Yu",
				"Jung Alexander W",
				"Torne Ramon Vi\u00f1as",
				"Gonzalez Santiago",
				"V\u00f6hringer Harald",
				"Shmatko Artem",
				"Yates Lucy R",
				"Jimenez-Linan Mercedes",
				"Moore Luiza",
				"Gerstung Moritz"
			],
			"DOI": "10.1038/s43018-020-0085-8",
			"date": "2022-04-14",
			"PMC": "",
			"citation": "",
			"abstract": "We use deep transfer learning to quantify histopathological patterns across 17,355 hematoxylin and eosin-stained histopathology slide images from 28 cancer types and correlate these with matched genomic, transcriptomic and survival data. This approach accurately classifies cancer types and provides spatially resolved tumor and normal tissue distinction. Automatically learned computational histopathological features correlate with a large range of recurrent genetic aberrations across cancer types. This includes whole-genome duplications, which display universal features across cancer types, individual chromosomal aneuploidies, focal amplifications and deletions, as well as driver gene mutations. There are widespread associations between bulk gene expression levels and histopathology, which reflect tumor composition and enable the localization of transcriptomically defined tumor-infiltrating lymphocytes. Computational histopathology augments prognosis based on histopathological subtyping and grading, and highlights prognostically relevant areas such as necrosis or lymphocytic aggregates. These findings show the remarkable potential of computer vision in characterizing the molecular basis of tumor histopathology.",
			"category": 2,
			"name": "Fu Yu,2022"
		},
		{
			"PMID": 35121980,
			"title": "Delineating the evolutionary dynamics of cancer from theory to reality.",
			"journal": "Nature cancer",
			"authorList": [
				"Bozic Ivana",
				"Wu Catherine J"
			],
			"DOI": "10.1038/s43018-020-0079-6",
			"date": "2022-04-14",
			"PMC": "",
			"citation": "",
			"abstract": "Uncovering and quantifying the laws of the evolutionary dynamics of cancer, in particular in the context of specific genetic lesions and in individual patients, has the potential to revolutionize precision oncology. Recent technological advances in the study of human cancer have increased access to in vivo human data and have thereby facilitated the confirmation or refutation of existing theoretical models. In this Perspective, we discuss recent work at the intersection of quantitative mathematical models of cancer evolution and patient data that provides insights into different stages of tumor evolution, including premalignant and malignant progression and response to therapy.",
			"category": 2,
			"name": "Bozic Ivana,2022"
		},
		{
			"PMID": 35106210,
			"title": "Do We Need a New Approach to Cancer Biology Education for Radiation Oncology Residents?",
			"journal": "Cureus",
			"authorList": [
				"Vijayakumar Srinivasan",
				"King Maurice",
				"Nittala Mary R",
				"Duhe Roy J"
			],
			"DOI": "10.7759/cureus.20662",
			"date": "2022-02-04",
			"PMC": "",
			"citation": "",
			"abstract": "Traditional radiation oncology biology courses largely focus on radiation biology and oncology as needed for passing the boards.\u00a0Changes in the landscape of oncology necessitate a broader scope. Radiotherapy is an important component of cancer care. Approximately 70% of all cancer patients receive radiotherapy during the course of their disease.\u00a0With the revolution in precision medicine that is unfolding, genomics, proteomics, metabolomics, and microbiomics are being ever more integrated into the treatment of cancer.\u00a0Comprehensive knowledge of cancer biology beyond traditional radiation biology is essential for future advances in radiotherapy and unavoidable for radiation oncology trainees.\u00a0The importance of a newly designed curriculum to impart broader knowledge to future radiation oncologists is emphasized in this report. A paradigm shift in the approach to the traditional radiation biology course is required to train residents for the future of oncology.",
			"category": 2,
			"name": "Vijayakumar Srinivasan,2022"
		},
		{
			"PMID": 35096825,
			"title": "Deconstructing Pancreatic Cancer Using Next Generation-Omic Technologies-From Discovery to Knowledge-Guided Platforms for Better Patient Management.",
			"journal": "Frontiers in cell and developmental biology",
			"authorList": [
				"Schreyer Daniel",
				"Neoptolemos John P",
				"Barry Simon T",
				"Bailey Peter"
			],
			"DOI": "10.3389/fcell.2021.795735",
			"date": "2024-04-05",
			"PMC": "",
			"citation": "",
			"abstract": "Comprehensive molecular landscaping studies reveal a potentially brighter future for pancreatic ductal adenocarcinoma (PDAC) patients. Blood-borne biomarkers obtained from minimally invasive \"liquid biopsies\" are now being trialled for early disease detection and to track responses to therapy. Integrated genomic and transcriptomic studies using resectable tumour material have defined intrinsic patient subtypes and actionable genomic segments that promise a shift towards genome-guided patient management. Multimodal mapping of PDAC using spatially resolved single cell transcriptomics and imaging techniques has identified new potentially therapeutically actionable cellular targets and is providing new insights into PDAC tumour heterogeneity. Despite these rapid advances, defining biomarkers for patient selection remain limited. This review examines the current PDAC cancer biomarker ecosystem (identified in tumour and blood) and explores how advances in single cell sequencing and spatially resolved imaging modalities are being used to uncover new targets for therapeutic intervention and are transforming our understanding of this difficult to treat disease.",
			"category": 2,
			"name": "Schreyer Daniel,2024"
		},
		{
			"PMID": 35058638,
			"title": "Life histories of myeloproliferative neoplasms inferred from phylogenies.",
			"journal": "Nature",
			"authorList": [
				"Williams Nicholas",
				"Lee Joe",
				"Mitchell Emily",
				"Moore Luiza",
				"Baxter E Joanna",
				"Hewinson James",
				"Dawson Kevin J",
				"Menzies Andrew",
				"Godfrey Anna L",
				"Green Anthony R",
				"Campbell Peter J",
				"Nangalia Jyoti"
			],
			"DOI": "10.1038/s41586-021-04312-6",
			"date": "2022-04-19",
			"PMC": "",
			"citation": "",
			"abstract": "Mutations in cancer-associated genes drive tumour outgrowth, but our knowledge of the timing of driver mutations and subsequent clonal dynamics is limited",
			"category": 2,
			"name": "Williams Nicholas,2022"
		},
		{
			"PMID": 35042965,
			"title": "Rare germline copy number variants (CNVs) and breast cancer risk.",
			"journal": "Communications biology",
			"authorList": [
				"Dennis Joe",
				"Tyrer Jonathan P",
				"Walker Logan C",
				"Michailidou Kyriaki",
				"Dorling Leila",
				"Bolla Manjeet K",
				"Wang Qin",
				"Ahearn Thomas U",
				"Andrulis Irene L",
				"Anton-Culver Hoda",
				"Antonenkova Natalia N",
				"Arndt Volker",
				"Aronson Kristan J",
				"Freeman Laura E Beane",
				"Beckmann Matthias W",
				"Behrens Sabine",
				"Benitez Javier",
				"Bermisheva Marina",
				"Bogdanova Natalia V",
				"Bojesen Stig E",
				"Brenner Hermann",
				"Castelao Jose E",
				"Chang-Claude Jenny",
				"Chenevix-Trench Georgia",
				"Clarke Christine L",
				"NBCS Collaborators",
				"Coll\u00e9e J Margriet",
				"CTS Consortium",
				"Couch Fergus J",
				"Cox Angela",
				"Cross Simon S",
				"Czene Kamila",
				"Devilee Peter",
				"D\u00f6rk Thilo",
				"Dossus Laure",
				"Eliassen A Heather",
				"Eriksson Mikael",
				"Evans D Gareth",
				"Fasching Peter A",
				"Figueroa Jonine",
				"Fletcher Olivia",
				"Flyger Henrik",
				"Fritschi Lin",
				"Gabrielson Marike",
				"Gago-Dominguez Manuela",
				"Garc\u00eda-Closas Montserrat",
				"Giles Graham G",
				"Gonz\u00e1lez-Neira Anna",
				"Gu\u00e9nel Pascal",
				"Hahnen Eric",
				"Haiman Christopher A",
				"Hall Per",
				"Hollestelle Antoinette",
				"Hoppe Reiner",
				"Hopper John L",
				"Howell Anthony",
				"ABCTB Investigators",
				"kConFab/AOCS Investigators",
				"Jager Agnes",
				"Jakubowska Anna",
				"John Esther M",
				"Johnson Nichola",
				"Jones Michael E",
				"Jung Audrey",
				"Kaaks Rudolf",
				"Keeman Renske",
				"Khusnutdinova Elza",
				"Kitahara Cari M",
				"Ko Yon-Dschun",
				"Kosma Veli-Matti",
				"Koutros Stella",
				"Kraft Peter",
				"Kristensen Vessela N",
				"Kubelka-Sabit Katerina",
				"Kurian Allison W",
				"Lacey James V",
				"Lambrechts Diether",
				"Larson Nicole L",
				"Linet Martha",
				"Ogrodniczak Alicja",
				"Mannermaa Arto",
				"Manoukian Siranoush",
				"Margolin Sara",
				"Mavroudis Dimitrios",
				"Milne Roger L",
				"Muranen Taru A",
				"Murphy Rachel A",
				"Nevanlinna Heli",
				"Olson Janet E",
				"Olsson H\u00e5kan",
				"Park-Simon Tjoung-Won",
				"Perou Charles M",
				"Peterlongo Paolo",
				"Plaseska-Karanfilska Dijana",
				"Pylk\u00e4s Katri",
				"Rennert Gad",
				"Saloustros Emmanouil",
				"Sandler Dale P",
				"Sawyer Elinor J",
				"Schmidt Marjanka K",
				"Schmutzler Rita K",
				"Shibli Rana",
				"Smeets Ann",
				"Soucy Penny",
				"Southey Melissa C",
				"Swerdlow Anthony J",
				"Tamimi Rulla M",
				"Taylor Jack A",
				"Teras Lauren R",
				"Terry Mary Beth",
				"Tomlinson Ian",
				"Troester Melissa A",
				"Truong Th\u00e9r\u00e8se",
				"Vachon Celine M",
				"Wendt Camilla",
				"Winqvist Robert",
				"Wolk Alicja",
				"Yang Xiaohong R",
				"Zheng Wei",
				"Ziogas Argyrios",
				"Simard Jacques",
				"Dunning Alison M",
				"Pharoah Paul D P",
				"Easton Douglas F"
			],
			"DOI": "10.1038/s42003-021-02990-6",
			"date": "2022-03-03",
			"PMC": "",
			"citation": "",
			"abstract": "Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P\u2009=\u20093.7E-18). Nine other genes were associated with a p-value\u2009<\u20090.01 including known susceptibility genes CHEK2 (P\u2009=\u20090.0008), ATM (P\u2009=\u20090.002) and BRCA2 (P\u2009=\u20090.008). Outside the known genes we detected associations with p-values\u2009<\u20090.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.",
			"category": 2,
			"name": "Dennis Joe,2022"
		},
		{
			"PMID": 35023616,
			"title": "The clinicopathological and molecular characteristics of resected EGFR-mutant lung adenocarcinoma.",
			"journal": "Cancer medicine",
			"authorList": [
				"Zhou Wensheng",
				"Liu Zhichao",
				"Wang Yanan",
				"Zhang Yanwei",
				"Qian Fangfei",
				"Lu Jun",
				"Wang Huimin",
				"Gu Ping",
				"Hu Minjuan",
				"Chen Ya",
				"Yang Zhengyu",
				"Zhao Ruiying",
				"Lou Yuqing",
				"Han Baohui",
				"Zhang Wei"
			],
			"DOI": "10.1002/cam4.4543",
			"date": "2022-04-18",
			"PMC": "",
			"citation": "",
			"abstract": "Epidermal growth factor receptor (EGFR) mutations were frequently found with concomitant genetic alterations in lung adenocarcinoma (LUAD). This study aimed to investigate the profile of concomitant alterations of EGFR-mutant LUAD \u22643\u00a0cm in size and its prognostic effect on recurrence.",
			"category": 2,
			"name": "Zhou Wensheng,2022"
		},
		{
			"PMID": 35017538,
			"title": "Age influences on the molecular presentation of tumours.",
			"journal": "Nature communications",
			"authorList": [
				"Li Constance H",
				"Haider Syed",
				"Boutros Paul C"
			],
			"DOI": "10.1038/s41467-021-27889-y",
			"date": "2022-02-08",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is often called a disease of aging. There are numerous ways in which cancer epidemiology and behaviour change with the age of the patient. The molecular bases for these relationships remain largely underexplored. To characterise them, we analyse age-associations in the nuclear and mitochondrial somatic mutational landscape of 20,033 tumours across 35 tumour-types. Age influences both the number of mutations in a tumour (0.077 mutations per megabase per year) and their evolutionary timing. Specific mutational signatures are associated with age, reflecting differences in exogenous and endogenous oncogenic processes such as a greater influence of tobacco use in the tumours of younger patients, but higher activity of DNA damage repair signatures in those of older patients. We find that known cancer driver genes such as CDKN2A and CREBBP are mutated in age-associated frequencies, and these alter the transcriptome and predict for clinical outcomes. These effects are most striking in brain cancers where alterations like SUFU loss and ATRX mutation are age-dependent prognostic biomarkers. Using three cancer datasets, we show that age shapes the somatic mutational landscape of cancer, with clinical implications.",
			"category": 2,
			"name": "Li Constance H,2022"
		},
		{
			"PMID": 34986026,
			"title": "ScalpelSig Designs Targeted Genomic Panels from Data to Detect Activity of Mutational Signatures.",
			"journal": "Journal of computational biology : a journal of computational molecular cell biology",
			"authorList": [
				"Franzese Nicholas",
				"Fan Jason",
				"Sharan Roded",
				"Leiserson Mark D M"
			],
			"DOI": "10.1089/cmb.2021.0453",
			"date": "2022-03-28",
			"PMC": "",
			"citation": "",
			"abstract": "Over the past decade, a promising line of cancer research has utilized machine learning to mine statistical patterns of mutations in cancer genomes for information. Recent work shows that these statistical patterns, commonly referred to as \"mutational signatures,\" have diverse therapeutic potential as biomarkers for cancer therapies. However, translating this potential into reality is hindered by limited access to sequencing in the clinic. Almost all methods for mutational signature analysis (MSA) rely on whole genome or whole exome sequencing data, while sequencing in the clinic is typically limited to small gene panels. To improve clinical access to MSA, we considered the question of whether targeted panels could be designed for the purpose of mutational signature detection. Here we present ScalpelSig, to our knowledge the first algorithm that automatically designs genomic panels optimized for detection of a given mutational signature. The algorithm learns from data to identify genome regions that are particularly indicative of signature activity. Using a cohort of breast cancer genomes as training data, we show that ScalpelSig panels substantially improve accuracy of signature detection compared to baselines. We find that some ScalpelSig panels even approach the performance of whole exome sequencing, which observes over 10\u2009\u00d7\u2009as much genomic material. We test our algorithm under a variety of conditions, showing that its performance generalizes to another dataset of breast cancers, to smaller panel sizes, and to lesser amounts of training data.",
			"category": 2,
			"name": "Franzese Nicholas,2022"
		},
		{
			"PMID": 34978574,
			"title": "Molecular Biologic and Epidemiologic Insights for Preventability of Colorectal Cancer.",
			"journal": "Journal of the National Cancer Institute",
			"authorList": [
				"Giovannucci Edward"
			],
			"DOI": "10.1093/jnci/djab229",
			"date": "2022-05-11",
			"PMC": "",
			"citation": "",
			"abstract": "The etiology of colorectal cancer (CRC) has been informed from both a molecular biology perspective, which concerns the study of the nature, timing, and consequences of mutations in driver genes, and epidemiology, which focuses on identifying risk factors for cancer. For the most part, these fields have developed independently, and it is thus important to consider them in a more integrated manner. The molecular mutational perspective has stressed the importance of mutations due to replication of adult stem cells, and the molecular fingerprint of most CRCs does not suggest the importance of direct carcinogens. Epidemiology has identified numerous modifiable risk factors that account for most CRCs, most of which are not direct mutagens. The distribution of CRCs across the large bowel is not uniform, which is possibly caused by regional differences in the microbiota. Some risk factors are likely to act through or interact with the microbiota. The mutational perspective informs when risk factors may begin to operate in life and when they may cease to operate. Evidence from the mutational model and epidemiology supports that CRC risk factors begin early in life and may contribute to the risk of early-onset CRC. Later in carcinogenesis, there may be a \"point of no return\" when sufficient mutations have accumulated, and some risk factors do not affect cancer risk. This period may be at least 5-15\u2009years for some risk factors. A more precise knowledge of timing of risk factor to cancer is required to inform preventive efforts.",
			"category": 2,
			"name": "Giovannucci Edward,2022"
		},
		{
			"PMID": 34953682,
			"title": "Anticancer drug resistance: An update and perspective.",
			"journal": "Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy",
			"authorList": [
				"Nussinov Ruth",
				"Tsai Chung-Jung",
				"Jang Hyunbum"
			],
			"DOI": "10.1016/j.drup.2021.100796",
			"date": "2022-03-04",
			"PMC": "",
			"citation": "",
			"abstract": "Driver mutations promote initiation and progression of cancer. Pharmacological treatment can inhibit the action of the mutant protein; however, drug resistance almost invariably emerges. Multiple studies revealed that cancer drug resistance is based upon a plethora of distinct mechanisms. Drug resistance mutations can occur in the same protein or in different proteins; as well as in the same pathway or in parallel pathways, bypassing the intercepted signaling. The dilemma that the clinical oncologist is facing is that not all the genomic alterations as well as alterations in the tumor microenvironment that facilitate cancer cell proliferation are known, and neither are the alterations that are likely to promote metastasis. For example, the common KRas",
			"category": 2,
			"name": "Nussinov Ruth,2022"
		},
		{
			"PMID": 34949822,
			"title": "Spatial structure governs the mode of tumour evolution.",
			"journal": "Nature ecology & evolution",
			"authorList": [
				"Noble Robert",
				"Burri Dominik",
				"Le Sueur C\u00e9cile",
				"Lemant Jeanne",
				"Viossat Yannick",
				"Kather Jakob Nikolas",
				"Beerenwinkel Niko"
			],
			"DOI": "10.1038/s41559-021-01615-9",
			"date": "2022-03-16",
			"PMC": "",
			"citation": "",
			"abstract": "Characterizing the mode-the way, manner or pattern-of evolution in tumours is important for clinical forecasting and optimizing cancer treatment. Sequencing studies have inferred various modes, including branching, punctuated and neutral evolution, but it is unclear why a particular pattern predominates in any given tumour. Here we propose that tumour architecture is key to explaining the variety of observed genetic patterns. We examine this hypothesis using spatially explicit population genetics models and demonstrate that, within biologically relevant parameter ranges, different spatial structures can generate four tumour evolutionary modes: rapid clonal expansion, progressive diversification, branching evolution and effectively almost neutral evolution. Quantitative indices for describing and classifying these evolutionary modes are presented. Using these indices, we show that our model predictions are consistent with empirical observations for cancer types with corresponding spatial structures. The manner of cell dispersal and the range of cell-cell interactions are found to be essential factors in accurately characterizing, forecasting and controlling tumour evolution.",
			"category": 2,
			"name": "Noble Robert,2022"
		},
		{
			"PMID": 34918118,
			"title": "Origins of biallelic inactivation of NF2 in neurofibromatosis type 2.",
			"journal": "Neuro-oncology",
			"authorList": [
				"Xue Lu",
				"He Weiwei",
				"Zhang Yi",
				"Wang Zhigang",
				"Chen Hongsai",
				"Chen Zhe",
				"Zhu Weidong",
				"Liu Dongmei",
				"Jia Huan",
				"Jiang Yi",
				"Wang Zhaoyan",
				"Wu Hao"
			],
			"DOI": "10.1093/neuonc/noab287",
			"date": "2022-06-03",
			"PMC": "",
			"citation": "",
			"abstract": "Elucidating the mechanism by which biallelic inactivation evolved could provide a mechanistic understanding for NF2 tumorigenesis and also a rationale for clinical management.",
			"category": 2,
			"name": "Xue Lu,2022"
		},
		{
			"PMID": 34917899,
			"title": "Changes in gene-gene interactions associated with cancer onset and progression are largely independent of changes in gene expression.",
			"journal": "iScience",
			"authorList": [
				"Arshad Zainab",
				"McDonald John F"
			],
			"DOI": "10.1016/j.isci.2021.103522",
			"date": "2021-12-18",
			"PMC": "",
			"citation": "",
			"abstract": "Recent findings indicate that changes underlying cancer onset and progression are not only attributable to changes in DNA structure and expression of individual genes but to changes in interactions among these genes as well. We examined co-expression changes in gene-network structure occurring during the onset and progression of nine different cancer types. Network complexity is generally reduced in the transition from normal precursor tissues to corresponding primary tumors. Cross-tissue cancer network similarity generally increases in early-stage cancers followed by a subsequent loss in cross-tissue cancer similarity as tumors reacquire cancer-specific network complexity. Gene-gene connections remaining stable through cancer development are enriched for \"housekeeping\" gene functions, whereas newly acquired interactions are associated with established cancer-promoting functions. Surprisingly, >90% of changes in gene-gene network interactions in cancers are not associated with changes in the expression of network genes relative to normal precursor tissues.",
			"category": 2,
			"name": "Arshad Zainab,2021"
		},
		{
			"PMID": 34916492,
			"title": "Targeting PI3K/Akt signal transduction for cancer therapy.",
			"journal": "Signal transduction and targeted therapy",
			"authorList": [
				"He Yan",
				"Sun Miao Miao",
				"Zhang Guo Geng",
				"Yang Jing",
				"Chen Kui Sheng",
				"Xu Wen Wen",
				"Li Bin"
			],
			"DOI": "10.1038/s41392-021-00828-5",
			"date": "2022-03-22",
			"PMC": "",
			"citation": "",
			"abstract": "The phosphatidylinositol 3-kinase (PI3K)/Akt pathway plays a crucial role in various cellular processes and is aberrantly activated in cancers, contributing to the occurrence and progression of tumors. Examining the upstream and downstream nodes of this pathway could allow full elucidation of its function. Based on accumulating evidence, strategies targeting major components of the pathway might provide new insights for cancer drug discovery. Researchers have explored the use of some inhibitors targeting this pathway to block survival pathways. However, because oncogenic PI3K pathway activation occurs through various mechanisms, the clinical efficacies of these inhibitors are limited. Moreover, pathway activation is accompanied by the development of therapeutic resistance. Therefore, strategies involving pathway inhibitors and other cancer treatments in combination might solve the therapeutic dilemma. In this review, we discuss the roles of the PI3K/Akt pathway in various cancer phenotypes, review the current statuses of different PI3K/Akt inhibitors, and introduce combination therapies consisting of signaling inhibitors and conventional cancer therapies. The information presented herein suggests that cascading inhibitors of the PI3K/Akt signaling pathway, either alone or in combination with other therapies, are the most effective treatment strategy for cancer.",
			"category": 2,
			"name": "He Yan,2022"
		},
		{
			"PMID": 34912115,
			"title": "Spatial genomics enables multi-modal study of clonal heterogeneity in tissues.",
			"journal": "Nature",
			"authorList": [
				"Zhao Tongtong",
				"Chiang Zachary D",
				"Morriss Julia W",
				"LaFave Lindsay M",
				"Murray Evan M",
				"Del Priore Isabella",
				"Meli Kevin",
				"Lareau Caleb A",
				"Nadaf Naeem M",
				"Li Jilong",
				"Earl Andrew S",
				"Macosko Evan Z",
				"Jacks Tyler",
				"Buenrostro Jason D",
				"Chen Fei"
			],
			"DOI": "10.1038/s41586-021-04217-4",
			"date": "2022-03-29",
			"PMC": "",
			"citation": "",
			"abstract": "The state and behaviour of a cell can be influenced by both genetic and environmental factors. In particular, tumour progression is determined by underlying genetic aberrations",
			"category": 2,
			"name": "Zhao Tongtong,2022"
		},
		{
			"PMID": 34911933,
			"title": "Epigenetic loss of heterogeneity from low to high grade localized prostate tumours.",
			"journal": "Nature communications",
			"authorList": [
				"Eksi Sebnem Ece",
				"Chitsazan Alex",
				"Sayar Zeynep",
				"Thomas George V",
				"Fields Andrew J",
				"Kopp Ryan P",
				"Spellman Paul T",
				"Adey Andrew C"
			],
			"DOI": "10.1038/s41467-021-27615-8",
			"date": "2022-01-18",
			"PMC": "",
			"citation": "",
			"abstract": "Identifying precise molecular subtypes attributable to specific stages of localized prostate cancer has proven difficult due to high levels of heterogeneity. Bulk assays represent a population-average, which mask the heterogeneity that exists at the single-cell level. In this work, we sequence the accessible chromatin regions of 14,424 single-cells from 18 flash-frozen prostate tumours. We observe shared chromatin features among low-grade prostate cancer cells are lost in high-grade tumours. Despite this loss, high-grade tumours exhibit an enrichment for FOXA1, HOXB13 and CDX2 transcription factor binding sites, indicating a shared trans-regulatory programme. We identify two unique genes encoding neuronal adhesion molecules that are highly accessible in high-grade prostate tumours. We show NRXN1 and NLGN1 expression in epithelial, endothelial, immune and neuronal cells in prostate cancer using cyclic immunofluorescence. Our results provide a deeper understanding of the active gene regulatory networks in primary prostate tumours, critical for molecular stratification of the disease.",
			"category": 2,
			"name": "Eksi Sebnem Ece,2022"
		},
		{
			"PMID": 34885017,
			"title": "Combining ReACp53 with Carboplatin to Target High-Grade Serous Ovarian Cancers.",
			"journal": "Cancers",
			"authorList": [
				"Neal Adam",
				"Lai Tiffany",
				"Singh Tanya",
				"Rahseparian Neela",
				"Grogan Tristan",
				"Elashoff David",
				"Scott Peter",
				"Pellegrini Matteo",
				"Memarzadeh Sanaz"
			],
			"DOI": "10.3390/cancers13235908",
			"date": "2023-06-17",
			"PMC": "",
			"citation": "",
			"abstract": "Ovarian malignancies are a leading cause of cancer-related death for US women. High-grade serous ovarian carcinomas (HGSOCs), the most common ovarian cancer subtype, are aggressive tumors with poor outcomes. Mutations in TP53 are common in HGSOCs, with a subset resulting in p53 aggregation and misregulation. ReACp53 is a peptide designed to inhibit mutant p53 aggregation and has been shown efficacious in targeting cancer cells in vitro and in vivo. As p53 regulates apoptosis, combining ReACp53 with carboplatin represents a logical therapeutic strategy. The efficacy of this combinatorial approach was tested in eight ovarian cancer cell lines and 10 patient HGSOC samples using an in vitro organoid drug assay, with the SynergyFinder tool utilized for calculating drug interactions. Results demonstrate that the addition of ReACp53 to carboplatin enhanced tumor cell targeting in the majority of samples tested, with synergistic effects measured in 2 samples, additivity measured in 14 samples, and antagonism measured in 1 sample. This combination was found to be synergistic in OVCAR3 ovarian cancer cells in vitro through enhanced apoptosis, and survival of mice bearing OVCAR3 intraperitoneal xenografts was extended when treated with the addition of ReACp53 to carboplatin versus carboplatin alone. Results suggest that carboplatin and ReACp53 may be a potential strategy in targeting a subset of HGSOCs.",
			"category": 2,
			"name": "Neal Adam,2023"
		},
		{
			"PMID": 34882582,
			"title": "Genomic and transcriptomic profiling reveals distinct molecular subsets associated with outcomes in mantle cell lymphoma.",
			"journal": "The Journal of clinical investigation",
			"authorList": [
				"Yi Shuhua",
				"Yan Yuting",
				"Jin Meiling",
				"Bhattacharya Supriyo",
				"Wang Yi",
				"Wu Yiming",
				"Yang Lu",
				"Gine Eva",
				"Clot Guillem",
				"Chen Lu",
				"Yu Ying",
				"Zou Dehui",
				"Wang Jun",
				"Phan An T",
				"Cui Rui",
				"Li Fei",
				"Sun Qi",
				"Zhai Qiongli",
				"Wang Tingyu",
				"Yu Zhen",
				"Liu Lanting",
				"Liu Wei",
				"Lyv Rui",
				"Sui Weiwei",
				"Huang Wenyang",
				"Xiong Wenjie",
				"Wang Huijun",
				"Li Chengwen",
				"Xiao Zhijian",
				"Hao Mu",
				"Wang Jianxiang",
				"Cheng Tao",
				"Bea Silvia",
				"Herrera Alex F",
				"Danilov Alexey",
				"Campo Elias",
				"Ngo Vu N",
				"Qiu Lugui",
				"Wang Lili"
			],
			"DOI": "10.1172/JCI153283",
			"date": "2022-03-28",
			"PMC": "",
			"citation": "",
			"abstract": "Mantle cell lymphoma (MCL) is a phenotypically and genetically heterogeneous malignancy in which the genetic alterations determining clinical indications are not fully understood. Here, we performed a comprehensive whole-exome sequencing analysis of 152 primary samples derived from 134 MCL patients, including longitudinal samples from 16 patients and matched RNA-Seq data from 48 samples. We classified MCL into 4 robust clusters (C1-C4). C1 featured mutated immunoglobulin heavy variable (IGHV), CCND1 mutation, amp(11q13), and active B cell receptor (BCR) signaling. C2 was enriched with del(11q)/ATM mutations and upregulation of NF-\u03baB and DNA repair pathways. C3 was characterized by mutations in SP140, NOTCH1, and NSD2, with downregulation of BCR signaling and MYC targets. C4 harbored del(17p)/TP53 mutations, del(13q), and del(9p), and active MYC pathway and hyperproliferation signatures. Patients in these 4 clusters had distinct outcomes (5-year overall survival [OS] rates for C1-C4 were 100%, 56.7%, 48.7%, and 14.2%, respectively). We also inferred the temporal order of genetic events and studied clonal evolution of 16 patients before treatment and at progression/relapse. Eleven of these samples showed drastic clonal evolution that was associated with inferior survival, while the other samples showed modest or no evolution. Our study thus identifies genetic subsets that clinically define this malignancy and delineates clonal evolution patterns and their impact on clinical outcomes.",
			"category": 2,
			"name": "Yi Shuhua,2022"
		},
		{
			"PMID": 34880424,
			"title": "Computational analysis of cancer genome sequencing data.",
			"journal": "Nature reviews. Genetics",
			"authorList": [
				"Cort\u00e9s-Ciriano Isidro",
				"Gulhan Doga C",
				"Lee Jake June-Koo",
				"Melloni Giorgio E M",
				"Park Peter J"
			],
			"DOI": "10.1038/s41576-021-00431-y",
			"date": "2022-04-22",
			"PMC": "",
			"citation": "",
			"abstract": "Distilling biologically meaningful information from cancer genome sequencing data requires comprehensive identification of somatic alterations using rigorous computational methods. As the amount and complexity of sequencing data have increased, so has the number of tools for analysing them. Here, we describe the main steps involved in the bioinformatic analysis of cancer genomes, review key algorithmic developments and highlight popular tools and emerging technologies. These tools include those that identify point mutations, copy number alterations, structural variations and mutational signatures in cancer genomes. We also discuss issues in experimental design, the strengths and limitations of sequencing modalities and methodological challenges for the future.",
			"category": 2,
			"name": "Cort\u00e9s-Ciriano Isidro,2022"
		},
		{
			"PMID": 34850073,
			"title": "Evolution under Spatially Heterogeneous Selection in Solid Tumors.",
			"journal": "Molecular biology and evolution",
			"authorList": [
				"Li Guanghao",
				"Yang Zuyu",
				"Wu Dafei",
				"Liu Sixue",
				"Li Xuening",
				"Li Tao",
				"Li Yawei",
				"Liang Liji",
				"Zou Weilong",
				"Wu Chung-I",
				"Wang Hurng-Yi",
				"Lu Xuemei"
			],
			"DOI": "10.1093/molbev/msab335",
			"date": "2022-03-31",
			"PMC": "",
			"citation": "",
			"abstract": "Spatial genetic and phenotypic diversity within solid tumors has been well documented. Nevertheless, how this heterogeneity affects temporal dynamics of tumorigenesis has not been rigorously examined because solid tumors do not evolve as the standard population genetic model due to the spatial constraint. We therefore, propose a neutral spatial (NS) model whereby the mutation accumulation increases toward the periphery; the genealogical relationship is spatially determined and the selection efficacy is blunted (due to kin competition). In this model, neutral mutations are accrued and spatially distributed in manners different from those of advantageous mutations. Importantly, the distinctions could be blurred in the conventional model. To test the NS model, we performed a three-dimensional multiple microsampling of two hepatocellular carcinomas. Whole-genome sequencing (WGS) revealed a 2-fold increase in mutations going from the center to the periphery. The operation of natural selection can then be tested by examining the spatially determined clonal relationships and the clonal sizes. Due to limited migration, only the expansion of highly advantageous clones can sweep through a large part of the tumor to reveal the selective advantages. Hence, even multiregional sampling can only reveal a fraction of fitness differences in solid tumors. Our results suggest that the NS patterns are crucial for testing the influence of natural selection during tumorigenesis, especially for small solid tumors.",
			"category": 2,
			"name": "Li Guanghao,2022"
		},
		{
			"PMID": 34845880,
			"title": "COSINE: A web server for clonal and subclonal structure inference and evolution in cancer genomics.",
			"journal": "Zoological research",
			"authorList": [
				"Yuan Xi-Guo",
				"Zhao Yuan",
				"Guo Yang",
				"Ge Lin-Mei",
				"Liu Wei",
				"Wen Shi-Yu",
				"Li Qi",
				"Wan Zhang-Bo",
				"Zheng Pei-Na",
				"Guo Tao",
				"Li Zhi-Da",
				"Peifer Martin",
				"Cun Yu-Peng"
			],
			"DOI": "10.24272/j.issn.2095-8137.2021.250",
			"date": "2022-02-10",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Yuan Xi-Guo,2022"
		},
		{
			"PMID": 34836952,
			"title": "Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes.",
			"journal": "Nature communications",
			"authorList": [
				"Ansari-Pour Naser",
				"Zheng Yonglan",
				"Yoshimatsu Toshio F",
				"Sanni Ayodele",
				"Ajani Mustapha",
				"Reynier Jean-Baptiste",
				"Tapinos Avraam",
				"Pitt Jason J",
				"Dentro Stefan",
				"Woodard Anna",
				"Rajagopal Padma Sheila",
				"Fitzgerald Dominic",
				"Gruber Andreas J",
				"Odetunde Abayomi",
				"Popoola Abiodun",
				"Falusi Adeyinka G",
				"Babalola Chinedum Peace",
				"Ogundiran Temidayo",
				"Ibrahim Nasiru",
				"Barretina Jordi",
				"Van Loo Peter",
				"Chen Mengjie",
				"White Kevin P",
				"Ojengbede Oladosu",
				"Obafunwa John",
				"Huo Dezheng",
				"Wedge David C",
				"Olopade Olufunmilayo I"
			],
			"DOI": "10.1038/s41467-021-27079-w",
			"date": "2022-01-07",
			"PMC": "",
			"citation": "",
			"abstract": "Black women across the African diaspora experience more aggressive breast cancer with higher mortality rates than white women of European ancestry. Although inter-ethnic germline variation is known, differential somatic evolution has not been investigated in detail. Analysis of deep whole genomes of 97 breast cancers, with RNA-seq in a subset, from women in Nigeria in comparison with The Cancer Genome Atlas (n\u2009=\u200976) reveal a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonal GATA3 mutations with a 10.5-year younger age at diagnosis. We also find non-coding mutations in bona fide drivers (ZNF217 and SYPL1) and a previously unreported INDEL signature strongly associated with African ancestry proportion, underscoring the need to expand inclusion of diverse populations in biomedical research. Finally, we demonstrate that characterizing tumors for homologous recombination deficiency has significant clinical relevance in stratifying patients for potentially life-saving therapies.",
			"category": 2,
			"name": "Ansari-Pour Naser,2022"
		},
		{
			"PMID": 34804073,
			"title": "Implementing Logic Gates for Safer Immunotherapy of Cancer.",
			"journal": "Frontiers in immunology",
			"authorList": [
				"Savanur Mohammed Azharuddin",
				"Weinstein-Marom Hadas",
				"Gross Gideon"
			],
			"DOI": "10.3389/fimmu.2021.780399",
			"date": "2022-02-14",
			"PMC": "",
			"citation": "",
			"abstract": "Targeting solid tumors with absolute precision is a long-standing challenge in cancer immunotherapy. The identification of antigens, which are expressed by a large fraction of tumors of a given type and, preferably, across various types, but not by normal cells, holds the key to developing safe, off-the-shelf immunotherapies. Although the quest for widely shared, strictly tumor-specific antigens has been the focus of tremendous effort, only few such candidates have been implicated. Almost all antigens that are currently explored as targets for chimeric antigen receptor (CAR) or T cell receptor (TCR)-T cell therapy are also expressed by healthy cells and the risk of on-target off-tumor toxicity has remained a major concern. Recent studies suggest that this risk could be obviated by targeting instead combinations of two or more antigens, which are co-expressed by tumor but not normal cells and, as such, are tumor-specific. Moreover, the expression of a shared tumor antigen along with the lack of a second antigen that is expressed by normal tissues can also be exploited for precise recognition. Additional cues, antigenic or non-antigenic ones, which characterize the tumor microenvironment, could be harnessed to further increase precision. This review focuses on attempts to define the targetable signatures of tumors and assesses different strategies employing advanced synthetic biology for translating such information into safer modes of immunotherapy, implementing the principles of Boolean logic gates.",
			"category": 2,
			"name": "Savanur Mohammed Azharuddin,2022"
		},
		{
			"PMID": 34789870,
			"title": "Pancreatic cancer evolution and heterogeneity: integrating omics and clinical data.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Connor Ashton A",
				"Gallinger Steven"
			],
			"DOI": "10.1038/s41568-021-00418-1",
			"date": "2022-03-17",
			"PMC": "",
			"citation": "",
			"abstract": "Pancreatic ductal adenocarcinoma (PDAC), already among the deadliest epithelial malignancies, is rising in both incidence and contribution to overall cancer deaths. Decades of research have improved our understanding of PDAC carcinogenesis, including characterizing germline predisposition, the cell of origin, precursor lesions, the sequence of genetic alterations, including simple and structural alterations, transcriptional changes and subtypes, tumour heterogeneity, metastatic progression and the tumour microenvironment. These fundamental advances inform contemporary translational efforts in primary prevention, screening and early detection, multidisciplinary management and survivorship, as prospective clinical trials begin to adopt molecular-based selection criteria to guide targeted therapies. Genomic and transcriptomic data on PDAC were also included in the international pan-cancer analysis of approximately 2,600 cancers, a milestone in cancer research that allows further insight through comparison with other tumour types. Thus, this is an ideal time to review our current knowledge of PDAC evolution and heterogeneity, gained from the study of preclinical models and patient biospecimens, and to propose a model of PDAC evolution that takes into consideration findings from varied sources, with a particular focus on the genomics of human PDAC.",
			"category": 2,
			"name": "Connor Ashton A,2022"
		},
		{
			"PMID": 34788626,
			"title": "Genomic and molecular features distinguish young adult cancer from later-onset cancer.",
			"journal": "Cell reports",
			"authorList": [
				"Lee William",
				"Wang Zishan",
				"Saffern Miriam",
				"Jun Tomi",
				"Huang Kuan-Lin"
			],
			"DOI": "10.1016/j.celrep.2021.110005",
			"date": "2022-02-14",
			"PMC": "",
			"citation": "",
			"abstract": "Young adult cancer has increased in incidence worldwide, but its molecular etiologies remain unclear. We systematically characterize genomic profiles of young adult tumors with ages of onset \u226450 years and compare them to later-onset tumors using over 6,000 cases across 14 cancer types. While young adult tumors generally show lower mutation burdens and comparable copy-number variation rates compared to later-onset cases, they are enriched for multiple driver mutations and copy-number alterations in subtype-specific contexts. Characterization of tumor immune microenvironments reveals pan-cancer patterns of elevated TGF-\u03b2 response/dendritic cells and lower IFN-\u03b3 response/macrophages relative to later-onset tumors, corresponding to age-related responses to immunotherapy in several cancer types. Finally, we identify prevalent clinically actionable events that disproportionally affect young adult or later-onset cases. The resulting catalog of age-related molecular drivers can guide precision diagnostics and treatments for young adult cancer.",
			"category": 2,
			"name": "Lee William,2022"
		},
		{
			"PMID": 34771477,
			"title": "3p Arm Loss and Survival in Head and Neck Cancer: An Analysis of TCGA Dataset.",
			"journal": "Cancers",
			"authorList": [
				"Kim Hugh Andrew Jinwook",
				"Shaikh Mushfiq Hassan",
				"Lee Mark",
				"Zeng Peter Y F",
				"Sorgini Alana",
				"Akintola Temitope",
				"Deng Xiaoxiao",
				"Jarycki Laura",
				"Khan Halema",
				"MacNeil Danielle",
				"Khan Mohammed Imran",
				"Mendez Adrian",
				"Yoo John",
				"Fung Kevin",
				"Lang Pencilla",
				"Palma David A",
				"Patel Krupal",
				"Mymryk Joe S",
				"Barrett John W",
				"Boutros Paul C",
				"Morris Luc G T",
				"Nichols Anthony C"
			],
			"DOI": "10.3390/cancers13215313",
			"date": "2023-09-21",
			"PMC": "",
			"citation": "",
			"abstract": "Loss of the 3p chromosome arm has previously been reported to be a biomarker of poorer outcome in both human papillomavirus (HPV)-positive and HPV-negative head and neck cancer. However, the precise operational measurement of 3p arm loss is unclear and the mutational profile associated with the event has not been thoroughly characterized. We downloaded the clinical, single nucleotide variation (SNV), copy number aberration (CNA), RNA sequencing, and reverse phase protein assay (RPPA) data from The Cancer Genome Atlas (TCGA) and The Cancer Proteome Atlas HNSCC cohorts. Survival data and hypoxia scores were downloaded from published studies. In addition, we report the inclusion of an independent Memorial Sloan Kettering cohort. We assessed the frequency of loci deletions across the 3p arm separately in HPV-positive and -negative disease. We found that deletions on chromosome 3p were almost exclusively an all or none event in the HPV-negative cohort; patients either had <1% or >97% of the arm deleted. 3p arm loss, defined as >97% deletion in HPV-positive patients and >50% in HPV-negative patients, had no impact on survival (",
			"category": 2,
			"name": "Kim Hugh Andrew Jinwook,2023"
		},
		{
			"PMID": 34749812,
			"title": "Multiscale heterogeneity in gastric adenocarcinoma evolution is an obstacle to precision medicine.",
			"journal": "Genome medicine",
			"authorList": [
				"R\u00f6cken Christoph",
				"Amallraja Anu",
				"Halske Christine",
				"Opasic Luka",
				"Traulsen Arne",
				"Behrens Hans-Michael",
				"Kr\u00fcger Sandra",
				"Liu Anne",
				"Haag Jochen",
				"Egberts Jan-Hendrik",
				"Rosenstiel Philip",
				"Mei\u00dfner Tobias"
			],
			"DOI": "10.1186/s13073-021-00975-y",
			"date": "2022-02-21",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a somatic evolutionary disease and adenocarcinomas of the stomach and gastroesophageal junction (GC) may serve as a two-dimensional model of cancer expansion, in which tumor subclones are not evenly mixed during tumor progression but rather spatially separated and diversified. We hypothesize that precision medicine efforts are compromised when clinical decisions are based on a single-sample analysis, which ignores the mechanisms of cancer evolution and resulting intratumoral heterogeneity. Using multiregional whole-exome sequencing, we investigated the effect of somatic evolution on intratumoral heterogeneity aiming to shed light on the evolutionary biology of GC.",
			"category": 2,
			"name": "R\u00f6cken Christoph,2022"
		},
		{
			"PMID": 34738311,
			"title": "Down-regulation of MYH10 driven by chromosome 17p13.1 deletion promotes hepatocellular carcinoma metastasis through activation of the EGFR pathway.",
			"journal": "Journal of cellular and molecular medicine",
			"authorList": [
				"Jin Qian",
				"Cheng Min",
				"Xia Xia",
				"Han Yuqing",
				"Zhang Jing",
				"Cao Pengbo",
				"Zhou Gangqiao"
			],
			"DOI": "10.1111/jcmm.17036",
			"date": "2022-03-23",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic copy number alterations (CNAs) are a genomic hallmark of cancers. Among them, the chromosome 17p13.1 deletions are recurrent in hepatocellular carcinoma (HCC). Here, utilizing an integrative omics analysis, we screened out a novel tumour suppressor gene within 17p13.1, myosin heavy chain 10 (MYH10). We observed frequent deletions (~38%) and significant down-regulation of MYH10 in primary HCC tissues. Deletion or decreased expression of MYH10 was a potential indicator of poor outcomes in HCC patients. Knockdown of MYH10\u00a0significantly promotes HCC cell migration and invasion in vitro, and overexpression of MYH10 exhibits opposite effects. Further, inhibition of MYH10\u00a0markedly potentiates HCC metastasis in vivo. We preliminarily elucidated the mechanism by which loss of MYH10 promotes HCC metastasis by facilitating EGFR pathway activation. In conclusion, our study suggests that MYH10, a candidate target gene for 17p13 deletion, acts as a tumour suppressor and may serve as a potential prognostic indicator for HCC patients.",
			"category": 2,
			"name": "Jin Qian,2022"
		},
		{
			"PMID": 34734181,
			"title": "Clone decomposition based on mutation signatures provides novel insights into mutational processes.",
			"journal": "NAR genomics and bioinformatics",
			"authorList": [
				"Matsutani Taro",
				"Hamada Michiaki"
			],
			"DOI": "10.1093/nargab/lqab093",
			"date": "2023-09-21",
			"PMC": "",
			"citation": "",
			"abstract": "Intra-tumor heterogeneity is a phenomenon in which mutation profiles differ from cell to cell within the same tumor and is observed in almost all tumors. Understanding intra-tumor heterogeneity is essential from the clinical perspective. Numerous methods have been developed to predict this phenomenon based on variant allele frequency. Among the methods, CloneSig models the variant allele frequency and mutation signatures simultaneously and provides an accurate clone decomposition. However, this method has limitations in terms of clone number selection and modeling. We propose SigTracer, a novel hierarchical Bayesian approach for analyzing intra-tumor heterogeneity based on mutation signatures to tackle these issues. We show that SigTracer predicts more reasonable clone decompositions than the existing methods against artificial data that mimic cancer genomes. We applied SigTracer to whole-genome sequences of blood cancer samples. The results were consistent with past findings that single base substitutions caused by a specific signature (previously reported as SBS9) related to the activation-induced cytidine deaminase intensively lie within immunoglobulin-coding regions for chronic lymphocytic leukemia samples. Furthermore, we showed that this signature mutates regions responsible for cell-cell adhesion. Accurate assignments of mutations to signatures by SigTracer can provide novel insights into signature origins and mutational processes.",
			"category": 2,
			"name": "Matsutani Taro,2023"
		},
		{
			"PMID": 34721546,
			"title": "Signatures Beyond Oncogenic Mutations in Cell-Free DNA Sequencing for Non-Invasive, Early Detection of Cancer.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"De Subhajyoti"
			],
			"DOI": "10.3389/fgene.2021.759832",
			"date": "2021-11-28",
			"PMC": "",
			"citation": "",
			"abstract": "Early detection of cancer saves lives, but an effective detection strategy in public health settings requires a delicate balance - periodic screening should neither miss rapidly progressing disease nor fail to detect rare tumors at unusual locations; on the other hand, even a modest false positive rate carries risks of over-diagnosis and over-treatment of relatively indolent non-malignant disease. Genomic profiling of cell-free DNA from liquid biopsy using massively parallel sequencing is emerging as an attractive, non-invasive screening platform for sensitive detection of multiple types of cancer in a single assay. Genomic data from cell-free DNA can not only identify oncogenic mutation status, but also additional molecular signatures related to potential tissue of origin, the extent of clonal growth, and malignant disease states. Utilization of the full potential of the molecular signatures from cfDNA sequencing data can guide clinical management strategies for targeted follow-ups using imaging or molecular marker-based diagnostic platforms and treatment options.",
			"category": 2,
			"name": "De Subhajyoti,2021"
		},
		{
			"PMID": 34711268,
			"title": "Novel temporal and spatial patterns of metastatic colonization from breast cancer rapid-autopsy tumor biopsies.",
			"journal": "Genome medicine",
			"authorList": [
				"Huang Xiaomeng",
				"Qiao Yi",
				"Brady Samuel W",
				"Factor Rachel E",
				"Downs-Kelly Erinn",
				"Farrell Andrew",
				"McQuerry Jasmine A",
				"Shrestha Gajendra",
				"Jenkins David",
				"Johnson W Evan",
				"Cohen Adam L",
				"Bild Andrea H",
				"Marth Gabor T"
			],
			"DOI": "10.1186/s13073-021-00989-6",
			"date": "2022-02-21",
			"PMC": "",
			"citation": "",
			"abstract": "Metastatic breast cancer is a deadly disease with a low 5-year survival rate. Tracking metastatic spread in living patients is difficult and thus poorly understood.",
			"category": 2,
			"name": "Huang Xiaomeng,2022"
		},
		{
			"PMID": 34695806,
			"title": "Profound synchrony of age-specific incidence rates and tumor suppression for different cancer types as revealed by the multistage-senescence model of carcinogenesis.",
			"journal": "Aging",
			"authorList": [
				"Richardson Richard B",
				"Anghel Catalina V",
				"Deng Dennis S"
			],
			"DOI": "10.18632/aging.203651",
			"date": "2022-01-28",
			"PMC": "",
			"citation": "",
			"abstract": "The age-specific trend of cancer incidence rates, but not its magnitude, is well described employing the multistage theory of carcinogenesis by Armitage and Doll in combination with the senescence model of Pompei and Wilson. We derived empirical parameters of the multistage-senescence model from U.S. Surveillance, Epidemiology, and End Results (SEER) incidence data from 2000-2003 and 2010-2013 for The Cancer Genome Atlas (TCGA) cancer types. Under the assumption of a constant tumor-specific transition rate between stages, there is an extremely strong linear relationship (",
			"category": 2,
			"name": "Richardson Richard B,2022"
		},
		{
			"PMID": 34680239,
			"title": "The Evolution of Clinically Aggressive Triple-Negative Breast Cancer Shows a Large Mutational Diversity and Early Metastasis to Lymph Nodes.",
			"journal": "Cancers",
			"authorList": [
				"Mart\u00ednez-Gregorio H\u00e9ctor",
				"Rojas-Jim\u00e9nez Ernesto",
				"Mej\u00eda-G\u00f3mez Javier C\u00e9sar",
				"D\u00edaz-Vel\u00e1squez Clara",
				"Quezada-Urban Rosal\u00eda",
				"Vallejo-Lecuona Fernando",
				"de la Cruz-Montoya Aldo",
				"Porras-Reyes Fany Iris",
				"P\u00e9rez-S\u00e1nchez V\u00edctor Manuel",
				"Maldonado-Mart\u00ednez H\u00e9ctor Aquiles",
				"Robles-Estrada Maybelline",
				"Bargall\u00f3-Rocha Enrique",
				"Cabrera-Galeana Paula",
				"Ramos-Ram\u00edrez Maritza",
				"Chirino Yolanda Irasema",
				"Alonso Herrera Luis",
				"Terrazas Luis Ignacio",
				"Frecha Cecilia",
				"Oliver Javier",
				"Perdomo Sandra",
				"Vaca-Paniagua Felipe"
			],
			"DOI": "10.3390/cancers13205091",
			"date": "2024-03-24",
			"PMC": "",
			"citation": "",
			"abstract": "In triple-negative breast cancer (TNBC), only 30% of patients treated with neoadjuvant chemotherapy achieve a pathological complete response after treatment and more than 90% die due to metastasis formation. The diverse clinical responses and metastatic developments are attributed to extensive intrapatient genetic heterogeneity and tumor evolution acting on this neoplasm. In this work, we aimed to evaluate genomic alterations and tumor evolution in TNBC patients with aggressive disease. We sequenced the whole exome of 16 lesions from four patients who did not respond to therapy, and took several follow-up samples, including samples from tumors before and after treatment, as well as from the lymph nodes and skin metastases. We found substantial intrapatient genetic heterogeneity, with a variable tumor mutational composition. Early truncal events were ",
			"category": 2,
			"name": "Mart\u00ednez-Gregorio H\u00e9ctor,2024"
		},
		{
			"PMID": 34680076,
			"title": "Immunoaffinity Capillary Electrophoresis in the Era of Proteoforms, Liquid Biopsy and Preventive Medicine: A Potential Impact in the Diagnosis and Monitoring of Disease Progression.",
			"journal": "Biomolecules",
			"authorList": [
				"Guzman Norberto A",
				"Guzman Daniel E"
			],
			"DOI": "10.3390/biom11101443",
			"date": "2022-01-18",
			"PMC": "",
			"citation": "",
			"abstract": "Over the years, multiple biomarkers have been used to aid in disease screening, diagnosis, prognosis, and response to therapy. As of late, protein biomarkers are gaining strength in their role for early disease diagnosis and prognosis in part due to the advancements in identification and characterization of a distinct functional pool of proteins known as proteoforms. Proteoforms are defined as all of the different molecular forms of a protein derived from a single gene caused by genetic variations, alternative spliced RNA transcripts and post-translational modifications. Monitoring the structural changes of each proteoform of a particular protein is essential to elucidate the complex molecular mechanisms that guide the course of disease. Clinical proteomics therefore holds the potential to offer further insight into disease pathology, progression, and prevention. Nevertheless, more technologically advanced diagnostic methods are needed to improve the reliability and clinical applicability of proteomics in preventive medicine. In this manuscript, we review the use of immunoaffinity capillary electrophoresis (IACE) as an emerging powerful diagnostic tool to isolate, separate, detect and characterize proteoform biomarkers obtained from liquid biopsy. IACE is an affinity capture-separation technology capable of isolating, concentrating and analyzing a wide range of biomarkers present in biological fluids. Isolation and concentration of target analytes is accomplished through binding to one or more biorecognition affinity ligands immobilized to a solid support, while separation and analysis are achieved by high-resolution capillary electrophoresis (CE) coupled to one or more detectors. IACE has the potential to generate rapid results with significant accuracy, leading to reliability and reproducibility in diagnosing and monitoring disease. Additionally, IACE has the capability of monitoring the efficacy of therapeutic agents by quantifying companion and complementary protein biomarkers. With advancements in telemedicine and artificial intelligence, the implementation of proteoform biomarker detection and analysis may significantly improve our capacity to identify medical conditions early and intervene in ways that improve health outcomes for individuals and populations.",
			"category": 2,
			"name": "Guzman Norberto A,2022"
		},
		{
			"PMID": 34638371,
			"title": "Clonal Architecture and Evolutionary Dynamics in Acute Myeloid Leukemias.",
			"journal": "Cancers",
			"authorList": [
				"Duchmann Matthieu",
				"Laplane Lucie",
				"Itzykson Raphael"
			],
			"DOI": "10.3390/cancers13194887",
			"date": "2024-04-03",
			"PMC": "",
			"citation": "",
			"abstract": "Acute myeloid leukemias (AML) results from the accumulation of genetic and epigenetic alterations, often in the context of an aging hematopoietic environment. The development of high-throughput sequencing-and more recently, of single-cell technologies-has shed light on the intratumoral diversity of leukemic cells. Taking AML as a model disease, we review the multiple sources of genetic, epigenetic, and functional heterogeneity of leukemic cells and discuss the definition of a leukemic clone extending its definition beyond genetics. After introducing the two dimensions contributing to clonal diversity, namely, richness (number of leukemic clones) and evenness (distribution of clone sizes), we discuss the mechanisms at the origin of clonal emergence (mutation rate, number of generations, and effective size of the leukemic population) and the causes of clonal dynamics. We discuss the possible role of neutral drift, but also of cell-intrinsic and -extrinsic influences on clonal fitness. After reviewing available data on the prognostic role of genetic and epigenetic diversity of leukemic cells on patients' outcome, we discuss how a better understanding of AML as an evolutionary process could lead to the design of novel therapeutic strategies in this disease.",
			"category": 2,
			"name": "Duchmann Matthieu,2024"
		},
		{
			"PMID": 34635759,
			"title": "Novel genomic alteration in superficial esophageal squamous cell neoplasms in non-smoker non-drinker females.",
			"journal": "Scientific reports",
			"authorList": [
				"Onozato Yusuke",
				"Sasaki Yu",
				"Abe Yasuhiko",
				"Sato Hidenori",
				"Yagi Makoto",
				"Mizumoto Naoko",
				"Kon Takashi",
				"Sakai Takayuki",
				"Ito Minami",
				"Umehara Matsuki",
				"Koseki Ayumi",
				"Ueno Yoshiyuki"
			],
			"DOI": "10.1038/s41598-021-99790-z",
			"date": "2022-01-24",
			"PMC": "",
			"citation": "",
			"abstract": "Alcohol consumption and smoking pose a significant risk for esophageal squamous cell neoplasia (ESCN) development in males; however, ESCN is often diagnosed in non-drinking and non-smoking females. The mechanisms underlying these differences remain elusive, and understanding them can potentially identify novel pathways involved in ESCN development. We performed short-read sequencing to identify somatic variants on a cancer panel targeting 409 genes using DNA extracted from the superficial squamous cell carcinoma (ESCC) tissues and adjacent non-neoplastic epithelium (NE), and immunohistochemical staining of the protein encoded by the target gene. All male patients (n\u2009=\u2009117) were drinkers or smokers, whereas 45% of the female patients (n\u2009=\u200933) were not. Somatic variants were compared among three age-matched groups: 13 female ESCC patients with smoking and drinking habits (known-risk group, F-KR), 13 female ESCC patients without these habits (unknown-risk group, F-UR), and 27 males with ESCC and smoking and drinking habits (M-KR). In the NE, the frequencies of CDKN2A variants were significantly higher in F-UR than in F-KR and M-KR. In both ESCC and NE, p14ARF was significantly overexpressed in F-UR than in the other groups. In conclusion, CDKN2A might be important in ESCC development, independent of known risk factors.",
			"category": 2,
			"name": "Onozato Yusuke,2022"
		},
		{
			"PMID": 34611608,
			"title": "A molecular taxonomy of tumors independent of tissue-of-origin.",
			"journal": "iScience",
			"authorList": [
				"Nguyen Peter T",
				"Coetzee Simon G",
				"Lakeland Daniel L",
				"Hazelett Dennis J"
			],
			"DOI": "10.1016/j.isci.2021.103084",
			"date": "2021-10-08",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is an organism-level disease, impacting processes from cellular metabolism and the microenvironment to systemic immune response. Nevertheless, efforts to distinguish overarching mutational processes from interactions with the cell of origin for a tumor have seen limited success, presenting a barrier to individualized medicine. Here we present a pathway-centric approach, extracting somatic mutational profiles within and between tissues, largely orthogonal to cell of origin, mutational burden, or stage. Known predisposition variants are equally distributed among clusters, and largely independent of molecular subtype. Prognosis and risk of death vary jointly by cancer type and cluster. Analysis of metastatic tumors reveals that differences are largely cluster-specific and complementary, implicating convergent mechanisms that combine familiar driver genes with diverse low-frequency lesions in tumor-promoting pathways, ultimately producing distinct molecular phenotypes. The results shed new light on the interplay between organism-level dysfunction and tissue-specific lesions.",
			"category": 2,
			"name": "Nguyen Peter T,2021"
		},
		{
			"PMID": 34568068,
			"title": "Bridging Tumorigenesis and Therapy Resistance With a Non-Darwinian and Non-Lamarckian Mechanism of Adaptive Evolution.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Catania Francesco",
				"Ujvari Beata",
				"Roche Benjamin",
				"Capp Jean-Pascal",
				"Thomas Fr\u00e9d\u00e9ric"
			],
			"DOI": "10.3389/fonc.2021.732081",
			"date": "2023-11-01",
			"PMC": "",
			"citation": "",
			"abstract": "Although neo-Darwinian (and less often Lamarckian) dynamics are regularly invoked to interpret cancer's multifarious molecular profiles, they shine little light on how tumorigenesis unfolds and often fail to fully capture the frequency and breadth of resistance mechanisms. This uncertainty frames one of the most problematic gaps between science and practice in modern times. Here, we offer a theory of adaptive cancer evolution, which builds on a molecular mechanism that lies outside neo-Darwinian and Lamarckian schemes. This mechanism coherently integrates non-genetic and genetic changes, ecological and evolutionary time scales, and shifts the spotlight away from positive selection towards purifying selection, genetic drift, and the creative-disruptive power of environmental change. The surprisingly simple ",
			"category": 2,
			"name": "Catania Francesco,2023"
		},
		{
			"PMID": 34565215,
			"title": "Cancer Biology, Epidemiology, and Treatment in the 21st Century: Current Status and Future Challenges From a Biomedical Perspective.",
			"journal": "Cancer control : journal of the Moffitt Cancer Center",
			"authorList": [
				"Pi\u00f1a-S\u00e1nchez Patricia",
				"Ch\u00e1vez-Gonz\u00e1lez Antonieta",
				"Ruiz-Tachiqu\u00edn Martha",
				"Vadillo Eduardo",
				"Monroy-Garc\u00eda Alberto",
				"Montesinos Juan Jos\u00e9",
				"Grajales Roc\u00edo",
				"Guti\u00e9rrez de la Barrera Marcos",
				"Mayani Hector"
			],
			"DOI": "10.1177/10732748211038735",
			"date": "2022-01-13",
			"PMC": "",
			"citation": "",
			"abstract": "Since the second half of the 20th century, our knowledge about the biology of cancer has made extraordinary progress. Today, we understand cancer at the genomic and epigenomic levels, and we have identified the cell that starts neoplastic transformation and characterized the mechanisms for the invasion of other tissues. This knowledge has allowed novel drugs to be designed that act on specific molecular targets, the immune system to be trained and manipulated to increase its efficiency, and ever more effective therapeutic strategies to be developed. Nevertheless, we are still far from winning the war against cancer, and thus biomedical research in oncology must continue to be a global priority. Likewise, there is a need to reduce unequal access to medical services and improve prevention programs, especially in countries with a low human development index.",
			"category": 2,
			"name": "Pi\u00f1a-S\u00e1nchez Patricia,2022"
		},
		{
			"PMID": 34561273,
			"title": "Combinatorial CRISPR/Cas9 Screening Reveals Epistatic Networks of Interacting Tumor Suppressor Genes and Therapeutic Targets in Human Breast Cancer.",
			"journal": "Cancer research",
			"authorList": [
				"Zhao Xiaoyu",
				"Li Jinyu",
				"Liu Zhimin",
				"Powers Scott"
			],
			"DOI": "10.1158/0008-5472.CAN-21-2555",
			"date": "2022-01-06",
			"PMC": "",
			"citation": "",
			"abstract": "The majority of cancers are driven by multiple genetic alterations, but how these changes collaborate during tumorigenesis remains largely unknown. To gain mechanistic insights into tumor-promoting genetic interactions among tumor suppressor genes (TSG), we conducted combinatorial CRISPR screening coupled with single-cell transcriptomic profiling in human mammary epithelial cells. As expected, different driver gene alterations in mammary epithelial cells influenced the repertoire of tumor suppressor alterations capable of inducing tumor formation. More surprisingly, TSG interaction networks were comprised of numerous cliques-sets of three or four genes such that each TSG within the clique showed oncogenic cooperation with all other genes in the clique. Genetic interaction profiling indicated that the predominant cooperating TSGs shared overlapping functions rather than distinct or complementary functions. Single-cell transcriptomic profiling of CRISPR double knockouts revealed that cooperating TSGs that synergized in promoting tumorigenesis and growth factor independence showed transcriptional epistasis, whereas noncooperating TSGs did not. These epistatic transcriptional changes, both buffering and synergistic, affected expression of oncogenic mediators and therapeutic targets, including CDK4, SRPK1, and DNMT1. Importantly, the epistatic expression alterations caused by dual inactivation of TSGs in this system, such as ",
			"category": 2,
			"name": "Zhao Xiaoyu,2022"
		},
		{
			"PMID": 34545238,
			"title": "Evolution and progression of Barrett's oesophagus to oesophageal cancer.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Killcoyne Sarah",
				"Fitzgerald Rebecca C"
			],
			"DOI": "10.1038/s41568-021-00400-x",
			"date": "2021-12-15",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer cells are shaped through an evolutionary process of DNA mutation, cell selection and population expansion. Early steps in this process are driven by a set of mutated driver genes and structural alterations to the genome through copy number gains or losses. Oesophageal adenocarcinoma (EAC) and the pre-invasive tissue, Barrett's oesophagus (BE), provide an ideal example in which to observe and study this evolution. BE displays early genomic instability, specifically in copy number changes that may later be observed in EAC. Furthermore, these early changes result in patterns of progression (that is, 'born bad', gradual or catastrophic) that may help to describe the evolution of EAC. As only a small proportion of patients with BE will go on to develop cancer, a better understanding of these patterns and the resulting genomic changes should improve early detection in EAC and may provide clues for the evolution of cancer more broadly.",
			"category": 2,
			"name": "Killcoyne Sarah,2021"
		},
		{
			"PMID": 34504347,
			"title": "Establishing community reference samples, data and call sets for benchmarking cancer mutation detection using whole-genome sequencing.",
			"journal": "Nature biotechnology",
			"authorList": [
				"Fang Li Tai",
				"Zhu Bin",
				"Zhao Yongmei",
				"Chen Wanqiu",
				"Yang Zhaowei",
				"Kerrigan Liz",
				"Langenbach Kurt",
				"de Mars Maryellen",
				"Lu Charles",
				"Idler Kenneth",
				"Jacob Howard",
				"Zheng Yuanting",
				"Ren Luyao",
				"Yu Ying",
				"Jaeger Erich",
				"Schroth Gary P",
				"Abaan Ogan D",
				"Talsania Keyur",
				"Lack Justin",
				"Shen Tsai-Wei",
				"Chen Zhong",
				"Stanbouly Seta",
				"Tran Bao",
				"Shetty Jyoti",
				"Kriga Yuliya",
				"Meerzaman Daoud",
				"Nguyen Cu",
				"Petitjean Virginie",
				"Sultan Marc",
				"Cam Margaret",
				"Mehta Monika",
				"Hung Tiffany",
				"Peters Eric",
				"Kalamegham Rasika",
				"Sahraeian Sayed Mohammad Ebrahim",
				"Mohiyuddin Marghoob",
				"Guo Yunfei",
				"Yao Lijing",
				"Song Lei",
				"Lam Hugo Y K",
				"Drabek Jiri",
				"Vojta Petr",
				"Maestro Roberta",
				"Gasparotto Daniela",
				"K\u00f5ks Sulev",
				"Reimann Ene",
				"Scherer Andreas",
				"Nordlund Jessica",
				"Liljedahl Ulrika",
				"Jensen Roderick V",
				"Pirooznia Mehdi",
				"Li Zhipan",
				"Xiao Chunlin",
				"Sherry Stephen T",
				"Kusko Rebecca",
				"Moos Malcolm",
				"Donaldson Eric",
				"Tezak Zivana",
				"Ning Baitang",
				"Tong Weida",
				"Li Jing",
				"Duerken-Hughes Penelope",
				"Catalanotti Claudia",
				"Maheshwari Shamoni",
				"Shuga Joe",
				"Liang Winnie S",
				"Keats Jonathan",
				"Adkins Jonathan",
				"Tassone Erica",
				"Zismann Victoria",
				"McDaniel Timothy",
				"Trent Jeffrey",
				"Foox Jonathan",
				"Butler Daniel",
				"Mason Christopher E",
				"Hong Huixiao",
				"Shi Leming",
				"Wang Charles",
				"Xiao Wenming",
				"Somatic Mutation Working Group of Sequencing Quality Control Phase II Consortium"
			],
			"DOI": "10.1038/s41587-021-00993-6",
			"date": "2021-09-22",
			"PMC": "",
			"citation": "",
			"abstract": "The lack of samples for generating standardized DNA datasets for setting up a sequencing pipeline or benchmarking the performance of different algorithms limits the implementation and uptake of cancer genomics. Here, we describe reference call sets obtained from paired tumor-normal genomic DNA (gDNA) samples derived from a breast cancer cell line-which is highly heterogeneous, with an aneuploid genome, and enriched in somatic alterations-and a matched lymphoblastoid cell line. We partially validated both somatic mutations and germline variants in these call sets via whole-exome sequencing (WES) with different sequencing platforms and targeted sequencing with >2,000-fold coverage, spanning 82% of genomic regions with high confidence. Although the gDNA reference samples are not representative of primary cancer cells from a clinical sample, when setting up a sequencing pipeline, they not only minimize potential biases from technologies, assays and informatics but also provide a unique resource for benchmarking 'tumor-only' or 'matched tumor-normal' analyses.",
			"category": 2,
			"name": "Fang Li Tai,2021"
		},
		{
			"PMID": 34504064,
			"title": "CloneSig can jointly infer intra-tumor heterogeneity and mutational signature activity in bulk tumor sequencing data.",
			"journal": "Nature communications",
			"authorList": [
				"Ab\u00e9cassis Judith",
				"Reyal Fabien",
				"Vert Jean-Philippe"
			],
			"DOI": "10.1038/s41467-021-24992-y",
			"date": "2021-10-19",
			"PMC": "",
			"citation": "",
			"abstract": "Systematic DNA sequencing of cancer samples has highlighted the importance of two aspects of cancer genomics: intra-tumor heterogeneity (ITH) and mutational processes. These two aspects may not always be independent, as different mutational processes could be involved in different stages or regions of the tumor, but existing computational approaches to study them largely ignore this potential dependency. Here, we present CloneSig, a computational method to jointly infer ITH and mutational processes in a tumor from bulk-sequencing data. Extensive simulations show that CloneSig outperforms current methods for ITH inference and detection of mutational processes when the distribution of mutational signatures changes between clones. Applied to a large cohort of 8,951 tumors with whole-exome sequencing data from The Cancer Genome Atlas, and on a pan-cancer dataset of 2,632 whole-genome sequencing tumor samples from the Pan-Cancer Analysis of Whole Genomes initiative, CloneSig obtains results overall coherent with previous studies.",
			"category": 2,
			"name": "Ab\u00e9cassis Judith,2021"
		},
		{
			"PMID": 34495981,
			"title": "Glioblastoma signature in the DNA of blood-derived cells.",
			"journal": "PloS one",
			"authorList": [
				"Jain Siddharth",
				"Mazaheri Bijan",
				"Raviv Netanel",
				"Bruck Jehoshua"
			],
			"DOI": "10.1371/journal.pone.0256831",
			"date": "2021-11-22",
			"PMC": "",
			"citation": "",
			"abstract": "Current approach for the detection of cancer is based on identifying genetic mutations typical to tumor cells. This approach is effective only when cancer has already emerged, however, it might be in a stage too advanced for effective treatment. Cancer is caused by the continuous accumulation of mutations; is it possible to measure the time-dependent information of mutation accumulation and predict the emergence of cancer? We hypothesize that the mutation history derived from the tandem repeat regions in blood-derived DNA carries information about the accumulation of the cancer driver mutations in other tissues. To validate our hypothesis, we computed the mutation histories from the tandem repeat regions in blood-derived exomic DNA of 3874 TCGA patients with different cancer types and found a statistically significant signal with specificity ranging from 66% to 93% differentiating Glioblastoma patients from other cancer patients. Our approach and findings offer a new direction for future cancer prediction and early cancer detection based on information derived from blood-derived DNA.",
			"category": 2,
			"name": "Jain Siddharth,2021"
		},
		{
			"PMID": 34493867,
			"title": "Genomic and evolutionary classification of lung cancer in never smokers.",
			"journal": "Nature genetics",
			"authorList": [
				"Zhang Tongwu",
				"Joubert Philippe",
				"Ansari-Pour Naser",
				"Zhao Wei",
				"Hoang Phuc H",
				"Lokanga Rachel",
				"Moye Aaron L",
				"Rosenbaum Jennifer",
				"Gonzalez-Perez Abel",
				"Mart\u00ednez-Jim\u00e9nez Francisco",
				"Castro Andrea",
				"Muscarella Lucia Anna",
				"Hofman Paul",
				"Consonni Dario",
				"Pesatori Angela C",
				"Kebede Michael",
				"Li Mengying",
				"Gould Rothberg Bonnie E",
				"Peneva Iliana",
				"Schabath Matthew B",
				"Poeta Maria Luana",
				"Costantini Manuela",
				"Hirsch Daniela",
				"Heselmeyer-Haddad Kerstin",
				"Hutchinson Amy",
				"Olanich Mary",
				"Lawrence Scott M",
				"Lenz Petra",
				"Duggan Maire",
				"Bhawsar Praphulla M S",
				"Sang Jian",
				"Kim Jung",
				"Mendoza Laura",
				"Saini Natalie",
				"Klimczak Leszek J",
				"Islam S M Ashiqul",
				"Otlu Burcak",
				"Khandekar Azhar",
				"Cole Nathan",
				"Stewart Douglas R",
				"Choi Jiyeon",
				"Brown Kevin M",
				"Caporaso Neil E",
				"Wilson Samuel H",
				"Pommier Yves",
				"Lan Qing",
				"Rothman Nathaniel",
				"Almeida Jonas S",
				"Carter Hannah",
				"Ried Thomas",
				"Kim Carla F",
				"Lopez-Bigas Nuria",
				"Garcia-Closas Montserrat",
				"Shi Jianxin",
				"Boss\u00e9 Yohan",
				"Zhu Bin",
				"Gordenin Dmitry A",
				"Alexandrov Ludmil B",
				"Chanock Stephen J",
				"Wedge David C",
				"Landi Maria Teresa"
			],
			"DOI": "10.1038/s41588-021-00920-0",
			"date": "2021-10-14",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer in never smokers (LCINS) is a common cause of cancer mortality but its genomic landscape is poorly characterized. Here high-coverage whole-genome sequencing of 232 LCINS showed 3 subtypes defined by copy number aberrations. The dominant subtype (piano), which is rare in lung cancer in smokers, features somatic UBA1 mutations, germline AR variants and stem cell-like properties, including low mutational burden, high intratumor heterogeneity, long telomeres, frequent KRAS mutations and slow growth, as suggested by the occurrence of cancer drivers' progenitor cells many years before tumor diagnosis. The other subtypes are characterized by specific amplifications and EGFR mutations (mezzo-forte) and whole-genome doubling (forte). No strong tobacco smoking signatures were detected, even in cases with exposure to secondhand tobacco smoke. Genes within the receptor tyrosine kinase-Ras pathway had distinct impacts on survival; five genomic alterations independently doubled mortality. These findings create avenues for personalized treatment in LCINS.",
			"category": 2,
			"name": "Zhang Tongwu,2021"
		},
		{
			"PMID": 34485119,
			"title": "Transcriptomic Analyses Reveal B-Cell Translocation Gene 2 as a Potential Therapeutic Target in Ovarian Cancer.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Wang Jia",
				"Li Haonan",
				"Wang Liang",
				"Zhang Jing",
				"Li Man",
				"Qiao Liang",
				"Zhang Jun",
				"Liu Likun",
				"Zhang Cuili",
				"Gao Jingchun",
				"Li Weiling"
			],
			"DOI": "10.3389/fonc.2021.681250",
			"date": "2021-09-07",
			"PMC": "",
			"citation": "",
			"abstract": "Ovarian cancer is the most common and aggressive type of tumor of the female reproductive system. Two factors account for this detrimental clinical presentation: (i) the lack of early detection methods and (ii) the inherently aggressive nature of this malignancy. Currently, transcriptomic analyses have become important tools to identify new targets in different cancer types. In this study, by measuring expression levels in ovarian cancer samples and stem cell samples, we identified 24 tumor suppressor genes consistently associated with poor prognosis. Combined results further revealed a potential therapeutic candidate, BTG2, which belongs to the antiproliferative gene family. Our results showed that BTG2 expression regulated ovarian cancer cell proliferation ",
			"category": 2,
			"name": "Wang Jia,2021"
		},
		{
			"PMID": 34483003,
			"title": "Therapeutic and prognostic insights from the analysis of cancer mutational signatures.",
			"journal": "Trends in genetics : TIG",
			"authorList": [
				"Brady Samuel W",
				"Gout Alexander M",
				"Zhang Jinghui"
			],
			"DOI": "10.1016/j.tig.2021.08.007",
			"date": "2022-03-09",
			"PMC": "",
			"citation": "",
			"abstract": "The somatic mutations in each cancer genome are caused by multiple mutational processes, each of which leaves a characteristic imprint (or 'signature'), potentially caused by specific etiologies or exposures. Deconvolution of these signatures offers a glimpse into the evolutionary history of individual tumors. Recent work has shown that mutational signatures may also yield therapeutic and prognostic insights, including the identification of cell-intrinsic signatures as biomarkers of drug response and prognosis. For example, mutational signatures indicating homologous recombination deficiency are associated with poly(ADP)-ribose polymerase (PARP) inhibitor sensitivity, whereas APOBEC-associated signatures are associated with ataxia telangiectasia and Rad3-related kinase (ATR) inhibitor sensitivity. Furthermore, therapy-induced mutational signatures implicated in cancer progression have also been uncovered, including the identification of thiopurine-induced TP53 mutations in leukemia. In this review, we explore the various ways mutational signatures can reveal new therapeutic and prognostic insights, thus extending their traditional role in identifying disease etiology.",
			"category": 2,
			"name": "Brady Samuel W,2022"
		},
		{
			"PMID": 34459009,
			"title": "Cancer evolution: Darwin and beyond.",
			"journal": "The EMBO journal",
			"authorList": [
				"Vendramin Roberto",
				"Litchfield Kevin",
				"Swanton Charles"
			],
			"DOI": "10.15252/embj.2021108389",
			"date": "2021-12-06",
			"PMC": "",
			"citation": "",
			"abstract": "Clinical and laboratory studies over recent decades have established branched evolution as a feature of cancer. However, while grounded in somatic selection, several lines of evidence suggest a Darwinian model alone is insufficient to fully explain cancer evolution. First, the role of macroevolutionary events in tumour initiation and progression contradicts Darwin's central thesis of gradualism. Whole-genome doubling, chromosomal chromoplexy and chromothripsis represent examples of single catastrophic events which can drive tumour evolution. Second, neutral evolution can play a role in some tumours, indicating that selection is not always driving evolution. Third, increasing appreciation of the role of the ageing soma has led to recent generalised theories of age-dependent carcinogenesis. Here, we review these concepts and others, which collectively argue for a model of cancer evolution which extends beyond Darwin. We also highlight clinical opportunities which can be grasped through targeting cancer vulnerabilities arising from non-Darwinian patterns of evolution.",
			"category": 2,
			"name": "Vendramin Roberto,2021"
		},
		{
			"PMID": 34446006,
			"title": "The current issues and future perspective of artificial intelligence for developing new treatment strategy in non-small cell lung cancer: harmonization of molecular cancer biology and artificial intelligence.",
			"journal": "Cancer cell international",
			"authorList": [
				"Tanaka Ichidai",
				"Furukawa Taiki",
				"Morise Masahiro"
			],
			"DOI": "10.1186/s12935-021-02165-7",
			"date": "2021-08-31",
			"PMC": "",
			"citation": "",
			"abstract": "Comprehensive analysis of omics data, such as genome, transcriptome, proteome, metabolome, and interactome, is a crucial technique for elucidating the complex mechanism of cancer onset and progression. Recently, a variety of new findings have been reported based on multi-omics analysis in combination with various clinical information. However, integrated analysis of multi-omics data is extremely labor intensive, making the development of new analysis technology indispensable. Artificial intelligence (AI), which has been under development in recent years, is quickly becoming an effective approach to reduce the labor involved in analyzing large amounts of complex data and to obtain valuable information that is often overlooked in manual analysis and experiments. The use of AI, such as machine learning approaches and deep learning systems, allows for the efficient analysis of massive omics data combined with accurate clinical information and can lead to comprehensive predictive models that will be desirable for further developing individual treatment strategies of immunotherapy and molecular target therapy. Here, we aim to review the potential of AI in the integrated analysis of omics data and clinical information with a special focus on recent advances in the discovery of new biomarkers and the future direction of personalized medicine in non-small lung cancer.",
			"category": 2,
			"name": "Tanaka Ichidai,2021"
		},
		{
			"PMID": 34434669,
			"title": "The Erlang distribution approximates the age distribution of incidence of childhood and young adulthood cancers.",
			"journal": "PeerJ",
			"authorList": [
				"Belikov Aleksey V",
				"Vyatkin Alexey",
				"Leonov Sergey V"
			],
			"DOI": "10.7717/peerj.11976",
			"date": "2022-04-26",
			"PMC": "",
			"citation": "",
			"abstract": "It is widely believed that cancers develop upon acquiring a particular number of (epi) mutations in driver genes, but the law governing the kinetics of this process is not known. We have previously shown that the age distribution of incidence for the 20 most prevalent cancers of old age is best approximated by the Erlang probability distribution. The Erlang distribution describes the probability of several successive random events occurring by the given time according to the Poisson process, which allows an estimate for the number of critical driver events.",
			"category": 2,
			"name": "Belikov Aleksey V,2022"
		},
		{
			"PMID": 34431477,
			"title": "The roles of history, chance, and natural selection in the evolution of antibiotic resistance.",
			"journal": "eLife",
			"authorList": [
				"Santos-Lopez Alfonso",
				"Marshall Christopher W",
				"Haas Allison L",
				"Turner Caroline",
				"Rasero Javier",
				"Cooper Vaughn S"
			],
			"DOI": "10.7554/eLife.70676",
			"date": "2021-11-09",
			"PMC": "",
			"citation": "",
			"abstract": "History, chance, and selection are the fundamental factors that drive and constrain evolution. We designed evolution experiments to disentangle and quantify effects of these forces on the evolution of antibiotic resistance. Previously, we showed that selection of the pathogen ",
			"category": 2,
			"name": "Santos-Lopez Alfonso,2021"
		},
		{
			"PMID": 34430406,
			"title": "Comprehensive data analysis of genomics, epigenomics, and transcriptomics to identify specific biomolecular markers for prostate adenocarcinoma.",
			"journal": "Translational andrology and urology",
			"authorList": [
				"Ye Chunwei",
				"Wang Haifeng",
				"Li Zhipeng",
				"Xia Chengxing",
				"Yuan Shunhui",
				"Yan Ruping",
				"Yang Xiaofang",
				"Ma Tao",
				"Wen Xingqiao",
				"Yang Delin"
			],
			"DOI": "10.21037/tau-21-576",
			"date": "2022-09-10",
			"PMC": "",
			"citation": "",
			"abstract": "Multiomics data analysis based on high-throughput sequencing technology has become a hotspot in tumor investigation. The present study aimed to explore prognostic biomarkers via investigating DNA copy number variation (CNV) and methylation variation (MET) data in prostate cancer.",
			"category": 2,
			"name": "Ye Chunwei,2022"
		},
		{
			"PMID": 34416171,
			"title": "DeCiFering the elusive cancer cell fraction in tumor heterogeneity and evolution.",
			"journal": "Cell systems",
			"authorList": [
				"Satas Gryte",
				"Zaccaria Simone",
				"El-Kebir Mohammed",
				"Raphael Benjamin J"
			],
			"DOI": "10.1016/j.cels.2021.07.006",
			"date": "2022-04-06",
			"PMC": "",
			"citation": "",
			"abstract": "The cancer cell fraction (CCF), or proportion of cancerous cells in a tumor containing a single-nucleotide variant (SNV), is a fundamental statistic used to quantify tumor heterogeneity and evolution. Existing CCF estimation methods from bulk DNA sequencing data assume that every cell with an SNV contains the same number of copies of the SNV. This assumption is unrealistic in tumors with copy-number aberrations that alter SNV multiplicities. Furthermore, the CCF does not account for SNV losses due to copy-number aberrations, confounding downstream phylogenetic analyses. We introduce DeCiFer, an algorithm that overcomes these limitations by clustering SNVs using a novel statistic, the descendant cell fraction (DCF). The DCF quantifies both the prevalence of an SNV at the present time and its past evolutionary history using an evolutionary model that allows mutation losses. We show that DeCiFer yields more parsimonious reconstructions of tumor evolution than previously reported for 49 prostate cancer samples.",
			"category": 2,
			"name": "Satas Gryte,2022"
		},
		{
			"PMID": 34415294,
			"title": "Comparison of approaches to transcriptomic analysis in multi-sampled tumors.",
			"journal": "Briefings in bioinformatics",
			"authorList": [
				"Ku Anson T",
				"Wilkinson Scott",
				"Sowalsky Adam G"
			],
			"DOI": "10.1093/bib/bbab337",
			"date": "2022-03-09",
			"PMC": "",
			"citation": "",
			"abstract": "Intratumoral heterogeneity is a well-documented feature of human cancers and is associated with outcome and treatment resistance. However, a heterogeneous tumor transcriptome contributes an unknown level of variability to analyses of differentially expressed genes (DEGs) that may contribute to phenotypes of interest, including treatment response. Although current clinical practice and the vast majority of research studies use a single sample from each patient, decreasing costs of sequencing technologies and computing power have made repeated-measures analyses increasingly economical. Repeatedly sampling the same tumor increases the statistical power of DEG analysis, which is indispensable toward downstream analysis and also increases one's understanding of within-tumor variance, which may affect conclusions. Here, we compared five different methods for analyzing gene expression profiles derived from repeated sampling of human prostate tumors in two separate cohorts of patients. We also benchmarked the sensitivity of generalized linear models to linear mixed models for identifying DEGs contributing to relevant prostate cancer pathways based on a ground-truth model.",
			"category": 2,
			"name": "Ku Anson T,2022"
		},
		{
			"PMID": 34395236,
			"title": "Risk Signature of Cancer-Associated Fibroblast-Secreted Cytokines Associates With Clinical Outcomes of Breast Cancer.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Sun Chunxiao",
				"Wang Siwei",
				"Zhang Yuchen",
				"Yang Fan",
				"Zeng Tianyu",
				"Meng Fanchen",
				"Yang Mengzhu",
				"Yang Yiqi",
				"Hua Yijia",
				"Fu Ziyi",
				"Li Jun",
				"Huang Xiang",
				"Wu Hao",
				"Yin Yongmei",
				"Li Wei"
			],
			"DOI": "10.3389/fonc.2021.628677",
			"date": "2024-04-03",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer-associated fibroblasts (CAFs) are key components in tumor microenvironment (TME). The secreted products of CAFs play important roles in regulating tumor cells and further impacting clinical prognosis. This study aims to reveal the relationship between CAF-secreted cytokines and breast cancer (BC) by constructing the risk signature. We performed three algorithms to reveal CAF-related cytokines in the TCGA BC dataset and identified five prognosis-related cytokines. Then we used single-cell RNA sequencing (ScRNA-Seq) datasets of BC to confirm the expression level of these five cytokines in CAFs. METABRIC and other independent datasets were utilized to validate the findings in further analyses. Based on the identified five-cytokine signature derived from CAFs, BC patients with high-risk score (RS) had shorter overall survival than low-RS cases. Further analysis suggested that the high-RS level correlated with cell proliferation and mast cell infiltration in BCs of the Basal-like subtype. The results also indicated that the level of RS could discriminate the high-risk BC cases harboring driver mutations (i.e., PI3KCA, CDH1, and TP53). Additionally, the status of five-cytokine signature was associated with the frequency and molecular timing of whole genome duplication (WGD) events. Intratumor heterogeneity (ITH) analysis among BC samples indicated that the high-RS level was associated with the increase of tumor subclones. This work demonstrated that the prognostic signature based on CAF-secreted cytokines was associated with clinical outcome, tumor progression, and genetic alteration. Our findings may provide insights to develop novel strategies for early intervention and prognostic prediction of BC.",
			"category": 2,
			"name": "Sun Chunxiao,2024"
		},
		{
			"PMID": 34385450,
			"title": "Estimating the predictive power of silent mutations on cancer classification and prognosis.",
			"journal": "NPJ genomic medicine",
			"authorList": [
				"Gutman Tal",
				"Goren Guy",
				"Efroni Omri",
				"Tuller Tamir"
			],
			"DOI": "10.1038/s41525-021-00229-1",
			"date": "2024-04-03",
			"PMC": "",
			"citation": "",
			"abstract": "In recent years it has been shown that silent mutations, in and out of the coding region, can affect gene expression and may be related to tumorigenesis and cancer cell fitness. However, the predictive ability of these mutations for cancer type diagnosis and prognosis has not been evaluated yet. In the current study, based on the analysis of 9,915 cancer genomes and approximately three million mutations, we provide a comprehensive quantitative evaluation of the predictive power of various types of silent and non-silent mutations over cancer classification and prognosis. The results indicate that silent-mutation models outperform the equivalent null models in classifying all examined cancer types and in estimating the probability of survival 10 years after the initial diagnosis. Additionally, combining both non-silent and silent mutations achieved the best classification results for 68% of the cancer types and the best survival estimation results for up to nine years after the diagnosis. Thus, silent mutations hold considerable predictive power over both cancer classification and prognosis, most likely due to their effect on gene expression. It is highly advised that silent mutations are integrated in cancer research in order to unravel the full genomic landscape of cancer and its ramifications on cancer fitness.",
			"category": 2,
			"name": "Gutman Tal,2024"
		},
		{
			"PMID": 34381934,
			"title": null,
			"journal": "JCO precision oncology",
			"authorList": [
				"Yu Yao",
				"Fan Dan",
				"Song Xinmao",
				"Zakeri Kaveh",
				"Chen Linda",
				"Kang Jung",
				"McBride Sean",
				"Tsai C Jillian",
				"Dunn Lara",
				"Sherman Eric",
				"Katabi Nora",
				"Dogan Snjezana",
				"Cracchiolo Jennifer",
				"Cohen Marc",
				"Boyle Jay O",
				"Lee Mark",
				"Valero Cristina",
				"Wang Jingming",
				"Wong Richard",
				"Morris Luc",
				"Riaz Nadeem",
				"Lee Nancy"
			],
			"DOI": "10.1200/PO.20.00515",
			"date": "2022-03-23",
			"PMC": "",
			"citation": "",
			"abstract": "Telomerase reverse transcriptase (",
			"category": 2,
			"name": "Yu Yao,2022"
		},
		{
			"PMID": 34376657,
			"title": "The evolution of hematopoietic cells under cancer therapy.",
			"journal": "Nature communications",
			"authorList": [
				"Pich Oriol",
				"Cortes-Bullich Albert",
				"Mui\u00f1os Ferran",
				"Pratcorona Marta",
				"Gonzalez-Perez Abel",
				"Lopez-Bigas Nuria"
			],
			"DOI": "10.1038/s41467-021-24858-3",
			"date": "2021-08-23",
			"PMC": "",
			"citation": "",
			"abstract": "Chemotherapies may increase mutagenesis of healthy cells and change the selective pressures in tissues, thus influencing their evolution. However, their contributions to the mutation burden and clonal expansions of healthy somatic tissues are not clear. Here, exploiting the mutational footprint of some chemotherapies, we explore their influence on the evolution of hematopoietic cells. Cells of Acute Myeloid Leukemia (AML) secondary to treatment with platinum-based drugs show the mutational footprint of these drugs, indicating that non-malignant blood cells receive chemotherapy mutations. No trace of the\u00a05-fluorouracil (5FU) mutational signature is found in AMLs secondary to exposure to 5FU, suggesting that cells establishing the\u00a0leukemia could be quiescent during treatment. Using the platinum-based mutational signature as a barcode, we determine that the clonal expansion originating the secondary AMLs begins after the start of the cytotoxic treatment. Its absence in clonal hematopoiesis cases is consistent with the start of the clonal expansion predating the exposure to platinum-based drugs.",
			"category": 2,
			"name": "Pich Oriol,2021"
		},
		{
			"PMID": 34374148,
			"title": "Current and future applications of biomarkers in samples collected through minimally invasive methods for cancer medicine and population-based research.",
			"journal": "American journal of human biology : the official journal of the Human Biology Council",
			"authorList": [
				"DeLouize Alicia M",
				"Eick Geeta",
				"Karam Sana D",
				"Snodgrass J Josh"
			],
			"DOI": "10.1002/ajhb.23665",
			"date": "2022-11-09",
			"PMC": "",
			"citation": "",
			"abstract": "Despite advances in cancer medicine and research, invasive and potentially risky procedures such as biopsies, venous blood tests, imaging, colonoscopy, and pap smear tests are still primarily used for screening, staging, and assessing response to therapy. The development and interdisciplinary use of biomarkers from urine, feces, saliva, scent, and capillary blood collected with minimally invasive methods represents a potential opportunity for integration with biomarker analysis for cancers, both in clinical practice (e.g., in screening, treatment, and disease monitoring, and improved quality of life for patients) and population-based research (e.g., in epidemiology/public health, studies of social and environmental determinants, and evolutionary medicine). In this article, we review the scientific rationale, benefits, challenges, and potential opportunities for measuring cancer-related biomarkers in samples collected through minimally invasive methods.",
			"category": 2,
			"name": "DeLouize Alicia M,2022"
		},
		{
			"PMID": 34373653,
			"title": "Limited evolution of the actionable metastatic cancer genome under therapeutic pressure.",
			"journal": "Nature medicine",
			"authorList": [
				"van de Haar Joris",
				"Hoes Louisa R",
				"Roepman Paul",
				"Lolkema Martijn P",
				"Verheul Henk M W",
				"Gelderblom Hans",
				"de Langen Adrianus J",
				"Smit Egbert F",
				"Cuppen Edwin",
				"Wessels Lodewyk F A",
				"Voest Emile E"
			],
			"DOI": "10.1038/s41591-021-01448-w",
			"date": "2021-10-08",
			"PMC": "",
			"citation": "",
			"abstract": "Genomic profiling is critical for the identification of treatment options for patients with metastatic cancer, but it remains unclear how frequently this procedure should be repeated during the course of the disease. To address this, we analyzed whole-genome sequencing (WGS) data of 250 biopsy pairs, longitudinally collected over the treatment course of 231 adult patients with a representative variety of metastatic solid malignancies. Within the biopsy interval (median, 6.4\u2009months), patients received one or multiple lines of (mostly) standard-of-care (SOC) treatments, with all major treatment modalities being broadly represented. SOC biomarkers and biomarkers for clinical trial enrollment could be identified in 23% and 72% of biopsies, respectively. For SOC genomic biomarkers, we observed full concordance between the first and the second biopsy in 99% of pairs. Of the 219 biomarkers for clinical trial enrollment that were identified in the first biopsies, we recovered 94% in the follow-up biopsies. Furthermore, a second WGS analysis did not identify additional biomarkers for clinical trial enrollment in 91% of patients. More-frequent genomic evolution was observed when considering specific genes targeted by small-molecule inhibitors or hormonal therapies (21% and 22% of cases, respectively). Together, our data demonstrate that there is limited evolution of the actionable genome of treated metastases. A single WGS analysis of a metastatic biopsy is generally sufficient to identify SOC genomic biomarkers and to identify investigational treatment opportunities.",
			"category": 2,
			"name": "van de Haar Joris,2021"
		},
		{
			"PMID": 34364910,
			"title": "The somatic molecular evolution of cancer: Mutation, selection, and epistasis.",
			"journal": "Progress in biophysics and molecular biology",
			"authorList": [
				"Dasari Krishna",
				"Somarelli Jason A",
				"Kumar Sudhir",
				"Townsend Jeffrey P"
			],
			"DOI": "10.1016/j.pbiomolbio.2021.08.003",
			"date": "2021-11-25",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer progression has been attributed to somatic changes in single-nucleotide variants, copy-number aberrations, loss of heterozygosity, chromosomal instability, epistatic interactions, and the tumor microenvironment. It is not entirely clear which of these changes are essential and which are ancillary to cancer. The dynamic nature of cancer evolution in a patient can be illuminated using several concepts and tools from classical evolutionary biology. Neutral mutation rates in cancer cells are calculable from genomic data such as synonymous mutations, and selective pressures are calculable from rates of fixation occurring beyond the expectation by neutral mutation and drift. However, these cancer effect sizes of mutations are complicated by epistatic interactions that can determine the likely sequence of gene mutations. In turn, longitudinal phylogenetic analyses of somatic cancer progression offer an opportunity to identify key moments in cancer evolution, relating the timing of driver mutations to corresponding landmarks in the clinical timeline. These analyses reveal temporal aspects of genetic and phenotypic change during tumorigenesis and across clinical timescales. Using a related framework, clonal deconvolution, physical locations of clones, and their phylogenetic relations can be used to infer tumor migration histories. Additionally, genetic interactions with the tumor microenvironment can be analyzed with longstanding approaches applied to organismal genotype-by-environment interactions. Fitness landscapes for cancer evolution relating to genotype, phenotype, and environment could enable more accurate, personalized therapeutic strategies. An understanding of the trajectories underlying the evolution of neoplasms, primary, and metastatic tumors promises fundamental advances toward accurate and personalized predictions of therapeutic response.",
			"category": 2,
			"name": "Dasari Krishna,2021"
		},
		{
			"PMID": 34359818,
			"title": "Biomarkers and Lung Cancer Early Detection: State of the Art.",
			"journal": "Cancers",
			"authorList": [
				"Dama Elisa",
				"Colangelo Tommaso",
				"Fina Emanuela",
				"Cremonesi Marco",
				"Kallikourdis Marinos",
				"Veronesi Giulia",
				"Bianchi Fabrizio"
			],
			"DOI": "10.3390/cancers13153919",
			"date": "2021-08-10",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer burden is increasing, with 2 million deaths/year worldwide. Current limitations in early detection impede lung cancer diagnosis when the disease is still localized and thus more curable by surgery or multimodality treatment. Liquid biopsy is emerging as an important tool for lung cancer early detection and for monitoring therapy response. Here, we reviewed recent advances in liquid biopsy for early diagnosis of lung cancer. We summarized DNA- or RNA-based biomarkers, proteins, autoantibodies circulating in the blood, as well as circulating tumor cells (CTCs), and compared the most promising studies in terms of biomarkers prediction performance. While we observed an overall good performance for the proposed biomarkers, we noticed some critical aspects which may complicate the successful translation of these biomarkers into the clinical setting. We, therefore, proposed a roadmap for successful development of lung cancer biomarkers during the discovery, prioritization, and clinical validation phase. The integration of innovative minimally invasive biomarkers in screening programs is highly demanded to augment lung cancer early detection.",
			"category": 2,
			"name": "Dama Elisa,2021"
		},
		{
			"PMID": 34351900,
			"title": "Forecasting of phenotypic and genetic outcomes of experimental evolution in Pseudomonas protegens.",
			"journal": "PLoS genetics",
			"authorList": [
				"Pentz Jennifer T",
				"Lind Peter A"
			],
			"DOI": "10.1371/journal.pgen.1009722",
			"date": "2021-12-07",
			"PMC": "",
			"citation": "",
			"abstract": "Experimental evolution with microbes is often highly repeatable under identical conditions, suggesting the possibility to predict short-term evolution. However, it is not clear to what degree evolutionary forecasts can be extended to related species in non-identical environments, which would allow testing of general predictive models and fundamental biological assumptions. To develop an extended model system for evolutionary forecasting, we used previous data and models of the genotype-to-phenotype map from the wrinkly spreader system in Pseudomonas fluorescens SBW25 to make predictions of evolutionary outcomes on different biological levels for Pseudomonas protegens Pf-5. In addition to sequence divergence (78% amino acid and 81% nucleotide identity) for the genes targeted by mutations, these species also differ in the inability of Pf-5 to make cellulose, which is the main structural basis for the adaptive phenotype in SBW25. The experimental conditions were changed compared to the SBW25 system to test if forecasts were extendable to a non-identical environment. Forty-three mutants with increased ability to colonize the air-liquid interface were isolated, and the majority had reduced motility and was partly dependent on the Pel exopolysaccharide as a structural component. Most (38/43) mutations are expected to disrupt negative regulation of the same three diguanylate cyclases as in SBW25, with a smaller number of mutations in promoter regions, including an uncharacterized polysaccharide synthase operon. A mathematical model developed for SBW25 predicted the order of the three main pathways and the genes targeted by mutations, but differences in fitness between mutants and mutational biases also appear to influence outcomes. Mutated regions in proteins could be predicted in most cases (16/22), but parallelism at the nucleotide level was low and mutational hot spot sites were not conserved. This study demonstrates the potential of short-term evolutionary forecasting in experimental populations and provides testable predictions for evolutionary outcomes in other Pseudomonas species.",
			"category": 2,
			"name": "Pentz Jennifer T,2021"
		},
		{
			"PMID": 34351567,
			"title": "Improvement in the risk assessment of oral leukoplakia through morphology-related copy number analysis.",
			"journal": "Science China. Life sciences",
			"authorList": [
				"Li Xiaotian",
				"Liu Lu",
				"Zhang Jianyun",
				"Ma Ming",
				"Sun Lisha",
				"Li Xuefen",
				"Zhang Heyu",
				"Wang Jianbin",
				"Huang Yanyi",
				"Li Tiejun"
			],
			"DOI": "10.1007/s11427-021-1965-x",
			"date": "2022-01-06",
			"PMC": "",
			"citation": "",
			"abstract": "Oral leukoplakia is the most common type of oral potentially malignant disorders and considered a precursor lesion to oral squamous cell carcinoma. However, a predictor of oral leukoplakia prognosis has not yet been identified. We investigated whether copy number alteration patterns may effectively predict the prognostic outcomes of oral leukoplakia using routinely processed paraffin sections. Comparison of copy number alteration patterns between oral leukoplakia with hyperplasia (HOL, n=22) and dysplasia (DOL, n=21) showed that oral leukoplakia with dysplasia had a higher copy number alteration rate (86%) than oral leukoplakia with hyperplasia (46%). Oral leukoplakia with dysplasia exhibited a wider range of genomic variations across all chromosomes compared with oral leukoplakia with hyperplasia. We also examined a retrospective cohort of 477 patients with oral leukoplakia with hyperplasia with detailed follow-up information. The malignant transformation (MT, n=19) and leukoplakia recurrence (LR, n=253) groups had higher frequencies of aneuploidy events and copy number loss rate than the free of disease (FD, n=205) group. Together, our results revealed the association between the degree of copy number alterations and the histological grade of oral leukoplakia and demonstrated that copy number alteration may be effective for prognosis prediction in oral leukoplakia patients with hyperplasia.",
			"category": 2,
			"name": "Li Xiaotian,2022"
		},
		{
			"PMID": 34341072,
			"title": "Unraveling Ewing Sarcoma Tumorigenesis Originating from Patient-Derived Mesenchymal Stem Cells.",
			"journal": "Cancer research",
			"authorList": [
				"Sole Anna",
				"Grosset\u00eate Sandrine",
				"Heintz\u00e9 Maxime",
				"Babin Loelia",
				"Za\u00efdi Sakina",
				"Revy Patrick",
				"Renouf Benjamin",
				"De Cian Anne",
				"Giovannangeli Carine",
				"Pierre-Eug\u00e8ne C\u00e9cile",
				"Janoueix-Lerosey Isabelle",
				"Couronn\u00e9 Lucile",
				"Kaltenbach Sophie",
				"Tomishima Mark",
				"Jasin Maria",
				"Gr\u00fcnewald Thomas G P",
				"Delattre Olivier",
				"Surdez Didier",
				"Brunet Erika"
			],
			"DOI": "10.1158/0008-5472.CAN-20-3837",
			"date": "2022-01-03",
			"PMC": "",
			"citation": "",
			"abstract": "Ewing sarcoma is characterized by pathognomonic translocations, most frequently fusing ",
			"category": 2,
			"name": "Sole Anna,2022"
		},
		{
			"PMID": 34337548,
			"title": "Combined Longitudinal Clinical and Autopsy Phenomic Assessment in Lethal Metastatic Prostate Cancer: Recommendations for Advancing Precision Medicine.",
			"journal": "European urology open science",
			"authorList": [
				"Jasu Juho",
				"Tolonen Teemu",
				"Antonarakis Emmanuel S",
				"Beltran Himisha",
				"Halabi Susan",
				"Eisenberger Mario A",
				"Carducci Michael A",
				"Loriot Yohann",
				"Van der Eecken Kim",
				"Lolkema Martijn",
				"Ryan Charles J",
				"Taavitsainen Sinja",
				"Gillessen Silke",
				"H\u00f6gn\u00e4s Gunilla",
				"Talvitie Timo",
				"Taylor Robert J",
				"Koskenalho Antti",
				"Ost Piet",
				"Murtola Teemu J",
				"Rinta-Kiikka Irina",
				"Tammela Teuvo",
				"Auvinen Anssi",
				"Kujala Paula",
				"Smith Thomas J",
				"Kellokumpu-Lehtinen Pirkko-Liisa",
				"Isaacs William B",
				"Nykter Matti",
				"Kesseli Juha",
				"Bova G Steven"
			],
			"DOI": "10.1016/j.euros.2021.05.011",
			"date": "2024-04-02",
			"PMC": "",
			"citation": "",
			"abstract": "Systematic identification of data essential for outcome prediction in metastatic prostate cancer (mPC) would accelerate development of precision oncology.",
			"category": 2,
			"name": "Jasu Juho,2024"
		},
		{
			"PMID": 34330826,
			"title": "PolyG-DS: An ultrasensitive polyguanine tract-profiling method to detect clonal expansions and trace cell lineage.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Zhang Yuezheng",
				"Kohrn Brendan F",
				"Yang Ming",
				"Nachmanson Daniela",
				"Soong T Rinda",
				"Lee I-Hsiu",
				"Tao Yong",
				"Clevers Hans",
				"Swisher Elizabeth M",
				"Brentnall Teresa A",
				"Loeb Lawrence A",
				"Kennedy Scott R",
				"Salk Jesse J",
				"Naxerova Kamila",
				"Risques Rosa Ana"
			],
			"DOI": "10.1073/pnas.2023373118",
			"date": "2021-12-07",
			"PMC": "",
			"citation": "",
			"abstract": "Polyguanine tracts (PolyGs) are short guanine homopolymer repeats that are prone to accumulating mutations when cells divide. This feature makes them especially suitable for cell lineage tracing, which has been exploited to detect and characterize precancerous and cancerous somatic evolution. PolyG genotyping, however, is challenging because of the inherent biochemical difficulties in amplifying and sequencing repetitive regions. To overcome this limitation, we developed PolyG-DS, a next-generation sequencing (NGS) method that combines the error-correction capabilities of duplex sequencing (DS) with enrichment of PolyG loci using CRISPR-Cas9-targeted genomic fragmentation. PolyG-DS markedly reduces technical artifacts by comparing the sequences derived from the complementary strands of each original DNA molecule. We demonstrate that PolyG-DS genotyping is accurate, reproducible, and highly sensitive, enabling the detection of low-frequency alleles (<0.01) in spike-in samples using a panel of only 19 PolyG markers. PolyG-DS replicated prior results based on PolyG fragment length analysis by capillary electrophoresis, and exhibited higher sensitivity for identifying clonal expansions in the nondysplastic colon of patients with ulcerative colitis. We illustrate the utility of this method for resolving the phylogenetic relationship among precancerous lesions in ulcerative colitis and for tracing the metastatic dissemination of ovarian cancer. PolyG-DS enables the study of tumor evolution without prior knowledge of tumor driver mutations and provides a tool to perform cost-effective and easily scalable ultra-accurate NGS-based PolyG genotyping for multiple applications in biology, genetics, and cancer research.",
			"category": 2,
			"name": "Zhang Yuezheng,2021"
		},
		{
			"PMID": 34321609,
			"title": "Genetics of autosomal mosaic chromosomal alteration (mCA).",
			"journal": "Journal of human genetics",
			"authorList": [
				"Liu Xiaoxi",
				"Kamatani Yoichiro",
				"Terao Chikashi"
			],
			"DOI": "10.1038/s10038-021-00964-4",
			"date": "2022-01-05",
			"PMC": "",
			"citation": "",
			"abstract": "Mosaic chromosomal alterations (mCAs) are frequently observed in cancer cells and are regarded as one of the common features of cancers. Strikingly, accumulating studies demonstrated that mCAs are also prevalent in elderly individuals without cancer, implying mCA could be a feature of aging and not necessarily a cancerous state. However, the genetic basis of mCA has been mostly unknown. Recent studies of autosomal mCA based on biobank-scale datasets, including UK Biobank and Biobank Japan, provided a glimpse into the underlying genetic mechanism. In this concise review, we briefly introduced mCA, its link with cancer and aging, and the emerging genetic mechanisms of this phenomenon. We highlighted the following aspects: (1) the interplay between somatic and inherited germline mutations in generating mosaicism; (2) monogenic and polygenic architectures of mCA; and (3) population-specific profiles of mCA. We provided a future perspective emphasizing the need to understand the connection between mCA and other characteristics of aging, in particular, the epigenetic and immunologic features.",
			"category": 2,
			"name": "Liu Xiaoxi,2022"
		},
		{
			"PMID": 34282324,
			"title": "A pan-cancer landscape of somatic mutations in non-unique regions of the human genome.",
			"journal": "Nature biotechnology",
			"authorList": [
				"Tarabichi Maxime",
				"Demeulemeester Jonas",
				"Verfaillie Annelien",
				"Flanagan Adrienne M",
				"Van Loo Peter",
				"Konopka Tomasz"
			],
			"DOI": "10.1038/s41587-021-00971-y",
			"date": "2022-04-19",
			"PMC": "",
			"citation": "",
			"abstract": "A substantial fraction of the human genome displays high sequence similarity with at least one other genomic sequence, posing a challenge for the identification of somatic mutations from short-read sequencing data. Here we annotate genomic variants in 2,658 cancers from the Pan-Cancer Analysis of Whole Genomes (PCAWG) cohort with links to similar sites across the human genome. We train a machine learning model to use signals distributed over multiple genomic sites to call somatic events in non-unique regions and validate the data against linked-read sequencing in an independent dataset. Using this approach, we uncover previously hidden mutations in ~1,700 coding sequences and in thousands of regulatory elements, including in known cancer genes, immunoglobulins and highly mutated gene families. Mutations in non-unique regions are consistent with mutations in unique regions in terms of mutation burden and substitution profiles. The analysis provides a systematic summary of the mutation events in non-unique regions at a genome-wide scale across multiple human cancers.",
			"category": 2,
			"name": "Tarabichi Maxime,2022"
		},
		{
			"PMID": 34274486,
			"title": "Breast cancer heterogeneity through the lens of single-cell analysis and spatial pathologies.",
			"journal": "Seminars in cancer biology",
			"authorList": [
				"Zhao Na",
				"Rosen Jeffrey M"
			],
			"DOI": "10.1016/j.semcancer.2021.07.010",
			"date": "2022-05-17",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer ecosystems are composed of complex cell types, including tumor, stromal and immune cells, each of which can assume diverse phenotypes. Both the heterogeneous composition and spatially distinct tumor microenvironment impact breast cancer progression, treatment response and therapeutic resistance. Thus, a deeper understanding of breast cancer heterogeneity may help facilitate the development of novel therapies and improve outcomes for patients. The advent of paradigm shifting single-cell analysis and spatial pathologies allows for a comprehensive analysis of the tumor ecosystem as well as the interactions between its components at unprecedented resolution. In this review, we discuss the insights gained through single-cell analysis and spatial pathologies on breast cancer heterogeneity.",
			"category": 2,
			"name": "Zhao Na,2022"
		},
		{
			"PMID": 34245122,
			"title": "Global mapping of cancers: The Cancer Genome Atlas and beyond.",
			"journal": "Molecular oncology",
			"authorList": [
				"Ganini Carlo",
				"Amelio Ivano",
				"Bertolo Riccardo",
				"Bove Pierluigi",
				"Buonomo Oreste Claudio",
				"Candi Eleonora",
				"Cipriani Chiara",
				"Di Daniele Nicola",
				"Juhl Hartmut",
				"Mauriello Alessandro",
				"Marani Carla",
				"Marshall John",
				"Melino Sonia",
				"Marchetti Paolo",
				"Montanaro Manuela",
				"Natale Maria Emanuela",
				"Novelli Flavia",
				"Palmieri Giampiero",
				"Piacentini Mauro",
				"Rendina Erino Angelo",
				"Roselli Mario",
				"Sica Giuseppe",
				"Tesauro Manfredi",
				"Rovella Valentina",
				"Tisone Giuseppe",
				"Shi Yufang",
				"Wang Ying",
				"Melino Gerry"
			],
			"DOI": "10.1002/1878-0261.13056",
			"date": "2022-04-07",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer genomes have been explored from the early 2000s through massive exome sequencing efforts, leading to the publication of The Cancer Genome Atlas in 2013. Sequencing techniques have been developed alongside this project and have allowed scientists to bypass the limitation of costs for whole-genome sequencing (WGS) of single specimens by developing more accurate and extensive cancer sequencing projects, such as deep sequencing of whole genomes and transcriptomic analysis. The Pan-Cancer Analysis of Whole Genomes recently published WGS data from more than 2600 human cancers together with almost 1200 related transcriptomes. The application of WGS on a large database allowed, for the first time in history, a global analysis of features such as molecular signatures, large structural variations and noncoding regions of the genome, as well as the evaluation of RNA alterations in the absence of underlying DNA mutations. The vast amount of data generated still needs to be thoroughly deciphered, and the advent of machine-learning approaches will be the next step towards the generation of personalized approaches for cancer medicine. The present manuscript wants to give a broad perspective on some of the biological evidence derived from the largest sequencing attempts on human cancers so far, discussing advantages and limitations of this approach and its power in the era of machine learning.",
			"category": 2,
			"name": "Ganini Carlo,2022"
		},
		{
			"PMID": 34222845,
			"title": "p53 mitigates the effects of oncogenic HRAS in urothelial cells via the repression of ",
			"journal": "iScience",
			"authorList": [
				"Jung Jewon",
				"Liao Han",
				"Coker Shannon A",
				"Liang Hong",
				"Hancock John F",
				"Denicourt Catherine",
				"Venkatachalam Kartik"
			],
			"DOI": "10.1016/j.isci.2021.102701",
			"date": "2024-05-05",
			"PMC": "",
			"citation": "",
			"abstract": "Inhibition of TRPML1, which is encoded by ",
			"category": 2,
			"name": "Jung Jewon,2024"
		},
		{
			"PMID": 34215622,
			"title": "Genetic Determinants of Somatic Selection of Mutational Processes in 3,566 Human Cancers.",
			"journal": "Cancer research",
			"authorList": [
				"Guo Jintao",
				"Zhou Ying",
				"Xu Chaoqun",
				"Chen Qinwei",
				"Sztupinszki Zs\u00f3fia",
				"B\u00f6rcs\u00f6k Judit",
				"Xu Canqiang",
				"Ye Feng",
				"Tang Weiwei",
				"Kang Jiapeng",
				"Yang Lu",
				"Zhong Jiaxin",
				"Zhong Taoling",
				"Hu Tianhui",
				"Yu Rongshan",
				"Szallasi Zoltan",
				"Deng Xianming",
				"Li Qiyuan"
			],
			"DOI": "10.1158/0008-5472.CAN-21-0086",
			"date": "2022-01-07",
			"PMC": "",
			"citation": "",
			"abstract": "The somatic landscape of the cancer genome results from different mutational processes represented by distinct \"mutational signatures.\" Although several mutagenic mechanisms are known to cause specific mutational signatures in cell lines, the variation of somatic mutational activities in patients, which is mostly attributed to somatic selection, is still poorly explained. Here, we introduce a quantitative trait, mutational propensity (MP), and describe an integrated method to infer genetic determinants of variations in the mutational processes in 3,566 cancers with specific underlying mechanisms. As a result, we report 2,314 candidate determinants with both significant germline and somatic effects on somatic selection of mutational processes, of which, 485 act via cancer gene expression and 1,427 act through the tumor-immune microenvironment. These data demonstrate that the genetic determinants of MPs provide complementary information to known cancer driver genes, clonal evolution, and clinical biomarkers. SIGNIFICANCE: The genetic determinants of the somatic mutational processes in cancer elucidate the biology underlying somatic selection and evolution of cancers and demonstrate complementary predictive power across cancer types.",
			"category": 2,
			"name": "Guo Jintao,2022"
		},
		{
			"PMID": 34208086,
			"title": "The Etiology and Pathophysiology Genesis of Benign Prostatic Hyperplasia and Prostate Cancer: A New Perspective.",
			"journal": "Medicines (Basel, Switzerland)",
			"authorList": [
				"Phua Teow J"
			],
			"DOI": "10.3390/medicines8060030",
			"date": "2021-07-14",
			"PMC": "",
			"citation": "",
			"abstract": "The etiology of benign prostatic hyperplasia and prostate cancer are unknown, with ageing being the greatness risk factor.",
			"category": 2,
			"name": "Phua Teow J,2021"
		},
		{
			"PMID": 34185418,
			"title": "Deregulation of apolipoprotein C2 gene in cancer: A potential metabolic vulnerability.",
			"journal": "Clinical and translational medicine",
			"authorList": [
				"Liu Yuqiao",
				"Meng Yiting",
				"Zhang Tian",
				"Alachkar Houda"
			],
			"DOI": "10.1002/ctm2.406",
			"date": "2022-02-08",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Liu Yuqiao,2022"
		},
		{
			"PMID": 34168047,
			"title": "Intratumor CMS Heterogeneity Impacts Patient Prognosis in Localized Colon Cancer.",
			"journal": "Clinical cancer research : an official journal of the American Association for Cancer Research",
			"authorList": [
				"Marisa Laetitia",
				"Blum Yuna",
				"Taieb Julien",
				"Ayadi Mira",
				"Pilati Camilla",
				"Le Malicot Karine",
				"Lepage C\u00f4me",
				"Salazar Ramon",
				"Aust Daniela",
				"Duval Alex",
				"Blons H\u00e9l\u00e8ne",
				"Taly Val\u00e9rie",
				"Gentien David",
				"Rapinat Audrey",
				"Selves Janick",
				"Mouillet-Richard Sophie",
				"Boige Val\u00e9rie",
				"Emile Jean-Fran\u00e7ois",
				"de Reyni\u00e8s Aur\u00e9lien",
				"Laurent-Puig Pierre"
			],
			"DOI": "10.1158/1078-0432.CCR-21-0529",
			"date": "2022-04-04",
			"PMC": "",
			"citation": "",
			"abstract": "The consensus molecular subtypes (CMS) represent a significant advance in the understanding of intertumor heterogeneity in colon cancer. Intratumor heterogeneity (ITH) is the new frontier for refining prognostication and understanding treatment resistance. This study aims at deciphering the transcriptomic ITH of colon cancer and understanding its potential prognostic implications.",
			"category": 2,
			"name": "Marisa Laetitia,2022"
		},
		{
			"PMID": 34168010,
			"title": "Evolution and genomic signatures of spontaneous somatic mutation in ",
			"journal": "Genome research",
			"authorList": [
				"Riddiford Nick",
				"Siudeja Katarzyna",
				"van den Beek Marius",
				"Boumard Benjamin",
				"Bardin Allison J"
			],
			"DOI": "10.1101/gr.268441.120",
			"date": "2022-03-10",
			"PMC": "",
			"citation": "",
			"abstract": "Spontaneous mutations can alter tissue dynamics and lead to cancer initiation. Although large-scale sequencing projects have illuminated processes that influence somatic mutation and subsequent tumor evolution, the mutational dynamics operating in the very early stages of cancer development are currently not well understood. To explore mutational processes in the early stages of cancer evolution, we exploited neoplasia arising spontaneously in the ",
			"category": 2,
			"name": "Riddiford Nick,2022"
		},
		{
			"PMID": 34163070,
			"title": "Clonal fitness inferred from time-series modelling of single-cell cancer genomes.",
			"journal": "Nature",
			"authorList": [
				"Salehi Sohrab",
				"Kabeer Farhia",
				"Ceglia Nicholas",
				"Andronescu Mirela",
				"Williams Marc J",
				"Campbell Kieran R",
				"Masud Tehmina",
				"Wang Beixi",
				"Biele Justina",
				"Brimhall Jazmine",
				"Gee David",
				"Lee Hakwoo",
				"Ting Jerome",
				"Zhang Allen W",
				"Tran Hoa",
				"O'Flanagan Ciara",
				"Dorri Fatemeh",
				"Rusk Nicole",
				"de Algara Teresa Ruiz",
				"Lee So Ra",
				"Cheng Brian Yu Chieh",
				"Eirew Peter",
				"Kono Takako",
				"Pham Jenifer",
				"Grewal Diljot",
				"Lai Daniel",
				"Moore Richard",
				"Mungall Andrew J",
				"Marra Marco A",
				"IMAXT Consortium",
				"McPherson Andrew",
				"Bouchard-C\u00f4t\u00e9 Alexandre",
				"Aparicio Samuel",
				"Shah Sohrab P"
			],
			"DOI": "10.1038/s41586-021-03648-3",
			"date": "2022-01-11",
			"PMC": "",
			"citation": "",
			"abstract": "Progress in defining genomic fitness landscapes in cancer, especially those defined by copy number alterations (CNAs), has been impeded by lack of time-series single-cell sampling of polyclonal populations and temporal statistical models",
			"category": 2,
			"name": "Salehi Sohrab,2022"
		},
		{
			"PMID": 34131071,
			"title": "HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase.",
			"journal": "Molecular cancer research : MCR",
			"authorList": [
				"Ginzel Joshua D",
				"Acharya Chaitanya R",
				"Lubkov Veronica",
				"Mori Hidetoshi",
				"Boone Peter G",
				"Rochelle Lauren K",
				"Roberts Wendy L",
				"Everitt Jeffrey I",
				"Hartman Zachary C",
				"Crosby Erika J",
				"Barak Lawrence S",
				"Caron Marc G",
				"Chen Jane Q",
				"Hubbard Neil E",
				"Cardiff Robert D",
				"Borowsky Alexander D",
				"Lyerly H Kim",
				"Snyder Joshua C"
			],
			"DOI": "10.1158/1541-7786.MCR-21-0215",
			"date": "2022-02-15",
			"PMC": "",
			"citation": "",
			"abstract": "HER2-positive breast cancers are among the most heterogeneous breast cancer subtypes. The early amplification of HER2 and its known oncogenic isoforms provide a plausible mechanism in which distinct programs of tumor heterogeneity could be traced to the initial oncogenic event. Here a Cancer rainbow mouse simultaneously expressing fluorescently barcoded wildtype (",
			"category": 2,
			"name": "Ginzel Joshua D,2022"
		},
		{
			"PMID": 34127844,
			"title": "PI3K inhibitors are finally coming of age.",
			"journal": "Nature reviews. Drug discovery",
			"authorList": [
				"Vanhaesebroeck Bart",
				"Perry Matthew W D",
				"Brown Jennifer R",
				"Andr\u00e9 Fabrice",
				"Okkenhaug Klaus"
			],
			"DOI": "10.1038/s41573-021-00209-1",
			"date": "2021-10-08",
			"PMC": "",
			"citation": "",
			"abstract": "Overactive phosphoinositide 3-kinase (PI3K) in cancer and immune dysregulation has spurred extensive efforts to develop therapeutic PI3K inhibitors. Although progress has been hampered by issues such as poor drug tolerance and drug resistance, several PI3K inhibitors have now received regulatory approval - the PI3K\u03b1 isoform-selective inhibitor alpelisib for the treatment of breast cancer and inhibitors mainly aimed at the leukocyte-enriched PI3K\u03b4 in B cell malignancies. In addition to targeting cancer cell-intrinsic PI3K activity, emerging evidence highlights the potential of PI3K inhibitors in cancer immunotherapy. This Review summarizes key discoveries that aid the clinical translation of PI3K\u03b1 and PI3K\u03b4 inhibitors, highlighting lessons learnt and future opportunities.",
			"category": 2,
			"name": "Vanhaesebroeck Bart,2021"
		},
		{
			"PMID": 34097189,
			"title": "Decoding human cancer with whole genome sequencing: a review of PCAWG Project studies published in February 2020.",
			"journal": "Cancer metastasis reviews",
			"authorList": [
				"Giunta Simona"
			],
			"DOI": "10.1007/s10555-021-09969-z",
			"date": "2021-12-30",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is underlined by genetic changes. In an unprecedented international effort, the Pan-Cancer Analysis of Whole Genomes (PCAWG) of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) sequenced the tumors of over two thousand five hundred patients across 38 different cancer types, as well as the\u00a0corresponding healthy tissue, with the aim of identifying genome-wide mutations exclusively found in cancer and uncovering new genetic changes that drive tumor formation. What set this project apart from earlier efforts is the use of whole genome sequencing (WGS) that enabled to explore alterations beyond the\u00a0coding DNA, into cancer's non-coding genome. WGS of the entire cohort allowed to tease apart driving mutations that initiate and support carcinogenesis from passenger mutations that do not play an overt role in the disease. At least one causative mutation was found in 95% of all cancers, with many tumors showing an average of 5 driver mutations. The\u00a0PCAWG Project also assessed the transcriptional output altered in cancer and rebuilt the evolutionary history of each tumor showing that initial driver mutations can\u00a0occur years if not decades prior to a diagnosis. Here, I provide a concise review of the\u00a0Pan-Cancer Project papers published on February 2020, along with key computational tools and the\u00a0digital framework generated as part of the project. This represents an historic effort by hundreds of international collaborators, which provides a comprehensive understanding of cancer genetics, with publicly available data and resources representing a treasure trove of information to advance cancer research for years to come.",
			"category": 2,
			"name": "Giunta Simona,2021"
		},
		{
			"PMID": 34067731,
			"title": "Rely on Each Other: DNA Binding Cooperativity Shapes p53 Functions in Tumor Suppression and Cancer Therapy.",
			"journal": "Cancers",
			"authorList": [
				"Timofeev Oleg",
				"Stiewe Thorsten"
			],
			"DOI": "10.3390/cancers13102422",
			"date": "2023-09-20",
			"PMC": "",
			"citation": "",
			"abstract": "p53 is a tumor suppressor that is mutated in half of all cancers. The high clinical relevance has made p53 a model transcription factor for delineating general mechanisms of transcriptional regulation. p53 forms tetramers that bind DNA in a highly cooperative manner. The DNA binding cooperativity of p53 has been studied by structural and molecular biologists as well as clinical oncologists. These experiments have revealed the structural basis for cooperative DNA binding and its impact on sequence specificity and target gene spectrum. Cooperativity was found to be critical for the control of p53-mediated cell fate decisions and tumor suppression. Importantly, an estimated number of 34,000 cancer patients per year world-wide have mutations of the amino acids mediating cooperativity, and knock-in mouse models have confirmed such mutations to be tumorigenic. While p53 cancer mutations are classically subdivided into \"contact\" and \"structural\" mutations, \"cooperativity\" mutations form a mechanistically distinct third class that affect the quaternary structure but leave DNA contacting residues and the three-dimensional folding of the DNA-binding domain intact. In this review we discuss the concept of DNA binding cooperativity and highlight the unique nature of cooperativity mutations and their clinical implications for cancer therapy.",
			"category": 2,
			"name": "Timofeev Oleg,2023"
		},
		{
			"PMID": 34050156,
			"title": "Multimodal analysis of cell-free DNA whole-genome sequencing for pediatric cancers with low mutational burden.",
			"journal": "Nature communications",
			"authorList": [
				"Peneder Peter",
				"St\u00fctz Adrian M",
				"Surdez Didier",
				"Krumbholz Manuela",
				"Semper Sabine",
				"Chicard Mathieu",
				"Sheffield Nathan C",
				"Pierron Gaelle",
				"Lapouble Eve",
				"T\u00f6tzl Marcus",
				"Erg\u00fcner Bekir",
				"Barreca Daniele",
				"Rendeiro Andr\u00e9 F",
				"Agaimy Abbas",
				"Boztug Heidrun",
				"Engstler Gernot",
				"Dworzak Michael",
				"Bernkopf Marie",
				"Taschner-Mandl Sabine",
				"Ambros Inge M",
				"Myklebost Ola",
				"Marec-B\u00e9rard Perrine",
				"Burchill Susan Ann",
				"Brennan Bernadette",
				"Strauss Sandra J",
				"Whelan Jeremy",
				"Schleiermacher Gudrun",
				"Schaefer Christiane",
				"Dirksen Uta",
				"Hutter Caroline",
				"Boye Kjetil",
				"Ambros Peter F",
				"Delattre Olivier",
				"Metzler Markus",
				"Bock Christoph",
				"Tomazou Eleni M"
			],
			"DOI": "10.1038/s41467-021-23445-w",
			"date": "2021-06-08",
			"PMC": "",
			"citation": "",
			"abstract": "Sequencing of cell-free DNA in the blood of cancer patients (liquid biopsy) provides attractive opportunities for early diagnosis, assessment of treatment response, and minimally invasive disease monitoring. To unlock liquid biopsy analysis for pediatric tumors with few genetic aberrations, we introduce an integrated genetic/epigenetic analysis method and demonstrate its utility on 241 deep whole-genome sequencing profiles of 95 patients with Ewing sarcoma and 31 patients with other pediatric sarcomas. Our method achieves sensitive detection and classification of circulating tumor DNA in peripheral blood independent of any genetic alterations. Moreover, we benchmark different metrics for cell-free DNA fragmentation analysis, and we introduce the LIQUORICE algorithm for detecting circulating tumor DNA based on cancer-specific chromatin signatures. Finally, we combine several fragmentation-based metrics into an integrated machine learning classifier for liquid biopsy analysis that exploits widespread epigenetic deregulation and\u00a0is tailored to cancers with low mutation rates. Clinical associations highlight the potential value of cfDNA fragmentation patterns as prognostic biomarkers in Ewing sarcoma. In summary, our study provides a comprehensive analysis of circulating tumor DNA beyond recurrent genetic aberrations, and it renders the benefits of liquid biopsy more readily accessible for childhood cancers.",
			"category": 2,
			"name": "Peneder Peter,2021"
		},
		{
			"PMID": 34035948,
			"title": "Genetic diversity through social heterosis can increase virulence in RNA viral infections and cancer progression.",
			"journal": "Royal Society open science",
			"authorList": [
				"Ebrahimi Saba",
				"Nonacs Peter"
			],
			"DOI": "10.1098/rsos.202219",
			"date": "2024-04-02",
			"PMC": "",
			"citation": "",
			"abstract": "In viral infections and cancer tumours, negative health outcomes often correlate with increasing genetic diversity. Possible evolutionary processes for such relationships include mutant lineages escaping host control or diversity, ",
			"category": 2,
			"name": "Ebrahimi Saba,2024"
		},
		{
			"PMID": 34017094,
			"title": "Mutational signatures impact the evolution of anti-EGFR antibody resistance in colorectal cancer.",
			"journal": "Nature ecology & evolution",
			"authorList": [
				"Woolston Andrew",
				"Barber Louise J",
				"Griffiths Beatrice",
				"Pich Oriol",
				"Lopez-Bigas Nuria",
				"Matthews Nik",
				"Rao Sheela",
				"Watkins David",
				"Chau Ian",
				"Starling Naureen",
				"Cunningham David",
				"Gerlinger Marco"
			],
			"DOI": "10.1038/s41559-021-01470-8",
			"date": "2021-08-02",
			"PMC": "",
			"citation": "",
			"abstract": "Anti-EGFR antibodies such as cetuximab are active against KRAS/NRAS wild-type colorectal cancers (CRCs), but acquired resistance invariably evolves. It is unknown which mutational mechanisms enable resistance evolution and whether adaptive mutagenesis (a transient cetuximab-induced increase in mutation generation) contributes in patients. Here, we investigate these questions in exome sequencing data from 42 baseline and progression biopsies from cetuximab-treated CRCs. Mutation loads did not increase from baseline to progression, and evidence for a contribution of adaptive mutagenesis was limited. However, the chemotherapy-induced mutational signature SBS17b was the main contributor of specific KRAS/NRAS and EGFR driver mutations that are enriched at acquired resistance. Detectable SBS17b activity before treatment predicted shorter progression-free survival and the evolution of these specific mutations during subsequent cetuximab treatment. This result suggests that chemotherapy mutagenesis can accelerate resistance evolution. Mutational signatures may be a new class of cancer evolution predictor.",
			"category": 2,
			"name": "Woolston Andrew,2021"
		},
		{
			"PMID": 34003820,
			"title": "Mathematical modeling of multiple pathways in colorectal carcinogenesis using dynamical systems with Kronecker structure.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Haupt Saskia",
				"Zeilmann Alexander",
				"Ahadova Aysel",
				"Bl\u00e4ker Hendrik",
				"von Knebel Doeberitz Magnus",
				"Kloor Matthias",
				"Heuveline Vincent"
			],
			"DOI": "10.1371/journal.pcbi.1008970",
			"date": "2021-09-14",
			"PMC": "",
			"citation": "",
			"abstract": "Like many other types of cancer, colorectal cancer (CRC) develops through multiple pathways of carcinogenesis. This is also true for colorectal carcinogenesis in Lynch syndrome (LS), the most common inherited CRC syndrome. However, a comprehensive understanding of the distribution of these pathways of carcinogenesis, which allows for tailored clinical treatment and even prevention, is still lacking. We suggest a linear dynamical system modeling the evolution of different pathways of colorectal carcinogenesis based on the involved driver mutations. The model consists of different components accounting for independent and dependent mutational processes. We define the driver gene mutation graphs and combine them using the Cartesian graph product. This leads to matrix components built by the Kronecker sum and product of the adjacency matrices of the gene mutation graphs enabling a thorough mathematical analysis and medical interpretation. Using the Kronecker structure, we developed a mathematical model which we applied exemplarily to the three pathways of colorectal carcinogenesis in LS. Beside a pathogenic germline variant in one of the DNA mismatch repair (MMR) genes, driver mutations in APC, CTNNB1, KRAS and TP53 are considered. We exemplarily incorporate mutational dependencies, such as increased point mutation rates after MMR deficiency, and based on recent experimental data, biallelic somatic CTNNB1 mutations as common drivers of LS-associated CRCs. With the model and parameter choice, we obtained simulation results that are in concordance with clinical observations. These include the evolution of MMR-deficient crypts as early precursors in LS carcinogenesis and the influence of variants in MMR genes thereon. The proportions of MMR-deficient and MMR-proficient APC-inactivated crypts as first measure for the distribution among the pathways in LS-associated colorectal carcinogenesis are compatible with clinical observations. The approach provides a modular framework for modeling multiple pathways of carcinogenesis yielding promising results in concordance with clinical observations in LS CRCs.",
			"category": 2,
			"name": "Haupt Saskia,2021"
		},
		{
			"PMID": 33986299,
			"title": "The landscape and driver potential of site-specific hotspots across cancer genomes.",
			"journal": "NPJ genomic medicine",
			"authorList": [
				"Juul Randi Istrup",
				"Nielsen Morten Muhlig",
				"Juul Malene",
				"Feuerbach Lars",
				"Pedersen Jakob Skou"
			],
			"DOI": "10.1038/s41525-021-00197-6",
			"date": "2021-05-18",
			"PMC": "",
			"citation": "",
			"abstract": "Large sets of whole cancer genomes make it possible to study mutation hotspots genome-wide. Here we detect, categorize, and characterize site-specific hotspots using 2279 whole cancer genomes from the Pan-Cancer Analysis of Whole Genomes project and provide a resource of annotated hotspots genome-wide. We investigate the excess of hotspots in both protein-coding and gene regulatory regions and develop measures of positive selection and functional impact for individual hotspots. Using cancer allele fractions, expression aberrations, mutational signatures, and a variety of genomic features, such as potential gain or loss of transcription factor binding sites, we annotate and prioritize all highly mutated hotspots. Genome-wide we find more high-frequency SNV and indel hotspots than expected given mutational background models. Protein-coding regions are generally enriched for SNV hotspots compared to other regions. Gene regulatory hotspots show enrichment of potential same-patient second-hit missense mutations, consistent with enrichment of hotspot driver mutations compared to singletons. For protein-coding regions, splice-sites, promoters, and enhancers, we see an excess of hotspots associated with cancer genes. Interestingly, missense hotspot mutations in tumor suppressors are associated with elevated expression, suggesting localized amino-acid changes with functional impact. For individual non-coding hotspots, only a small number show clear signs of positive selection, including known sites in the TERT promoter and the 5' UTR of TP53. Most of the new candidates have few mutations and limited driver evidence. However, a hotspot in an enhancer of the oncogene POU2AF1, which may create a transcription factor binding site, presents multiple lines of driver-consistent evidence.",
			"category": 2,
			"name": "Juul Randi Istrup,2021"
		},
		{
			"PMID": 33969622,
			"title": "Mutated circulating tumor DNA as a liquid biopsy in lung cancer detection and treatment.",
			"journal": "Molecular oncology",
			"authorList": [
				"Filipska Martyna",
				"Rosell Rafael"
			],
			"DOI": "10.1002/1878-0261.12983",
			"date": "2022-03-21",
			"PMC": "",
			"citation": "",
			"abstract": "Over the past decade, substantial developments have been made in the detection of circulating tumor DNA (ctDNA)-cell-free DNA (cfDNA) fragments released into the circulation from tumor cells and displaying the genetic alterations of those cells. As such, ctDNA detected in liquid biopsies serves as a powerful tool for cancer patient stratification, therapy guidance, detection of resistance, and relapse monitoring. In this Review, we describe lung cancer diagnosis and monitoring strategies using ctDNA detection technologies and compile recent evidence regarding lung cancer-related mutation detection in liquid biopsy. We focus not only on epidermal growth factor receptor (EGFR) alterations, but also on significant co-mutations that shed more light on novel ctDNA-based liquid biopsy applications. Finally, we discuss future perspectives of early-cancer detection and clonal hematopoiesis filtering strategies, with possible inclusion of microbiome-driven liquid biopsy.",
			"category": 2,
			"name": "Filipska Martyna,2022"
		},
		{
			"PMID": 33941236,
			"title": "Functional and genetic determinants of mutation rate variability in regulatory elements of cancer genomes.",
			"journal": "Genome biology",
			"authorList": [
				"Lee Christian A",
				"Abd-Rabbo Diala",
				"Reimand J\u00fcri"
			],
			"DOI": "10.1186/s13059-021-02318-x",
			"date": "2022-01-19",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer genomes are shaped by mutational processes with complex spatial variation at multiple scales. Entire classes of regulatory elements are affected by local variations in mutation frequency. However, the underlying mechanisms with functional and genetic determinants remain poorly understood.",
			"category": 2,
			"name": "Lee Christian A,2022"
		},
		{
			"PMID": 33922503,
			"title": "Mechanisms of High-Grade Serous Carcinogenesis in the Fallopian Tube and Ovary: Current Hypotheses, Etiologic Factors, and Molecular Alterations.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Otsuka Isao"
			],
			"DOI": "10.3390/ijms22094409",
			"date": "2021-05-28",
			"PMC": "",
			"citation": "",
			"abstract": "Ovarian high-grade serous carcinomas (HGSCs) are a heterogeneous group of diseases. They include fallopian-tube-epithelium (FTE)-derived and ovarian-surface-epithelium (OSE)-derived tumors. The risk/protective factors suggest that the etiology of HGSCs is multifactorial. Inflammation caused by ovulation and retrograde bleeding may play a major role. HGSCs are among the most genetically altered cancers, and ",
			"category": 2,
			"name": "Otsuka Isao,2021"
		},
		{
			"PMID": 33919355,
			"title": "RGB-Marking to Identify Patterns of Selection and Neutral Evolution in Human Osteosarcoma Models.",
			"journal": "Cancers",
			"authorList": [
				"Gambera Stefano",
				"Pati\u00f1o-Garcia Ana",
				"Alfranca Arantzazu",
				"Garcia-Castro Javier"
			],
			"DOI": "10.3390/cancers13092003",
			"date": "2023-09-20",
			"PMC": "",
			"citation": "",
			"abstract": "Osteosarcoma (OS) is a highly aggressive tumor characterized by malignant cells producing pathologic bone; the disease presents a natural tendency to metastasize. Genetic studies indicate that the OS genome is extremely complex, presenting signs of macro-evolution, and linear and branched patterns of clonal development. However, those studies were based on the phylogenetic reconstruction of next-generation sequencing (NGS) data, which present important limitations. Thus, testing clonal evolution in experimental models could be useful for validating this hypothesis. In the present study, lentiviral LeGO-vectors were employed to generate colorimetric red, green, blue (RGB)-marking in murine, canine, and human OS. With this strategy, we studied tumor heterogeneity and the clonal dynamics occurring in vivo in immunodeficient NOD.Cg-Prkdcscid-Il2rgtm1Wjl/SzJ (NSG) mice. Based on colorimetric label, tumor clonal composition was analyzed by confocal microscopy, flow cytometry, and different types of supervised and unsupervised clonal analyses. With this approach, we observed a consistent reduction in the clonal composition of RGB-marked tumors and identified evident clonal selection at the first passage in immunodeficient mice. Furthermore, we also demonstrated that OS could follow a neutral model of growth, where the disease is defined by the coexistence of different tumor sub-clones. Our study demonstrates the importance of rigorous testing of the selective forces in commonly used experimental models.",
			"category": 2,
			"name": "Gambera Stefano,2023"
		},
		{
			"PMID": 33878947,
			"title": "Genome instability and loss of protein homeostasis: converging paths to neurodegeneration?",
			"journal": "Open biology",
			"authorList": [
				"Ainslie Anna",
				"Huiting Wouter",
				"Barazzuol Lara",
				"Bergink Steven"
			],
			"DOI": "10.1098/rsob.200296",
			"date": "2022-02-02",
			"PMC": "",
			"citation": "",
			"abstract": "Genome instability and loss of protein homeostasis are hallmark events of age-related diseases that include neurodegeneration. Several neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis are characterized by protein aggregation, while an impaired DNA damage response (DDR) as in many genetic DNA repair disorders leads to pronounced neuropathological features. It remains unclear to what degree these cellular events interconnect with each other in the development of neurological diseases. This review highlights how the loss of protein homeostasis and genome instability influence one other. We will discuss studies that illustrate this connection. DNA damage contributes to many neurodegenerative diseases, as shown by an increased level of DNA damage in patients, possibly due to the effects of protein aggregates on chromatin, the sequestration of DNA repair proteins and novel putative DNA repair functions. Conversely, genome stability is also important for protein homeostasis. For example, gene copy number variations and the loss of key DDR components can lead to marked proteotoxic stress. An improved understanding of how protein homeostasis and genome stability are mechanistically connected is needed and promises to lead to the development of novel therapeutic interventions.",
			"category": 2,
			"name": "Ainslie Anna,2022"
		},
		{
			"PMID": 33856447,
			"title": "Familial patterns of hematologic precursors.",
			"journal": "Blood",
			"authorList": [
				"Landgren Ola",
				"Maura Francesco"
			],
			"DOI": "10.1182/blood.2020010035",
			"date": "2021-09-13",
			"PMC": "",
			"citation": "",
			"abstract": "In this issue of ",
			"category": 2,
			"name": "Landgren Ola,2021"
		},
		{
			"PMID": 33846893,
			"title": "Contribution of Genomics to the Surgical Management and Study of Oral Cancer.",
			"journal": "Annals of surgical oncology",
			"authorList": [
				"Saidak Zuzana",
				"Lailler Claire",
				"Testelin Sylvie",
				"Chauffert Bruno",
				"Clatot Florian",
				"Galmiche Antoine"
			],
			"DOI": "10.1245/s10434-021-09904-0",
			"date": "2021-09-27",
			"PMC": "",
			"citation": "",
			"abstract": "Oral squamous cell carcinoma (OSCC) is the most frequent type of tumor arising from the oral cavity. Surgery is the cornerstone of the treatment of these cancers. Tumor biology has long been overlooked as an important contributor to the outcome of surgical procedures, but recent studies are challenging this concept. Molecular analyses of tumor DNA or RNA provide a rich source of information about the biology of OSCC.",
			"category": 2,
			"name": "Saidak Zuzana,2021"
		},
		{
			"PMID": 33832990,
			"title": "Interpretation of allele-specific chromatin accessibility using cell state-aware deep learning.",
			"journal": "Genome research",
			"authorList": [
				"Atak Zeynep Kalender",
				"Taskiran Ibrahim Ihsan",
				"Demeulemeester Jonas",
				"Flerin Christopher",
				"Mauduit David",
				"Minnoye Liesbeth",
				"Hulselmans Gert",
				"Christiaens Valerie",
				"Ghanem Ghanem-Elias",
				"Wouters Jasper",
				"Aerts Stein"
			],
			"DOI": "10.1101/gr.260851.120",
			"date": "2022-03-09",
			"PMC": "",
			"citation": "",
			"abstract": "Genomic sequence variation within enhancers and promoters can have a significant impact on the cellular state and phenotype. However, sifting through the millions of candidate variants in a personal genome or a cancer genome, to identify those that impact ",
			"category": 2,
			"name": "Atak Zeynep Kalender,2022"
		},
		{
			"PMID": 33817298,
			"title": "Adriamycin-resistant cells are significantly less fit than adriamycin-sensitive cells in cervical cancer.",
			"journal": "Open life sciences",
			"authorList": [
				"Qi Min",
				"Xie Lijuan",
				"Duan Guihua"
			],
			"DOI": "10.1515/biol-2021-0004",
			"date": "2021-04-06",
			"PMC": "",
			"citation": "",
			"abstract": "Adriamycin (ADR) is an important chemotherapy agent in many advanced cancers, but the emergence of drug resistance during treatment is a major limitation to its successful use. Recent studies have suggested that drug-resistant cells become less fit and their growth could be inhibited by parental cells without cytotoxic treatment. In this study, we examined the fitness differences between HeLa and HeLa/ADR cells. Compared with the parental cell line, HeLa/ADR cells showed significantly lower growth rates, both ",
			"category": 2,
			"name": "Qi Min,2021"
		},
		{
			"PMID": 33803592,
			"title": "Translational Research in the Era of Precision Medicine: Where We Are and Where We Will Go.",
			"journal": "Journal of personalized medicine",
			"authorList": [
				"De Maria Marchiano Ruggero",
				"Di Sante Gabriele",
				"Piro Geny",
				"Carbone Carmine",
				"Tortora Giampaolo",
				"Boldrini Luca",
				"Pietragalla Antonella",
				"Daniele Gennaro",
				"Tredicine Maria",
				"Cesario Alfredo",
				"Valentini Vincenzo",
				"Gallo Daniela",
				"Babini Gabriele",
				"D'Oria Marika",
				"Scambia Giovanni"
			],
			"DOI": "10.3390/jpm11030216",
			"date": "2023-11-11",
			"PMC": "",
			"citation": "",
			"abstract": "The advent of Precision Medicine has globally revolutionized the approach of translational research suggesting a patient-centric vision with therapeutic choices driven by the identification of specific predictive biomarkers of response to avoid ineffective therapies and reduce adverse effects. The spread of \"multi-omics\" analysis and the use of sensors, together with the ability to acquire clinical, behavioral, and environmental information on a large scale, will allow the digitization of the state of health or disease of each person, and the creation of a global health management system capable of generating real-time knowledge and new opportunities for prevention and therapy in the individual person (high-definition medicine). Real world data-based translational applications represent a promising alternative to the traditional evidence-based medicine (EBM) approaches that are based on the use of randomized clinical trials to test the selected hypothesis. Multi-modality data integration is necessary for example in precision oncology where an Avatar interface allows several simulations in order to define the best therapeutic scheme for each cancer patient.",
			"category": 2,
			"name": "De Maria Marchiano Ruggero,2023"
		},
		{
			"PMID": 33802828,
			"title": "How Chaotic Is Genome Chaos?",
			"journal": "Cancers",
			"authorList": [
				"Shapiro James A"
			],
			"DOI": "10.3390/cancers13061358",
			"date": "2021-04-08",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer genomes evolve in a punctuated manner during tumor evolution. Abrupt genome restructuring at key steps in this evolution has been called \"genome chaos.\" To answer whether widespread genome change is truly chaotic, this review (i) summarizes the limited number of cell and molecular systems that execute genome restructuring, (ii) describes the characteristic signatures of DNA changes that result from activity of those systems, and (iii) examines two cases where genome restructuring is determined to a significant degree by cell type or viral infection. The conclusion is that many restructured cancer genomes display sufficiently unchaotic signatures to identify the cellular systems responsible for major oncogenic transitions, thereby identifying possible targets for therapies to inhibit tumor progression to greater aggressiveness.",
			"category": 2,
			"name": "Shapiro James A,2021"
		},
		{
			"PMID": 33802493,
			"title": "The Burden of Post-Translational Modification (PTM)-Disrupting Mutations in the Tumor Matrisome.",
			"journal": "Cancers",
			"authorList": [
				"Holstein Elisa",
				"Dittmann Annalena",
				"K\u00e4\u00e4ri\u00e4inen Anni",
				"Pesola Vilma",
				"Koivunen Jarkko",
				"Pihlajaniemi Taina",
				"Naba Alexandra",
				"Izzi Valerio"
			],
			"DOI": "10.3390/cancers13051081",
			"date": "2023-09-19",
			"PMC": "",
			"citation": "",
			"abstract": "To evaluate the occurrence of mutations affecting post-translational modification (PTM) sites in matrisome genes across different tumor types, in light of their genomic and functional contexts and in comparison with the rest of the genome.",
			"category": 2,
			"name": "Holstein Elisa,2023"
		},
		{
			"PMID": 33792193,
			"title": "Breaking the paradigm: early insights from mammalian DNA breakomes.",
			"journal": "The FEBS journal",
			"authorList": [
				"Saayman Xanita",
				"Esashi Fumiko"
			],
			"DOI": "10.1111/febs.15849",
			"date": "2022-05-04",
			"PMC": "",
			"citation": "",
			"abstract": "DNA double-strand breaks (DSBs) can result from both exogenous and endogenous sources and are potentially toxic lesions to the human genome. If improperly repaired, DSBs can threaten genome integrity and contribute to premature ageing, neurodegenerative disorders and carcinogenesis. Through decades of work on genome stability, it has become evident that certain regions of the genome are inherently more prone to breakage than others, known as genome instability hotspots. Recent advancements in sequencing-based technologies now enable the profiling of genome-wide distributions of DSBs, also known as breakomes, to systematically map these instability hotspots. Here, we review the application of these technologies and their implications for our current understanding of the genomic regions most likely to drive genome instability. These breakomes ultimately highlight both new and established breakage hotspots including actively transcribed regions, loop boundaries and early-replicating regions of the genome. Further, these breakomes challenge the paradigm that DNA breakage primarily occurs in hard-to-replicate regions. With these advancements, we begin to gain insights into the biological mechanisms both invoking and protecting against genome instability.",
			"category": 2,
			"name": "Saayman Xanita,2022"
		},
		{
			"PMID": 33785256,
			"title": "Nascent Prostate Cancer Heterogeneity Drives Evolution and Resistance to Intense Hormonal Therapy.",
			"journal": "European urology",
			"authorList": [
				"Wilkinson Scott",
				"Ye Huihui",
				"Karzai Fatima",
				"Harmon Stephanie A",
				"Terrigino Nicholas T",
				"VanderWeele David J",
				"Bright John R",
				"Atway Rayann",
				"Trostel Shana Y",
				"Carrabba Nicole V",
				"Whitlock Nichelle C",
				"Walker Stephanie M",
				"Lis Rosina T",
				"Abdul Sater Houssein",
				"Capaldo Brian J",
				"Madan Ravi A",
				"Gulley James L",
				"Chun Guinevere",
				"Merino Maria J",
				"Pinto Peter A",
				"Salles Daniela C",
				"Kaur Harsimar B",
				"Lotan Tamara L",
				"Venzon David J",
				"Choyke Peter L",
				"Turkbey Baris",
				"Dahut William L",
				"Sowalsky Adam G"
			],
			"DOI": "10.1016/j.eururo.2021.03.009",
			"date": "2022-04-18",
			"PMC": "",
			"citation": "",
			"abstract": "Patients diagnosed with high risk localized prostate cancer have variable outcomes following surgery. Trials of intense neoadjuvant androgen deprivation therapy (NADT) have shown lower rates of recurrence among patients with minimal residual disease after treatment. The molecular features that distinguish exceptional responders from poor responders are not known.",
			"category": 2,
			"name": "Wilkinson Scott,2022"
		},
		{
			"PMID": 33782566,
			"title": "Promises and challenges of adoptive T-cell therapies for solid tumours.",
			"journal": "British journal of cancer",
			"authorList": [
				"Morotti Matteo",
				"Albukhari Ashwag",
				"Alsaadi Abdulkhaliq",
				"Artibani Mara",
				"Brenton James D",
				"Curbishley Stuart M",
				"Dong Tao",
				"Dustin Michael L",
				"Hu Zhiyuan",
				"McGranahan Nicholas",
				"Miller Martin L",
				"Santana-Gonzalez Laura",
				"Seymour Leonard W",
				"Shi Tingyan",
				"Van Loo Peter",
				"Yau Christopher",
				"White Helen",
				"Wietek Nina",
				"Church David N",
				"Wedge David C",
				"Ahmed Ahmed A"
			],
			"DOI": "10.1038/s41416-021-01353-6",
			"date": "2021-12-15",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a leading cause of death worldwide and, despite new targeted therapies and immunotherapies, many patients with advanced-stage- or high-risk cancers still die, owing to metastatic disease. Adoptive T-cell therapy, involving the autologous or allogeneic transplant of tumour-infiltrating lymphocytes or genetically modified T cells expressing novel T-cell receptors or chimeric antigen receptors, has shown promise in the treatment of cancer patients, leading to durable responses and, in some cases, cure. Technological advances in genomics, computational biology, immunology and cell manufacturing have brought the aspiration of individualised therapies for cancer patients closer to reality. This new era of cell-based individualised therapeutics challenges the traditional standards of therapeutic interventions and provides opportunities for a paradigm shift in our approach to cancer therapy. Invited speakers at a 2020 symposium discussed three areas-cancer genomics, cancer immunology and cell-therapy manufacturing-that are essential to the effective translation of T-cell therapies in the treatment of solid malignancies. Key advances have been made in understanding genetic intratumour heterogeneity, and strategies to accurately identify neoantigens, overcome T-cell exhaustion and circumvent tumour immunosuppression after cell-therapy infusion are being developed. Advances are being made in cell-manufacturing approaches that have the potential to establish cell-therapies as credible therapeutic options. T-cell therapies face many challenges but hold great promise for improving clinical outcomes for patients with solid tumours.",
			"category": 2,
			"name": "Morotti Matteo,2021"
		},
		{
			"PMID": 33782531,
			"title": "mmsig: a fitting approach to accurately identify somatic mutational signatures in hematological malignancies.",
			"journal": "Communications biology",
			"authorList": [
				"Rustad Even H",
				"Nadeu Ferran",
				"Angelopoulos Nicos",
				"Ziccheddu Bachisio",
				"Bolli Niccol\u00f2",
				"Puente Xose S",
				"Campo Elias",
				"Landgren Ola",
				"Maura Francesco"
			],
			"DOI": "10.1038/s42003-021-01938-0",
			"date": "2021-08-05",
			"PMC": "",
			"citation": "",
			"abstract": "Mutational signatures have emerged as powerful biomarkers in cancer patients, with prognostic and therapeutic implications. Wider clinical utility requires access to reproducible algorithms, which allow characterization of mutational signatures in a given tumor sample. Here, we show how mutational signature fitting can be applied to hematological cancer genomes to identify biologically and clinically important mutational processes, highlighting the importance of careful interpretation in light of biological knowledge. Our newly released R package mmsig comes with a dynamic error-suppression procedure that improves specificity in important clinical and biological settings. In particular, mmsig allows accurate detection of mutational\u00a0signatures with low abundance, such as those introduced by APOBEC cytidine deaminases. This is particularly important in the most recent mutational signature reference (COSMIC v3.1) where each signature is more clearly defined. Our mutational signature fitting algorithm mmsig is a robust tool that can be implemented immediately in the clinic.",
			"category": 2,
			"name": "Rustad Even H,2021"
		},
		{
			"PMID": 33772115,
			"title": "CENP-A overexpression promotes distinct fates in human cells, depending on p53 status.",
			"journal": "Communications biology",
			"authorList": [
				"Jeffery Daniel",
				"Gatto Alberto",
				"Podsypanina Katrina",
				"Renaud-Pageot Charl\u00e8ne",
				"Ponce Landete Rebeca",
				"Bonneville Lorraine",
				"Dumont Marie",
				"Fachinetti Daniele",
				"Almouzni Genevi\u00e8ve"
			],
			"DOI": "10.1038/s42003-021-01941-5",
			"date": "2021-08-05",
			"PMC": "",
			"citation": "",
			"abstract": "Tumour evolution is driven by both genetic and epigenetic changes. CENP-A, the centromeric histone H3 variant, is an epigenetic mark that directly perturbs genetic stability and chromatin when overexpressed. Although CENP-A overexpression is a common feature of many cancers, how this impacts cell fate and response to therapy remains unclear. Here, we established a tunable system of inducible and reversible CENP-A overexpression combined with a switch in p53 status in human cell lines. Through clonogenic survival assays, single-cell RNA-sequencing and cell trajectory analysis, we uncover the tumour suppressor p53 as a key determinant of how CENP-A impacts cell state, cell identity and therapeutic response. If p53 is functional, CENP-A overexpression promotes senescence and radiosensitivity. Surprisingly, when we inactivate p53, CENP-A overexpression instead promotes epithelial-mesenchymal transition, an essential process in mammalian development but also a precursor for tumour cell invasion and metastasis. Thus, we uncover an unanticipated function of CENP-A overexpression to promote cell fate reprogramming, with important implications for development and tumour evolution.",
			"category": 2,
			"name": "Jeffery Daniel,2021"
		},
		{
			"PMID": 33767199,
			"title": "Whole-genome sequencing reveals progressive versus stable myeloma precursor conditions as two distinct entities.",
			"journal": "Nature communications",
			"authorList": [
				"Oben B\u00e9nedith",
				"Froyen Guy",
				"Maclachlan Kylee H",
				"Leongamornlert Daniel",
				"Abascal Federico",
				"Zheng-Lin Binbin",
				"Yellapantula Venkata",
				"Derkach Andriy",
				"Geerdens Ellen",
				"Diamond Benjamin T",
				"Arijs Ingrid",
				"Maes Brigitte",
				"Vanhees Kimberly",
				"Hultcrantz Malin",
				"Manasanch Elisabet E",
				"Kazandjian Dickran",
				"Lesokhin Alexander",
				"Dogan Ahmet",
				"Zhang Yanming",
				"Mikulasova Aneta",
				"Walker Brian",
				"Morgan Gareth",
				"Campbell Peter J",
				"Landgren Ola",
				"Rummens Jean-Luc",
				"Bolli Niccol\u00f2",
				"Maura Francesco"
			],
			"DOI": "10.1038/s41467-021-22140-0",
			"date": "2021-04-07",
			"PMC": "",
			"citation": "",
			"abstract": "Multiple myeloma (MM) is consistently preceded by precursor conditions recognized clinically as monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM). We interrogate the whole genome sequence (WGS) profile of 18 MGUS and compare them with those from 14 SMMs and 80 MMs. We show that cases with a non-progressing, clinically stable myeloma precursor condition (n\u2009=\u200915) are characterized by later initiation in the patient's life and by the absence of myeloma defining genomic events including: chromothripsis, templated insertions, mutations in driver genes, aneuploidy, and canonical APOBEC mutational activity. This data provides evidence that WGS can be used to recognize two biologically and clinically distinct myeloma precursor entities that are either progressive or stable.",
			"category": 2,
			"name": "Oben B\u00e9nedith,2021"
		},
		{
			"PMID": 33762732,
			"title": "Breast tumours maintain a reservoir of subclonal diversity during expansion.",
			"journal": "Nature",
			"authorList": [
				"Minussi Darlan C",
				"Nicholson Michael D",
				"Ye Hanghui",
				"Davis Alexander",
				"Wang Kaile",
				"Baker Toby",
				"Tarabichi Maxime",
				"Sei Emi",
				"Du Haowei",
				"Rabbani Mashiat",
				"Peng Cheng",
				"Hu Min",
				"Bai Shanshan",
				"Lin Yu-Wei",
				"Schalck Aislyn",
				"Multani Asha",
				"Ma Jin",
				"McDonald Thomas O",
				"Casasent Anna",
				"Barrera Angelica",
				"Chen Hui",
				"Lim Bora",
				"Arun Banu",
				"Meric-Bernstam Funda",
				"Van Loo Peter",
				"Michor Franziska",
				"Navin Nicholas E"
			],
			"DOI": "10.1038/s41586-021-03357-x",
			"date": "2021-08-31",
			"PMC": "",
			"citation": "",
			"abstract": "Our knowledge of copy number evolution during the expansion of primary breast tumours is limited",
			"category": 2,
			"name": "Minussi Darlan C,2021"
		},
		{
			"PMID": 33762108,
			"title": "What are the molecular mechanisms driving the switch from MPNs to leukemia?",
			"journal": "Best practice & research. Clinical haematology",
			"authorList": [
				"Wang Xiaoli",
				"Hoffman Ronald"
			],
			"DOI": "10.1016/j.beha.2021.101254",
			"date": "2022-01-13",
			"PMC": "",
			"citation": "",
			"abstract": "Myeloproliferative neoplasm-blast phase (MPN-BP) is a form of acute leukemia which is distinct from de novo acute myeloid leukemia with each entity being characterized by specific complex cytogenetic abnormalities and myeloid gene mutational patterns. MPN-BP patients have a particularly dismal prognosis with a medium overall survival of 5.8 months with currently available therapies. Large-scale sequencing studies have unraveled the mutational landscape of the chronic MPNs and MPN-BP, demonstrating importance of clonal heterogeneity and the role of somatic mutations in disease progression and their use to determine patient outcomes. JAK inhibitors represent the standard of care for intermediate/high-risk MF patients and have been shown to improve clinical symptoms. However, this therapeutic approach leads to a modest reduction in the variant allele frequency of the known MPN driver mutations in most patients and does not substantially delay or prevent the evolution to MPN-BP. In this article, we will review molecular mechanisms driving the progression from chronic MPNs to a BP, the impact of genetic changes on MPN-BP evolution, and the role of clonal evolution in response to JAK inhibitor therapy and disease progression. We will also discuss our ongoing functional studies of cells responsible for the development of MPN-BP.",
			"category": 2,
			"name": "Wang Xiaoli,2022"
		},
		{
			"PMID": 33761356,
			"title": "On the role of p53 in the cellular response to aneuploidy.",
			"journal": "Cell reports",
			"authorList": [
				"Narkar Akshay",
				"Johnson Blake A",
				"Bharne Pandurang",
				"Zhu Jin",
				"Padmanaban Veena",
				"Biswas Debojyoti",
				"Fraser Andrew",
				"Iglesias Pablo A",
				"Ewald Andrew J",
				"Li Rong"
			],
			"DOI": "10.1016/j.celrep.2021.108892",
			"date": "2022-01-27",
			"PMC": "",
			"citation": "",
			"abstract": "Most solid tumors are aneuploid, and p53 has been implicated as the guardian of the euploid genome. Previous experiments using human cell lines showed that aneuploidy induction leads to p53 accumulation and p21-mediated G1 cell cycle arrest. We find that adherent 2-dimensional (2D) cultures of human immortalized or cancer cell lines activate p53 upon aneuploidy induction, whereas suspension cultures of a human lymphoid cell line undergo a p53-independent cell cycle arrest. Surprisingly, 3D human and mouse organotypic cultures from neural, intestinal, or mammary epithelial tissues do not activate p53 or arrest in G1 following aneuploidy induction. p53-deficient colon organoids have increased aneuploidy and frequent lagging chromosomes and multipolar spindles during mitosis. These data suggest that p53 may not act as a universal surveillance factor restricting the proliferation of aneuploid cells but instead helps directly or indirectly ensure faithful chromosome transmission likely by preventing polyploidization and influencing spindle mechanics.",
			"category": 2,
			"name": "Narkar Akshay,2022"
		},
		{
			"PMID": 33727690,
			"title": "Genetic and non-genetic clonal diversity in cancer evolution.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Black James R M",
				"McGranahan Nicholas"
			],
			"DOI": "10.1038/s41568-021-00336-2",
			"date": "2021-07-27",
			"PMC": "",
			"citation": "",
			"abstract": "The observation and analysis of intra-tumour heterogeneity (ITH), particularly in genomic studies, has advanced our understanding of the evolutionary forces that shape cancer growth and development. However, only a subset of the variation observed in a single tumour will have an impact on cancer evolution, highlighting the need to distinguish between functional and non-functional ITH. Emerging studies highlight a role for the cancer epigenome, transcriptome and immune microenvironment in functional ITH. Here, we consider the importance of both genetic and non-genetic ITH and their role in tumour evolution, and present the rationale for a broad research focus beyond the cancer genome. Systems-biology analytical approaches will be necessary to outline the scale and importance of functional ITH. By allowing a deeper understanding of tumour evolution this will, in time, encourage development of novel therapies and improve outcomes for patients.",
			"category": 2,
			"name": "Black James R M,2021"
		},
		{
			"PMID": 33659038,
			"title": "Kr\u00fcppel-like factor 4 promotes survival and expansion in acute myeloid leukemia cells.",
			"journal": "Oncotarget",
			"authorList": [
				"Lewis Andrew Henry",
				"Bridges Cory Seth",
				"Punia Viraaj Singh",
				"Cooper Abraham Fausto Jornada",
				"Puppi Monica",
				"Lacorazza H Daniel"
			],
			"DOI": "10.18632/oncotarget.27878",
			"date": "2024-05-02",
			"PMC": "",
			"citation": "",
			"abstract": "Acute myeloid leukemia (AML) is an aggressive hematological malignancy of the bone marrow that affects mostly elderly adults. Alternative therapies are needed for AML patients because the overall prognosis with current standard of care, high dose chemotherapy and allogeneic transplantation, remains poor due to the emergence of refractory and relapsed disease. Here, we found expression of the transcription factor KLF4 in AML cell lines is not silenced through ",
			"category": 2,
			"name": "Lewis Andrew Henry,2024"
		},
		{
			"PMID": 33657326,
			"title": "Drivers of dynamic intratumor heterogeneity and phenotypic plasticity.",
			"journal": "American journal of physiology. Cell physiology",
			"authorList": [
				"Biswas Antara",
				"De Subhajyoti"
			],
			"DOI": "10.1152/ajpcell.00575.2020",
			"date": "2021-05-10",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a clonal disease, i.e., all tumor cells within a malignant lesion trace their lineage back to a precursor somatic cell that acquired oncogenic mutations during development and aging. And yet, those tumor cells tend to have genetic and nongenetic variations among themselves-which is denoted as intratumor heterogeneity. Although some of these variations are inconsequential, others tend to contribute to cell state transition and phenotypic heterogeneity, providing a substrate for somatic evolution. Tumor cell phenotypes can dynamically change under the influence of genetic mutations, epigenetic modifications, and microenvironmental contexts. Although epigenetic and microenvironmental changes are adaptive, genetic mutations are usually considered permanent. Emerging reports suggest that certain classes of genetic alterations show extensive reversibility in tumors in clinically relevant timescales, contributing as major drivers of dynamic intratumor heterogeneity and phenotypic plasticity. Dynamic heterogeneity and phenotypic plasticity can confer resistance to treatment, promote metastasis, and enhance evolvability in cancer. Here, we first highlight recent efforts to characterize intratumor heterogeneity at genetic, epigenetic, and microenvironmental levels. We then discuss phenotypic plasticity and cell state transition by tumor cells, under the influence of genetic and nongenetic determinants and their clinical significance in classification of tumors and therapeutic decision-making.",
			"category": 2,
			"name": "Biswas Antara,2021"
		},
		{
			"PMID": 33649470,
			"title": "Evidence that polyploidy in esophageal adenocarcinoma originates from mitotic slippage caused by defective chromosome attachments.",
			"journal": "Cell death and differentiation",
			"authorList": [
				"Scott Stacey J",
				"Li Xiaodun",
				"Jammula Sriganesh",
				"Devonshire Ginny",
				"Lindon Catherine",
				"Fitzgerald Rebecca C",
				"D'Avino Pier Paolo"
			],
			"DOI": "10.1038/s41418-021-00745-8",
			"date": "2022-03-04",
			"PMC": "",
			"citation": "",
			"abstract": "Polyploidy is present in many cancer types and is increasingly recognized as an important factor in promoting chromosomal instability, genome evolution, and heterogeneity in cancer cells. However, the mechanisms that trigger polyploidy in cancer cells are largely unknown. In this study, we investigated the origin of polyploidy in esophageal adenocarcinoma (EAC), a highly heterogenous cancer, using a combination of genomics and cell biology approaches in EAC cell lines, organoids, and tumors. We found the EAC cells and organoids present specific mitotic defects consistent with problems in the attachment of chromosomes to the microtubules of the mitotic spindle. Time-lapse analyses confirmed that EAC cells have problems in congressing and aligning their chromosomes, which can ultimately culminate in mitotic slippage and polyploidy. Furthermore, whole-genome sequencing, RNA-seq, and quantitative immunofluorescence analyses revealed alterations in the copy number, expression, and cellular distribution of several proteins known to be involved in the mechanics and regulation of chromosome dynamics during mitosis. Together, these results provide evidence that an imbalance in the amount of proteins implicated in the attachment of chromosomes to spindle microtubules is the molecular mechanism underlying mitotic slippage in EAC. Our findings that the likely origin of polyploidy in EAC is mitotic failure caused by problems in chromosomal attachments not only improves our understanding of cancer evolution and diversification, but may also aid in the classification and treatment of EAC and possibly other highly heterogeneous cancers.",
			"category": 2,
			"name": "Scott Stacey J,2022"
		},
		{
			"PMID": 33649166,
			"title": "Targeting a neoantigen derived from a common ",
			"journal": "Science (New York, N.Y.)",
			"authorList": [
				"Hsiue Emily Han-Chung",
				"Wright Katharine M",
				"Douglass Jacqueline",
				"Hwang Michael S",
				"Mog Brian J",
				"Pearlman Alexander H",
				"Paul Suman",
				"DiNapoli Sarah R",
				"Konig Maximilian F",
				"Wang Qing",
				"Schaefer Annika",
				"Miller Michelle S",
				"Skora Andrew D",
				"Azurmendi P Aitana",
				"Murphy Michael B",
				"Liu Qiang",
				"Watson Evangeline",
				"Li Yana",
				"Pardoll Drew M",
				"Bettegowda Chetan",
				"Papadopoulos Nickolas",
				"Kinzler Kenneth W",
				"Vogelstein Bert",
				"Gabelli Sandra B",
				"Zhou Shibin"
			],
			"DOI": "10.1126/science.abc8697",
			"date": "2021-03-31",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "Hsiue Emily Han-Chung,2021"
		},
		{
			"PMID": 33634984,
			"title": "Epigenome screening highlights that JMJD6 confers an epigenetic vulnerability and mediates sunitinib sensitivity in renal cell carcinoma.",
			"journal": "Clinical and translational medicine",
			"authorList": [
				"Zhang Chuanjie",
				"Lu Xuan",
				"Huang Jingyi",
				"He Hongchao",
				"Chen Li",
				"Liu Yihan",
				"Wang Haofei",
				"Xu Yang",
				"Xing Siwei",
				"Ruan Xiaohao",
				"Yang Xiaoqun",
				"Chen Lu",
				"Xu Danfeng"
			],
			"DOI": "10.1002/ctm2.328",
			"date": "2021-12-23",
			"PMC": "",
			"citation": "",
			"abstract": "Aberrant epigenetic reprogramming represents a hallmark of renal cell carcinoma (RCC) tumorigenesis and progression. Whether there existed other epigenetic vulnerabilities that could serve as therapeutic targets remained unclear and promising. Here, we combined the clustered regularly interspaced short palindromic repeats functional screening results and multiple RCC datasets to identify JMJD6 as the potent target in RCC. JMJD6 expression correlated with poor survival outcomes of RCC patients and promoted RCC progression in vitro and in vivo. Mechanistically, aberrant p300 led to high JMJD6 expression, which activated a series of oncogenic crosstalk. Particularly, high-throughput sequencing data revealed that JMJD6 could assemble super-enhancers to drive a list of identity\u00a0genes in kidney cancer, including VEGFA, \u03b2-catenin, and SRC. Moreover, this JMJD6-mediated oncogenic effect could be suppressed by a novel JMJD6 inhibitor (SKLB325), which was further demonstrated in RCC cells, patient-derived organoid models, and in vivo. Given the probable overlapped crosstalk between JMJD6 signature and tyrosine kinase inhibitors downstream targets, targeting JMJD6 sensitized RCC to sunitinib and was synergistic when they were combined together. Collectively, this study indicated that targeting JMJD6 was an effective approach to treat RCC patients.",
			"category": 2,
			"name": "Zhang Chuanjie,2021"
		},
		{
			"PMID": 33631295,
			"title": "Impact of cancer evolution on immune surveillance and checkpoint inhibitor response.",
			"journal": "Seminars in cancer biology",
			"authorList": [
				"Wu Yin",
				"Biswas Dhruva",
				"Swanton Charles"
			],
			"DOI": "10.1016/j.semcancer.2021.02.013",
			"date": "2022-06-30",
			"PMC": "",
			"citation": "",
			"abstract": "Intratumour heterogeneity (ITH) is pervasive across all cancers studied and may provide the evolving tumour multiple routes to escape immune surveillance. Immune checkpoint inhibitors (CPIs) are rapidly becoming standard of care for many cancers. Here, we discuss recent work investigating the influence of ITH on patient response to immune checkpoint inhibitor (CPI) therapy. At its simplest, ITH may confound the diagnostic accuracy of predictive biomarkers used to stratify patients for CPI therapy. Furthermore, ITH is fuelled by mechanisms of genetic instability that can both engage immune surveillance and drive immune evasion. A greater appreciation of the interplay between ITH and the immune system may hold the key to increasing the proportion of patients experiencing durable responses from CPI therapy.",
			"category": 2,
			"name": "Wu Yin,2022"
		},
		{
			"PMID": 33622385,
			"title": "MEDALT: single-cell copy number lineage tracing enabling gene discovery.",
			"journal": "Genome biology",
			"authorList": [
				"Wang Fang",
				"Wang Qihan",
				"Mohanty Vakul",
				"Liang Shaoheng",
				"Dou Jinzhuang",
				"Han Jincheng",
				"Minussi Darlan Conterno",
				"Gao Ruli",
				"Ding Li",
				"Navin Nicholas",
				"Chen Ken"
			],
			"DOI": "10.1186/s13059-021-02291-5",
			"date": "2022-01-12",
			"PMC": "",
			"citation": "",
			"abstract": "We present a Minimal Event Distance Aneuploidy Lineage Tree (MEDALT) algorithm that infers the evolution history of a cell population based on single-cell copy number (SCCN) profiles, and a statistical routine named lineage speciation analysis (LSA), whichty facilitates discovery of fitness-associated alterations and genes from SCCN lineage trees. MEDALT appears more accurate than phylogenetics approaches in reconstructing copy number lineage. From data from 20 triple-negative breast cancer patients, our approaches effectively prioritize genes that are essential for breast cancer cell fitness and predict patient survival, including those implicating convergent evolution.The source code of our study is available at https://github.com/KChen-lab/MEDALT .",
			"category": 2,
			"name": "Wang Fang,2022"
		},
		{
			"PMID": 33607950,
			"title": "Mutational concordance analysis provides supportive information for double cancer diagnosis.",
			"journal": "BMC cancer",
			"authorList": [
				"Hatakeyama Keiichi",
				"Nagashima Takeshi",
				"Notsu Akifumi",
				"Ohshima Keiichi",
				"Ohnami Sumiko",
				"Ohnami Shumpei",
				"Shimoda Yuji",
				"Naruoka Akane",
				"Maruyama Koji",
				"Iizuka Akira",
				"Ashizawa Tadashi",
				"Kenmotsu Hirotsugu",
				"Mochizuki Tohru",
				"Urakami Kenichi",
				"Akiyama Yasuto",
				"Yamaguchi Ken"
			],
			"DOI": "10.1186/s12885-021-07899-1",
			"date": "2021-05-18",
			"PMC": "",
			"citation": "",
			"abstract": "Mutation analysis using next-generation sequencing highlights the features of tumors with somatic alterations. However, the mutation profile of double cancer remains unclear. Here, we analyzed tumors derived from the same patient using whole exome sequencing (WES) to investigate the coherence of somatic mutations in double cancer.",
			"category": 2,
			"name": "Hatakeyama Keiichi,2021"
		},
		{
			"PMID": 33574607,
			"title": "Intratumoral heterogeneity in cancer progression and response to immunotherapy.",
			"journal": "Nature medicine",
			"authorList": [
				"Vitale Ilio",
				"Shema Efrat",
				"Loi Sherene",
				"Galluzzi Lorenzo"
			],
			"DOI": "10.1038/s41591-021-01233-9",
			"date": "2021-02-26",
			"PMC": "",
			"citation": "",
			"abstract": "Most (if not all) tumors emerge and progress under a strong evolutionary pressure imposed by trophic, metabolic, immunological, and therapeutic factors. The relative impact of these factors on tumor evolution changes over space and time, ultimately favoring the establishment of a neoplastic microenvironment that exhibits considerable genetic, phenotypic, and behavioral heterogeneity in all its components. Here, we discuss the main sources of intratumoral heterogeneity and its impact on the natural history of the disease, including sensitivity to treatment, as we delineate potential strategies to target such a detrimental feature of aggressive malignancies.",
			"category": 2,
			"name": "Vitale Ilio,2021"
		},
		{
			"PMID": 33554123,
			"title": "Systematic identification of non-coding somatic single nucleotide variants associated with altered transcription and DNA methylation in adult and pediatric cancers.",
			"journal": "NAR cancer",
			"authorList": [
				"Chen Fengju",
				"Zhang Yiqun",
				"Creighton Chad J"
			],
			"DOI": "10.1093/narcan/zcab001",
			"date": "2022-08-30",
			"PMC": "",
			"citation": "",
			"abstract": "Whole-genome sequencing combined with transcriptomics can reveal impactful non-coding single nucleotide variants (SNVs) in cancer. Here, we developed an integrative analytical approach that, as a first step, identifies genes altered in expression or DNA methylation in association with nearby somatic SNVs, in contrast to alternative approaches that first identify mutational hotspots. Using genomic datasets from the Pan-Cancer Analysis of Whole Genomes (PCAWG) consortium and the Children's Brain Tumor Tissue Consortium (CBTTC), we identified hundreds of genes and associated CpG islands for which the nearby presence of a non-coding somatic SNV recurrently associated with altered expression or DNA methylation, respectively. Genomic regions upstream or downstream of genes, gene introns and gene untranslated regions were all involved. The PCAWG adult cancer cohort yielded different significant SNV-expression associations from the CBTTC pediatric brain tumor cohort. The SNV-expression associations involved a wide range of cancer types and histologies, as well as potential gain or loss of transcription factor binding sites. Notable genes with SNV-associated increased expression include ",
			"category": 2,
			"name": "Chen Fengju,2022"
		},
		{
			"PMID": 33529175,
			"title": "Hierarchical tumor heterogeneity mediated by cell contact between distinct genetic subclones.",
			"journal": "The Journal of clinical investigation",
			"authorList": [
				"Karthikeyan Swathi",
				"Waters Ian G",
				"Dennison Lauren",
				"Chu David",
				"Donaldson Joshua",
				"Shin Dong Ho",
				"Rosen D Marc",
				"Gonzalez-Ericsson Paula I",
				"Sanchez Violeta",
				"Sanders Melinda E",
				"Pantone Morgan V",
				"Bergman Riley E",
				"Davidson Brad A",
				"Reed Sarah C",
				"Zabransky Daniel J",
				"Cravero Karen",
				"Kyker-Snowman Kelly",
				"Button Berry",
				"Wong Hong Yuen",
				"Hurley Paula J",
				"Croessmann Sarah",
				"Park Ben Ho"
			],
			"DOI": "10.1172/JCI143557",
			"date": "2021-09-29",
			"PMC": "",
			"citation": "",
			"abstract": "Intratumor heterogeneity is an important mediator of poor outcomes in many cancers, including breast cancer. Genetic subclones frequently contribute to this heterogeneity; however, their growth dynamics and interactions remain poorly understood. PIK3CA and HER2 alterations are known to coexist in breast and other cancers. Herein, we present data that describe the ability of oncogenic PIK3CA mutant cells to induce the proliferation of quiescent HER2 mutant cells through a cell contact-mediated mechanism. Interestingly, the HER2 cells proliferated to become the major subclone over PIK3CA counterparts both in vitro and in vivo. Furthermore, this phenotype was observed in both hormone receptor-positive and -negative cell lines, and was dependent on the expression of fibronectin from mutant PIK3CA cells. Analysis of human tumors demonstrated similar HER2:PIK3CA clonal dynamics and fibronectin expression. Our study provides insight into nonrandom subclonal architecture of heterogenous tumors, which may aid the understanding of tumor evolution and inform future strategies for personalized medicine.",
			"category": 2,
			"name": "Karthikeyan Swathi,2021"
		},
		{
			"PMID": 33510149,
			"title": "Proliferative polyploid cells give rise to tumors via ploidy reduction.",
			"journal": "Nature communications",
			"authorList": [
				"Matsumoto Tomonori",
				"Wakefield Leslie",
				"Peters Alexander",
				"Peto Myron",
				"Spellman Paul",
				"Grompe Markus"
			],
			"DOI": "10.1038/s41467-021-20916-y",
			"date": "2021-02-22",
			"PMC": "",
			"citation": "",
			"abstract": "Polyploidy is a hallmark of cancer, and closely related to chromosomal instability involved in cancer progression. Importantly, polyploid cells also exist in some normal tissues. Polyploid hepatocytes proliferate and dynamically reduce their ploidy during liver regeneration. This raises the question whether proliferating polyploids are prone to cancer via chromosome missegregation during mitosis and/or ploidy reduction. Conversely polyploids could be resistant to tumor development due to their redundant genomes. Therefore, the tumor-initiation risk of physiologic polyploidy and ploidy reduction is still unclear. Using in vivo lineage tracing we here show that polyploid hepatocytes readily form liver tumors via frequent ploidy reduction. Polyploid hepatocytes give rise to regenerative nodules with chromosome aberrations, which are enhanced by ploidy reduction. Although polyploidy should theoretically prevent tumor suppressor loss, the high frequency of ploidy reduction negates this protection. Importantly, polyploid hepatocytes that undergo multiple rounds of cell division become predominantly mononucleated and are resistant to ploidy reduction. Our results suggest that ploidy reduction is an early step in the initiation of carcinogenesis from polyploid hepatocytes.",
			"category": 2,
			"name": "Matsumoto Tomonori,2021"
		},
		{
			"PMID": 33504553,
			"title": "Initial Whole-Genome Sequencing of Plasma Cell Neoplasms in First Responders and Recovery Workers Exposed to the World Trade Center Attack of September 11, 2001.",
			"journal": "Clinical cancer research : an official journal of the American Association for Cancer Research",
			"authorList": [
				"Maura Francesco",
				"Diamond Benjamin",
				"Maclachlan Kylee H",
				"Derkach Andriy",
				"Yellapantula Venkata D",
				"Rustad Even H",
				"Hultcrantz Malin",
				"Shah Urvi A",
				"Hong Jessica",
				"Landau Heather J",
				"Iacobuzio-Donahue Christine A",
				"Papaemmanuil Elli",
				"Irby Shani",
				"Crowley Laura",
				"Crane Michael",
				"Webber Mayris P",
				"Goldfarb David G",
				"Zeig-Owens Rachel",
				"Giricz Orsi",
				"Verma Amit",
				"Prezant David J",
				"Dogan Ahmet",
				"Shah Sohrab P",
				"Zhang Yanming",
				"Landgren Ola"
			],
			"DOI": "10.1158/1078-0432.CCR-20-2245",
			"date": "2022-03-09",
			"PMC": "",
			"citation": "",
			"abstract": "The World Trade Center (WTC) attack of September 11, 2001 created an unprecedented environmental exposure to known and suspected carcinogens. High incidence of multiple myeloma and precursor conditions has been reported among first responders to the WTC disaster. To expand on our prior screening studies, and to characterize the genomic impact of the exposure to known and potential carcinogens in the WTC debris, we were motivated to perform whole-genome sequencing (WGS) of WTC first responders and recovery workers who developed a plasma cell disorder after the attack.",
			"category": 2,
			"name": "Maura Francesco,2022"
		},
		{
			"PMID": 33465079,
			"title": "Reconstructing tumor evolutionary histories and clone trees in polynomial-time with SubMARine.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Sundermann Linda K",
				"Wintersinger Jeff",
				"R\u00e4tsch Gunnar",
				"Stoye Jens",
				"Morris Quaid"
			],
			"DOI": "10.1371/journal.pcbi.1008400",
			"date": "2021-05-14",
			"PMC": "",
			"citation": "",
			"abstract": "Tumors contain multiple subpopulations of genetically distinct cancer cells. Reconstructing their evolutionary history can improve our understanding of how cancers develop and respond to treatment. Subclonal reconstruction methods cluster mutations into groups that co-occur within the same subpopulations, estimate the frequency of cells belonging to each subpopulation, and infer the ancestral relationships among the subpopulations by constructing a clone tree. However, often multiple clone trees are consistent with the data and current methods do not efficiently capture this uncertainty; nor can these methods scale to clone trees with a large number of subclonal populations. Here, we formalize the notion of a partially-defined clone tree (partial clone tree for short) that defines a subset of the pairwise ancestral relationships in a clone tree, thereby implicitly representing the set of all clone trees that have these defined pairwise relationships. Also, we introduce a special partial clone tree, the Maximally-Constrained Ancestral Reconstruction (MAR), which summarizes all clone trees fitting the input data equally well. Finally, we extend commonly used clone tree validity conditions to apply to partial clone trees and describe SubMARine, a polynomial-time algorithm producing the subMAR, which approximates the MAR and guarantees that its defined relationships are a subset of those present in the MAR. We also extend SubMARine to work with subclonal copy number aberrations and define equivalence constraints for this purpose. Further, we extend SubMARine to permit noise in the estimates of the subclonal frequencies while retaining its validity conditions and guarantees. In contrast to other clone tree reconstruction methods, SubMARine runs in time and space that scale polynomially in the number of subclones. We show through extensive noise-free simulation, a large lung cancer dataset and a prostate cancer dataset that the subMAR equals the MAR in all cases where only a single clone tree exists and that it is a perfect match to the MAR in most of the other cases. Notably, SubMARine runs in less than 70 seconds on a single thread with less than one Gb of memory on all datasets presented in this paper, including ones with 50 nodes in a clone tree. On the real-world data, SubMARine almost perfectly recovers the previously reported trees and identifies minor errors made in the expert-driven reconstructions of those trees. The freely-available open-source code implementing SubMARine can be downloaded at https://github.com/morrislab/submarine.",
			"category": 2,
			"name": "Sundermann Linda K,2021"
		},
		{
			"PMID": 33436578,
			"title": "Interplay between chromosomal alterations and gene mutations shapes the evolutionary trajectory of clonal hematopoiesis.",
			"journal": "Nature communications",
			"authorList": [
				"Gao Teng",
				"Ptashkin Ryan",
				"Bolton Kelly L",
				"Sirenko Maria",
				"Fong Christopher",
				"Spitzer Barbara",
				"Menghrajani Kamal",
				"Ossa Juan E Arango",
				"Zhou Yangyu",
				"Bernard Elsa",
				"Levine Max",
				"Martinez Juan S Medina",
				"Zhang Yanming",
				"Franch-Exp\u00f3sito Sebasti\u00e0",
				"Patel Minal",
				"Braunstein Lior Z",
				"Kelly Daniel",
				"Yabe Mariko",
				"Benayed Ryma",
				"Caltabellotta Nicole M",
				"Philip John",
				"Paraiso Ederlinda",
				"Mantha Simon",
				"Solit David B",
				"Diaz Luis A",
				"Berger Michael F",
				"Klimek Virginia",
				"Levine Ross L",
				"Zehir Ahmet",
				"Devlin Sean M",
				"Papaemmanuil Elli"
			],
			"DOI": "10.1038/s41467-020-20565-7",
			"date": "2021-01-21",
			"PMC": "",
			"citation": "",
			"abstract": "Stably acquired mutations in hematopoietic cells represent substrates of selection that may lead to clonal hematopoiesis (CH), a common state in cancer patients that is associated with a heightened risk of leukemia development. Owing to technical and sample size limitations, most CH studies have characterized gene mutations or mosaic chromosomal alterations (mCAs) individually. Here we leverage peripheral blood sequencing data from 32,442 cancer patients to jointly characterize gene mutations (n\u2009=\u200914,789) and mCAs (n\u2009=\u2009383) in CH. Recurrent composite genotypes resembling known genetic interactions in leukemia genomes underlie 23% of all detected autosomal alterations, indicating that these selection mechanisms are operative early in clonal evolution. CH with composite genotypes defines a patient group at high risk of leukemia progression (3-year cumulative incidence 14.6%, CI: 7-22%). Multivariable analysis identifies mCA as an independent risk factor for leukemia development (HR\u2009=\u200914, 95% CI: 6-33, P\u2009<\u20090.001). Our results suggest that mCA should be considered in conjunction with gene mutations in the surveillance of patients at risk of hematologic neoplasms.",
			"category": 2,
			"name": "Gao Teng,2021"
		},
		{
			"PMID": 33432169,
			"title": "Aneuploidy as a promoter and suppressor of malignant growth.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Vasudevan Anand",
				"Schukken Klaske M",
				"Sausville Erin L",
				"Girish Vishruth",
				"Adebambo Oluwadamilare A",
				"Sheltzer Jason M"
			],
			"DOI": "10.1038/s41568-020-00321-1",
			"date": "2021-02-16",
			"PMC": "",
			"citation": "",
			"abstract": "Aneuploidy has been recognized as a hallmark of tumorigenesis for more than 100 years, but the connection between chromosomal errors and malignant growth has remained obscure. New evidence emerging from both basic and clinical research has illuminated a complicated relationship: despite its frequency in human tumours, aneuploidy is not a universal driver of cancer development and instead can exert substantial tumour-suppressive effects. The specific consequences of aneuploidy are highly context dependent and are influenced by a cell's genetic and environmental milieu. In this Review, we discuss the diverse facets of cancer biology that are shaped by aneuploidy, including metastasis, drug resistance and immune recognition, and we highlight aneuploidy's distinct roles as both a tumour promoter and an anticancer vulnerability.",
			"category": 2,
			"name": "Vasudevan Anand,2021"
		},
		{
			"PMID": 33427197,
			"title": "Use of signals of positive and negative selection to distinguish cancer genes and passenger genes.",
			"journal": "eLife",
			"authorList": [
				"B\u00e1nyai L\u00e1szl\u00f3",
				"Trexler Maria",
				"Kerekes Krisztina",
				"Csuka Orsolya",
				"Patthy L\u00e1szl\u00f3"
			],
			"DOI": "10.7554/eLife.59629",
			"date": "2022-02-03",
			"PMC": "",
			"citation": "",
			"abstract": "A major goal of cancer genomics is to identify all genes that play critical roles in carcinogenesis. Most approaches focused on genes positively selected for mutations that drive carcinogenesis and neglected the role of negative selection. Some studies have actually concluded that negative selection has no role in cancer evolution. We have re-examined the role of negative selection in tumor evolution through the analysis of the patterns of somatic mutations affecting the coding sequences of human genes. Our analyses have confirmed that tumor suppressor genes are positively selected for inactivating mutations, oncogenes, however, were found to display signals of both negative selection for inactivating mutations and positive selection for activating mutations. Significantly, we have identified numerous human genes that show signs of strong negative selection during tumor evolution, suggesting that their functional integrity is essential for the growth and survival of tumor cells.",
			"category": 2,
			"name": "B\u00e1nyai L\u00e1szl\u00f3,2022"
		},
		{
			"PMID": 33408383,
			"title": "The influence of evolutionary history on human health and disease.",
			"journal": "Nature reviews. Genetics",
			"authorList": [
				"Benton Mary Lauren",
				"Abraham Abin",
				"LaBella Abigail L",
				"Abbot Patrick",
				"Rokas Antonis",
				"Capra John A"
			],
			"DOI": "10.1038/s41576-020-00305-9",
			"date": "2021-07-26",
			"PMC": "",
			"citation": "",
			"abstract": "Nearly all genetic variants that influence disease risk have human-specific origins; however, the systems they influence have ancient roots that often trace back to evolutionary events long before the origin of humans. Here, we review how advances in our understanding of the genetic architectures of diseases, recent human evolution and deep evolutionary history can help explain how and why humans in modern environments become ill. Human populations exhibit differences in the prevalence of many common and rare genetic diseases. These differences are largely the result of the diverse environmental, cultural, demographic and genetic histories of modern human populations. Synthesizing our growing knowledge of evolutionary history with genetic medicine, while accounting for environmental and social factors, will help to achieve the promise of personalized genomics and realize the potential hidden in an individual's DNA sequence to guide clinical decisions. In short, precision medicine is fundamentally evolutionary medicine, and integration of evolutionary perspectives into the clinic will support the realization of its full potential.",
			"category": 2,
			"name": "Benton Mary Lauren,2021"
		},
		{
			"PMID": 33400146,
			"title": "Emerging molecular subtypes and therapeutic targets in B-cell precursor acute lymphoblastic leukemia.",
			"journal": "Frontiers of medicine",
			"authorList": [
				"Li Jianfeng",
				"Dai Yuting",
				"Wu Liang",
				"Zhang Ming",
				"Ouyang Wen",
				"Huang Jinyan",
				"Chen Saijuan"
			],
			"DOI": "10.1007/s11684-020-0821-6",
			"date": "2021-07-01",
			"PMC": "",
			"citation": "",
			"abstract": "B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by genetic alterations with high heterogeneity. Precise subtypes with distinct genomic and/or gene expression patterns have been recently revealed using high-throughput sequencing technology. Most of these profiles are associated with recurrent non-overlapping rearrangements or hotspot point mutations that are analogous to the established subtypes, such as DUX4 rearrangements, MEF2D rearrangements, ZNF384/ZNF362 rearrangements, NUTM1 rearrangements, BCL2/MYC and/or BCL6 rearrangements, ETV6-RUNX1-like gene expression, PAX5alt (diverse PAX5 alterations, including rearrangements, intragenic amplifications, or mutations), and hotspot mutations PAX5 (p.Pro80Arg) with biallelic PAX5 alterations, IKZF1 (p.Asn159Tyr), and ZEB2 (p.His1038Arg). These molecular subtypes could be classified by gene expression patterns with RNA-seq technology. Refined molecular classification greatly improved the treatment strategy. Multiagent therapy regimens, including target inhibitors (e.g., imatinib), immunomodulators, monoclonal antibodies, and chimeric antigen receptor T-cell (CAR-T) therapy, are transforming the clinical practice from chemotherapy drugs to personalized medicine in the field of risk-directed disease management. We provide an update on our knowledge of emerging molecular subtypes and therapeutic targets in BCP-ALL.",
			"category": 2,
			"name": "Li Jianfeng,2021"
		},
		{
			"PMID": 33398189,
			"title": "A practical guide to cancer subclonal reconstruction from DNA sequencing.",
			"journal": "Nature methods",
			"authorList": [
				"Tarabichi Maxime",
				"Salcedo Adriana",
				"Deshwar Amit G",
				"Ni Leathlobhair M\u00e1ire",
				"Wintersinger Jeff",
				"Wedge David C",
				"Van Loo Peter",
				"Morris Quaid D",
				"Boutros Paul C"
			],
			"DOI": "10.1038/s41592-020-01013-2",
			"date": "2021-03-31",
			"PMC": "",
			"citation": "",
			"abstract": "Subclonal reconstruction from bulk tumor DNA sequencing has become a pillar of cancer evolution studies, providing insight into the clonality and relative ordering of mutations and mutational processes. We provide an outline of the complex computational approaches used for subclonal reconstruction from single and multiple tumor samples. We identify the underlying assumptions and uncertainties in each step and suggest best practices for analysis and quality assessment. This guide provides a pragmatic resource for the growing user community of subclonal reconstruction methods.",
			"category": 2,
			"name": "Tarabichi Maxime,2021"
		},
		{
			"PMID": 33328650,
			"title": "Genomic and phenotypic heterogeneity in prostate cancer.",
			"journal": "Nature reviews. Urology",
			"authorList": [
				"Haffner Michael C",
				"Zwart Wilbert",
				"Roudier Martine P",
				"True Lawrence D",
				"Nelson William G",
				"Epstein Jonathan I",
				"De Marzo Angelo M",
				"Nelson Peter S",
				"Yegnasubramanian Srinivasan"
			],
			"DOI": "10.1038/s41585-020-00400-w",
			"date": "2021-08-30",
			"PMC": "",
			"citation": "",
			"abstract": "From a clinical, morphological and molecular perspective, prostate cancer is a heterogeneous disease. Primary prostate cancers are often multifocal, having topographically and morphologically distinct tumour foci. Sequencing studies have revealed that individual tumour foci can arise as clonally distinct lesions with no shared driver gene alterations. This finding demonstrates that multiple genomically and phenotypically distinct primary prostate cancers can be present in an individual patient. Lethal metastatic prostate cancer seems to arise from a single clone in the primary tumour but can exhibit subclonal heterogeneity at the genomic, epigenetic and phenotypic levels. Collectively, this complex heterogeneous constellation of molecular alterations poses obstacles for the diagnosis and treatment of prostate cancer. However, advances in our understanding of intra-tumoural heterogeneity and the development of novel technologies will allow us to navigate these challenges, refine approaches for translational research and ultimately improve patient care.",
			"category": 2,
			"name": "Haffner Michael C,2021"
		},
		{
			"PMID": 33304455,
			"title": "Computational methods for detecting cancer hotspots.",
			"journal": "Computational and structural biotechnology journal",
			"authorList": [
				"Martinez-Ledesma Emmanuel",
				"Flores David",
				"Trevino Victor"
			],
			"DOI": "10.1016/j.csbj.2020.11.020",
			"date": "2023-11-04",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer mutations that are recurrently observed among patients are known as hotspots. Hotspots are highly relevant because they are, presumably, likely functional. Known hotspots in BRAF, PIK3CA, TP53, KRAS, IDH1 support this idea. However, hundreds of hotspots have never been validated experimentally. The detection of hotspots nevertheless is challenging because background mutations obscure their statistical and computational identification. Although several algorithms have been applied to identify hotspots, they have not been reviewed before. Thus, in this mini-review, we summarize more than 40 computational methods applied to detect cancer hotspots in coding and non-coding DNA. We first organize the methods in ",
			"category": 2,
			"name": "Martinez-Ledesma Emmanuel,2023"
		},
		{
			"PMID": 33297360,
			"title": "Mutations and Copy Number Alterations in ",
			"journal": "Biomedicines",
			"authorList": [
				"\u00dclgen Ege",
				"Karacan S\u0131la",
				"Gerlevik Umut",
				"Can \u00d6zge",
				"Bilguvar Kaya",
				"Oktay Yavuz",
				"B Akyerli Cemaliye",
				"K Y\u00fcksel \u015eirin",
				"E Danyeli Ay\u00e7a",
				"Tihan Tar\u0131k",
				"Sezerman O U\u011fur",
				"Yak\u0131c\u0131er M Cengiz",
				"Pamir M Necmettin",
				"\u00d6zduman Koray"
			],
			"DOI": "10.3390/biomedicines8120574",
			"date": "2021-09-18",
			"PMC": "",
			"citation": "",
			"abstract": "Little is known about the mutational processes that shape the genetic landscape of gliomas. Numerous mutational processes leave marks on the genome in the form of mutations, copy number alterations, rearrangements or their combinations. To explore gliomagenesis, we hypothesized that gliomas with different underlying oncogenic mechanisms would have differences in the burden of various forms of these genomic alterations. This was an analysis on adult diffuse gliomas, but ",
			"category": 2,
			"name": "\u00dclgen Ege,2021"
		},
		{
			"PMID": 33288765,
			"title": "Quantifying the influence of mutation detection on tumour subclonal reconstruction.",
			"journal": "Nature communications",
			"authorList": [
				"Liu Lydia Y",
				"Bhandari Vinayak",
				"Salcedo Adriana",
				"Espiritu Shadrielle M G",
				"Morris Quaid D",
				"Kislinger Thomas",
				"Boutros Paul C"
			],
			"DOI": "10.1038/s41467-020-20055-w",
			"date": "2020-12-28",
			"PMC": "",
			"citation": "",
			"abstract": "Whole-genome sequencing can be used to estimate subclonal populations in tumours and this intra-tumoural heterogeneity is linked to clinical outcomes. Many algorithms have been developed for subclonal reconstruction, but their variabilities and consistencies are largely unknown. We evaluate sixteen pipelines for reconstructing the evolutionary histories of 293 localized prostate cancers from single samples, and eighteen pipelines for the reconstruction of 10 tumours with multi-region sampling. We show that predictions of subclonal architecture and timing of somatic mutations vary extensively across pipelines. Pipelines show consistent types of biases, with those incorporating SomaticSniper and Battenberg preferentially predicting homogenous cancer cell populations and those using MuTect tending to predict multiple populations of cancer cells. Subclonal reconstructions using multi-region sampling confirm that single-sample reconstructions systematically underestimate intra-tumoural heterogeneity, predicting on average fewer than half of the cancer cell populations identified by multi-region sequencing. Overall, these biases suggest caution in interpreting specific architectures and subclonal variants.",
			"category": 2,
			"name": "Liu Lydia Y,2020"
		},
		{
			"PMID": 33276489,
			"title": "Angiogenesis-Related Functions of Wnt Signaling in Colorectal Carcinogenesis.",
			"journal": "Cancers",
			"authorList": [
				"Kasprzak Aldona"
			],
			"DOI": "10.3390/cancers12123601",
			"date": "2020-12-26",
			"PMC": "",
			"citation": "",
			"abstract": "Aberrant activation of the Wnt/Fzd/\u03b2-catenin signaling pathway is one of the major molecular mechanisms of colorectal cancer (CRC) development and progression. On the other hand, one of the most common clinical CRC characteristics include high levels of angiogenesis, which is a key event in cancer cell dissemination and distant metastasis. The canonical Wnt/\u03b2-catenin downstream signaling regulates the most important pro-angiogenic molecules including vascular endothelial growth factor (VEGF) family members, matrix metalloproteinases (MMPs), and chemokines. Furthermore, mutations of the \u03b2-catenin gene associated with nuclear localization of the protein have been mainly detected in microsatellite unstable CRC. Elevated nuclear \u03b2-catenin increases the expression of many genes involved in tumor angiogenesis. Factors regulating angiogenesis with the participation of Wnt/\u03b2-catenin signaling include different groups of biologically active molecules including Wnt pathway components (e.g., Wnt2, DKK, BCL9 proteins), and non-Wnt pathway factors (e.g., chemoattractant cytokines, enzymatic proteins, and bioactive compounds of plants). Several lines of evidence argue for the use of angiogenesis inhibition in the treatment of CRC. In the context of this paper, components of the Wnt pathway are among the most promising targets for CRC therapy. This review summarizes the current knowledge about the role of the Wnt/Fzd/\u03b2-catenin signaling pathway in the process of CRC angiogenesis, aiming to improve the understanding of the mechanisms of metastasis as well as improvements in the management of this cancer.",
			"category": 2,
			"name": "Kasprzak Aldona,2020"
		},
		{
			"PMID": 33257848,
			"title": "Mutation-selection balance and compensatory mechanisms in tumour evolution.",
			"journal": "Nature reviews. Genetics",
			"authorList": [
				"Persi Erez",
				"Wolf Yuri I",
				"Horn David",
				"Ruppin Eytan",
				"Demichelis Francesca",
				"Gatenby Robert A",
				"Gillies Robert J",
				"Koonin Eugene V"
			],
			"DOI": "10.1038/s41576-020-00299-4",
			"date": "2021-05-04",
			"PMC": "",
			"citation": "",
			"abstract": "Intratumour heterogeneity and phenotypic plasticity, sustained by a range of somatic aberrations, as well as epigenetic and metabolic adaptations, are the principal mechanisms that enable cancers to resist treatment and survive under environmental stress. A comprehensive picture of the interplay between different somatic aberrations, from point mutations to whole-genome duplications, in tumour initiation and progression is lacking. We posit that different genomic aberrations generally exhibit a temporal order, shaped by a balance between the levels of mutations and selective pressures. Repeat instability emerges first, followed by larger aberrations, with compensatory effects leading to robust tumour fitness maintained throughout the tumour progression. A better understanding of the interplay between genetic aberrations, the microenvironment, and epigenetic and metabolic cellular states is essential for early detection and prevention of cancer as well as development of efficient therapeutic strategies.",
			"category": 2,
			"name": "Persi Erez,2021"
		},
		{
			"PMID": 33257699,
			"title": "Genomic and transcriptomic alterations associated with drug vulnerabilities and prognosis in adenocarcinoma at the gastroesophageal junction.",
			"journal": "Nature communications",
			"authorList": [
				"Lin Yuan",
				"Luo Yingying",
				"Sun Yanxia",
				"Guo Wenjia",
				"Zhao Xuan",
				"Xi Yiyi",
				"Ma Yuling",
				"Shao Mingming",
				"Tan Wen",
				"Gao Ge",
				"Wu Chen",
				"Lin Dongxin"
			],
			"DOI": "10.1038/s41467-020-19949-6",
			"date": "2020-12-21",
			"PMC": "",
			"citation": "",
			"abstract": "Adenocarcinoma at the gastroesophageal junction (ACGEJ) has dismal clinical outcomes, and there are currently few specific effective therapies because of limited knowledge on its genomic and transcriptomic alterations. The present study investigates genomic and transcriptomic changes in ACGEJ from Chinese patients and analyzes their drug vulnerabilities and associations with the survival time. Here we show that the major genomic changes of Chinese ACGEJ patients are chromosome instability promoted tumorigenic focal copy-number variations and COSMIC Signature 17-featured single nucleotide variations. We provide a comprehensive profile of genetic changes that are potentially vulnerable to existing therapeutic agents and identify Signature 17-correlated IFN-\u03b1 response pathway as a prognostic marker that might have practical value for clinical prognosis of ACGEJ. These findings further our understanding on the molecular biology of ACGEJ and may help develop more effective therapeutic strategies.",
			"category": 2,
			"name": "Lin Yuan,2020"
		},
		{
			"PMID": 33230757,
			"title": "Clonal evolution and supratentorial dissemination of a spinal cord glioma.",
			"journal": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology",
			"authorList": [
				"Kong Ziren",
				"Chen Wenlin",
				"Zhao Dachun",
				"Wang Yu",
				"Ma Wenbin"
			],
			"DOI": "10.1007/s10072-020-04924-2",
			"date": "2021-05-14",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Kong Ziren,2021"
		},
		{
			"PMID": 33225950,
			"title": "The evolution of relapse of adult T cell acute lymphoblastic leukemia.",
			"journal": "Genome biology",
			"authorList": [
				"Sent\u00eds In\u00e9s",
				"Gonzalez Santiago",
				"Genesc\u00e0 Eulalia",
				"Garc\u00eda-Hern\u00e1ndez Violeta",
				"Mui\u00f1os Ferran",
				"Gonzalez Celia",
				"L\u00f3pez-Arribillaga Erika",
				"Gonzalez Jessica",
				"Fernandez-Ibarrondo Lierni",
				"Mularoni Loris",
				"Espinosa Llu\u00eds",
				"Bellosillo Beatriz",
				"Ribera Josep-Maria",
				"Bigas Anna",
				"Gonzalez-Perez Abel",
				"Lopez-Bigas Nuria"
			],
			"DOI": "10.1186/s13059-020-02192-z",
			"date": "2021-11-30",
			"PMC": "",
			"citation": "",
			"abstract": "Adult T cell acute lymphoblastic leukemia (T-ALL) is a rare disease that affects less than 10 individuals in one million. It has been less studied than its cognate pediatric malignancy, which is more prevalent. A higher percentage of the adult patients relapse, compared to children. It is thus essential to study the mechanisms of relapse of adult T-ALL cases.",
			"category": 2,
			"name": "Sent\u00eds In\u00e9s,2021"
		},
		{
			"PMID": 33216890,
			"title": "Transient expansion of TP53 mutated clones in polycythemia vera patients treated with idasanutlin.",
			"journal": "Blood advances",
			"authorList": [
				"Marcellino Bridget K",
				"Farnoud Noushin",
				"Cassinat Bruno",
				"Lu Min",
				"Verger Emanuelle",
				"McGovern Erin",
				"Patel Minal",
				"Medina-Martinez Juan",
				"Levine Max Fine",
				"Arango Ossa Juanes E",
				"Zhou Yangyu",
				"Kosiorek Heidi",
				"Mehrotra Meenakshi",
				"Houldsworth Jane",
				"Dueck Amylou",
				"Rossi Michael",
				"Mascarenhas John",
				"Kiladjian Jean-Jacques",
				"Rampal Raajit K",
				"Hoffman Ronald"
			],
			"DOI": "10.1182/bloodadvances.2020002379",
			"date": "2021-05-14",
			"PMC": "",
			"citation": "",
			"abstract": "Activation of the P53 pathway through inhibition of MDM2 using nutlins has shown clinical promise in the treatment of solid tumors and hematologic malignancies. There is concern, however, that nutlin therapy might stimulate the emergence or expansion of TP53-mutated subclones. We recently published the results of a phase 1 trial of idasanutlin in patients with polycythemia vera (PV) that revealed tolerability and clinical activity. Here, we present data indicating that idasanutlin therapy is associated with expansion of TP53 mutant subclones. End-of-study sequencing of patients found that 5 patients in this trial harbored 12 TP53 mutations; however, only 1 patient had been previously identified as having a TP53 mutation at baseline. To identify the origin of these mutations, further analysis of raw sequencing data of baseline samples was performed and revealed that a subset of these mutations was present at baseline and expanded during treatment with idasanutlin. Follow-up samples were obtained from 4 of 5 patients in this cohort, and we observed that after cessation of idasanutlin, the variant allele frequency (VAF) of 8 of 9 TP53 mutations decreased. Furthermore, disease progression to myelofibrosis or myeloproliferative neoplasm blast phase was not observed in any of these patients after 19- to 32-month observation. These data suggest that idasanutlin treatment may promote transient TP53 mutant clonal expansion. A larger study geared toward high-resolution detection of low VAF mutations is required to explore whether patients acquire de novo TP53 mutations after idasanutlin therapy.",
			"category": 2,
			"name": "Marcellino Bridget K,2021"
		},
		{
			"PMID": 33211929,
			"title": "Lineage-Independent Tumors in Bilateral Neuroblastoma.",
			"journal": "The New England journal of medicine",
			"authorList": [
				"Coorens Tim H H",
				"Farndon Sarah J",
				"Mitchell Thomas J",
				"Jain Neha",
				"Lee Sangjin",
				"Hubank Michael",
				"Sebire Neil",
				"Anderson John",
				"Behjati Sam"
			],
			"DOI": "10.1056/NEJMoa2000962",
			"date": "2020-12-08",
			"PMC": "",
			"citation": "",
			"abstract": "Childhood tumors that occur synchronously in different anatomical sites usually represent metastatic disease. However, such tumors can be independent neoplasms. We investigated whether cases of bilateral neuroblastoma represented independent tumors in two children with pathogenic germline mutations by genotyping somatic mutations shared between tumors and blood. Our results suggested that in both children, the lineages that had given rise to the tumors had segregated within the first cell divisions of the zygote, without being preceded by a common premalignant clone. In one patient, the tumors had parallel evolution, including distinct second hits in ",
			"category": 2,
			"name": "Coorens Tim H H,2020"
		},
		{
			"PMID": 33168103,
			"title": "Chromosome structural variation in tumorigenesis: mechanisms of formation and carcinogenesis.",
			"journal": "Epigenetics & chromatin",
			"authorList": [
				"Wang Wen-Jun",
				"Li Ling-Yu",
				"Cui Jiu-Wei"
			],
			"DOI": "10.1186/s13072-020-00371-7",
			"date": "2021-05-10",
			"PMC": "",
			"citation": "",
			"abstract": "With the rapid development of next-generation sequencing technology, chromosome structural variation has gradually gained increased clinical significance in tumorigenesis. However, the molecular mechanism(s) underlying this structural variation remain poorly understood. A search of the literature shows that a three-dimensional chromatin state plays a vital role in inducing structural variation and in the gene expression profiles in tumorigenesis. Structural variants may result in changes in copy number or deletions of coding sequences, as well as the perturbation of structural chromatin features, especially topological domains, and disruption of interactions between genes and their regulatory elements. This review focuses recent work aiming at elucidating how structural variations develop and misregulate oncogenes and tumor suppressors, to provide general insights into tumor formation mechanisms and to provide potential targets for future anticancer therapies.",
			"category": 2,
			"name": "Wang Wen-Jun,2021"
		},
		{
			"PMID": 33159552,
			"title": "Systemic and rapid restructuring of the genome: a new perspective on punctuated equilibrium.",
			"journal": "Current genetics",
			"authorList": [
				"Heasley Lydia R",
				"Sampaio Nadia M V",
				"Argueso Juan Lucas"
			],
			"DOI": "10.1007/s00294-020-01119-2",
			"date": "2021-07-06",
			"PMC": "",
			"citation": "",
			"abstract": "The rates and patterns by which cells acquire mutations profoundly shape their evolutionary trajectories and phenotypic potential. Conventional models maintain that mutations are acquired independently of one another over many successive generations. Yet, recent evidence suggests that cells can also experience mutagenic processes that drive rapid genome evolution. One such process manifests as punctuated bursts of genomic instability, in which multiple new mutations are acquired simultaneously during transient episodes of genomic instability. This mutational mode is reminiscent of the theory of punctuated equilibrium, proposed by Stephen Jay Gould and Niles Eldredge in 1972 to explain the burst-like appearance of new species in the fossil record. In this review, we survey the dominant and emerging theories of eukaryotic genome evolution with a particular focus on the growing body of work that substantiates the existence and importance of punctuated bursts of genomic instability. In addition, we summarize and discuss two recent studies from our own group, the results of which indicate that punctuated bursts systemic genomic instability (SGI) can rapidly reconfigure the structure of the diploid genome of Saccharomyces cerevisiae.",
			"category": 2,
			"name": "Heasley Lydia R,2021"
		},
		{
			"PMID": 33128047,
			"title": "Are carcinogens direct mutagens?",
			"journal": "Nature genetics",
			"authorList": [
				"Lopez-Bigas Nuria",
				"Gonzalez-Perez Abel"
			],
			"DOI": "10.1038/s41588-020-00730-w",
			"date": "2020-12-17",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Lopez-Bigas Nuria,2020"
		},
		{
			"PMID": 33117968,
			"title": "Tumor Phylogeny Topology Inference via Deep Learning.",
			"journal": "iScience",
			"authorList": [
				"Sadeqi Azer Erfan",
				"Haghir Ebrahimabadi Mohammad",
				"Maliki\u0107 Salem",
				"Khardon Roni",
				"Sahinalp S Cenk"
			],
			"DOI": "10.1016/j.isci.2020.101655",
			"date": "2024-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "Principled computational approaches for tumor phylogeny reconstruction via single-cell sequencing typically aim to build the most likely perfect phylogeny tree from the noisy genotype matrix - which represents genotype calls of single cells. This problem is NP-hard, and as a result, existing approaches aim to solve relatively small instances of it through combinatorial optimization techniques or Bayesian inference. As expected, even when the goal is to infer basic topological features of the tumor phylogeny, rather than reconstructing the topology entirely, these approaches could be prohibitively slow. In this paper, we introduce fast deep learning solutions to the problems of inferring whether the most likely tree has a linear (chain) or branching topology and whether a perfect phylogeny is feasible from a given genotype matrix. We also present a reinforcement learning approach for reconstructing the most likely tumor phylogeny. This preliminary work demonstrates that data-driven approaches can reconstruct key features of tumor evolution.",
			"category": 2,
			"name": "Sadeqi Azer Erfan,2024"
		},
		{
			"PMID": 33114182,
			"title": "New Insights into Therapy-Induced Progression of Cancer.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Shnaider Polina V",
				"Ivanova Olga M",
				"Malyants Irina K",
				"Anufrieva Ksenia S",
				"Semenov Ilya A",
				"Pavlyukov Marat S",
				"Lagarkova Maria A",
				"Govorun Vadim M",
				"Shender Victoria O"
			],
			"DOI": "10.3390/ijms21217872",
			"date": "2021-03-01",
			"PMC": "",
			"citation": "",
			"abstract": "The malignant tumor is a complex heterogeneous set of cells functioning in a no less heterogeneous microenvironment. Like any dynamic system, cancerous tumors evolve and undergo changes in response to external influences, including therapy. Initially, most tumors are susceptible to treatment. However, remaining cancer cells may rapidly reestablish the tumor after a temporary remission. These new populations of malignant cells usually have increased resistance not only to the first-line agent, but also to the second- and third-line drugs, leading to a significant decrease in patient survival. Multiple studies describe the mechanism of acquired therapy resistance. In past decades, it became clear that, in addition to the simple selection of pre-existing resistant clones, therapy induces a highly complicated and tightly regulated molecular response that allows tumors to adapt to current and even subsequent therapeutic interventions. This review summarizes mechanisms of acquired resistance, such as secondary genetic alterations, impaired function of drug transporters, and autophagy. Moreover, we describe less obvious molecular aspects of therapy resistance in cancers, including epithelial-to-mesenchymal transition, cell cycle alterations, and the role of intercellular communication. Understanding these molecular mechanisms will be beneficial in finding novel therapeutic approaches for cancer therapy.",
			"category": 2,
			"name": "Shnaider Polina V,2021"
		},
		{
			"PMID": 33106418,
			"title": "Characterization of systemic genomic instability in budding yeast.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Sampaio Nadia M V",
				"Ajith V P",
				"Watson Ruth A",
				"Heasley Lydia R",
				"Chakraborty Parijat",
				"Rodrigues-Prause Aline",
				"Malc Ewa P",
				"Mieczkowski Piotr A",
				"Nishant Koodali T",
				"Argueso Juan Lucas"
			],
			"DOI": "10.1073/pnas.2010303117",
			"date": "2021-01-04",
			"PMC": "",
			"citation": "",
			"abstract": "Conventional models of genome evolution are centered around the principle that mutations form independently of each other and build up slowly over time. We characterized the occurrence of bursts of genome-wide loss-of-heterozygosity (LOH) in ",
			"category": 2,
			"name": "Sampaio Nadia M V,2021"
		},
		{
			"PMID": 33064882,
			"title": "Recurrent co-alteration of HDGF and SETDB1 on chromosome 1q drives cutaneous melanoma progression and poor prognosis.",
			"journal": "Pigment cell & melanoma research",
			"authorList": [
				"Fazio Maurizio",
				"van Rooijen Ellen",
				"Mito Jeffrey K",
				"Modhurima Rodsy",
				"Weiskopf Erika",
				"Yang Song",
				"Zon Leonard I"
			],
			"DOI": "10.1111/pcmr.12937",
			"date": "2022-01-10",
			"PMC": "",
			"citation": "",
			"abstract": "A progressive increase in copy number variation (CNV) characterizes the natural history of cutaneous melanoma progression toward later disease stages, but our understanding of genetic drivers underlying chromosomal arm-level CNVs remains limited. To identify candidate progression drivers, we mined the TCGA SKCM dataset and identified HDGF as a recurrently amplified gene whose high mRNA expression correlates with poor patient survival. Using melanocyte-specific overexpression in the zebrafish BRAF",
			"category": 2,
			"name": "Fazio Maurizio,2022"
		},
		{
			"PMID": 33054808,
			"title": "Cancer predictive studies.",
			"journal": "Biology direct",
			"authorList": [
				"Amelio Ivano",
				"Bertolo Riccardo",
				"Bove Pierluigi",
				"Candi Eleonora",
				"Chiocchi Marcello",
				"Cipriani Chiara",
				"Di Daniele Nicola",
				"Ganini Carlo",
				"Juhl Hartmut",
				"Mauriello Alessandro",
				"Marani Carla",
				"Marshall John",
				"Montanaro Manuela",
				"Palmieri Giampiero",
				"Piacentini Mauro",
				"Sica Giuseppe",
				"Tesauro Manfredi",
				"Rovella Valentina",
				"Tisone Giuseppe",
				"Shi Yufang",
				"Wang Ying",
				"Melino Gerry"
			],
			"DOI": "10.1186/s13062-020-00274-3",
			"date": "2021-08-11",
			"PMC": "",
			"citation": "",
			"abstract": "The identification of individual or clusters of predictive genetic alterations might help in defining the outcome of cancer treatment, allowing for the stratification of patients into distinct cohorts for selective therapeutic protocols. Neuroblastoma (NB) is the most common extracranial childhood tumour, clinically defined in five distinct stages (1-4 & 4S), where stages 3-4 define chemotherapy-resistant, highly aggressive disease phases. NB is a model for geneticists and molecular biologists to classify genetic abnormalities and identify causative disease genes. Despite highly intensive basic research, improvements on clinical outcome have been predominantly observed for less aggressive cancers, that is stages 1,2 and 4S. Therefore, stages 3-4 NB are still complicated at the therapeutic level and require more intense fundamental research. Using neuroblastoma as a model system, here we herein outline how cancer prediction studies can help at steering preclinical and clinical research toward the identification and exploitation of specific genetic landscape. This might result in maximising the therapeutic success and minimizing harmful effects in cancer patients.",
			"category": 2,
			"name": "Amelio Ivano,2021"
		},
		{
			"PMID": 33023945,
			"title": "Field Carcinogenesis in Cancer Evolution: What the Cell Is Going On?",
			"journal": "Cancer research",
			"authorList": [
				"Sinjab Ansam",
				"Han Guangchun",
				"Wang Linghua",
				"Kadara Humam"
			],
			"DOI": "10.1158/0008-5472.CAN-20-1956",
			"date": "2021-02-12",
			"PMC": "",
			"citation": "",
			"abstract": "Field carcinogenesis describes the prevalence of tumor-related alterations in normal appearing tissues. Here, we summarize recent efforts in profiling molecular field dynamics for resolving early events in cancer evolution. We also highlight gaps in our knowledge of the molecular and cellular heterogeneity of field carcinogenesis and propose directions to tackle these voids using single-cell-based approaches and unique tissue sampling models. By interrogating both the mutagenized epithelium and its microenvironment, we surmise that single-cell-guided studies will help chart the spatiotemporal molecular and cellular \"atlas\" of field carcinogenesis, will further delineate preneoplastic initiation and progression, and will help identify cancer prevention and early intervention targets.",
			"category": 2,
			"name": "Sinjab Ansam,2021"
		},
		{
			"PMID": 33022659,
			"title": "STARCH: copy number and clone inference from spatial transcriptomics data.",
			"journal": "Physical biology",
			"authorList": [
				"Elyanow Rebecca",
				"Zeira Ron",
				"Land Max",
				"Raphael Benjamin J"
			],
			"DOI": "10.1088/1478-3975/abbe99",
			"date": "2021-10-21",
			"PMC": "",
			"citation": "",
			"abstract": "Tumors are highly heterogeneous, consisting of cell populations with both transcriptional and genetic diversity. These diverse cell populations are spatially organized within a tumor, creating a distinct tumor microenvironment. A new technology called spatial transcriptomics can measure spatial patterns of gene expression within a tissue by sequencing RNA transcripts from a grid of spots, each containing a small number of cells. In tumor cells, these gene expression patterns represent the combined contribution of regulatory mechanisms, which alter the rate at which a gene is transcribed, and genetic diversity, particularly copy number aberrations (CNAs) which alter the number of copies of a gene in the genome. CNAs are common in tumors and often promote cancer growth through upregulation of oncogenes or downregulation of tumor-suppressor genes. We introduce a new method STARCH (spatial transcriptomics algorithm reconstructing copy-number heterogeneity) to infer CNAs from spatial transcriptomics data. STARCH overcomes challenges in inferring CNAs from RNA-sequencing data by leveraging the observation that cells located nearby in a tumor are likely to share similar CNAs. We find that STARCH outperforms existing methods for inferring CNAs from RNA-sequencing data without incorporating spatial information.",
			"category": 2,
			"name": "Elyanow Rebecca,2021"
		},
		{
			"PMID": 32978226,
			"title": "An Epigenetic Mechanism Underlying Chromosome 17p Deletion-Driven Tumorigenesis.",
			"journal": "Cancer discovery",
			"authorList": [
				"Chen Mei",
				"Chen Xuelan",
				"Li Shujun",
				"Pan Xiangyu",
				"Gong Yanqiu",
				"Zheng Jianan",
				"Xu Jing",
				"Zhao Chengjian",
				"Zhang Qi",
				"Zhang Shan",
				"Qi Lu",
				"Wang Zhongwang",
				"Shi Kaidou",
				"Ding Bi-Sen",
				"Xue Zhihong",
				"Chen Lu",
				"Yang Shengyong",
				"Wang Yuan",
				"Niu Ting",
				"Dai Lunzhi",
				"Lowe Scott W",
				"Chen Chong",
				"Liu Yu"
			],
			"DOI": "10.1158/2159-8290.CD-20-0336",
			"date": "2021-06-04",
			"PMC": "",
			"citation": "",
			"abstract": "Chromosome copy-number variations are a hallmark of cancer. Among them, the prevalent chromosome 17p deletions are associated with poor prognosis and can promote tumorigenesis more than ",
			"category": 2,
			"name": "Chen Mei,2021"
		},
		{
			"PMID": 32973296,
			"title": "The role of genomics in global cancer prevention.",
			"journal": "Nature reviews. Clinical oncology",
			"authorList": [
				"Ginsburg Ophira",
				"Ashton-Prolla Patricia",
				"Cantor Anna",
				"Mariosa Daniela",
				"Brennan Paul"
			],
			"DOI": "10.1038/s41571-020-0428-5",
			"date": "2021-03-31",
			"PMC": "",
			"citation": "",
			"abstract": "Despite improvements in the understanding of cancer causation, much remains unknown regarding the mechanisms by which genomic and non-genomic factors initiate carcinogenesis, drive cell invasion and metastasis, and enable cancer to develop. Technological advances have enabled the analysis of whole genomes, comprising thousands of tumours across populations worldwide, with the aim of identifying mutation signatures associated with particular tumour types. Large collaborative efforts have resulted in the identification and improved understanding of causal factors, and have shed light on new opportunities to prevent cancer. In this new era in cancer genomics, discoveries from studies conducted on an international scale can inform evidence-based strategies in cancer control along the cancer care continuum, from prevention to treatment. In this Review, we present the relevant history and emerging frontiers of cancer genetics and genomics from the perspective of global cancer prevention. We highlight the importance of local context in the adoption of new technologies and emergent evidence, with illustrative examples from worldwide. We emphasize the challenges in implementing important genomic findings in clinical settings with disparate resource availability and present a conceptual framework for the translation of such findings into clinical practice, and evidence-based policies in order to maximize the utility for a population.",
			"category": 2,
			"name": "Ginsburg Ophira,2021"
		},
		{
			"PMID": 32952853,
			"title": "Hunting down the dominating subclone of cancer stem cells as a potential new therapeutic target in multiple myeloma: An artificial intelligence perspective.",
			"journal": "World journal of stem cells",
			"authorList": [
				"Lee Lisa X",
				"Li Shengwen Calvin"
			],
			"DOI": "10.4252/wjsc.v12.i8.706",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "The development of single-cell subclones, which can rapidly switch from dormant to dominant subclones, occur in the natural pathophysiology of multiple myeloma (MM) but is often \"pressed\" by the standard treatment of MM. These emerging subclones present a challenge, providing reservoirs for chemoresistant mutations. Technological advancement is required to track MM subclonal changes, as understanding MM's mechanism of evolution at the cellular level can prompt the development of new targeted ways of treating this disease. Current methods to study the evolution of subclones in MM rely on technologies capable of phenotypically and genotypically characterizing plasma cells, which include immunohistochemistry, flow cytometry, or cytogenetics. Still, all of these technologies may be limited by the sensitivity for picking up rare events. In contrast, more incisive methods such as RNA sequencing, comparative genomic hybridization, or whole-genome sequencing are not yet commonly used in clinical practice. Here we introduce the epidemiological diagnosis and prognosis of MM and review current methods for evaluating MM subclone evolution, such as minimal residual disease/multiparametric flow cytometry/next-generation sequencing, and their respective advantages and disadvantages. In addition, we propose our new single-cell method of evaluation to understand MM's mechanism of evolution at the molecular and cellular level and to prompt the development of new targeted ways of treating this disease, which has a broad prospect.",
			"category": 2,
			"name": "Lee Lisa X,2020"
		},
		{
			"PMID": 32932620,
			"title": "The Origin and Immune Recognition of Tumor-Specific Antigens.",
			"journal": "Cancers",
			"authorList": [
				"Apavaloaei Anca",
				"Hardy Marie-Pierre",
				"Thibault Pierre",
				"Perreault Claude"
			],
			"DOI": "10.3390/cancers12092607",
			"date": "2024-03-29",
			"PMC": "",
			"citation": "",
			"abstract": "The dominant paradigm holds that spontaneous and therapeutically induced anti-tumor responses are mediated mainly by CD8 T cells and directed against tumor-specific antigens (TSAs). The presence of specific TSAs on cancer cells can only be proven by mass spectrometry analyses. Bioinformatic predictions and reverse immunology studies cannot provide this type of conclusive evidence. Most TSAs are coded by unmutated non-canonical transcripts that arise from cancer-specific epigenetic and splicing aberrations. When searching for TSAs, it is therefore important to perform mass spectrometry analyses that interrogate not only the canonical reading frame of annotated exome but all reading frames of the entire translatome. The majority of aberrantly expressed TSAs (aeTSAs) derive from unstable short-lived proteins that are good substrates for direct major histocompatibility complex (MHC) I presentation but poor substrates for cross-presentation. This is an important caveat, because cancer cells are poor antigen-presenting cells, and the immune system, therefore, depends on cross-presentation by dendritic cells (DCs) to detect the presence of TSAs. We, therefore, postulate that, in the untreated host, most aeTSAs are undetected by the immune system. We present evidence suggesting that vaccines inducing direct aeTSA presentation by DCs may represent an attractive strategy for cancer treatment.",
			"category": 2,
			"name": "Apavaloaei Anca,2024"
		},
		{
			"PMID": 32929562,
			"title": "Current methods in translational cancer research.",
			"journal": "Cancer metastasis reviews",
			"authorList": [
				"Lee Michael W",
				"Miljanic Mihailo",
				"Triplett Todd",
				"Ramirez Craig",
				"Aung Kyaw L",
				"Eckhardt S Gail",
				"Capasso Anna"
			],
			"DOI": "10.1007/s10555-020-09931-5",
			"date": "2021-11-25",
			"PMC": "",
			"citation": "",
			"abstract": "Recent developments in pre-clinical screening tools, that more reliably predict the clinical effects and adverse events of candidate therapeutic agents, has ushered in a new era of drug development and screening. However, given the rapid pace with which these models have emerged, the individual merits of these translational research tools warrant careful evaluation in order to furnish clinical researchers with appropriate information to conduct pre-clinical screening in an accelerated and rational manner. This review assesses the predictive utility of both well-established and emerging pre-clinical methods in terms of their suitability as a screening platform for treatment response, ability to represent pharmacodynamic and pharmacokinetic drug properties, and lastly debates the translational limitations and benefits of these models. To this end, we will describe the current literature on cell culture, organoids, in vivo mouse models, and in silico computational approaches. Particular focus will be devoted to discussing gaps and unmet needs in the literature as well as current advancements and innovations achieved in the field, such as co-clinical trials and future avenues for refinement.",
			"category": 2,
			"name": "Lee Michael W,2021"
		},
		{
			"PMID": 32887685,
			"title": "Reconstruction of clone- and haplotype-specific cancer genome karyotypes from bulk tumor samples.",
			"journal": "Genome research",
			"authorList": [
				"Aganezov Sergey",
				"Raphael Benjamin J"
			],
			"DOI": "10.1101/gr.256701.119",
			"date": "2021-10-29",
			"PMC": "",
			"citation": "",
			"abstract": "Many cancer genomes are extensively rearranged with aberrant chromosomal karyotypes. Deriving these karyotypes from high-throughput DNA sequencing of bulk tumor samples is complicated because most tumors are a heterogeneous mixture of normal cells and subpopulations of cancer cells, or clones, that harbor distinct somatic mutations. We introduce a new algorithm, Reconstructing Cancer Karyotypes (RCK), to reconstruct haplotype-specific karyotypes of one or more rearranged cancer genomes from DNA sequencing data from a bulk tumor sample. RCK leverages evolutionary constraints on the somatic mutational process in cancer to reduce ambiguity in the deconvolution of admixed sequencing data into multiple haplotype-specific cancer karyotypes. RCK models mixtures containing an arbitrary number of derived genomes and allows the incorporation of information both from short-read and long-read DNA sequencing technologies. We compare RCK to existing approaches on 17 primary and metastatic prostate cancer samples. We find that RCK infers cancer karyotypes that better explain the DNA sequencing data and conform to a reasonable evolutionary model. RCK's reconstructions of clone- and haplotype-specific karyotypes will aid further studies of the role of intra-tumor heterogeneity in cancer development and response to treatment. RCK is freely available as open source software.",
			"category": 2,
			"name": "Aganezov Sergey,2021"
		},
		{
			"PMID": 32879509,
			"title": "Subclonal reconstruction of tumors by using machine learning and population genetics.",
			"journal": "Nature genetics",
			"authorList": [
				"Caravagna Giulio",
				"Heide Timon",
				"Williams Marc J",
				"Zapata Luis",
				"Nichol Daniel",
				"Chkhaidze Ketevan",
				"Cross William",
				"Cresswell George D",
				"Werner Benjamin",
				"Acar Ahmet",
				"Chesler Louis",
				"Barnes Chris P",
				"Sanguinetti Guido",
				"Graham Trevor A",
				"Sottoriva Andrea"
			],
			"DOI": "10.1038/s41588-020-0675-5",
			"date": "2020-10-29",
			"PMC": "",
			"citation": "",
			"abstract": "Most cancer genomic data are generated from bulk samples composed of mixtures of cancer subpopulations, as well as normal cells. Subclonal reconstruction methods based on machine learning aim to separate those subpopulations in a sample and infer their evolutionary history. However, current approaches are entirely data driven and agnostic to evolutionary theory. We demonstrate that systematic errors occur in the analysis if evolution is not accounted for, and this is exacerbated with multi-sampling of the same tumor. We present a novel approach for model-based tumor subclonal reconstruction, called MOBSTER, which combines machine learning with theoretical population genetics. Using public whole-genome sequencing data from 2,606 samples from different cohorts, new data and synthetic validation, we show that this method is more robust and accurate than current techniques in single-sample, multiregion and longitudinal data. This approach minimizes the confounding factors of nonevolutionary methods, thus leading to more accurate recovery of the evolutionary history of human cancers.",
			"category": 2,
			"name": "Caravagna Giulio,2020"
		},
		{
			"PMID": 32872162,
			"title": "Pharmacogenomics to Predict Tumor Therapy Response: A Focus on ATP-Binding Cassette Transporters and Cytochromes P450.",
			"journal": "Journal of personalized medicine",
			"authorList": [
				"Hlav\u00e1\u010d Viktor",
				"Hol\u00fd Petr",
				"Sou\u010dek Pavel"
			],
			"DOI": "10.3390/jpm10030108",
			"date": "2020-10-27",
			"PMC": "",
			"citation": "",
			"abstract": "Pharmacogenomics is an evolving tool of precision medicine. Recently, due to the introduction of next-generation sequencing and projects generating \"Big Data\", a plethora of new genetic variants in pharmacogenes have been discovered. Cancer resistance is a major complication often preventing successful anticancer treatments. Pharmacogenomics of both somatic mutations in tumor cells and germline variants may help optimize targeted treatments and improve the response to conventional oncological therapy. In addition, integrative approaches combining copy number variations and long noncoding RNA profiling with germline and somatic variations seem to be a promising approach as well. In pharmacology, expression and enzyme activity are traditionally the more studied aspects of ATP-binding cassette transporters and cytochromes P450. In this review, we briefly introduce the field of pharmacogenomics and the advancements driven by next-generation sequencing and outline the possible roles of genetic variation in the two large pharmacogene superfamilies. Although the evidence needs further substantiation, somatic and copy number variants as well as rare variants and common polymorphisms in these genes could all affect response to cancer therapy. Regulation by long noncoding RNAs has also been shown to play a role. However, in all these areas, more comprehensive studies on larger sets of patients are needed.",
			"category": 2,
			"name": "Hlav\u00e1\u010d Viktor,2020"
		},
		{
			"PMID": 32867043,
			"title": "Challenges and Opportunities in Clinical Applications of Blood-Based Proteomics in Cancer.",
			"journal": "Cancers",
			"authorList": [
				"Bhawal Ruchika",
				"Oberg Ann L",
				"Zhang Sheng",
				"Kohli Manish"
			],
			"DOI": "10.3390/cancers12092428",
			"date": "2021-05-15",
			"PMC": "",
			"citation": "",
			"abstract": "Blood is a readily accessible biofluid containing a plethora of important proteins, nucleic acids, and metabolites that can be used as clinical diagnostic tools in diseases, including cancer. Like the on-going efforts for cancer biomarker discovery using the liquid biopsy detection of circulating cell-free and cell-based tumor nucleic acids, the circulatory proteome has been underexplored for clinical cancer biomarker applications. A comprehensive proteome analysis of human serum/plasma with high-quality data and compelling interpretation can potentially provide opportunities for understanding disease mechanisms, although several challenges will have to be met. Serum/plasma proteome biomarkers are present in very low abundance, and there is high complexity involved due to the heterogeneity of cancers, for which there is a compelling need to develop sensitive and specific proteomic technologies and analytical platforms. To date, liquid chromatography mass spectrometry (LC-MS)-based quantitative proteomics has been a dominant analytical workflow to discover new potential cancer biomarkers in serum/plasma. This review will summarize the opportunities of serum proteomics for clinical applications; the challenges in the discovery of novel biomarkers in serum/plasma; and current proteomic strategies in cancer research for the application of serum/plasma proteomics for clinical prognostic, predictive, and diagnostic applications, as well as for monitoring minimal residual disease after treatments. We will highlight some of the recent advances in MS-based proteomics technologies with appropriate sample collection, processing uniformity, study design, and data analysis, focusing on how these integrated workflows can identify novel potential cancer biomarkers for clinical applications.",
			"category": 2,
			"name": "Bhawal Ruchika,2021"
		},
		{
			"PMID": 32860009,
			"title": "Current evidence on screening for renal cancer.",
			"journal": "Nature reviews. Urology",
			"authorList": [
				"Usher-Smith Juliet",
				"Simmons Rebecca K",
				"Rossi Sabrina H",
				"Stewart Grant D"
			],
			"DOI": "10.1038/s41585-020-0363-3",
			"date": "2022-01-27",
			"PMC": "",
			"citation": "",
			"abstract": "Renal cell carcinoma (RCC) incidence is increasing worldwide. A high proportion of individuals are asymptomatic at diagnosis, but RCC has a high mortality rate. These facts suggest that RCC meets some of the criteria for screening, and a new analysis shows that screening for RCC could potentially be cost-effective. Targeted screening of high-risk individuals is likely to be the most cost-effective strategy to maximize the benefits and reduce the harms of screening. However, the size of the benefit of earlier initiation of treatment and the overall cost-effectiveness of screening remains uncertain. The optimal screening modality and target population is also unclear, and uncertainties exist regarding the specification and implementation of a screening programme. Before moving to a fully powered trial of screening, future work should focus on the following: developing and validating accurate risk prediction models; developing non-invasive methods of early RCC detection; establishing the feasibility, public acceptability and potential uptake of screening; establishing the prevalence of RCC and stage distribution of RCC detected by screening; and evaluating the potential harms of screening, including the impact on quality of life, overdiagnosis and over-treatment.",
			"category": 2,
			"name": "Usher-Smith Juliet,2022"
		},
		{
			"PMID": 32827212,
			"title": "Organized immune cell interactions within tumors sustain a productive T-cell response.",
			"journal": "International immunology",
			"authorList": [
				"Cardenas Maria A",
				"Prokhnevska Nataliya",
				"Kissick Haydn T"
			],
			"DOI": "10.1093/intimm/dxaa057",
			"date": "2022-02-09",
			"PMC": "",
			"citation": "",
			"abstract": "Tumor-infiltrating CD8 T cells are associated with improved patient survival and response to immunotherapy in various cancers. Persistent antigen leads to CD8 T-cell exhaustion, where proliferation/self-renewal and killing are divided within distinct subsets of CD8 T cells in the tumor. CD8 T-cell responses in chronic antigen settings must be maintained for long periods of time, suggesting that mechanisms that regulate chronic CD8 T-cell responses may differ from those in acute settings. Currently, factors that regulate the maintenance of stem-like CD8 T cells in the tumor or their differentiation into terminally differentiated cells are unknown. In this review, we discuss the role of dendritic cells in the activation and differentiation of CD8 T-cell subsets within secondary lymphoid tissue and tumors. In addition, we examine changes in CD4 T-cell differentiation in response to chronic antigens and consider how subset-specific mechanisms could assist the stem-like and terminally differentiated CD8 T-cell subsets. Finally, we highlight how tumor-infiltrating CD4 T cells and dendritic cells interact with CD8 T cells within organized lymphoid-like areas in the tumor and propose a CD8 T-cell differentiation model that requires the collaboration of CD4 T cells and dendritic cells. These organized interactions coordinate the anti-tumor response and control disease progression by mechanisms that regulate CD8 T-cell differentiation, which permit the maintenance of an effective balance of stem-like and terminally differentiated CD8 T cells.",
			"category": 2,
			"name": "Cardenas Maria A,2022"
		},
		{
			"PMID": 32807900,
			"title": "Integrating genetic and non-genetic determinants of cancer evolution by single-cell multi-omics.",
			"journal": "Nature reviews. Genetics",
			"authorList": [
				"Nam Anna S",
				"Chaligne Ronan",
				"Landau Dan A"
			],
			"DOI": "10.1038/s41576-020-0265-5",
			"date": "2021-02-19",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer represents an evolutionary process through which growing malignant populations genetically diversify, leading to tumour progression, relapse and resistance to therapy. In addition to genetic diversity, the cell-to-cell variation that fuels evolutionary selection also manifests in cellular states, epigenetic profiles, spatial distributions and interactions with the microenvironment. Therefore, the study of cancer requires the integration of multiple heritable dimensions at the resolution of the single cell - the atomic unit of somatic evolution. In this Review, we discuss emerging analytic and experimental technologies for single-cell multi-omics that enable the capture and integration of multiple data modalities to inform the study of cancer evolution. These data show that cancer results from a complex interplay between genetic and non-genetic determinants of somatic evolution.",
			"category": 2,
			"name": "Nam Anna S,2021"
		},
		{
			"PMID": 32788368,
			"title": "Mathematical model of colorectal cancer initiation.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Paterson Chay",
				"Clevers Hans",
				"Bozic Ivana"
			],
			"DOI": "10.1073/pnas.2003771117",
			"date": "2020-10-28",
			"PMC": "",
			"citation": "",
			"abstract": "Quantifying evolutionary dynamics of cancer initiation and progression can provide insights into more effective strategies of early detection and treatment. Here we develop a mathematical model of colorectal cancer initiation through inactivation of two tumor suppressor genes and activation of one oncogene, accounting for the well-known path to colorectal cancer through loss of tumor suppressors ",
			"category": 2,
			"name": "Paterson Chay,2020"
		},
		{
			"PMID": 32704031,
			"title": "The genetics of ductal adenocarcinoma of the pancreas in the year 2020: dramatic progress, but far to go.",
			"journal": "Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc",
			"authorList": [
				"Thompson Elizabeth D",
				"Roberts Nicholas J",
				"Wood Laura D",
				"Eshleman James R",
				"Goggins Michael G",
				"Kern Scott E",
				"Klein Alison P",
				"Hruban Ralph H"
			],
			"DOI": "10.1038/s41379-020-0629-6",
			"date": "2021-10-12",
			"PMC": "",
			"citation": "",
			"abstract": "The publication of the \"Pan-Cancer Atlas\" by the Pan-Cancer Analysis of Whole Genomes Consortium, a partnership formed by The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC), provides a wonderful opportunity to reflect on where we stand in our understanding of the genetics of pancreatic cancer, as well as on the opportunities to translate this understanding to patient care. From germline variants that predispose to the development of pancreatic cancer, to somatic mutations that are therapeutically targetable, genetics is now providing hope, where there once was no hope, for those diagnosed with pancreatic cancer.",
			"category": 2,
			"name": "Thompson Elizabeth D,2021"
		},
		{
			"PMID": 32699225,
			"title": "A G-quadruplex-binding compound shows potent activity in human gemcitabine-resistant pancreatic cancer cells.",
			"journal": "Scientific reports",
			"authorList": [
				"Ahmed Ahmed Abdullah",
				"Marchetti Chiara",
				"Ohnmacht Stephan A",
				"Neidle Stephen"
			],
			"DOI": "10.1038/s41598-020-68944-w",
			"date": "2020-12-16",
			"PMC": "",
			"citation": "",
			"abstract": "Gemcitabine is a drug of choice in the treatment of human pancreatic cancer. Chemo-resistance to this drug is common and has been attributed to a variety of distinct mechanisms, involving\u2009>\u2009100 genes. A recently developed small-molecule G-quadruplex ligand, the trisubstituted naphthalene diimide compound CM03, has previously been shown to have equivalent potency to gemcitabine in the pancreatic cancer cell line MIA PaCa-2. We report here on cell lines of increased resistance to gemcitabine that have been generated from this line, with the most resistant having 1,000-fold reduced sensitivity to gemcitabine. These resistant lines retain nM sensitivity to CM03. The molecular basis for the retention of potency by this G-quadruplex ligand has been examined using whole transcriptome data analysis with RNA-seq. This has revealed that the pattern of pathways down\u00a0regulated by CM03 in the parental MIA PaCa-2 cell line is largely unaffected in the gemcitabine-resistant line. The analysis has also shown that the expression patterns of numerous genes involved in gemcitabine sensitivity are down regulated in the resistant line upon CM03 treatment. These results are supportive of the concept that G-quadruplex small molecules such as CM03 have potential for clinical use in the treatment of gemcitabine-resistant human pancreatic cancer.",
			"category": 2,
			"name": "Ahmed Ahmed Abdullah,2020"
		},
		{
			"PMID": 32698135,
			"title": "Intratumor heterogeneity of prognostic DNA-based molecular markers in adrenocortical carcinoma.",
			"journal": "Endocrine connections",
			"authorList": [
				"Jouinot Anne",
				"Lippert Juliane",
				"Fassnacht Martin",
				"de La Villeon Bruno",
				"Septier Amandine",
				"Neou Mario",
				"Perlemoine Karine",
				"Appenzeller Silke",
				"Sibony Mathilde",
				"Gaujoux S\u00e9bastien",
				"Dousset Bertrand",
				"Libe Rossella",
				"Groussin Lionel",
				"Ronchi Cristina L",
				"Assi\u00e9 Guillaume",
				"Bertherat J\u00e9r\u00f4me"
			],
			"DOI": "10.1530/EC-20-0228",
			"date": "2022-04-15",
			"PMC": "",
			"citation": "",
			"abstract": "The prognosis of adrenocortical carcinoma (ACC) is heterogeneous. Genomic studies have identified ACC subgroups characterized by specific molecular alterations, including features measured at DNA level (somatic mutations, chromosome alterations, DNA methylation), which are closely associated with outcome. The aim of this study was to evaluate intratumor heterogeneity of prognostic molecular markers at the DNA level.",
			"category": 2,
			"name": "Jouinot Anne,2022"
		},
		{
			"PMID": 32697969,
			"title": "Somatic Evolution in Non-neoplastic IBD-Affected Colon.",
			"journal": "Cell",
			"authorList": [
				"Olafsson Sigurgeir",
				"McIntyre Rebecca E",
				"Coorens Tim",
				"Butler Timothy",
				"Jung Hyunchul",
				"Robinson Philip S",
				"Lee-Six Henry",
				"Sanders Mathijs A",
				"Arestang Kenneth",
				"Dawson Claire",
				"Tripathi Monika",
				"Strongili Konstantina",
				"Hooks Yvette",
				"Stratton Michael R",
				"Parkes Miles",
				"Martincorena Inigo",
				"Raine Tim",
				"Campbell Peter J",
				"Anderson Carl A"
			],
			"DOI": "10.1016/j.cell.2020.06.036",
			"date": "2021-03-29",
			"PMC": "",
			"citation": "",
			"abstract": "Inflammatory bowel disease (IBD) is a chronic inflammatory disease associated with increased risk of gastrointestinal cancers. We whole-genome sequenced 446 colonic crypts from 46 IBD patients and compared these to 412 crypts from 41 non-IBD controls from our previous publication on the mutation landscape of the normal colon. The average mutation rate of affected colonic epithelial cells is 2.4-fold that of healthy colon, and this increase is mostly driven by acceleration of mutational processes ubiquitously observed in normal colon. In contrast to the normal colon, where clonal expansions outside the confines of the crypt are rare, we observed widespread millimeter-scale clonal expansions. We discovered non-synonymous mutations in ARID1A, FBXW7, PIGR, ZC3H12A, and genes in the interleukin 17 and Toll-like receptor pathways, under positive selection in IBD. These results suggest distinct selection mechanisms in the colitis-affected colon and that somatic mutations potentially play a causal role in IBD pathogenesis.",
			"category": 2,
			"name": "Olafsson Sigurgeir,2021"
		},
		{
			"PMID": 32662546,
			"title": "Characterization of tumors with ultralow tumor mutational burden in Japanese cancer patients.",
			"journal": "Cancer science",
			"authorList": [
				"Hatakeyama Keiichi",
				"Nagashima Takeshi",
				"Ohshima Keiichi",
				"Ohnami Sumiko",
				"Ohnami Shumpei",
				"Shimoda Yuji",
				"Naruoka Akane",
				"Maruyama Koji",
				"Iizuka Akira",
				"Ashizawa Tadashi",
				"Mochizuki Tohru",
				"Urakami Kenichi",
				"Akiyama Yasuto",
				"Yamaguchi Ken"
			],
			"DOI": "10.1111/cas.14572",
			"date": "2020-12-15",
			"PMC": "",
			"citation": "",
			"abstract": "Tumor mutational burden analysis using whole-exome sequencing highlights features of tumors with various mutations or known driver alterations. Cancers with few changes in the exon regions have unclear characteristics, even though low-mutated tumors are often detected in pan-cancer analysis. In the present study, we analyzed tumors with low tumor mutational burden listed in the Japanese version of The Cancer Genome Atlas, a data set of 5020 primary solid tumors. Our analysis revealed that detection rates of known driver mutations and copy number variation were decreased in samples with tumor mutational burden below 1.0 (ultralow tumor), compared with those in samples with low tumor mutational burden (\u22645 mutations/Mb). This trend was also observed in The Cancer Genome Atlas data set. In the ultralow tumor mutational burden tumors, expression analysis showed decreased TP53 inactivation and chromosomal instability. TP53 inactivation frequently correlated with PI3K/mTOR-related gene expression, implying suppression of the PI3K/mTOR pathway in ultralow tumor mutational burden tumors. In common with mutational burden, the T cell-inflamed gene expression profiling signature was a potential marker for prediction of an immune checkpoint inhibitor response, and some ultralow tumor mutational burden tumor populations highly expressed this signature. Our analysis focused on how these tumors could provide insight into tumors with low somatic alteration that are difficult to detect solely using whole-exome sequencing.",
			"category": 2,
			"name": "Hatakeyama Keiichi,2020"
		},
		{
			"PMID": 32657354,
			"title": "Copy number evolution with weighted aberrations in cancer.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Zeira Ron",
				"Raphael Benjamin J"
			],
			"DOI": "10.1093/bioinformatics/btaa470",
			"date": "2021-03-08",
			"PMC": "",
			"citation": "",
			"abstract": "Copy number aberrations (CNAs), which delete or amplify large contiguous segments of the genome, are a common type of somatic mutation in cancer. Copy number profiles, representing the number of copies of each region of a genome, are readily obtained from whole-genome sequencing or microarrays. However, modeling copy number evolution is a substantial challenge, because different CNAs may overlap with one another on the genome. A recent popular model for copy number evolution is the copy number distance (CND), defined as the length of a shortest sequence of deletions and amplifications of contiguous segments that transforms one profile into the other. In the CND, all events contribute equally; however, it is well known that rates of CNAs vary by length, genomic position and type (amplification versus deletion).",
			"category": 2,
			"name": "Zeira Ron,2021"
		},
		{
			"PMID": 32647253,
			"title": "Exploring and modelling colon cancer inter-tumour heterogeneity: opportunities and challenges.",
			"journal": "Oncogenesis",
			"authorList": [
				"Buikhuisen Joyce Y",
				"Torang Arezo",
				"Medema Jan Paul"
			],
			"DOI": "10.1038/s41389-020-00250-6",
			"date": "2021-02-09",
			"PMC": "",
			"citation": "",
			"abstract": "Colon cancer inter-tumour heterogeneity is installed on multiple levels, ranging from (epi)genetic driver events to signalling pathway rewiring reflected by differential gene expression patterns. Although the existence of heterogeneity in colon cancer has been recognised for a longer period of time, it is sparingly incorporated as a determining factor in current clinical practice. Here we describe how unsupervised gene expression-based classification efforts, amongst which the consensus molecular subtypes (CMS), can stratify patients in biological subgroups associated with distinct disease outcome and responses to therapy. We will discuss what is needed to extend these subtyping efforts to the clinic and we will argue that preclinical models recapitulate CMS subtypes and can be of vital use to increase our understanding of treatment response and resistance and to discover novel targets for therapy.",
			"category": 2,
			"name": "Buikhuisen Joyce Y,2021"
		},
		{
			"PMID": 32637574,
			"title": "Chromosome Abnormalities: New Insights into Their Clinical Significance in Cancer.",
			"journal": "Molecular therapy oncolytics",
			"authorList": [
				"Kou Fan",
				"Wu Lei",
				"Ren Xiubao",
				"Yang Lili"
			],
			"DOI": "10.1016/j.omto.2020.05.010",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Chromosomal abnormalities, consisting of numerical and structural chromosome abnormalities, are a common characteristic of cancer. Numerical chromosome abnormalities, mainly including aneuploidy and chromosome instability, are caused by chromosome segregation errors in mitosis, whereas structural chromosome abnormalities are a consequence of DNA damage and comprise focal/arm-level chromosome gain or loss. Recent advances have started to unveil the mechanisms by which chromosomal abnormalities can facilitate tumorigenesis and change the cellular fitness and the expression or function of RNAs and proteins. Accumulating evidence suggests that chromosome abnormalities represent a genomic signature that is linked to cancer prognosis and reaction to chemotherapy and immunotherapy. In this review, we discuss the most recent findings on the role of chromosome abnormalities in tumorigenesis and cancer progression, with a particular emphasis on how aneuploidy and chromosome instability influence cancer therapy and prognosis. We also highlight the distribution and clinical application of the structural chromosome abnormalities in various cancer types. A better understanding of the role of chromosome abnormalities will be beneficial to the development of precision oncology and suggest future directions for the field.",
			"category": 2,
			"name": "Kou Fan,2020"
		},
		{
			"PMID": 32630305,
			"title": "The Bone's Role in Myeloid Neoplasia.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Kazianka Lukas",
				"Staber Philipp B"
			],
			"DOI": "10.3390/ijms21134712",
			"date": "2021-02-16",
			"PMC": "",
			"citation": "",
			"abstract": "The interaction of hematopoietic stem and progenitor cells with their direct neighboring cells in the bone marrow (the so called hematopoietic niche) evolves as a key principle for understanding physiological and malignant hematopoiesis. Significant progress in this matter has recently been achieved making use of emerging high-throughput techniques that allow characterization of the bone marrow microenvironment at single cell resolution. This review aims to discuss these single cell findings in the light of other conventional niche studies that together define the current notion of the niche's implication in i) normal hematopoiesis, ii) myeloid neoplasms and iii) disease-driving pathways that can be exploited to establish novel therapeutic strategies in the future.",
			"category": 2,
			"name": "Kazianka Lukas,2021"
		},
		{
			"PMID": 32623333,
			"title": "Visualizing Human Colorectal Cancer Intratumor Heterogeneity with Phylogeography.",
			"journal": "iScience",
			"authorList": [
				"Shibata Darryl"
			],
			"DOI": "10.1016/j.isci.2020.101304",
			"date": "2021-02-01",
			"PMC": "",
			"citation": "",
			"abstract": "Phylogeography combines ancestry with location and can be translated to intratumor heterogeneity (ITH) to visualize how tumors spread. ITH is common in human tumors, with many genetic and phenotypic differences between regions. The roles of ITH in progression are uncertain because many subclones lack discernable driver mutations. ITH can be visualized by mapping mutations onto microscopic sections, where subclones are directly associated with phenotypes, especially the deeper areas with the more invasive cells that confer worst clinical outcomes. Instead of a stepwise hierarchy where subclones segregate by phenotype with later branching subclones in more invasive areas, multiple subclones share superficial and invasive phenotype and are jigsaw arrayed in vertical columns. Phylogeography shows that both early and late subclones extend from the surface to the invasive front, suggesting that founder cells start with phenotypic plasticity and essentially all the drivers necessary to rapidly grow into large invasive tumors.",
			"category": 2,
			"name": "Shibata Darryl,2021"
		},
		{
			"PMID": 32575418,
			"title": "Hot Spot TERT Promoter Mutations Are Rare in Sporadic Pancreatic Neuroendocrine Neoplasms and Associated with Telomere Length and Epigenetic Expression Patterns.",
			"journal": "Cancers",
			"authorList": [
				"Posch Alexandra",
				"Hofer-Zeni Sarah",
				"Klieser Eckhard",
				"Primavesi Florian",
				"Naderlinger Elisabeth",
				"Brandstetter Anita",
				"Filipits Martin",
				"Urbas Romana",
				"Swiercynski Stefan",
				"J\u00e4ger Tarkan",
				"Winkelmann Paul",
				"Kiesslich Tobias",
				"Lu Lingeng",
				"Neureiter Daniel",
				"St\u00e4ttner Stefan",
				"Holzmann Klaus"
			],
			"DOI": "10.3390/cancers12061625",
			"date": "2021-09-19",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer cells activate a telomere maintenance mechanism like telomerase in order to proliferate indefinitely. Telomerase can be reactivated by gain-of-function Telomerase Reverse Transcriptase (TERT) promoter mutations (TPMs) that occur in several cancer subtypes with high incidence and association with diagnosis, prognosis and epigenetics. However, such information about TPMs in sporadic pancreatic neuroendocrine neoplasms (pNENs) including tumor (pNET) and carcinoma (pNEC) is less well defined. We have studied two hot spot TPMs and telomere length (TL) in pNEN and compared the results with clinicopathological information and proliferation-associated miRNA/HDAC expression profiles. DNA was isolated from formalin-fixed paraffin-embedded (FFPE) tissue of 58 sporadic pNEN patients. T allele frequency of C250T and C228T TPM was analyzed by pyrosequencing, relative TL as telomeric content by qPCR. In total, five pNEN cases (9%) including four pNETs and one pNEC were identified with TPMs, four cases with exclusive C250T as predominant TPM and one case with both C250T and C228T. T allele frequencies of DNA isolated from adjacent high tumor cell content FFPE tissue varied considerably, which may indicate TPM tumor heterogeneity. Overall and disease-free survival was not associated with TPM versus wild-type pNEN cases. Binary category analyses indicated a marginally significant relationship between TPM status and longer telomeres (",
			"category": 2,
			"name": "Posch Alexandra,2021"
		},
		{
			"PMID": 32535731,
			"title": "The issues with tissues: the wide range of cell fate separation enables the evolution of multicellularity and cancer.",
			"journal": "Medical oncology (Northwood, London, England)",
			"authorList": [
				"Hammarlund Emma U",
				"Amend Sarah R",
				"Pienta Kenneth J"
			],
			"DOI": "10.1007/s12032-020-01387-5",
			"date": "2020-11-12",
			"PMC": "",
			"citation": "",
			"abstract": "Our understanding of the rises of animal and cancer multicellularity face the same conceptual hurdles: what makes the clade originate and what makes it diversify. Between the events of origination and diversification lies complex tissue organization that gave rise to novel functionality for organisms and, unfortunately, for malignant transformation in cells. Tissue specialization with distinctly separated cell fates allowed novel functionality at organism level, such as for vertebrate animals, but also involved trade-offs at the cellular level that are potentially disruptive. These trade-offs are under-appreciated and here we discuss how the wide separation of cell phenotypes may contribute to cancer evolution by (a) how factors can reverse differentiated cells into a window of phenotypic plasticity, (b) the reversal to phenotypic plasticity coupled with asexual reproduction occurs in a way that the host cannot adapt, and (c) the power of the transformation factor correlates to the power needed to reverse tissue specialization. The role of reversed cell fate separation for cancer evolution is strengthened by how some tissues and organisms maintain high cell proliferation and plasticity without developing tumours at a corresponding rate. This demonstrates a potential proliferation paradox that requires further explanation. These insights from the cancer field, which observes tissue evolution in real time and closer than any other field, allow inferences to be made on evolutionary events in animal history. If a sweet spot of phenotypic and reproductive versatility is key to transformation, factors stimulating cell fate separation may have promoted also animal diversification on Earth.",
			"category": 2,
			"name": "Hammarlund Emma U,2020"
		},
		{
			"PMID": 32475383,
			"title": "From genome sequencing to the discovery of potential biomarkers in liver disease.",
			"journal": "BMB reports",
			"authorList": [
				"Oh Sumin",
				"Jo Yeeun",
				"Jung Sungju",
				"Yoon Sumin",
				"Yoo Kyung Hyun"
			],
			"DOI": "",
			"date": "2021-02-08",
			"PMC": "",
			"citation": "",
			"abstract": "Chronic liver disease progresses through several stages, fatty liver, steatohepatitis, cirrhosis, and eventually, it leads to hepatocellular carcinoma (HCC) over a long period of time. Since a large proportion of patients with HCC are accompanied by cirrhosis, it is considered to be an important factor in the diagnosis of liver cancer. This is because cirrhosis leads to an irreversible harmful effect, but the early stages of chronic liver disease could be reversed to a healthy state. Therefore, the discovery of biomarkers that could identify the early stages of chronic liver disease is important to prevent serious liver damage. Biomarker discovery at liver cancer and cirrhosis has enhanced the development of sequencing technology. Next generation sequencing (NGS) is one of the representative technical innovations in the biological field in the recent decades and it is the most important thing to design for research on what type of sequencing methods are suitable and how to handle the analysis steps for data integration. In this review, we comprehensively summarized NGS techniques for identifying genome, transcriptome, DNA methylome and 3D/4D chromatin structure, and introduced framework of processing data set and integrating multi-omics data for uncovering biomarkers. [BMB Reports 2020; 53(6): 299-310].",
			"category": 2,
			"name": "Oh Sumin,2021"
		},
		{
			"PMID": 32426418,
			"title": "Computational disease progression modeling can provide insights into cancer evolution.",
			"journal": "Oncoscience",
			"authorList": [
				"Goodison Steve",
				"Sherman Mark E",
				"Sun Yijun"
			],
			"DOI": "10.18632/oncoscience.501",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Goodison Steve,2020"
		},
		{
			"PMID": 32350471,
			"title": "The mutational landscape of normal human endometrial epithelium.",
			"journal": "Nature",
			"authorList": [
				"Moore Luiza",
				"Leongamornlert Daniel",
				"Coorens Tim H H",
				"Sanders Mathijs A",
				"Ellis Peter",
				"Dentro Stefan C",
				"Dawson Kevin J",
				"Butler Tim",
				"Rahbari Raheleh",
				"Mitchell Thomas J",
				"Maura Francesco",
				"Nangalia Jyoti",
				"Tarpey Patrick S",
				"Brunner Simon F",
				"Lee-Six Henry",
				"Hooks Yvette",
				"Moody Sarah",
				"Mahbubani Krishnaa T",
				"Jimenez-Linan Mercedes",
				"Brosens Jan J",
				"Iacobuzio-Donahue Christine A",
				"Martincorena Inigo",
				"Saeb-Parsy Kourosh",
				"Campbell Peter J",
				"Stratton Michael R"
			],
			"DOI": "10.1038/s41586-020-2214-z",
			"date": "2020-10-23",
			"PMC": "",
			"citation": "",
			"abstract": "All normal somatic cells are thought to acquire mutations, but understanding of the rates, patterns, causes and consequences of somatic mutations in normal cells is limited. The uterine endometrium adopts multiple physiological states over a lifetime and is lined by a gland-forming epithelium",
			"category": 2,
			"name": "Moore Luiza,2020"
		},
		{
			"PMID": 32333084,
			"title": "Circulating tumor cells as Trojan Horse for understanding, preventing, and treating cancer: a critical appraisal.",
			"journal": "Cellular and molecular life sciences : CMLS",
			"authorList": [
				"Mentis Alexios-Fotios A",
				"Grivas Petros D",
				"Dardiotis Efthimios",
				"Romas Nicholas A",
				"Papavassiliou Athanasios G"
			],
			"DOI": "10.1007/s00018-020-03529-4",
			"date": "2020-09-08",
			"PMC": "",
			"citation": "",
			"abstract": "Circulating tumor cells (CTCs) are regarded as harbingers of metastases. Their ability to predict response to therapy, relapse, and resistance to treatment has proposed their value as putative diagnostic and prognostic indicators. CTCs represent one of the zeniths of cancer evolution in terms of cell survival; however, the triggers of CTC generation, the identification of potentially metastatic CTCs, and the mechanisms contributing to their heterogeneity and aggressiveness represent issues not yet fully deciphered. Thus, prior to enabling liquid biopsy applications to reach clinical prime time, understanding how the above mechanistic information can be applied to improve treatment decisions is a key challenge. Here, we provide our perspective on how CTCs can provide mechanistic insights into tumor pathogenesis, as well as on CTC clinical value. In doing so, we aim to (a) describe how CTCs disseminate from the primary tumor, and their link to epithelial-mesenchymal transition (EMT); (b) trace the route of CTCs through the circulation, focusing on tumor self-seeding and the possibility of tertiary metastasis; (c) describe possible mechanisms underlying the enhanced metastatic potential of CTCs; (d) discuss how CTC could provide further information on the tissue of origin, especially in cancer of unknown primary origin. We also provide a comprehensive review of meta-analyses assessing the prognostic significance of CTCs, to highlight the emerging role of CTCs in clinical oncology. We also explore how cell-free circulating tumor DNA (ctDNA) analysis, using a combination of genomic and phylogenetic analysis, can offer insights into CTC biology, including our understanding of CTC heterogeneity and tumor evolution. Last, we discuss emerging technologies, such as high-throughput quantitative imaging, radiogenomics, machine learning approaches, and the emerging breath biopsy. These technologies could compliment CTC and ctDNA analyses, and they collectively represent major future steps in cancer detection, monitoring, and management.",
			"category": 2,
			"name": "Mentis Alexios-Fotios A,2020"
		},
		{
			"PMID": 32286297,
			"title": "Re-definition of claudin-low as a breast cancer phenotype.",
			"journal": "Nature communications",
			"authorList": [
				"Fougner Christian",
				"Bergholtz Helga",
				"Norum Jens Henrik",
				"S\u00f8rlie Therese"
			],
			"DOI": "10.1038/s41467-020-15574-5",
			"date": "2020-07-24",
			"PMC": "",
			"citation": "",
			"abstract": "The claudin-low breast cancer subtype is defined by gene expression characteristics and encompasses a remarkably diverse range of breast tumors. Here, we investigate genomic, transcriptomic, and clinical features of claudin-low breast tumors. We show that claudin-low is not simply a subtype analogous to the intrinsic subtypes (basal-like, HER2-enriched, luminal A, luminal B and normal-like) as previously portrayed, but is a complex additional phenotype which may permeate breast tumors of various intrinsic subtypes. Claudin-low tumors are distinguished by low genomic instability, mutational burden and proliferation levels, and high levels of immune and stromal cell infiltration. In other aspects, claudin-low tumors reflect characteristics of their intrinsic subtype. Finally, we explore an alternative method for identifying claudin-low tumors and thereby uncover potential weaknesses in the established claudin-low classifier. In sum, these findings elucidate the heterogeneity in claudin-low breast tumors, and substantiate a re-definition of claudin-low as a cancer phenotype.",
			"category": 2,
			"name": "Fougner Christian,2020"
		},
		{
			"PMID": 32255426,
			"title": "A highly accurate platform for clone-specific mutation discovery enables the study of active mutational processes.",
			"journal": "eLife",
			"authorList": [
				"KaramiNejadRanjbar Mohammad",
				"Sharifzadeh Sahand",
				"Wietek Nina C",
				"Artibani Mara",
				"El-Sahhar Salma",
				"Sauka-Spengler Tatjana",
				"Yau Christopher",
				"Tresp Volker",
				"Ahmed Ahmed A"
			],
			"DOI": "10.7554/eLife.55207",
			"date": "2021-03-24",
			"PMC": "",
			"citation": "",
			"abstract": "Bulk whole genome sequencing (WGS) enables the analysis of tumor evolution but, because of depth limitations, can only identify old mutational events. The discovery of current mutational processes for predicting the tumor's evolutionary trajectory requires dense sequencing of individual clones or single cells. Such studies, however, are inherently problematic because of the discovery of excessive false positive (FP) mutations when sequencing picogram quantities of DNA. Data pooling to increase the confidence in the discovered mutations, moves the discovery back in the past to a common ancestor. Here we report a robust WGS and analysis pipeline (DigiPico/MutLX) that virtually eliminates all F results while retaining an excellent proportion of true positives. Using our method, we identified, for the first time, a hyper-mutation (kataegis) event in a group of \u223c30 cancer cells from a recurrent ovarian carcinoma. This was unidentifiable from the bulk WGS data. Overall, we propose DigiPico/MutLX method as a powerful framework for the identification of clone-specific variants at an unprecedented accuracy.",
			"category": 2,
			"name": "KaramiNejadRanjbar Mohammad,2021"
		},
		{
			"PMID": 32049048,
			"title": "Comparative Molecular Life History of Spontaneous Canine and Human Gliomas.",
			"journal": "Cancer cell",
			"authorList": [
				"Amin Samirkumar B",
				"Anderson Kevin J",
				"Boudreau C Elizabeth",
				"Martinez-Ledesma Emmanuel",
				"Kocakavuk Emre",
				"Johnson Kevin C",
				"Barthel Floris P",
				"Varn Frederick S",
				"Kassab Cynthia",
				"Ling Xiaoyang",
				"Kim Hoon",
				"Barter Mary",
				"Lau Ching C",
				"Ngan Chew Yee",
				"Chapman Margaret",
				"Koehler Jennifer W",
				"Long James P",
				"Miller Andrew D",
				"Miller C Ryan",
				"Porter Brian F",
				"Rissi Daniel R",
				"Mazcko Christina",
				"LeBlanc Amy K",
				"Dickinson Peter J",
				"Packer Rebecca A",
				"Taylor Amanda R",
				"Rossmeisl John H",
				"Woolard Kevin D",
				"Heimberger Amy B",
				"Levine Jonathan M",
				"Verhaak Roel G W"
			],
			"DOI": "10.1016/j.ccell.2020.01.004",
			"date": "2020-07-21",
			"PMC": "",
			"citation": "",
			"abstract": "Sporadic gliomas in companion dogs provide a window on the interaction between tumorigenic mechanisms and host environment. We compared the molecular profiles of canine gliomas with those of human pediatric and adult gliomas to characterize evolutionarily conserved mammalian mutational processes in gliomagenesis. Employing whole-genome, exome, transcriptome, and methylation sequencing of 83 canine gliomas, we found alterations shared between canine and human gliomas such as the receptor tyrosine kinases, TP53 and cell-cycle pathways, and IDH1 R132. Canine gliomas showed high similarity with human pediatric gliomas per robust aneuploidy, mutational rates, relative timing of mutations, and DNA-methylation patterns. Our cross-species comparative genomic analysis provides unique insights into glioma etiology and the chronology of glioma-causing somatic alterations.",
			"category": 2,
			"name": "Amin Samirkumar B,2020"
		},
		{
			"PMID": 32025007,
			"title": "Pan-cancer analysis of whole genomes.",
			"journal": "Nature",
			"authorList": [
				"ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium"
			],
			"DOI": "10.1038/s41586-020-1969-6",
			"date": "2020-04-17",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale",
			"category": 2,
			"name": "ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium,2020"
		},
		{
			"PMID": 32024854,
			"title": "Pathway and network analysis of more than 2500 whole cancer genomes.",
			"journal": "Nature communications",
			"authorList": [
				"Reyna Matthew A",
				"Haan David",
				"Paczkowska Marta",
				"Verbeke Lieven P C",
				"Vazquez Miguel",
				"Kahraman Abdullah",
				"Pulido-Tamayo Sergio",
				"Barenboim Jonathan",
				"Wadi Lina",
				"Dhingra Priyanka",
				"Shrestha Raunak",
				"Getz Gad",
				"Lawrence Michael S",
				"Pedersen Jakob Skou",
				"Rubin Mark A",
				"Wheeler David A",
				"Brunak S\u00f8ren",
				"Izarzugaza Jose M G",
				"Khurana Ekta",
				"Marchal Kathleen",
				"von Mering Christian",
				"Sahinalp S Cenk",
				"Valencia Alfonso",
				"PCAWG Drivers and Functional Interpretation Working Group",
				"Reimand J\u00fcri",
				"Stuart Joshua M",
				"Raphael Benjamin J",
				"PCAWG Consortium"
			],
			"DOI": "10.1038/s41467-020-14367-0",
			"date": "2020-05-12",
			"PMC": "",
			"citation": "",
			"abstract": "The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.",
			"category": 2,
			"name": "Reyna Matthew A,2020"
		},
		{
			"PMID": 32024845,
			"title": "Inferring structural variant cancer cell fraction.",
			"journal": "Nature communications",
			"authorList": [
				"Cmero Marek",
				"Yuan Ke",
				"Ong Cheng Soon",
				"Schr\u00f6der Jan",
				"PCAWG Evolution and Heterogeneity Working Group",
				"Corcoran Niall M",
				"Papenfuss Tony",
				"Hovens Christopher M",
				"Markowetz Florian",
				"Macintyre Geoff",
				"PCAWG Consortium"
			],
			"DOI": "10.1038/s41467-020-14351-8",
			"date": "2020-05-12",
			"PMC": "",
			"citation": "",
			"abstract": "We present SVclone, a computational method for inferring the cancer cell fraction of structural variant (SV) breakpoints from whole-genome sequencing data. SVclone accurately determines the variant allele frequencies of both SV breakends, then simultaneously estimates the cancer cell fraction and SV copy number. We assess performance using in silico mixtures of real samples, at known proportions, created from two clonal metastases from the same patient. We find that SVclone's performance is comparable to single-nucleotide variant-based methods, despite having an order of magnitude fewer data points. As part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) consortium, which aggregated whole-genome sequencing data from 2658 cancers across 38 tumour types, we use SVclone to reveal a subset of liver, ovarian and pancreatic cancers with subclonally enriched copy-number neutral rearrangements that show decreased overall survival. SVclone enables improved characterisation of SV intra-tumour heterogeneity.",
			"category": 2,
			"name": "Cmero Marek,2020"
		},
		{
			"PMID": 32024834,
			"title": "Reconstructing evolutionary trajectories of mutation signature activities in cancer using TrackSig.",
			"journal": "Nature communications",
			"authorList": [
				"Rubanova Yulia",
				"Shi Ruian",
				"Harrigan Caitlin F",
				"Li Roujia",
				"Wintersinger Jeff",
				"Sahin Nil",
				"Deshwar Amit G",
				"PCAWG Evolution and Heterogeneity Working Group",
				"Morris Quaid D",
				"PCAWG Consortium"
			],
			"DOI": "10.1038/s41467-020-14352-7",
			"date": "2020-05-12",
			"PMC": "",
			"citation": "",
			"abstract": "The type and genomic context of cancer mutations depend on their causes. These causes have been characterized using signatures that represent mutation types that co-occur in the same tumours. However, it remains unclear how mutation processes change during cancer evolution due to the lack of reliable methods to reconstruct evolutionary trajectories of mutational signature activity. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data from 2658 cancers across 38 tumour types, we present TrackSig, a new method that reconstructs these trajectories using optimal, joint segmentation and deconvolution of mutation type and allele frequencies from a single tumour sample. In simulations, we find TrackSig has a 3-5% activity reconstruction error, and 12% false detection rate. It outperforms an aggressive baseline in situations with branching evolution, CNA gain, and neutral mutations. Applied to data from 2658 tumours and 38 cancer types, TrackSig permits pan-cancer insight into evolutionary changes in mutational processes.",
			"category": 2,
			"name": "Rubanova Yulia,2020"
		},
		{
			"PMID": 32024819,
			"title": "Divergent mutational processes distinguish hypoxic and normoxic tumours.",
			"journal": "Nature communications",
			"authorList": [
				"Bhandari Vinayak",
				"Li Constance H",
				"Bristow Robert G",
				"Boutros Paul C",
				"PCAWG Consortium"
			],
			"DOI": "10.1038/s41467-019-14052-x",
			"date": "2020-05-12",
			"PMC": "",
			"citation": "",
			"abstract": "Many primary tumours have low levels of molecular oxygen (hypoxia), and hypoxic tumours respond poorly to therapy. Pan-cancer molecular hallmarks of tumour hypoxia remain poorly understood, with limited comprehension of its associations with specific mutational processes, non-coding driver genes and evolutionary features. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we quantify hypoxia in 1188 tumours spanning 27 cancer types. Elevated hypoxia associates with increased mutational load across cancer types, irrespective of underlying mutational class. The proportion of mutations attributed to several mutational signatures of unknown aetiology directly associates with the level of hypoxia, suggesting underlying mutational processes for these signatures. At the gene level, driver mutations in TP53, MYC and PTEN are enriched in hypoxic tumours, and mutations in PTEN interact with hypoxia to direct tumour evolutionary trajectories. Overall, hypoxia plays a critical role in shaping the genomic and evolutionary landscapes of cancer.",
			"category": 2,
			"name": "Bhandari Vinayak,2020"
		},
		{
			"PMID": 31510674,
			"title": "Collaborative intra-tumor heterogeneity detection.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Khakabimamaghani Sahand",
				"Malikic Salem",
				"Tang Jeffrey",
				"Ding Dujian",
				"Morin Ryan",
				"Chindelevitch Leonid",
				"Ester Martin"
			],
			"DOI": "10.1093/bioinformatics/btz355",
			"date": "2020-06-12",
			"PMC": "",
			"citation": "",
			"abstract": "Despite the remarkable advances in sequencing and computational techniques, noise in the data and complexity of the underlying biological mechanisms render deconvolution of the phylogenetic relationships between cancer mutations difficult. Besides that, the majority of the existing datasets consist of bulk sequencing data of single tumor sample of an individual. Accurate inference of the phylogenetic order of mutations is particularly challenging in these cases and the existing methods are faced with several theoretical limitations. To overcome these limitations, new methods are required for integrating and harnessing the full potential of the existing data.",
			"category": 2,
			"name": "Khakabimamaghani Sahand,2020"
		},
		{
			"PMID": 31374965,
			"title": "Perspective: Potential Impact and Therapeutic Implications of Oncogenic PI3K Activation on Chromosomal Instability.",
			"journal": "Biomolecules",
			"authorList": [
				"Vanhaesebroeck Bart",
				"Bilanges Benoit",
				"Madsen Ralitsa R",
				"Dale Katie L",
				"Lau Evelyn",
				"Vladimirou Elina"
			],
			"DOI": "10.3390/biom9080331",
			"date": "2020-06-02",
			"PMC": "",
			"citation": "",
			"abstract": "Genetic activation of the class I PI3K pathway is very common in cancer. This mostly results from oncogenic mutations in PIK3CA, the gene encoding the ubiquitously expressed PI3K\u03b1 catalytic subunit, or from inactivation of the PTEN tumour suppressor, a lipid phosphatase that opposes class I PI3K signalling. The clinical impact of PI3K inhibitors in solid tumours, aimed at dampening cancer-cell-intrinsic PI3K activity, has thus far been limited. Challenges include poor drug tolerance, incomplete pathway inhibition and pre-existing or inhibitor-induced resistance. The principle of pharmacologically targeting cancer-cell-intrinsic PI3K activity also assumes that all cancer-promoting effects of PI3K activation are reversible, which might not be the case. Emerging evidence suggests that genetic PI3K pathway activation can induce and/or allow cells to tolerate chromosomal instability, which-even if occurring in a low fraction of the cell population-might help to facilitate and/or drive tumour evolution. While it is clear that such genomic events cannot be reverted pharmacologically, a role for PI3K in the regulation of chromosomal instability could be exploited by using PI3K pathway inhibitors to prevent those genomic events from happening and/or reduce the pace at which they are occurring, thereby dampening cancer development or progression. Such an impact might be most effective in tumours with clonal PI3K activation and achievable at lower drug doses than the maximum-tolerated doses of PI3K inhibitors currently used in the clinic.",
			"category": 2,
			"name": "Vanhaesebroeck Bart,2020"
		},
		{
			"PMID": 30889380,
			"title": "Undifferentiated Sarcomas Develop through Distinct Evolutionary Pathways.",
			"journal": "Cancer cell",
			"authorList": [
				"Steele Christopher D",
				"Tarabichi Maxime",
				"Oukrif Dahmane",
				"Webster Amy P",
				"Ye Hongtao",
				"Fittall Matthew",
				"Lombard Patrick",
				"Martincorena I\u00f1igo",
				"Tarpey Patrick S",
				"Collord Grace",
				"Haase Kerstin",
				"Strauss Sandra J",
				"Berisha Fitim",
				"Vaikkinen Heli",
				"Dhami Pawan",
				"Jansen Marnix",
				"Behjati Sam",
				"Amary M Fernanda",
				"Tirabosco Roberto",
				"Feber Andrew",
				"Campbell Peter J",
				"Alexandrov Ludmil B",
				"Van Loo Peter",
				"Flanagan Adrienne M",
				"Pillay Nischalan"
			],
			"DOI": "10.1016/j.ccell.2019.02.002",
			"date": "2019-12-23",
			"PMC": "",
			"citation": "",
			"abstract": "Undifferentiated sarcomas (USARCs) of adults are diverse, rare, and aggressive soft tissue cancers. Recent sequencing efforts have confirmed that USARCs exhibit one of the highest burdens of structural aberrations across human cancer. Here, we sought to unravel the molecular basis of the structural complexity in USARCs by integrating DNA sequencing, ploidy analysis, gene expression, and methylation profiling. We identified whole genome duplication as a prevalent and pernicious force in USARC tumorigenesis. Using mathematical deconvolution strategies to unravel the complex copy-number profiles and mutational timing models we infer distinct evolutionary pathways of these rare cancers. In addition, 15% of tumors exhibited raised mutational burdens that correlated with gene expression signatures of immune infiltration, and good prognosis.",
			"category": 2,
			"name": "Steele Christopher D,2019"
		},
		{
			"PMID": 39039280,
			"title": "Mitochondrial DNA mosaicism in normal human somatic cells.",
			"journal": "Nature genetics",
			"authorList": [
				"An Jisong",
				"Nam Chang Hyun",
				"Kim Ryul",
				"Lee Yunah",
				"Won Hyein",
				"Park Seongyeol",
				"Lee Won Hee",
				"Park Hansol",
				"Yoon Christopher J",
				"An Yohan",
				"Kim Jie-Hyun",
				"Jun Jong Kwan",
				"Bae Jeong Mo",
				"Shin Eui-Cheol",
				"Kim Bun",
				"Cha Yong Jun",
				"Kwon Hyun Woo",
				"Oh Ji Won",
				"Park Jee Yoon",
				"Kim Min Jung",
				"Ju Young Seok"
			],
			"DOI": "10.1038/s41588-024-01838-z",
			"date": "2024-07-22",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic cells accumulate genomic alterations with age; however, our understanding of mitochondrial DNA (mtDNA) mosaicism remains limited. Here we investigated the genomes of 2,096 clones derived from three cell types across 31 donors, identifying 6,451 mtDNA variants with heteroplasmy levels of \u22730.3%. While the majority of these variants were unique to individual clones, suggesting stochastic acquisition with age, 409 variants (6%) were shared across multiple embryonic lineages, indicating their origin from heteroplasmy in fertilized eggs. The mutational spectrum exhibited replication-strand bias, implicating mtDNA replication as a major mutational process. We evaluated the mtDNA mutation rate (5.0\u2009\u00d7\u200910",
			"category": 2,
			"name": "An Jisong,2024"
		},
		{
			"PMID": 38817681,
			"title": "SAP30, an oncogenic driver of progression, poor survival, and drug resistance in neuroblastoma.",
			"journal": "Molecular therapy. Nucleic acids",
			"authorList": [
				"Prathipati Philip",
				"Pathania Anup S",
				"Chaturvedi Nagendra K",
				"Gupta Subash C",
				"Byrareddy Siddappa N",
				"Coulter Don W",
				"Challagundla Kishore B"
			],
			"DOI": "10.1016/j.omtn.2022.03.014",
			"date": "2024-06-01",
			"PMC": "",
			"citation": "",
			"abstract": "Neuroblastoma is the most devastating extracranial solid malignancy in children. Despite an intense treatment regimen, the prognosis for high-risk neuroblastoma patients remains poor, with less than 40% survival. So far, ",
			"category": 2,
			"name": "Prathipati Philip,2024"
		},
		{
			"PMID": 38790221,
			"title": "The Association between Mutational Signatures and Clinical Outcomes among Patients with Early-Onset Breast Cancer.",
			"journal": "Genes",
			"authorList": [
				"Basmadjian Robert B",
				"O'Sullivan Dylan E",
				"Quan May Lynn",
				"Lupichuk Sasha",
				"Xu Yuan",
				"Cheung Winson Y",
				"Brenner Darren R"
			],
			"DOI": "10.3390/genes15050592",
			"date": "2024-05-25",
			"PMC": "",
			"citation": "",
			"abstract": "Early-onset breast cancer (EoBC), defined by a diagnosis <40 years of age, is associated with poor prognosis. This study investigated the mutational landscape of non-metastatic EoBC and the prognostic relevance of mutational signatures using 100 tumour samples from Alberta, Canada. The MutationalPatterns package in R/Bioconductor was used to extract de novo single-base substitution (SBS) and insertion-deletion (indel) mutational signatures and to fit COSMIC SBS and indel signatures. We assessed associations between these signatures and clinical characteristics of disease, in addition to recurrence-free (RFS) and overall survival (OS). Five SBS and two indel signatures were extracted. The SBS13-like signature had higher relative contributions in the HER2-enriched subtype. Patients with higher than median contribution tended to have better RFS after adjustment for other prognostic factors (HR = 0.29; 95% CI: 0.08-1.06). An unsupervised clustering algorithm based on absolute contribution revealed three clusters of fitted COSMIC SBS signatures, but cluster membership was not associated with clinical variables or survival outcomes. The results of this exploratory study reveal various SBS and indel signatures may be associated with clinical features of disease and prognosis. Future studies with larger samples are required to better understand the mechanistic underpinnings of disease progression and treatment response in EoBC.",
			"category": 2,
			"name": "Basmadjian Robert B,2024"
		},
		{
			"PMID": 38787171,
			"title": "Clinical Use of Molecular Biomarkers in Canine and Feline Oncology: Current and Future.",
			"journal": "Veterinary sciences",
			"authorList": [
				"Aupperle-Lellbach Heike",
				"Kehl Alexandra",
				"de Brot Simone",
				"van der Weyden Louise"
			],
			"DOI": "10.3390/vetsci11050199",
			"date": "2024-05-26",
			"PMC": "",
			"citation": "",
			"abstract": "Molecular biomarkers are central to personalised medicine for human cancer patients. It is gaining traction as part of standard veterinary clinical practice for dogs and cats with cancer. Molecular biomarkers can be somatic or germline genomic alterations and can be ascertained from tissues or body fluids using various techniques. This review discusses how these genomic alterations can be determined and the findings used in clinical settings as diagnostic, prognostic, predictive, and screening biomarkers. We showcase the somatic and germline genomic alterations currently available to date for testing dogs and cats in a clinical setting, discussing their utility in each biomarker class. We also look at some emerging molecular biomarkers that are promising for clinical use. Finally, we discuss the hurdles that need to be overcome in going 'bench to bedside', i.e., the translation from discovery of genomic alterations to adoption by veterinary clinicians. As we understand more of the genomics underlying canine and feline tumours, molecular biomarkers will undoubtedly become a mainstay in delivering precision veterinary care to dogs and cats with cancer.",
			"category": 2,
			"name": "Aupperle-Lellbach Heike,2024"
		},
		{
			"PMID": 38773187,
			"title": "The molecular evolution of cancer associated genes in mammals.",
			"journal": "Scientific reports",
			"authorList": [
				"MacDonald Nick",
				"Raven Nynke",
				"Diep Wendy",
				"Evans Samantha",
				"Pannipitiya Senuri",
				"Bramwell Georgina",
				"Vanbeek Caitlin",
				"Thomas Fr\u00e9d\u00e9ric",
				"Russell Tracey",
				"Dujon Antoine M",
				"Telonis-Scott Marina",
				"Ujvari Beata"
			],
			"DOI": "10.1038/s41598-024-62425-0",
			"date": "2024-05-21",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a disease that many multicellular organisms have faced for millions of years, and species have evolved various tumour suppression mechanisms to control oncogenesis. Although cancer occurs across the tree of life, cancer related mortality risks vary across mammalian orders, with Carnivorans particularly affected. Evolutionary theory predicts different selection pressures on genes associated with cancer progression and suppression, including oncogenes, tumour suppressor genes and immune genes. Therefore, we investigated the evolutionary history of cancer associated gene sequences across 384 mammalian taxa, to detect signatures of selection across categories of oncogenes (GRB2, FGL2 and CDC42), tumour suppressors (LITAF, Casp8 and BRCA2) and immune genes (IL2, CD274 and B2M). This approach allowed us to conduct a fine scale analysis of gene wide and site-specific signatures of selection across mammalian lineages under the lens of cancer susceptibility. Phylogenetic analyses revealed that for most species the evolution of cancer associated genes follows the species' evolution. The gene wide selection analyses revealed oncogenes being the most conserved, tumour suppressor and immune genes having similar amounts of episodic diversifying selection. Despite BRCA2's status as a key caretaker gene, episodic diversifying selection was detected across mammals. The site-specific selection analyses revealed that the two apoptosis associated domains of the Casp8 gene of bats (Chiroptera) are under opposing forces of selection (positive and negative respectively), highlighting the importance of site-specific selection analyses to understand the evolution of highly complex gene families. Our results highlighted the need to critically assess different types of selection pressure on cancer associated genes when investigating evolutionary adaptations to cancer across the tree of life. This study provides an extensive assessment of cancer associated genes in mammals with highly representative, and substantially large sample size for a comparative genomic analysis in the field and identifies various avenues for future research into the mechanisms of cancer resistance and susceptibility in mammals.",
			"category": 2,
			"name": "MacDonald Nick,2024"
		},
		{
			"PMID": 38753153,
			"title": "Deciphering fatty acid biosynthesis-driven molecular subtypes in pancreatic ductal adenocarcinoma with prognostic insights.",
			"journal": "Cellular oncology (Dordrecht, Netherlands)",
			"authorList": [
				"Xu Junyi",
				"Liu Mingzhu",
				"Xue Jing",
				"Lu Ping"
			],
			"DOI": "10.1007/s13402-024-00953-7",
			"date": "2024-06-25",
			"PMC": "",
			"citation": "",
			"abstract": "Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge due to its high heterogeneity and aggressiveness. Recognizing the urgency to delineate molecular subtypes, our study focused on the emerging field of lipid metabolism remodeling in PDAC, particularly exploring the prognostic potential and molecular classification associated with fatty acid biosynthesis.",
			"category": 2,
			"name": "Xu Junyi,2024"
		},
		{
			"PMID": 38750338,
			"title": "Targeting neutrophil elastase is a promising direction for future cancer treatment.",
			"journal": "Discover oncology",
			"authorList": [
				"Jia Wangqiang",
				"Mao Yudong",
				"Luo Qianwen",
				"Wu Jiang",
				"Guan Quanlin"
			],
			"DOI": "10.1007/s12672-024-01010-3",
			"date": "2024-05-18",
			"PMC": "",
			"citation": "",
			"abstract": "Neutrophil elastase (NE) is a proteolytic enzyme released extracellular during the formation of neutrophil extracellular traps (NETs) through degranulation. In addition to participating in the body's inflammatory response, NE also plays an important role in cancer. It can promote tumor proliferation, migration, and invasion, induce epithelial-mesenchymal transition (EMT), and change the tumor microenvironment (TME) to promote tumor progression. Concurrently, NE promotes systemic treatment resistance by inducing EMT. However, it can also selectively kill cancer cells and attenuate tumor development. Sivelestat is a specific NE inhibitor that can be used in the perioperative period of esophageal cancer patients to reduce the incidence of postoperative complications after esophagectomy. In addition, the combination of sivelestat and trastuzumab can enhance the efficacy of human epidermal growth factor receptor 2(HER 2) positive breast cancer patients. Meanwhile, targeting the human antibody domains and fragments of NE is also a new way to treat cancer and inflammation-related diseases. This review provides valuable insights into the role of NE in cancer treatment. Additionally, we discuss the challenges associated with the clinical application of sivelestat. By shedding light on the promising potential of NE, this review contributes to the advancement of cancer treatment strategies.",
			"category": 2,
			"name": "Jia Wangqiang,2024"
		},
		{
			"PMID": 38737683,
			"title": "Comprehensive pan-cancer analysis: essential role of ABCB family genes in cancer.",
			"journal": "Translational cancer research",
			"authorList": [
				"Xiao Hui-Ni",
				"Zhao Zi-Yue",
				"Li Jin-Ping",
				"Li Ao-Yu"
			],
			"DOI": "10.21037/tcr-23-2050",
			"date": "2024-05-14",
			"PMC": "",
			"citation": "",
			"abstract": "The adenosine triphosphate-binding-cassette (ABC) transporter orchestrates the transmembrane transport of diverse substrates with the aid of ATP as an energy source. ABC transporter constitutes a widespread superfamily of transporters prominently present on the cellular membrane of organisms. Advancements in understanding have unveiled additional roles beyond mere intracellular or extracellular transport functions for the ABC protein family, encompassing involvement in DNA repair, protein translation, and gene expression regulation. Yet its role in tumors is still unknown.",
			"category": 2,
			"name": "Xiao Hui-Ni,2024"
		},
		{
			"PMID": 38731892,
			"title": "Tumor Antigens beyond the Human Exome.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Emilius Lisabeth",
				"Bremm Franziska",
				"Binder Amanda Katharina",
				"Schaft Niels",
				"D\u00f6rrie Jan"
			],
			"DOI": "10.3390/ijms25094673",
			"date": "2024-05-11",
			"PMC": "",
			"citation": "",
			"abstract": "With the advent of immunotherapeutics, a new era in the combat against cancer has begun. Particularly promising are neo-epitope-targeted therapies as the expression of neo-antigens is tumor-specific. In turn, this allows the selective targeting and killing of cancer cells whilst healthy cells remain largely unaffected. So far, many advances have been made in the development of treatment options which are tailored to the individual neo-epitope repertoire. The next big step is the achievement of efficacious \"off-the-shelf\" immunotherapies. For this, shared neo-epitopes propose an optimal target. Given the tremendous potential, a thorough understanding of the underlying mechanisms which lead to the formation of neo-antigens is of fundamental importance. Here, we review the various processes which result in the formation of neo-epitopes. Broadly, the origin of neo-epitopes can be categorized into three groups: canonical, noncanonical, and viral neo-epitopes. For the canonical neo-antigens that arise in direct consequence of somatic mutations, we summarize past and recent findings. Beyond that, our main focus is put on the discussion of noncanonical and viral neo-epitopes as we believe that targeting those provides an encouraging perspective to shape the future of cancer immunotherapeutics.",
			"category": 2,
			"name": "Emilius Lisabeth,2024"
		},
		{
			"PMID": 38726194,
			"title": "The role of ",
			"journal": "Heliyon",
			"authorList": [
				"Wu Guang-Hao",
				"He Chao",
				"Che Gang",
				"Zhou Zheng",
				"Chen Bi-Ying",
				"Wu Hai-Ming",
				"Chen Jian-Feng",
				"Zhu Wei-Pu",
				"Yang Yan",
				"Zhou Zhan",
				"Teng Li-Song",
				"Wang Hai-Yong"
			],
			"DOI": "10.1016/j.heliyon.2024.e30505",
			"date": "2024-05-11",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "Wu Guang-Hao,2024"
		},
		{
			"PMID": 38674331,
			"title": "Comprehensive Analysis of Clinically Relevant Copy Number Alterations (CNAs) Using a 523-Gene Next-Generation Sequencing Panel and NxClinical Software in Solid Tumors.",
			"journal": "Genes",
			"authorList": [
				"Gupta Vivek",
				"Vashisht Vishakha",
				"Vashisht Ashutosh",
				"Mondal Ashis K",
				"Alptekin Ahmet",
				"Singh Harmanpreet",
				"Kolhe Ravindra"
			],
			"DOI": "10.3390/genes15040396",
			"date": "2024-04-27",
			"PMC": "",
			"citation": "",
			"abstract": "Copy number alterations (CNAs) are significant in tumor initiation and progression. Identifying these aberrations is crucial for targeted therapies and personalized cancer diagnostics. Next-generation sequencing (NGS) methods present advantages in scalability and cost-effectiveness, surpassing limitations associated with reference assemblies and probe capacities in traditional laboratory approaches. This retrospective study evaluated CNAs in 50 FFPE tumor samples (breast cancer, ovarian carcinoma, pancreatic cancer, melanoma, and prostate carcinoma) using Illumina's TruSight Oncology 500 (TSO500) and the Affymetrix Oncoscan Molecular Inversion Probe (OS-MIP) (ThermoFisher Scientific, Waltham, MA, USA). NGS analysis with the NxClinical 6.2 software demonstrated a high sensitivity and specificity (100%) for CNA detection, with a complete concordance rate as compared to the OS-MIP. All 54 known CNAs were identified by NGS, with gains being the most prevalent (63%). Notable CNAs were observed in ",
			"category": 2,
			"name": "Gupta Vivek,2024"
		},
		{
			"PMID": 38670159,
			"title": "CoT: a transformer-based method for inferring tumor clonal copy number substructure from scDNA-seq data.",
			"journal": "Briefings in bioinformatics",
			"authorList": [
				"Liu Furui",
				"Shi Fangyuan",
				"Du Fang",
				"Cao Xiangmei",
				"Yu Zhenhua"
			],
			"DOI": "10.1093/bib/bbae187",
			"date": "2024-04-26",
			"PMC": "",
			"citation": "",
			"abstract": "Single-cell DNA sequencing (scDNA-seq) has been an effective means to unscramble intra-tumor heterogeneity, while joint inference of tumor clones and their respective copy number profiles remains a challenging task due to the noisy nature of scDNA-seq data. We introduce a new bioinformatics method called CoT for deciphering clonal copy number substructure. The backbone of CoT is a Copy number Transformer autoencoder that leverages multi-head attention mechanism to explore correlations between different genomic regions, and thus capture global features to create latent embeddings for the cells. CoT makes it convenient to first infer cell subpopulations based on the learned embeddings, and then estimate single-cell copy numbers through joint analysis of read counts data for the cells belonging to the same cluster. This exploitation of clonal substructure information in copy number analysis helps to alleviate the effect of read counts non-uniformity, and yield robust estimations of the tumor copy numbers. Performance evaluation on synthetic and real datasets showcases that CoT outperforms the state of the arts, and is highly useful for deciphering clonal copy number substructure.",
			"category": 2,
			"name": "Liu Furui,2024"
		},
		{
			"PMID": 38639184,
			"title": "Cetuximab chemotherapy resistance: Insight into the homeostatic evolution of head and neck cancer (Review).",
			"journal": "Oncology reports",
			"authorList": [
				"Diniz Carlos Henrique De Paula",
				"Henrique Tiago",
				"Stefanini Ana Carolina B",
				"De Castro Tialfi Bergamin",
				"Tajara Eloiza H"
			],
			"DOI": "10.3892/or.2024.8739",
			"date": "2024-04-22",
			"PMC": "",
			"citation": "",
			"abstract": "The complex evolution of genetic alterations in cancer that occurs ",
			"category": 2,
			"name": "Diniz Carlos Henrique De Paula,2024"
		},
		{
			"PMID": 38622399,
			"title": "Fluid-Dynamic Culture of Tumour and Immune Cells for More Predictive Infiltration Studies and Immunotherapy Drug Screening.",
			"journal": "Methods in molecular biology (Clifton, N.J.)",
			"authorList": [
				"Palam\u00e0 Maria Elisabetta Federica",
				"Aiello Maurizio",
				"Scaglione Silvia"
			],
			"DOI": "10.1007/978-1-0716-3754-8_11",
			"date": "2024-04-17",
			"PMC": "",
			"citation": "",
			"abstract": "Immunotherapies represent one of the current most promising challenges in cancer treatment. They are based on the boost of natural immune responses, aimed at cancer eradication. However, the success of immunotherapeutic approaches strictly depends on the interaction between immune cells and cancer cells. Preclinical drug tests currently available are poor in fully predicting the actual safety and efficacy of immunotherapeutic treatments under development. Indeed, conventional 2D cell culture underrepresents the complexity of the tumour microenvironment, while in vivo animal models lack in mimicking the human immune cell responses. In this context, predictability, reliability, and complete immune compatibility still represent challenges to overcome. For this aim, novel 3D, fully humanized in vitro cancer tissue models have been recently optimized by adopting emerging technologies, such as organ-on-chips (OOC) and 3D cancer cell-laden hydrogels. In particular, a novel multi-in vitro organ (MIVO) OOC platform has been recently adopted to culture 3D clinically relevant size cancer tissues under proper physiological culture conditions to investigate anti-cancer treatments and immune-tumour cell crosstalk.The proposed immune-tumour OOC-based model offers a potential tool for accurately modelling human immune-related diseases and effectively assessing immunotherapy efficacy, finally offering promising experimental approaches for personalized medicine.",
			"category": 2,
			"name": "Palam\u00e0 Maria Elisabetta Federica,2024"
		},
		{
			"PMID": 38610953,
			"title": "The Application of Long-Read Sequencing to Cancer.",
			"journal": "Cancers",
			"authorList": [
				"Ermini Luca",
				"Driguez Patrick"
			],
			"DOI": "10.3390/cancers16071275",
			"date": "2024-04-25",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a multifaceted disease arising from numerous genomic aberrations that have been identified as a result of advancements in sequencing technologies. While next-generation sequencing (NGS), which uses short reads, has transformed cancer research and diagnostics, it is limited by read length. Third-generation sequencing (TGS), led by the Pacific Biosciences and Oxford Nanopore Technologies platforms, employs long-read sequences, which have marked a paradigm shift in cancer research. Cancer genomes often harbour complex events, and TGS, with its ability to span large genomic regions, has facilitated their characterisation, providing a better understanding of how complex rearrangements affect cancer initiation and progression. TGS has also characterised the entire transcriptome of various cancers, revealing cancer-associated isoforms that could serve as biomarkers or therapeutic targets. Furthermore, TGS has advanced cancer research by improving genome assemblies, detecting complex variants, and providing a more complete picture of transcriptomes and epigenomes. This review focuses on TGS and its growing role in cancer research. We investigate its advantages and limitations, providing a rigorous scientific analysis of its use in detecting previously hidden aberrations missed by NGS. This promising technology holds immense potential for both research and clinical applications, with far-reaching implications for cancer diagnosis and treatment.",
			"category": 2,
			"name": "Ermini Luca,2024"
		},
		{
			"PMID": 38600547,
			"title": "Lack of shared neoantigens in prevalent mutations in cancer.",
			"journal": "Journal of translational medicine",
			"authorList": [
				"Ragone Concetta",
				"Cavalluzzo Beatrice",
				"Mauriello Angela",
				"Tagliamonte Maria",
				"Buonaguro Luigi"
			],
			"DOI": "10.1186/s12967-024-05110-0",
			"date": "2024-04-12",
			"PMC": "",
			"citation": "",
			"abstract": "Tumors are mostly characterized by genetic instability, as result of mutations in surveillance mechanisms, such as DNA damage checkpoint, DNA repair machinery and mitotic checkpoint. Defect in one or more of these mechanisms causes additive accumulation of mutations. Some of these mutations are drivers of transformation and are positively selected during the evolution of the cancer, giving a growth advantage on the cancer cells. If such mutations would result in mutated neoantigens, these could be actionable targets for cancer vaccines and/or adoptive cell therapies. However, the results of the present analysis show, for the first time, that the most prevalent mutations identified in human cancers do not express mutated neoantigens. The hypothesis is that this is the result of the selection operated by the immune system in the very early stages of tumor development. At that stage, the tumor cells characterized by mutations giving rise to highly antigenic non-self-mutated neoantigens would be efficiently targeted and eliminated. Consequently, the outgrowing tumor cells cannot be controlled by the immune system, with an ultimate growth advantage to form large tumors embedded in an immunosuppressive tumor microenvironment (TME). The outcome of such a negative selection operated by the immune system is that the development of off-the-shelf vaccines, based on shared mutated neoantigens, does not seem to be at hand. This finding represents the first demonstration of the key role of the immune system on shaping the tumor antigen presentation and the implication in the development of antitumor immunological strategies.",
			"category": 2,
			"name": "Ragone Concetta,2024"
		},
		{
			"PMID": 38589653,
			"title": "Towards accurate indel calling for oncopanel sequencing through an international pipeline competition at precisionFDA.",
			"journal": "Scientific reports",
			"authorList": [
				"Gong Binsheng",
				"Lababidi Samir",
				"Kusko Rebecca",
				"Bouri Khaled",
				"Prezek Sarah",
				"Thovarai Vishal",
				"Prasanna Anish",
				"Maier Ezekiel J",
				"Golkaram Mahdi",
				"Sun Xingqiang",
				"Kyriakidis Konstantinos",
				"Kitajima Jo\u00e3o Paulo",
				"Ebrahim Sahraeian Sayed Mohammad",
				"Guo Yunfei",
				"Johanson Elaine",
				"Jones Wendell",
				"Tong Weida",
				"Xu Joshua"
			],
			"DOI": "10.1038/s41598-024-58573-y",
			"date": "2024-04-10",
			"PMC": "",
			"citation": "",
			"abstract": "Accurately calling indels with next-generation sequencing (NGS) data is critical for clinical application. The precisionFDA team collaborated with the U.S. Food and Drug Administration's (FDA's) National Center for Toxicological Research (NCTR) and successfully completed the NCTR Indel Calling from Oncopanel Sequencing Data Challenge, to evaluate the performance of indel calling pipelines. Top performers were selected based on precision, recall, and F1-score. The performance of many other pipelines was close to the top performers, which produced a top cluster of performers. The performance was significantly higher in high confidence regions and coding regions, and significantly lower in low complexity regions. Oncopanel capture and other issues may have occurred that affected the recall rate. Indels with higher variant allele frequency (VAF) may generally be called with higher confidence. Many of the indel calling pipelines had good performance. Some of them performed generally well across all three oncopanels, while others were better for a specific oncopanel. The performance of indel calling can further be improved by restricting the calls within high confidence intervals (HCIs) and coding regions, and by excluding low complexity regions (LCR) regions. Certain VAF cut-offs could be applied according to the applications.",
			"category": 2,
			"name": "Gong Binsheng,2024"
		},
		{
			"PMID": 38589557,
			"title": "Hallmarks of sex bias in immuno-oncology: mechanisms and therapeutic implications.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Xiao Tong",
				"Lee Juyeun",
				"Gauntner Timothy D",
				"Velegraki Maria",
				"Lathia Justin D",
				"Li Zihai"
			],
			"DOI": "10.1038/s41568-024-00680-z",
			"date": "2024-04-30",
			"PMC": "",
			"citation": "",
			"abstract": "Sex differences are present across multiple non-reproductive organ cancers, with male individuals generally experiencing higher incidence of cancer with poorer outcomes. Although some mechanisms underlying these differences are emerging, the immunological basis is not well understood. Observations from clinical trials also suggest a sex bias in conventional immunotherapies with male individuals experiencing a more favourable response and female individuals experiencing more severe adverse events to immune checkpoint blockade. In this Perspective article, we summarize the major biological hallmarks underlying sex bias in immuno-oncology. We focus on signalling from sex hormones and chromosome-encoded gene products, along with sex hormone-independent and chromosome-independent epigenetic mechanisms in tumour and immune cells such as myeloid cells and T cells. Finally, we highlight opportunities for future studies on sex differences that integrate sex hormones and chromosomes and other emerging cancer hallmarks such as ageing and the microbiome to provide a more comprehensive view of how sex differences underlie the response in cancer that can be leveraged for more effective immuno-oncology approaches.",
			"category": 2,
			"name": "Xiao Tong,2024"
		},
		{
			"PMID": 38585933,
			"title": "A benchmarked, high-efficiency prime editing platform for multiplexed dropout screening.",
			"journal": "bioRxiv : the preprint server for biology",
			"authorList": [
				"Cirincione Ann",
				"Simpson Danny",
				"Ravisankar Purnima",
				"Solley Sabrina C",
				"Yan Jun",
				"Singh Mona",
				"Adamson Britt"
			],
			"DOI": "10.1101/2024.03.25.585978",
			"date": "2024-04-25",
			"PMC": "",
			"citation": "",
			"abstract": "Prime editing installs precise edits into the genome with minimal unwanted byproducts, but low and variable editing efficiencies have complicated application of the approach to high-throughput functional genomics. Leveraging several recent advances, we assembled a prime editing platform capable of high-efficiency substitution editing across a set of engineered prime editing guide RNAs (epegRNAs) and corresponding target sequences (80% median intended editing). Then, using a custom library of 240,000 epegRNAs targeting >17,000 codons with 175 different substitution types, we benchmarked our platform for functional interrogation of small substitution variants (1-3 nucleotides) targeted to essential genes. Resulting data identified negative growth phenotypes for nonsense mutations targeted to ~8,000 codons, and comparing those phenotypes to results from controls demonstrated high specificity. We also observed phenotypes for synonymous mutations that disrupted splice site motifs at 3' exon boundaries. Altogether, we establish and benchmark a high-throughput prime editing approach for functional characterization of genetic variants with simple readouts from multiplexed experiments.",
			"category": 2,
			"name": "Cirincione Ann,2024"
		},
		{
			"PMID": 38553628,
			"title": "Characterization of tumor evolution by functional clonality and phylogenetics in hepatocellular carcinoma.",
			"journal": "Communications biology",
			"authorList": [
				"Kacar Zeynep",
				"Slud Eric",
				"Levy Doron",
				"Candia Juli\u00e1n",
				"Budhu Anuradha",
				"Forgues Marshonna",
				"Wu Xiaolin",
				"Raziuddin Arati",
				"Tran Bao",
				"Shetty Jyoti",
				"Pomyen Yotsawat",
				"Chaisaingmongkol Jittiporn",
				"Rabibhadana Siritida",
				"Pupacdi Benjarath",
				"Bhudhisawasdi Vajarabhongsa",
				"Lertprasertsuke Nirush",
				"Auewarakul Chirayu",
				"Sangrajrang Suleeporn",
				"Mahidol Chulabhorn",
				"Ruchirawat Mathuros",
				"Wang Xin Wei"
			],
			"DOI": "10.1038/s42003-024-06040-9",
			"date": "2024-04-01",
			"PMC": "",
			"citation": "",
			"abstract": "Hepatocellular carcinoma (HCC) is a molecularly heterogeneous solid malignancy, and its fitness may be shaped by how its tumor cells evolve. However, ability to monitor tumor cell evolution is hampered by the presence of numerous passenger mutations that do not provide any biological consequences. Here we develop a strategy to determine the tumor clonality of three independent HCC cohorts of 524 patients with diverse etiologies and race/ethnicity by utilizing somatic mutations in cancer driver genes. We identify two main types of tumor evolution, i.e., linear, and non-linear models where non-linear type could be further divided into classes, which we call shallow branching and deep branching. We find that linear evolving HCC is less aggressive than other types. GTF2IRD2B mutations are enriched in HCC with linear evolution, while TP53 mutations are the most frequent genetic alterations in HCC with non-linear models. Furthermore, we observe significant B cell enrichment in linear trees compared to non-linear trees suggesting the need for further research to uncover potential variations in immune cell types within genomically determined phylogeny types. These results hint at the possibility that tumor cells and their microenvironment may collectively influence the tumor evolution process.",
			"category": 2,
			"name": "Kacar Zeynep,2024"
		},
		{
			"PMID": 38550923,
			"title": "Building a precision medicine infrastructure at a national level: The Swedish experience.",
			"journal": "Cambridge prisms. Precision medicine",
			"authorList": [
				"Edsj\u00f6 Anders",
				"Lindstrand Anna",
				"Gisselsson David",
				"M\u00f6lling Paula",
				"Friedman Mikaela",
				"Cavelier Lucia",
				"Johansson Maria",
				"Ehrencrona Hans",
				"Fagerqvist Therese",
				"Strid Tobias",
				"Lovmar Lovisa",
				"Jacobsson Bo",
				"Johansson \u00c5sa",
				"Engstrand Lars",
				"Wheelock Craig E",
				"Sikora Per",
				"Wirta Valtteri",
				"Fioretos Thoas",
				"Rosenquist Richard",
				"Genomic Medicine Sweden (GMS)"
			],
			"DOI": "10.1017/pcm.2023.3",
			"date": "2024-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "Precision medicine has the potential to transform healthcare by moving from one-size-fits-all to personalised treatment and care. This transition has been greatly facilitated through new high-throughput sequencing technologies that can provide the unique molecular profile of each individual patient, along with the rapid development of targeted therapies directed to the Achilles heels of each disease. To implement precision medicine approaches in healthcare, many countries have adopted national strategies and initiated genomic/precision medicine initiatives to provide equal access to all citizens. In other countries, such as Sweden, this has proven more difficult due to regionally organised healthcare. Using a bottom-up approach, key stakeholders from academia, healthcare, industry and patient organisations joined forces and formed Genomic Medicine Sweden (GMS), a national infrastructure for the implementation of precision medicine across the country. To achieve this, Genomic Medicine Centres have been established to provide regionally distributed genomic services, and a national informatics infrastructure has been built to allow secure data handling and sharing. GMS has a broad scope focusing on rare diseases, cancer, pharmacogenomics, infectious diseases and complex diseases, while also providing expertise in informatics, ethical and legal issues, health economy, industry collaboration and education. In this review, we summarise our experience in building a national infrastructure for precision medicine. We also provide key examples how precision medicine already has been successfully implemented within our focus areas. Finally, we bring up challenges and opportunities associated with precision medicine implementation, the importance of international collaboration, as well as the future perspective in the field of precision medicine.",
			"category": 2,
			"name": "Edsj\u00f6 Anders,2024"
		},
		{
			"PMID": 38549156,
			"title": "Multi-omics cluster defines the subtypes of CRC with distinct prognosis and tumor microenvironment.",
			"journal": "European journal of medical research",
			"authorList": [
				"Ma Yuan",
				"Li Jing",
				"Zhao Xu",
				"Ji Chao",
				"Hu Weibin",
				"Ma YanFang",
				"Qu Fengyi",
				"Sun Yuchen",
				"Zhang Xiaozhi"
			],
			"DOI": "10.1186/s40001-024-01805-8",
			"date": "2024-04-01",
			"PMC": "",
			"citation": "",
			"abstract": "Colorectal cancer (CRC) is a complex malignancy characterized by diverse molecular profiles, clinical outcomes, and limited precision in prognostic markers. Addressing these challenges, this study utilized multi-omics data to define consensus molecular subtypes in CRC and elucidate their association with clinical outcomes and underlying biological processes.",
			"category": 2,
			"name": "Ma Yuan,2024"
		},
		{
			"PMID": 38534453,
			"title": "Personalized Driver Gene Prediction Using Graph Convolutional Networks with Conditional Random Fields.",
			"journal": "Biology",
			"authorList": [
				"Wei Pi-Jing",
				"Zhu An-Dong",
				"Cao Ruifen",
				"Zheng Chunhou"
			],
			"DOI": "10.3390/biology13030184",
			"date": "2024-03-29",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a complex and evolutionary disease mainly driven by the accumulation of genetic variations in genes. Identifying cancer driver genes is important. However, most related studies have focused on the population level. Cancer is a disease with high heterogeneity. Thus, the discovery of driver genes at the individual level is becoming more valuable but is a great challenge. Although there have been some computational methods proposed to tackle this challenge, few can cover all patient samples well, and there is still room for performance improvement. In this study, to identify individual-level driver genes more efficiently, we propose the PDGCN method. PDGCN integrates multiple types of data features, including mutation, expression, methylation, copy number data, and system-level gene features, along with network structural features extracted using Node2vec in order to construct a sample-gene interaction network. Prediction is performed using a graphical convolutional neural network model with a conditional random field layer, which is able to better combine the network structural features with biological attribute features. Experiments on the ACC (Adrenocortical Cancer) and KICH (Kidney Chromophobe) datasets from TCGA (The Cancer Genome Atlas) demonstrated that the method performs better compared to other similar methods. It can identify not only frequently mutated driver genes, but also rare candidate driver genes and novel biomarker genes. The results of the survival and enrichment analyses of these detected genes demonstrate that the method can identify important driver genes at the individual level.",
			"category": 2,
			"name": "Wei Pi-Jing,2024"
		},
		{
			"PMID": 38495115,
			"title": "A randomized trial of a wearable UV dosimeter for skin cancer prevention.",
			"journal": "Frontiers in medicine",
			"authorList": [
				"Dumont Emmanuel L P",
				"Kaplan Peter D",
				"Do Catherine",
				"Banerjee Shayak",
				"Barrer Melissa",
				"Ezzedine Khaled",
				"Zippin Jonathan H",
				"Varghese George I"
			],
			"DOI": "10.3389/fmed.2024.1259050",
			"date": "2024-03-19",
			"PMC": "",
			"citation": "",
			"abstract": "Non-melanoma skin cancer (NMSC) is the most prevalent cancer in the United States. Despite guidelines on ultraviolet (UV) avoidance, it remains difficult for people to assess their exposure, as UV is invisible and the onset of UV-induced symptoms is delayed.",
			"category": 2,
			"name": "Dumont Emmanuel L P,2024"
		},
		{
			"PMID": 38474079,
			"title": "Mitochondria at the Nanoscale: Physics Meets Biology-What Does It Mean for Medicine?",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Mourokh Lev",
				"Friedman Jonathan"
			],
			"DOI": "10.3390/ijms25052835",
			"date": "2024-03-14",
			"PMC": "",
			"citation": "",
			"abstract": "Mitochondria are commonly perceived as \"cellular power plants\". Intriguingly, power conversion is not their only function. In the first part of this paper, we review the role of mitochondria in the evolution of eukaryotic organisms and in the regulation of the human body, specifically focusing on cancer and autism in relation to mitochondrial dysfunction. In the second part, we overview our previous works, revealing the physical principles of operation for proton-pumping complexes in the inner mitochondrial membrane. Our proposed simple models reveal the physical mechanisms of energy exchange. They can be further expanded to answer open questions about mitochondrial functions and the medical treatment of diseases associated with mitochondrial disorders.",
			"category": 2,
			"name": "Mourokh Lev,2024"
		},
		{
			"PMID": 38464463,
			"title": "Identification of cancer driver genes based on hierarchical weak consensus model.",
			"journal": "Health information science and systems",
			"authorList": [
				"Li Gaoshi",
				"Hu Zhipeng",
				"Luo Xinlong",
				"Liu Jiafei",
				"Wu Jingli",
				"Peng Wei",
				"Zhu Xiaoshu"
			],
			"DOI": "10.1007/s13755-024-00279-6",
			"date": "2024-03-12",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a complex gene mutation disease that derives from the accumulation of mutations during somatic cell evolution. With the advent of high-throughput technology, a large amount of omics data has been generated, and how to find cancer-related driver genes from a large number of omics data is a challenge. In the early stage, the researchers developed many frequency-based driver genes identification methods, but they could not identify driver genes with low mutation rates well. Afterwards, researchers developed network-based methods by fusing multi-omics data, but they rarely considered the connection among features. In this paper, after analyzing a large number of methods for integrating multi-omics data, a hierarchical weak consensus model for fusing multiple features is proposed according to the connection among features. By analyzing the connection between PPI network and co-mutation hypergraph network, this paper firstly proposes a new topological feature, called co-mutation clustering coefficient (CMCC). Then, a hierarchical weak consensus model is used to integrate CMCC, mRNA and miRNA differential expression scores, and a new driver genes identification method HWC is proposed. In this paper, the HWC method and current 7 state-of-the-art methods are compared on three types of cancers. The comparison results show that HWC has the best identification performance in statistical evaluation index, functional consistency and the partial area under ROC curve.",
			"category": 2,
			"name": "Li Gaoshi,2024"
		},
		{
			"PMID": 38429380,
			"title": "Germline determinants of aberrant signaling pathways in cancer.",
			"journal": "NPJ precision oncology",
			"authorList": [
				"Dalfovo Davide",
				"Scandino Riccardo",
				"Paoli Marta",
				"Valentini Samuel",
				"Romanel Alessandro"
			],
			"DOI": "10.1038/s41698-024-00546-5",
			"date": "2024-03-04",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a complex disease influenced by a heterogeneous landscape of both germline genetic variants and somatic aberrations. While there is growing evidence suggesting an interplay between germline and somatic variants, and a substantial number of somatic aberrations in specific pathways are now recognized as hallmarks in many well-known forms of cancer, the interaction landscape between germline variants and the aberration of those pathways in cancer remains largely unexplored. Utilizing over 8500 human samples across 33 cancer types characterized by TCGA and considering binary traits defined using a large collection of somatic aberration profiles across ten well-known oncogenic signaling pathways, we conducted a series of GWAS and identified genome-wide and suggestive associations involving 276 SNPs. Among these, 94 SNPs revealed cis-eQTL links with cancer-related genes or with genes functionally correlated with the corresponding traits' oncogenic pathways. GWAS summary statistics for all tested traits were then used to construct a set of polygenic scores employing a customized computational strategy. Polygenic scores for 24 traits demonstrated significant performance and were validated using data from PCAWG and CCLE datasets. These scores showed prognostic value for clinical variables and exhibited significant effectiveness in classifying patients into specific cancer subtypes or stratifying patients with cancer-specific aggressive phenotypes. Overall, we demonstrate that germline genetics can describe patients' genetic liability to develop specific cancer molecular and clinical profiles.",
			"category": 2,
			"name": "Dalfovo Davide,2024"
		},
		{
			"PMID": 38375218,
			"title": "TOP1 and R-loops facilitate transcriptional DSBs at hypertranscribed cancer driver genes.",
			"journal": "iScience",
			"authorList": [
				"Hidmi Osama",
				"Oster Sara",
				"Monin Jonathan",
				"Aqeilan Rami I"
			],
			"DOI": "10.1016/j.isci.2024.109082",
			"date": "2024-02-21",
			"PMC": "",
			"citation": "",
			"abstract": "DNA double-stranded breaks (DSBs) pose a significant threat to genomic integrity, and their generation during essential cellular processes like transcription remains poorly understood. In this study, we employ several techniques to map DSBs, R-loops, and topoisomerase 1 cleavage complex (TOP1cc) to comprehensively investigate the interplay between transcription, DSBs, topoisomerase 1 (TOP1), and R-loops. Our findings reveal the presence of DSBs at highly expressed genes enriched with TOP1 and R-loops. Remarkably, transcription-associated DSBs at these loci are significantly reduced upon depletion of R-loops and TOP1, uncovering the pivotal roles of TOP1 and R-loops in transcriptional DSB formation. By elucidating the intricate interplay between TOP1cc trapping, R-loops, and DSBs, our study provides insights into the mechanisms underlying transcription-associated genomic instability. Moreover, we establish a link between transcriptional DSBs and early molecular changes driving cancer development, highlighting the distinct etiology and molecular characteristics of driver mutations compared to passenger mutations.",
			"category": 2,
			"name": "Hidmi Osama,2024"
		},
		{
			"PMID": 38370388,
			"title": "An Investigation of the Immune Microenvironment and Genome during Lung Adenocarcinoma Development.",
			"journal": "Journal of Cancer",
			"authorList": [
				"Wang Qingyi",
				"Xie Bin",
				"Sun Jingyue",
				"Li Zisheng",
				"Xiao Desheng",
				"Tao Yongguang",
				"She Xiaoling"
			],
			"DOI": "10.7150/jca.92101",
			"date": "2024-02-20",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "Wang Qingyi,2024"
		},
		{
			"PMID": 38359788,
			"title": "Quantitative and qualitative mutational impact of ionizing radiation on normal cells.",
			"journal": "Cell genomics",
			"authorList": [
				"Youk Jeonghwan",
				"Kwon Hyun Woo",
				"Lim Joonoh",
				"Kim Eunji",
				"Kim Taewoo",
				"Kim Ryul",
				"Park Seongyeol",
				"Yi Kijong",
				"Nam Chang Hyun",
				"Jeon Sara",
				"An Yohan",
				"Choi Jinwook",
				"Na Hyelin",
				"Lee Eon-Seok",
				"Cho Youngwon",
				"Min Dong-Wook",
				"Kim HyoJin",
				"Kang Yeong-Rok",
				"Choi Si Ho",
				"Bae Min Ji",
				"Lee Chang Geun",
				"Kim Joon-Goon",
				"Kim Young Seo",
				"Yu Tosol",
				"Lee Won-Chul",
				"Shin Jong-Yeon",
				"Lee Dong Soo",
				"Kim Tae-You",
				"Ku Taeyun",
				"Kim Su Yeon",
				"Lee Joo-Hyeon",
				"Koo Bon-Kyoung",
				"Lee Hyunsook",
				"Yi On Vox",
				"Han Eon Chul",
				"Chang Ji Hyun",
				"Kim Kyung Su",
				"Son Tae Gen",
				"Ju Young Seok"
			],
			"DOI": "10.1016/j.xgen.2024.100499",
			"date": "2024-02-19",
			"PMC": "",
			"citation": "",
			"abstract": "The comprehensive genomic impact of ionizing radiation (IR), a carcinogen, on healthy somatic cells remains unclear. Using large-scale whole-genome sequencing (WGS) of clones expanded from irradiated murine and\u00a0human single cells, we revealed that IR induces a characteristic spectrum of short insertions or deletions (indels) and structural variations (SVs), including balanced inversions, translocations, composite SVs (deletion-insertion, deletion-inversion, and deletion-translocation composites), and complex genomic rearrangements (CGRs), including chromoplexy, chromothripsis, and SV by breakage-fusion-bridge cycles. Our findings suggest that 1\u00a0Gy IR exposure causes an average of 2.33 mutational events per Gb genome, comprising 2.15 indels, 0.17 SVs, and 0.01 CGRs, despite a high level of inter-cellular stochasticity. The mutational burden was dependent on total irradiation dose, regardless of dose rate or cell type. The findings were further validated in IR-induced secondary cancers and single cells without clonalization. Overall, our study highlights a comprehensive and clear picture of IR effects on normal mammalian genomes.",
			"category": 2,
			"name": "Youk Jeonghwan,2024"
		},
		{
			"PMID": 38357004,
			"title": "The role of competing endogenous RNA network in the development of hepatocellular carcinoma: potential therapeutic targets.",
			"journal": "Frontiers in cell and developmental biology",
			"authorList": [
				"Tang Ziwei",
				"Li Xue",
				"Zheng Yanfeng",
				"Liu Jin",
				"Liu Chao",
				"Li Xia"
			],
			"DOI": "10.3389/fcell.2024.1341999",
			"date": "2024-02-16",
			"PMC": "",
			"citation": "",
			"abstract": "The current situation of hepatocellular carcinoma (HCC) management is challenging due to its high incidence, mortality, recurrence and metastasis. Recent advances in gene genetic and expression regulation have unveiled the significant role of non-coding RNA (ncRNA) in various cancers. This led to the formulation of the competing endogenous RNA (ceRNA) hypothesis, which posits that both coding RNA and ncRNA, containing miRNA response elements (MRE), can share the same miRNA sequence. This results in a competitive network between ncRNAs, such as lncRNA and mRNA, allowing them to regulate each other. Extensive research has highlighted the crucial role of the ceRNA network in HCC development, impacting various cellular processes including proliferation, metastasis, cell death, angiogenesis, tumor microenvironment, organismal immunity, and chemotherapy resistance. Additionally, the ceRNA network, mediated by lncRNA or circRNA, offers potential in early diagnosis and prevention of HCC. Consequently, ceRNAs are emerging as therapeutic targets for HCC. The complexity of these gene networks aligns with the multi-target approach of traditional Chinese medicine (TCM), presenting a novel perspective for TCM in combating HCC. Research is beginning to show that TCM compounds and prescriptions can affect HCC progression through the ceRNA network, inhibiting proliferation and metastasis, and inducing apoptosis. Currently, the lncRNAs TUG1, NEAT1, and CCAT1, along with their associated ceRNA networks, are among the most promising ncRNAs for HCC research. However, this field is still in its infancy, necessitating advanced technology and extensive basic research to fully understand the ceRNA network mechanisms of TCM in HCC treatment.",
			"category": 2,
			"name": "Tang Ziwei,2024"
		},
		{
			"PMID": 38351138,
			"title": "Utilizing nullomers in cell-free RNA for early cancer detection.",
			"journal": "Cancer gene therapy",
			"authorList": [
				"Montgomery Austin",
				"Tsiatsianis Georgios Christos",
				"Mouratidis Ioannis",
				"Chan Candace S Y",
				"Athanasiou Maria",
				"Papanastasiou Anastasios D",
				"Kantere Verena",
				"Syrigos Nikos",
				"Vathiotis Ioannis",
				"Syrigos Konstantinos",
				"Yee Nelson S",
				"Georgakopoulos-Soares Ilias"
			],
			"DOI": "10.1038/s41417-024-00741-3",
			"date": "2024-06-21",
			"PMC": "",
			"citation": "",
			"abstract": "Early detection of cancer can significantly improve patient outcomes; however, sensitive and highly specific biomarkers for cancer detection are currently missing. Nullomers are the shortest sequences that are absent from the human genome but can emerge due to somatic mutations in cancer. We examine over 10,000 whole exome sequencing matched tumor-normal samples to characterize nullomer emergence across exonic regions of the genome. We also identify nullomer emerging mutational hotspots within tumor genes. Finally, we provide evidence for the identification of nullomers in cell-free RNA from peripheral blood samples, enabling detection of multiple tumor types. We show multiple tumor classification models with an AUC greater than 0.9, including a hepatocellular carcinoma classifier with an AUC greater than 0.99.",
			"category": 2,
			"name": "Montgomery Austin,2024"
		},
		{
			"PMID": 38328209,
			"title": "3D genomic analysis reveals novel enhancer-hijacking caused by complex structural alterations that drive oncogene overexpression.",
			"journal": "bioRxiv : the preprint server for biology",
			"authorList": [
				"Mortenson Katelyn L",
				"Dawes Courtney",
				"Wilson Emily R",
				"Patchen Nathan E",
				"Johnson Hailey E",
				"Gertz Jason",
				"Bailey Swneke D",
				"Liu Yang",
				"Varley Katherine E",
				"Zhang Xiaoyang"
			],
			"DOI": "10.1101/2024.01.23.576965",
			"date": "2024-06-25",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer genomes are composed of many complex structural alterations on chromosomes and extrachromosomal DNA (ecDNA), making it difficult to identify non-coding enhancer regions that are hijacked to activate oncogene expression. Here, we describe a 3D genomics-based analysis called HAPI (Highly Active Promoter Interactions) to characterize enhancer hijacking. HAPI analysis of HiChIP data from 34 cancer cell lines identified enhancer hijacking events that activate both known and potentially novel oncogenes such as ",
			"category": 2,
			"name": "Mortenson Katelyn L,2024"
		},
		{
			"PMID": 38311377,
			"title": "Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy.",
			"journal": "Cancer communications (London, England)",
			"authorList": [
				"Song Bin",
				"Yang Ping",
				"Zhang Shuyu"
			],
			"DOI": "10.1002/cac2.12520",
			"date": "2024-03-25",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a leading cause of death worldwide. Targeted therapies aimed at key oncogenic driver mutations in combination with chemotherapy and radiotherapy as well as immunotherapy have benefited cancer patients considerably. Tumor protein p53 (TP53), a crucial tumor suppressor gene encoding p53, regulates numerous downstream genes and cellular phenotypes in response to various stressors. The affected genes are involved in diverse processes, including cell cycle arrest, DNA repair, cellular senescence, metabolic homeostasis, apoptosis, and autophagy. However, accumulating recent studies have continued to reveal novel and unexpected functions of p53 in governing the fate of tumors, for example, functions in ferroptosis, immunity, the tumor microenvironment and microbiome metabolism. Among the possibilities, the evolutionary plasticity of p53 is the most controversial, partially due to the dizzying array of biological functions that have been attributed to different regulatory mechanisms of p53 signaling. Nearly 40 years after its discovery, this key tumor suppressor remains somewhat enigmatic. The intricate and diverse functions of p53 in regulating cell fate during cancer treatment are only the tip of the iceberg with respect to its equally complicated structural biology, which has been painstakingly revealed. Additionally, TP53 mutation is one of the most significant genetic alterations in cancer, contributing to rapid cancer cell growth and tumor progression. Here, we summarized recent advances that implicate altered p53 in modulating the response to various cancer therapies, including chemotherapy, radiotherapy, and immunotherapy. Furthermore, we also discussed potential strategies for targeting p53 as a therapeutic option for cancer.",
			"category": 2,
			"name": "Song Bin,2024"
		},
		{
			"PMID": 38278146,
			"title": "Integrated characterization of hepatobiliary tumor organoids provides a potential landscape of pharmacogenomic interactions.",
			"journal": "Cell reports. Medicine",
			"authorList": [
				"Zhu Yanjing",
				"Tang Shijie",
				"Yuan Qiuyue",
				"Fu Jing",
				"He Juan",
				"Liu Zhuang",
				"Zhao Xiaofang",
				"Li Yunguang",
				"Zhao Yan",
				"Zhang Yani",
				"Zhang Xiaoyu",
				"Zhang Yangqianwen",
				"Zhu Yiqin",
				"Wang Wenwen",
				"Zheng Bo",
				"Wu Rui",
				"Wu Tong",
				"Yang Shuai",
				"Qiu Xinyao",
				"Shen Siyun",
				"Hu Ji",
				"Chen Luonan",
				"Wang Yong",
				"Wang Hongyang",
				"Gao Dong",
				"Chen Lei"
			],
			"DOI": "10.1016/j.xcrm.2023.101375",
			"date": "2024-02-23",
			"PMC": "",
			"citation": "",
			"abstract": "Despite considerable efforts to identify human liver cancer genomic alterations that might unveil druggable targets, the systematic translation of multiomics data remains challenging. Here, we report success in long-term culture of 64 patient-derived hepatobiliary tumor organoids (PDHOs) from a Chinese population. A divergent response to 265 metabolism- and epigenetics-related chemicals and 36 anti-cancer drugs is observed. Integration of the whole genome, transcriptome, chromatin accessibility profiles, and drug sensitivity results of 64 clinically relevant drugs defines over 32,000 genome-drug interactions. RUNX1 promoter mutation is associated with an increase in chromatin accessibility and a concomitant gene expression increase, promoting a cluster of drugs preferentially sensitive in hepatobiliary tumors. These results not only provide an annotated PDHO biobank of human liver cancer but also suggest a systematic approach for obtaining a comprehensive understanding of the gene-regulatory network of liver cancer, advancing the applications of potential personalized medicine.",
			"category": 2,
			"name": "Zhu Yanjing,2024"
		},
		{
			"PMID": 38275371,
			"title": "Switch-Independent 3A: An Epigenetic Regulator in Cancer with New Implications for Pulmonary Arterial Hypertension.",
			"journal": "Biomedicines",
			"authorList": [
				"Jankowski Katherine",
				"Jagana Vineeta",
				"Bisserier Malik",
				"Hadri Lahouaria"
			],
			"DOI": "10.3390/biomedicines12010010",
			"date": "2024-02-01",
			"PMC": "",
			"citation": "",
			"abstract": "Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNA, play a crucial role in the regulation of gene expression and are pivotal in biological processes like apoptosis, cell proliferation, and differentiation. SIN3a serves as a scaffold protein and facilitates interactions with transcriptional epigenetic partners and specific DNA-binding transcription factors to modulate gene expression by adding or removing epigenetic marks. However, the activation or repression of gene expression depends on the factors that interact with SIN3a, as it can recruit both transcriptional activators and repressors. The role of SIN3a has been extensively investigated in the context of cancer, including melanoma, lung, and breast cancer. Our group is interested in defining the roles of SIN3a and its partners in pulmonary vascular disease. Pulmonary arterial hypertension (PAH) is a multifactorial disease often described as a cancer-like disease and characterized by disrupted cellular metabolism, sustained vascular cell proliferation, and resistance to apoptosis. Molecularly, PAH shares many common signaling pathways with cancer cells, offering the opportunity to further consider therapeutic strategies used for cancer. As a result, many signaling pathways observed in cancer were studied in PAH and have encouraged new research studying SIN3a's role in PAH due to its impact on cancer growth. This comparison offers new therapeutic options. In this review, we delineate the SIN3a-associated epigenetic mechanisms in cancer and PAH cells and highlight their impact on cell survival and proliferation. Furthermore, we explore in detail the role of SIN3a in cancer to provide new insights into its emerging role in PAH pathogenesis.",
			"category": 2,
			"name": "Jankowski Katherine,2024"
		},
		{
			"PMID": 38256080,
			"title": "Navigating the Cytokine Seas: Targeting Cytokine Signaling Pathways in Cancer Therapy.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Stanilov Noyko",
				"Velikova Tsvetelina",
				"Stanilova Spaska"
			],
			"DOI": "10.3390/ijms25021009",
			"date": "2024-01-24",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer remains one of the leading causes of morbidity and mortality worldwide, necessitating continuous efforts to develop effective therapeutic strategies. Over the years, advancements in our understanding of the complex interplay between the immune system and cancer cells have led to the development of immunotherapies that revolutionize cancer treatment. Cytokines, as key regulators of the immune response, are involved in both the initiation and progression of cancer by affecting inflammation and manipulating multiple intracellular signaling pathways that regulate cell growth, proliferation, and migration. Cytokines, as key regulators of inflammation, have emerged as promising candidates for cancer therapy. This review article aims to provide an overview of the significance of cytokines in cancer development and therapy by highlighting the importance of targeting cytokine signaling pathways as a potential therapeutic approach.",
			"category": 2,
			"name": "Stanilov Noyko,2024"
		},
		{
			"PMID": 38250421,
			"title": "Review of Computational Methods and Database Sources for Predicting the Effects of Coding Frameshift Small Insertion and Deletion Variations.",
			"journal": "ACS omega",
			"authorList": [
				"Ge Fang",
				"Arif Muhammad",
				"Yan Zihao",
				"Alahmadi Hanin",
				"Worachartcheewan Apilak",
				"Shoombuatong Watshara"
			],
			"DOI": "10.1021/acsomega.3c07662",
			"date": "2024-01-23",
			"PMC": "",
			"citation": "",
			"abstract": "Genetic variations (including substitutions, insertions, and deletions) exert a profound influence on DNA sequences. These variations are systematically classified as synonymous, nonsynonymous, and nonsense, each manifesting distinct effects on proteins. The implementation of high-throughput sequencing has significantly augmented our comprehension of the intricate interplay between gene variations and protein structure and function, as well as their ramifications in the context of diseases. Frameshift variations, particularly small insertions and deletions (indels), disrupt protein coding and are instrumental in disease pathogenesis. This review presents a succinct review of computational methods, databases, current challenges, and future directions in predicting the consequences of coding frameshift small indels variations. We analyzed the predictive efficacy, reliability, and utilization of computational methods and variant account, reliability, and utilization of database. Besides, we also compared the prediction methodologies on GOF/LOF pathogenic variation data. Addressing the challenges pertaining to prediction accuracy and cross-species generalizability, nascent technologies such as AI and deep learning harbor immense potential to enhance predictive capabilities. The importance of interdisciplinary research and collaboration cannot be overstated for devising effective diagnosis, treatment, and prevention strategies concerning diseases associated with coding frameshift indels variations.",
			"category": 2,
			"name": "Ge Fang,2024"
		},
		{
			"PMID": 38236467,
			"title": "Molecular basis and current insights of atypical Rho small GTPase in cancer.",
			"journal": "Molecular biology reports",
			"authorList": [
				"Huang Hua",
				"Wang Sijia",
				"Guan Yifei",
				"Ren Jing",
				"Liu Xinhui"
			],
			"DOI": "10.1007/s11033-023-09140-7",
			"date": "2024-01-19",
			"PMC": "",
			"citation": "",
			"abstract": "Atypical Rho GTPases are a subtype of the Rho GTPase family that are involved in diverse cellular processes. The typical Rho GTPases, led by RhoA, Rac1 and Cdc42, have been well studied, while relative studies on atypical Rho GTPases are relatively still limited and have great exploration potential. With the increase in studies, current evidence suggests that atypical Rho GTPases regulate multiple biological processes and play important roles in the occurrence and development of human cancers. Therefore, this review mainly discusses the molecular basis of atypical Rho GTPases and their roles in cancer. We summarize the sequence characteristics, subcellular localization and biological functions of each atypical Rho GTPase. Moreover, we review the recent advances and potential mechanisms of atypical Rho GTPases in the development of multiple cancers. A comprehensive understanding and extensive exploration of the biological functions of atypical Rho GTPases and their molecular mechanisms in tumors will provide important insights into the pathophysiology of tumors and the development of cancer therapeutic strategies.",
			"category": 2,
			"name": "Huang Hua,2024"
		},
		{
			"PMID": 38219146,
			"title": "DNA polymerase \u03b5 and \u03b4 variants drive mutagenesis in polypurine tracts in human tumors.",
			"journal": "Cell reports",
			"authorList": [
				"Ostroverkhova Daria",
				"Tyryshkin Kathrin",
				"Beach Annette K",
				"Moore Elizabeth A",
				"Masoudi-Sobhanzadeh Yosef",
				"Barbari Stephanie R",
				"Rogozin Igor B",
				"Shaitan Konstantin V",
				"Panchenko Anna R",
				"Shcherbakova Polina V"
			],
			"DOI": "10.1016/j.celrep.2023.113655",
			"date": "2024-01-26",
			"PMC": "",
			"citation": "",
			"abstract": "Alterations in the exonuclease domain of DNA polymerase \u03b5 cause ultramutated cancers. These cancers accumulate AGA>ATA transversions; however, their genomic features beyond the trinucleotide motifs are obscure. We analyze the extended DNA context of ultramutation using whole-exome sequencing data from 524 endometrial and 395 colorectal tumors. We find that G>T transversions in POLE-mutant tumors predominantly affect sequences containing at least six consecutive purines, with a striking preference for certain positions within polypurine tracts. Using this signature, we develop a machine-learning classifier to identify tumors with hitherto unknown POLE drivers and validate two drivers, POLE-E978G and POLE-S461L, by functional assays in yeast. Unlike other pathogenic variants, the E978G substitution affects the polymerase domain of Pol \u03b5. We further show that tumors with POLD1 drivers share the extended signature of POLE ultramutation. These findings expand the understanding of ultramutation mechanisms and highlight peculiar mutagenic properties of polypurine tracts in the human genome.",
			"category": 2,
			"name": "Ostroverkhova Daria,2024"
		},
		{
			"PMID": 38187607,
			"title": "WNT Signalling Promotes NF-\u03baB Activation and Drug Resistance in KRAS-Mutant Colorectal Cancer.",
			"journal": "bioRxiv : the preprint server for biology",
			"authorList": [
				"Cong Bojie",
				"Stamou Evangelia",
				"Pennel Kathryn",
				"Mckenzie Molly",
				"Matly Amna",
				"Gopinath Sindhura",
				"Edwards Joanne",
				"Cagan Ross"
			],
			"DOI": "10.1101/2023.12.21.572810",
			"date": "2024-02-10",
			"PMC": "",
			"citation": "",
			"abstract": "Approximately 40% of colorectal cancer (CRC) cases are characterized by KRAS mutations, rendering them insensitive to most CRC therapies. While the reasons for this resistance remain incompletely understood, one key aspect is genetic complexity: in CRC, oncogenic KRAS is most commonly paired with mutations that alter WNT and P53 activities (\"RAP\"). Here, we demonstrate that elevated WNT activity upregulates canonical (NF-\u03baB) signalling in both ",
			"category": 2,
			"name": "Cong Bojie,2024"
		},
		{
			"PMID": 38187596,
			"title": "Heterogeneity-Preserving Discriminative Feature Selection for Subtype Discovery.",
			"journal": "bioRxiv : the preprint server for biology",
			"authorList": [
				"Basher Abdur Rahman M A",
				"Hallinan Caleb",
				"Lee Kwonmoo"
			],
			"DOI": "10.1101/2023.05.14.540686",
			"date": "2024-02-10",
			"PMC": "",
			"citation": "",
			"abstract": "The discovery of subtypes is pivotal for disease diagnosis and targeted therapy, considering the diverse responses of different cells or patients to specific treatments. Exploring the heterogeneity within disease or cell states provides insights into disease progression mechanisms and cell differentiation. The advent of high-throughput technologies has enabled the generation and analysis of various molecular data types, such as single-cell RNA-seq, proteomic, and imaging datasets, at large scales. While presenting opportunities for subtype discovery, these datasets pose challenges in finding relevant signatures due to their high dimensionality. Feature selection, a crucial step in the analysis pipeline, involves choosing signatures that reduce the feature size for more efficient downstream computational analysis. Numerous existing methods focus on selecting signatures that differentiate known diseases or cell states, yet they often fall short in identifying features that preserve heterogeneity and reveal subtypes. To identify features that can capture the diversity within each class while also maintaining the discrimination of known disease states, we employed deep metric learning-based feature embedding to conduct a detailed exploration of the statistical properties of features essential in preserving heterogeneity. Our analysis revealed that features with a significant difference in interquartile range (IQR) between classes possess crucial subtype information. Guided by this insight, we developed a robust statistical method, termed PHet (Preserving Heterogeneity) that performs iterative subsampling differential analysis of IQR and Fisher's method between classes, identifying a minimal set of heterogeneity-preserving discriminative features to optimize subtype clustering quality. Validation using public single-cell RNA-seq and microarray datasets showcased PHet's effectiveness in preserving sample heterogeneity while maintaining discrimination of known disease/cell states, surpassing the performance of previous outlier-based methods. Furthermore, analysis of a single-cell RNA-seq dataset from mouse tracheal epithelial cells revealed, through PHet-based features, the presence of two distinct basal cell subtypes undergoing differentiation toward a luminal secretory phenotype. Notably, one of these subtypes exhibited high expression of BPIFA1. Interestingly, previous studies have linked BPIFA1 secretion to the emergence of secretory cells during mucociliary differentiation of airway epithelial cells. PHet successfully pinpointed the basal cell subtype associated with this phenomenon, a distinction that pre-annotated markers and dispersion-based features failed to make due to their admixed feature expression profiles. These findings underscore the potential of our method to deepen our understanding of the mechanisms underlying diseases and cell differentiation and contribute significantly to personalized medicine.",
			"category": 2,
			"name": "Basher Abdur Rahman M A,2024"
		},
		{
			"PMID": 38173659,
			"title": "PTEN Deregulation Mechanisms in Salivary Gland Carcinomas.",
			"journal": "Cancer diagnosis & prognosis",
			"authorList": [
				"Papanikolaou Vasileios",
				"Chrysovergis Aristeidis",
				"Adamopoulou Maria",
				"Spyropoulou Despoina",
				"Roukas Dimitrios",
				"Papanastasiou George",
				"Mastronikoli Sofianiki",
				"Papouliakos Sotirios",
				"Manaios Loukas",
				"Tsiambas Evangelos",
				"Pantos Pavlos",
				"Ragos Vasileios",
				"Fotiades Panagotis",
				"Peschos Dimitrios",
				"Mastronikolis Nicholas",
				"Kyrodimos Efthymios"
			],
			"DOI": "10.21873/cdp.10280",
			"date": "2024-01-05",
			"PMC": "",
			"citation": "",
			"abstract": "Among the tumour suppressor genes that affect critically cell functions and homeostasis, phosphatase and tensin homolog deleted in chromosome 10 (PTEN- gene locus: 10q21) regulates the PI3K/Akt/mTOR signalling pathway. PTEN is deleted, mutated or epigenetically hyper-methylated in a variety of human solid malignancies. Salivary gland carcinomas (SGCs) belong to the head and neck carcinomas (HNCs) super category of solid malignancies. Histo-pathologically, they demonstrate a significant diversity due to a variety of distinct and mixed subtypes. Genetically, they are characterized by a broad spectrum of gene and chromosomal imbalances. Referring specifically to suppressor genes, PTEN deregulation plays a critical role in signaling transduction in the corresponding SGC pre- and malignant epithelia modifying the response rates to potential targeted therapeutic strategies. In the current review, we explored the role of PTEN deregulation mechanisms that are involved in the onset and progression of SGCs.",
			"category": 2,
			"name": "Papanikolaou Vasileios,2024"
		},
		{
			"PMID": 38172609,
			"title": "Cell competition and cancer from Drosophila to mammals.",
			"journal": "Oncogenesis",
			"authorList": [
				"Cong Bojie",
				"Cagan Ross L"
			],
			"DOI": "10.1038/s41389-023-00505-y",
			"date": "2024-02-10",
			"PMC": "",
			"citation": "",
			"abstract": "Throughout an individual's life, somatic cells acquire cancer-associated mutations. A fraction of these mutations trigger tumour formation, a phenomenon partly driven by the interplay of mutant and wild-type cell clones competing for dominance; conversely, other mutations function against tumour initiation. This mechanism of 'cell competition', can shift clone dynamics by evaluating the relative status of clonal populations, promoting 'winners' and eliminating 'losers'. This review examines the role of cell competition in the context of tumorigenesis, tumour progression and therapeutic intervention.",
			"category": 2,
			"name": "Cong Bojie,2024"
		},
		{
			"PMID": 38111812,
			"title": "Role of Tumor Molecular Profiling With FoundationOne\u00aeCDx in Advanced Solid Tumors: A Single-Centre Experience From Romania.",
			"journal": "Cureus",
			"authorList": [
				"Popa Ana Maria",
				"Stejeroiu Mihaela Andreea",
				"Iaciu Cristian",
				"Olaru Mihaela",
				"Orlov Slavu Cristina",
				"Parosanu Andreea",
				"Stanciu Ioana Miruna",
				"Pirlog Cristina",
				"Pavel Simina",
				"Nitipir Cornelia"
			],
			"DOI": "10.7759/cureus.50709",
			"date": "2023-12-20",
			"PMC": "",
			"citation": "",
			"abstract": "Background In the field of precision oncology, comprehensive genomic profiling tests play a very important role by providing a complex understanding of the molecular characteristics of malignant tumors. Therefore, next-generation sequencing (NGS) has become a valuable tool in various aspects of cancer care from diagnosis and monitoring to treatment selection and personalized cancer treatment. Our aim was to evaluate the role of tumor molecular profiling in tailored treatment selection. Methods In our study, we conducted a retrospective analysis to assess the practicality of utilizing NGS testing in patients with metastatic solid tumors. The genomic testing was performed on blood or tissue samples from a fresh biopsy, less than six months old, and the expression of programmed death-ligand 1 was evaluated by immunohistochemistry. Results A total of 75 tests were performed on 66 patients between 2019 and 2022, with a success rate of 80%. The most common pathologies were gastro-intestinal tract cancer (26%), breast cancer (14%), non-small cell lung cancer (11%), and pancreatic cancer\u00a0(11%). There were 9% liquid biopsies and 91% tissue biopsies.\u00a0From all 66 patients tested, 55 had at least one genetic alteration. The most frequent genetic alteration found was TP53 (n=32) followed by KRAS (n=15) and BRCA1/2 (n=12) mutations. There were nine patients tested (14%) that presented a high tumor mutational burden, and only one patient presented high microsatellite instability.\u00a0There were 37 patients (56%) with actionable alterations found from which 14 received matched therapy and four patients were enrolled in clinical trials. The NGS testing played a significant role in determining the next therapeutic strategy in 20 out of 66 patients (30.3%). Conclusion From all the patients included in our analysis, 83% had at least one mutation that is known to be of pathogenic significance but only 23% received treatment selected by the analysis of the tumor's genome, and only 6% were included in a clinical trial. This moderate success of personalized medicine using NGS testing highlights the importance of evaluating the factors that could lead to further improvement.",
			"category": 2,
			"name": "Popa Ana Maria,2023"
		},
		{
			"PMID": 38096571,
			"title": "Assigning mutational signatures to individual samples and individual somatic mutations with SigProfilerAssignment.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"D\u00edaz-Gay Marcos",
				"Vangara Raviteja",
				"Barnes Mark",
				"Wang Xi",
				"Islam S M Ashiqul",
				"Vermes Ian",
				"Duke Stephen",
				"Narasimman Nithish Bharadhwaj",
				"Yang Ting",
				"Jiang Zichen",
				"Moody Sarah",
				"Senkin Sergey",
				"Brennan Paul",
				"Stratton Michael R",
				"Alexandrov Ludmil B"
			],
			"DOI": "10.1093/bioinformatics/btad756",
			"date": "2023-12-25",
			"PMC": "",
			"citation": "",
			"abstract": "Analysis of mutational signatures is a powerful approach for understanding the mutagenic processes that have shaped the evolution of a cancer genome. To evaluate the mutational signatures operative in a cancer genome, one first needs to quantify their activities by estimating the number of mutations imprinted by each signature.",
			"category": 2,
			"name": "D\u00edaz-Gay Marcos,2023"
		},
		{
			"PMID": 38096269,
			"title": "Unravelling cancer subtype-specific driver genes in single-cell transcriptomics data with CSDGI.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Huang Meng",
				"Ma Jiangtao",
				"An Guangqi",
				"Ye Xiucai"
			],
			"DOI": "10.1371/journal.pcbi.1011450",
			"date": "2023-12-29",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is known as a heterogeneous disease. Cancer driver genes (CDGs) need to be inferred for understanding tumor heterogeneity in cancer. However, the existing computational methods have identified many common CDGs. A key challenge exploring cancer progression is to infer cancer subtype-specific driver genes (CSDGs), which provides guidane for the diagnosis, treatment and prognosis of cancer. The significant advancements in single-cell RNA-sequencing (scRNA-seq) technologies have opened up new possibilities for studying human cancers at the individual cell level. In this study, we develop a novel unsupervised method, CSDGI (Cancer Subtype-specific Driver Gene Inference), which applies Encoder-Decoder-Framework consisting of low-rank residual neural networks to inferring driver genes corresponding to potential cancer subtypes at the single-cell level. To infer CSDGs, we apply CSDGI to the tumor single-cell transcriptomics data. To filter the redundant genes before driver gene inference, we perform the differential expression genes (DEGs). The experimental results demonstrate CSDGI is effective to infer driver genes that are cancer subtype-specific. Functional and disease enrichment analysis shows these inferred CSDGs indicate the key biological processes and disease pathways. CSDGI is the first method to explore cancer driver genes at the cancer subtype level. We believe that it can be a useful method to understand the mechanisms of cell transformation driving tumours.",
			"category": 2,
			"name": "Huang Meng,2023"
		},
		{
			"PMID": 38091511,
			"title": "DriverMP enables improved identification of cancer driver genes.",
			"journal": "GigaScience",
			"authorList": [
				"Liu Yangyang",
				"Han Jiyun",
				"Kong Tongxin",
				"Xiao Nannan",
				"Mei Qinglin",
				"Liu Juntao"
			],
			"DOI": "10.1093/gigascience/giad106",
			"date": "2023-12-16",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is widely regarded as a complex disease primarily driven by genetic mutations. A critical concern and significant obstacle lies in discerning driver genes amid an extensive array of passenger genes.",
			"category": 2,
			"name": "Liu Yangyang,2023"
		},
		{
			"PMID": 38045808,
			"title": "Unlocking the power of nanomedicine: the future of nutraceuticals in oncology treatment.",
			"journal": "Frontiers in nutrition",
			"authorList": [
				"Singla Madhav",
				"Gupta Saurabh",
				"Behal Prateek",
				"Singh Sachin Kumar",
				"Preetam Subham",
				"Rustagi Sarvesh",
				"Bora Jutishna",
				"Mittal Pooja",
				"Malik Sumira",
				"Slama Petr"
			],
			"DOI": "10.3389/fnut.2023.1258516",
			"date": "2023-12-05",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer, an intricate and multifaceted disease, is characterized by the uncontrolled proliferation of cells that can lead to serious health complications and ultimately death. Conventional therapeutic strategies mainly target rapidly dividing cancer cells, but often indiscriminately harm healthy cells in the process. As a result, there is a growing interest in exploring novel therapies that are both effective and less toxic to normal cells. Herbs have long been used as natural remedies for various diseases and conditions. Some herbal compounds exhibit potent anti-cancer properties, making them potential candidates for nutraceutical-based treatments. However, despite their promising efficacy, there are considerable limitations in utilizing herbal preparations due to their poor solubility, low bioavailability, rapid metabolism and excretion, as well as potential interference with other medications. Nanotechnology offers a unique platform to overcome these challenges by encapsulating herbal compounds within nanoparticles. This approach not only increases solubility and stability but also enhances the cellular uptake of nutraceuticals, allowing for controlled and targeted delivery of therapeutic agents directly at tumor sites. By harnessing the power of nanotechnology-enabled therapy, this new frontier in cancer treatment presents an opportunity to minimize toxicity while maximizing efficacy. In conclusion, this manuscript provides compelling evidence for integrating nanotechnology with nutraceuticals derived from herbal sources to optimize cancer therapy outcomes. We explore the roadblocks associated with traditional herbal treatments and demonstrate how nanotechnology can help circumvent these issues, paving the way for safer and more effective cancer interventions in future oncological practice.",
			"category": 2,
			"name": "Singla Madhav,2023"
		},
		{
			"PMID": 38045311,
			"title": "Genome-wide detection of somatic mosaicism at short tandem repeats.",
			"journal": "bioRxiv : the preprint server for biology",
			"authorList": [
				"Sehgal Aarushi",
				"Ziaei-Jam Helyaneh",
				"Shen Andrew",
				"Gymrek Melissa"
			],
			"DOI": "10.1101/2023.11.22.568371",
			"date": "2023-12-12",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic mosaicism, in which a mutation occurs post-zygotically, has been implicated in several developmental disorders, cancers, and other diseases. Short tandem repeats (STRs) consist of repeated sequences of 1-6bp and comprise more than 1 million loci in the human genome. Somatic mosaicism at STRs is known to play a key role in the pathogenicity of loci implicated in repeat expansion disorders and is highly prevalent in cancers exhibiting microsatellite instability. While a variety of tools have been developed to genotype germline variation at STRs, a method for systematically identifying mosaic STRs (mSTRs) is lacking.",
			"category": 2,
			"name": "Sehgal Aarushi,2023"
		},
		{
			"PMID": 38040699,
			"title": "SMARCB1 loss activates patient-specific distal oncogenic enhancers in malignant rhabdoid tumors.",
			"journal": "Nature communications",
			"authorList": [
				"Liu Ning Qing",
				"Paassen Irene",
				"Custers Lars",
				"Zeller Peter",
				"Teunissen Hans",
				"Ayyildiz Dilara",
				"He Jiayou",
				"Buhl Juliane Laura",
				"Hoving Eelco Wieger",
				"van Oudenaarden Alexander",
				"de Wit Elzo",
				"Drost Jarno"
			],
			"DOI": "10.1038/s41467-023-43498-3",
			"date": "2023-12-04",
			"PMC": "",
			"citation": "",
			"abstract": "Malignant rhabdoid tumor (MRT) is a highly malignant and often lethal childhood cancer. MRTs are genetically defined by bi-allelic inactivating mutations in SMARCB1, a member of the BRG1/BRM-associated factors (BAF) chromatin remodeling complex. Mutations in BAF complex members are common in human cancer, yet their contribution to tumorigenesis remains in many cases poorly understood. Here, we study derailed regulatory landscapes as a consequence of SMARCB1 loss in the context of MRT. Our multi-omics approach on patient-derived MRT organoids reveals a dramatic reshaping of the regulatory landscape upon SMARCB1 reconstitution. Chromosome conformation capture experiments subsequently reveal patient-specific looping of distal enhancer regions with the promoter of the MYC oncogene. This intertumoral heterogeneity in MYC enhancer utilization is also present in patient MRT tissues as shown by combined single-cell RNA-seq and ATAC-seq. We show that loss of SMARCB1 activates patient-specific epigenetic reprogramming underlying MRT tumorigenesis.",
			"category": 2,
			"name": "Liu Ning Qing,2023"
		},
		{
			"PMID": 38035725,
			"title": "Evaluation of tissue- and plasma-derived tumor mutational burden (TMB) and genomic alterations of interest in CheckMate 848, a study of nivolumab combined with ipilimumab and nivolumab alone in patients with advanced or metastatic solid tumors with high TMB.",
			"journal": "Journal for immunotherapy of cancer",
			"authorList": [
				"He Jie",
				"Kalinava Natallia",
				"Doshi Parul",
				"Pavlick Dean C",
				"Albacker Lee A",
				"Ebot Ericka M",
				"Tukachinsky Hanna",
				"Pratt James",
				"Fusaro Gina",
				"Oxnard Geoffrey R",
				"Green George",
				"Fabrizio David",
				"Baden Jonathan"
			],
			"DOI": "10.1136/jitc-2023-007339",
			"date": "2023-12-04",
			"PMC": "",
			"citation": "",
			"abstract": "An accumulation of somatic mutations in tumors leads to increased neoantigen levels and antitumor immune response. Tumor mutational burden (TMB) reflects the rate of somatic mutations in the tumor genome, as determined from tumor tissue (tTMB) or blood (bTMB). While high tTMB is a biomarker of immune checkpoint inhibitor (ICI) treatment efficacy, few studies have explored the clinical utility of bTMB, a less invasive alternative for TMB assessment. Establishing the correlation between tTMB and bTMB would provide insight into whether bTMB is a potential substitute for tTMB. We explored the tumor genomes of patients enrolled in CheckMate 848 with measurable TMB. The correlation between tTMB and bTMB, and the factors affecting it, were evaluated.",
			"category": 2,
			"name": "He Jie,2023"
		},
		{
			"PMID": 38023160,
			"title": "The implication of next-generation sequencing in the diagnosis and clinical management of non-Hodgkin lymphomas.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Tomacinschii Victor",
				"Mosquera Orgueira Adrian",
				"Santos Carlos Aliste",
				"Robu Maria",
				"Buruiana Sanda",
				"Fraga Rodriguez Maximo Francisco"
			],
			"DOI": "10.3389/fonc.2023.1275327",
			"date": "2023-12-01",
			"PMC": "",
			"citation": "",
			"abstract": "Next generation sequencing (NGS) is a technology that broadens the horizon of knowledge of several somatic pathologies, especially in oncological and oncohematological pathology. In the case of NHL, the understanding of the mechanisms of tumorigenesis, tumor proliferation and the identification of genetic markers specific to different lymphoma subtypes led to more accurate classification and diagnosis. Similarly, the data obtained through NGS allowed the identification of recurrent somatic mutations that can serve as therapeutic targets that can be inhibited and thus reducing the rate of resistant cases. The article's purpose is to offer a comprehensive overview of the best ways of integrating of next-generation sequencing technologies for diagnosis, prognosis, classification, and selection of optimal therapy from the perspective of tailor-made medicine.",
			"category": 2,
			"name": "Tomacinschii Victor,2023"
		},
		{
			"PMID": 38003265,
			"title": "Association of Germline Variation in Driver Genes with Breast Cancer Risk in Chilean Population.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Morales-Pison Sebasti\u00e1n",
				"Tapia Julio C",
				"Morales-Gonz\u00e1lez Sarai",
				"Maldonado Edio",
				"Acu\u00f1a M\u00f3nica",
				"Calaf Gloria M",
				"Jara Lilian"
			],
			"DOI": "10.3390/ijms242216076",
			"date": "2023-11-27",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a genomic disease, with driver mutations contributing to tumorigenesis. These potentially heritable variants influence risk and underlie familial breast cancer (BC). This study evaluated associations between BC risk and 13 SNPs in driver genes ",
			"category": 2,
			"name": "Morales-Pison Sebasti\u00e1n,2023"
		},
		{
			"PMID": 37992135,
			"title": "A multiscale model of the role of microenvironmental factors in cell segregation and heterogeneity in breast cancer development.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Romero-Arias J Roberto",
				"Gonz\u00e1lez-Castro Carlos A",
				"Ram\u00edrez-Santiago Guillermo"
			],
			"DOI": "10.1371/journal.pcbi.1011673",
			"date": "2023-12-07",
			"PMC": "",
			"citation": "",
			"abstract": "We analyzed a quantitative multiscale model that describes the epigenetic dynamics during the growth and evolution of an avascular tumor. A gene regulatory network (GRN) formed by a set of ten genes that are believed to play an important role in breast cancer development was kinetically coupled to the microenvironmental agents: glucose, estrogens, and oxygen. The dynamics of spontaneous mutations was described by a Yule-Furry master equation whose solution represents the probability that a given cell in the tissue undergoes a certain number of mutations at a given time. We assumed that the mutation rate is modified by a spatial gradient of nutrients. The tumor mass was simulated by means of cellular automata supplemented with a set of reaction diffusion equations that described the transport of microenvironmental agents. By analyzing the epigenetic state space described by the GRN dynamics, we found three attractors that were identified with cellular epigenetic states: normal, precancer and cancer. For two-dimensional (2D) and three-dimensional (3D) tumors we calculated the spatial distribution of the following quantities: (i) number of mutations, (ii) mutation of each gene and, (iii) phenotypes. Using estrogen as the principal microenvironmental agent that regulates cell proliferation process, we obtained tumor shapes for different values of estrogen consumption and supply rates. It was found that he majority of mutations occurred in cells that were located close to the 2D tumor perimeter or close to the 3D tumor surface. Also, it was found that the occurrence of different phenotypes in the tumor are controlled by estrogen concentration levels since they can change the individual cell threshold and gene expression levels. All results were consistently observed for 2D and 3D tumors.",
			"category": 2,
			"name": "Romero-Arias J Roberto,2023"
		},
		{
			"PMID": 37947626,
			"title": "Functional Proteomics Characterization of the Role of SPRYD7 in Colorectal Cancer Progression and Metastasis.",
			"journal": "Cells",
			"authorList": [
				"Montero-Calle Ana",
				"Jim\u00e9nez de Oca\u00f1a Sof\u00eda",
				"Benavente-Naranjo Ruth",
				"Rejas-Gonz\u00e1lez Raquel",
				"Bartolom\u00e9 Rub\u00e9n A",
				"Mart\u00ednez-Useros Javier",
				"Sanz Rodrigo",
				"Dziakov\u00e1 Jana",
				"Fern\u00e1ndez-Ace\u00f1ero Mar\u00eda Jes\u00fas",
				"Mendiola Marta",
				"Casal Jos\u00e9 Ignacio",
				"Pel\u00e1ez-Garc\u00eda Alberto",
				"Barderas Rodrigo"
			],
			"DOI": "10.3390/cells12212548",
			"date": "2023-11-15",
			"PMC": "",
			"citation": "",
			"abstract": "SPRY domain-containing protein 7 (SPRYD7) is a barely known protein identified via spatial proteomics as being upregulated in highly metastatic-to-liver KM12SM colorectal cancer (CRC) cells in comparison to its isogenic poorly metastatic KM12C CRC cells. Here, we aimed to analyze SPRYD7's role in CRC via functional proteomics. Through immunohistochemistry, the overexpression of SPRYD7 was observed to be associated with the poor survival of CRC patients and with an aggressive and metastatic phenotype. Stable SPRYD7 overexpression was performed in KM12C and SW480 poorly metastatic CRC cells and in their isogenic highly metastatic-to-liver-KM12SM-and-to-lymph-nodes SW620 CRC cells, respectively. Upon upregulation of SPRYD7, in vitro and in vivo functional assays confirmed a key role of SPRYD7 in the invasion and migration of CRC cells and in liver homing and tumor growth. Additionally, transient siRNA SPRYD7 silencing allowed us to confirm in vitro functional results. Furthermore, SPRYD7 was observed as an inductor of angiogenesis. In addition, the dysregulated SPRYD7-associated proteome and SPRYD7 interactors were elucidated via 10-plex TMT quantitative proteins, immunoproteomics, and bioinformatics. After WB validation, the biological pathways associated with the stable overexpression of SPRYD7 were visualized. In conclusion, it was demonstrated here that SPRYD7 is a novel protein associated with CRC progression and metastasis. Thus, SPRYD7 and its interactors might be of relevance in identifying novel therapeutic targets for advanced CRC.",
			"category": 2,
			"name": "Montero-Calle Ana,2023"
		},
		{
			"PMID": 37945816,
			"title": "Investigation of GPR143 as a promising novel marker for the progression of skin cutaneous melanoma through bioinformatic analyses and cell experiments.",
			"journal": "Apoptosis : an international journal on programmed cell death",
			"authorList": [
				"Bai Ruimin",
				"Yin Pan",
				"Xing Zixuan",
				"Wu Shaobo",
				"Zhang Wen",
				"Ma Xinyu",
				"Gan Xinyi",
				"Liang Yuxia",
				"Zang Qijuan",
				"Lei Hao",
				"Wei Yi",
				"Zhang Chaonan",
				"Dai Bingling",
				"Zheng Yan"
			],
			"DOI": "10.1007/s10495-023-01913-6",
			"date": "2024-02-19",
			"PMC": "",
			"citation": "",
			"abstract": "Skin cutaneous melanoma (SKCM) is an aggressive and life-threatening skin cancer. G-protein coupled receptor 143 (GPR143) belongs to the superfamily of G protein-coupled receptors.",
			"category": 2,
			"name": "Bai Ruimin,2024"
		},
		{
			"PMID": 37907826,
			"title": "Expanded Alternatives of CRISPR-Cas9 Applications in Immunotherapy of Colorectal Cancer.",
			"journal": "Molecular diagnosis & therapy",
			"authorList": [
				"Arroyo-Olarte Rub\u00e9n",
				"Mej\u00eda-Mu\u00f1oz Aranza",
				"Le\u00f3n-Cabrera Sonia"
			],
			"DOI": "10.1007/s40291-023-00680-z",
			"date": "2024-01-15",
			"PMC": "",
			"citation": "",
			"abstract": "Immunotherapy for colorectal cancer (CRC) is limited to patients with advanced disease who have already undergone first-line chemotherapy and whose tumors exhibit microsatellite instability. Novel technical strategies are required to enhance therapeutic options and achieve a more robust immunological response. Therefore, exploring gene analysis and manipulation at the molecular level can further accelerate the development of advanced technologies to address these challenges. The emergence of advanced genome editing technology, particularly of clustered, regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) 9, holds promise in expanding the boundaries of cancer immunotherapy. In this manuscript, we provide a comprehensive review of the applications and perspectives of CRISPR technology in improving the design, generation, and efficiency of current immunotherapies, focusing on solid tumors such as colorectal cancer, where these approaches have not been as successful as in hematological conditions.",
			"category": 2,
			"name": "Arroyo-Olarte Rub\u00e9n,2024"
		},
		{
			"PMID": 37900243,
			"title": "Prognostic model of hepatocellular carcinoma based on cancer grade.",
			"journal": "World journal of clinical cases",
			"authorList": [
				"Zhang Guo-Xin",
				"Ding Xiao-Sheng",
				"Wang You-Li"
			],
			"DOI": "10.12998/wjcc.v11.i27.6383",
			"date": "2023-11-03",
			"PMC": "",
			"citation": "",
			"abstract": "Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. With highly invasive biological characteristics and a lack of obvious clinical manifestations, HCC usually has a poor prognosis and ranks fourth in cancer mortality. The aetiology and exact molecular mechanism of primary HCC are still unclear.",
			"category": 2,
			"name": "Zhang Guo-Xin,2023"
		},
		{
			"PMID": 37894789,
			"title": "Why Are There So Few FDA-Approved Therapeutics for Wound Healing?",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Chen Mei",
				"Chang Cheng",
				"Levian Brandon",
				"Woodley David T",
				"Li Wei"
			],
			"DOI": "10.3390/ijms242015109",
			"date": "2023-10-30",
			"PMC": "",
			"citation": "",
			"abstract": "Since the only and the milestone FDA approval of becaplermin gel (Regranex",
			"category": 2,
			"name": "Chen Mei,2023"
		},
		{
			"PMID": 37877158,
			"title": "Transcriptional background effects on a tumor driver gene in different pigment cell types of medaka.",
			"journal": "Journal of experimental zoology. Part B, Molecular and developmental evolution",
			"authorList": [
				"Abdulsahib Shahad",
				"Boswell William",
				"Boswell Mikki",
				"Savage Markita",
				"Schartl Manfred",
				"Lu Yuan"
			],
			"DOI": "10.1002/jez.b.23224",
			"date": "2024-04-30",
			"PMC": "",
			"citation": "",
			"abstract": "The Xiphophorus melanoma receptor kinase gene, xmrk, is a bona fide oncogene driving melanocyte tumorigenesis of Xiphophorus fish. When ectopically expressed in medaka, it not only induces development of several pigment cell tumor types in different strains of medaka but also induces different tumor types within the same animal, suggesting its oncogenic activity has a transcriptomic background effect. Although the central pathways that xmrk utilizes to lead to melanomagenesis are well documented, genes and genetic pathways that modulate the oncogenic effect and alter the course of disease have not been studied so far. To understand how the genetic networks between different histocytes of xmrk-driven tumors are composed, we isolated two types of tumors, melanoma and xanthoerythrophoroma, from the same xmrk transgenic medaka individuals, established the transcriptional profiles of both xmrk-driven tumors, and compared (1) genes that are co-expressed with xmrk in both tumor types, and (2) differentially expressed genes and their associated molecular functions, between the two tumor types. Transcriptomic comparisons between the two tumor types show melanoma and xanthoerythrophoroma are characterized by transcriptional features representing varied functions, indicating distinct molecular interactions between the driving oncogene and the cell-type-specific transcriptomes. Melanoma tumors exhibit gene signatures that are relevant to proliferation and invasion, while xanthoerythrophoroma tumors are characterized by expression profiles related to metabolism and DNA repair. We conclude the transcriptomic backgrounds, exemplified by cell-type-specific genes that are downstream of xmrk effected signaling pathways, contribute the potential to change the course of tumor development and may affect overall tumor outcomes.",
			"category": 2,
			"name": "Abdulsahib Shahad,2024"
		},
		{
			"PMID": 37873809,
			"title": "The ErbB Signaling Network and Its Potential Role in Endometrial Cancer.",
			"journal": "Epigenomes",
			"authorList": [
				"Androutsopoulos Georgios",
				"Styliara Ioanna",
				"Zarogianni Evgenia",
				"Lazurko Nadia",
				"Valasoulis George",
				"Michail Georgios",
				"Adonakis Georgios"
			],
			"DOI": "10.3390/epigenomes7040024",
			"date": "2023-10-27",
			"PMC": "",
			"citation": "",
			"abstract": "Endometrial cancer (EC) is the second most common malignancy of the female reproductive system worldwide. The updated EC classification emphasizes the significant role of various signaling pathways such as PIK3CA-PIK3R1-PTEN and RTK/RAS/\u03b2-catenin in EC pathogenesis. Some of these pathways are part of the EGF system signaling network, which becomes hyperactivated by various mechanisms and participates in cancer pathogenesis. In EC, the expression of ErbB receptors is significantly different, compared with the premenopausal and postmenopausal endometrium, mainly because of the increased transcriptional activity of ErbB encoding genes in EC cells. Moreover, there are some differences in ErbB-2 receptor profile among EC subgroups that could be explained by the alterations in pathophysiology and clinical behavior of various EC histologic subtypes. The fact that ErbB-2 receptor expression is more common in aggressive EC histologic subtypes (papillary serous and clear cell) could indicate a future role of ErbB-targeted therapies in well-defined EC subgroups with overexpression of ErbB receptors.",
			"category": 2,
			"name": "Androutsopoulos Georgios,2023"
		},
		{
			"PMID": 37870450,
			"title": "Genome-wide direct quantification of in vivo mutagenesis using high-accuracy paired-end and complementary consensus sequencing.",
			"journal": "Nucleic acids research",
			"authorList": [
				"You Xinyue",
				"Cao Yiyi",
				"Suzuki Takayoshi",
				"Shao Jie",
				"Zhu Benzhan",
				"Masumura Kenichi",
				"Xi Jing",
				"Liu Weiying",
				"Zhang Xinyu",
				"Luan Yang"
			],
			"DOI": "10.1093/nar/gkad909",
			"date": "2023-12-01",
			"PMC": "",
			"citation": "",
			"abstract": "Error-corrected next-generation sequencing (ecNGS) is an emerging technology for accurately measuring somatic mutations. Here, we report paired-end and complementary consensus sequencing (PECC-Seq), a high-accuracy ecNGS approach for genome-wide somatic mutation detection. We characterize a novel 2-aminoimidazolone lesion besides 7,8-dihydro-8-oxoguanine and the resulting end-repair artifacts originating from NGS library preparation that obscure the sequencing accuracy of NGS. We modify library preparation protocol for the enzymatic removal of end-repair artifacts and improve the accuracy of our previously developed duplex consensus sequencing method. Optimized PECC-Seq shows an error rate of\u00a0<5\u00a0\u00d7\u00a010-8 with consensus bases compressed from approximately 25 Gb of raw sequencing data, enabling the accurate detection of low-abundance somatic mutations. We apply PECC-Seq to the quantification of in vivo mutagenesis. Compared with the classic gpt gene mutation assay using gpt delta transgenic mice, PECC-Seq exhibits high sensitivity in quantitatively measuring dose-dependent mutagenesis induced by Aristolochic acid I (AAI). Moreover, PECC-Seq specifically characterizes the distinct genome-wide mutational signatures of AAI, Benzo[a]pyrene, N-Nitroso-N-ethylurea and N-nitrosodiethylamine and reveals the mutational signature of Quinoline in common mouse models. Overall, our findings demonstrate that high-accuracy PECC-Seq is a promising tool for genome-wide somatic mutagenesis quantification and for in\u00a0vivo mutagenicity testing.",
			"category": 2,
			"name": "You Xinyue,2023"
		},
		{
			"PMID": 37832550,
			"title": "Stem cell mutations, associated cancer risk, and consequences for regenerative medicine.",
			"journal": "Cell stem cell",
			"authorList": [
				"Derks Lucca L M",
				"van Boxtel Ruben"
			],
			"DOI": "10.1016/j.stem.2023.09.008",
			"date": "2023-11-06",
			"PMC": "",
			"citation": "",
			"abstract": "Mutation accumulation in stem cells has been associated with cancer risk. However, the presence of numerous mutant clones in healthy tissues has raised the question of what limits cancer initiation. Here, we review recent developments in characterizing mutation accumulation in healthy tissues and compare mutation rates in stem cells during development and adult life with corresponding cancer risk. A certain level of mutagenesis within the stem cell pool might be beneficial to limit the size of malignant clones through competition. This knowledge impacts our understanding of carcinogenesis with potential consequences for the use of stem cells in regenerative medicine.",
			"category": 2,
			"name": "Derks Lucca L M,2023"
		},
		{
			"PMID": 37805624,
			"title": "Recent advancement in targeted therapy and role of emerging technologies to treat cancer.",
			"journal": "Medical oncology (Northwood, London, England)",
			"authorList": [
				"Barot Shrikant",
				"Patel Henis",
				"Yadav Anjali",
				"Ban Igor"
			],
			"DOI": "10.1007/s12032-023-02184-6",
			"date": "2023-10-09",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a complex disease that causes abnormal cell growth and spread. DNA mutations, chemical or environmental exposure, viral infections, chronic inflammation, hormone abnormalities, etc., are underlying factors that can cause cancer. Drug resistance and toxicity complicate cancer treatment. Additionally, the variability of cancer makes it difficult to establish universal treatment guidelines. Next-generation sequencing has made genetic testing inexpensive. This uncovers genetic mutations that can be treated with specialty drugs. AI (artificial intelligence), machine learning, biopsy, next-generation sequencing, and digital pathology provide personalized cancer treatment. This allows for patient-specific biological targets and cancer treatment. Monoclonal antibodies, CAR-T, and cancer vaccines are promising cancer treatments. Recent trial data incorporating these therapies have shown superiority in clinical outcomes and drug tolerability over conventional chemotherapies. Combinations of these therapies with new technology can change cancer treatment and help many. This review discusses the development and challenges of targeted therapies like monoclonal antibodies (mAbs), bispecific antibodies (BsAbs), bispecific T cell engagers (BiTEs), dual variable domain (DVD) antibodies, CAR-T therapy, cancer vaccines, oncolytic viruses, lipid nanoparticle-based mRNA cancer vaccines, and their clinical outcomes in various cancers. We will also study how artificial intelligence and machine learning help find new cancer treatment targets.",
			"category": 2,
			"name": "Barot Shrikant,2023"
		},
		{
			"PMID": 37801170,
			"title": "Colorectal cancer cell membrane biomimetic ferroferric oxide nanomaterials for homologous bio-imaging and chemotherapy application.",
			"journal": "Medical oncology (Northwood, London, England)",
			"authorList": [
				"Li Jun",
				"Lin Chenyu",
				"Zhu Yuqian",
				"Shao Chengwei",
				"Wang Tiegong",
				"Chen Bingdi"
			],
			"DOI": "10.1007/s12032-023-02175-7",
			"date": "2023-10-09",
			"PMC": "",
			"citation": "",
			"abstract": "The research of nanomaterials for bio-imaging and theranostic are very active nowadays with unprecedented advantages in nanomedicine. Homologous targeting and bio-imaging greatly improve the ability of targeted drug delivery and enhance active targeting and treatment ability of nanomedicine for the tumor. In this work, lycorine hydrochloride (LH) and magnetic iron oxide nanoparticles coated with a colorectal cancer (CRC) cell membrane (LH-Fe",
			"category": 2,
			"name": "Li Jun,2023"
		},
		{
			"PMID": 37795042,
			"title": "Innovative Strategies of Reprogramming Immune System Cells by Targeting CRISPR/Cas9-Based Genome-Editing Tools: A New Era of Cancer Management.",
			"journal": "International journal of nanomedicine",
			"authorList": [
				"Allemailem Khaled S",
				"Alsahli Mohammed A",
				"Almatroudi Ahmad",
				"Alrumaihi Faris",
				"Al Abdulmonem Waleed",
				"Moawad Amira A",
				"Alwanian Wanian M",
				"Almansour Nahlah Makki",
				"Rahmani Arshad Husain",
				"Khan Amjad Ali"
			],
			"DOI": "10.2147/IJN.S424872",
			"date": "2023-10-06",
			"PMC": "",
			"citation": "",
			"abstract": "The recent developments in the study of clustered regularly interspaced short palindromic repeats/associated protein 9 (CRISPR/Cas9) system have revolutionized the art of genome-editing and its applications for cellular differentiation and immune response behavior. This technology has further helped in understanding the mysteries of cancer progression and possible designing of novel antitumor immunotherapies. CRISPR/Cas9-based genome-editing is now often used to engineer universal T-cells, equipped with recombinant T-cell receptor (TCR) or chimeric antigen receptor (CAR). In addition, this technology is used in cytokine stimulation, antibody designing, natural killer (NK) cell transfer, and to overcome immune checkpoints. The innovative potential of CRISPR/Cas9 in preparing the building blocks of adoptive cell transfer (ACT) immunotherapy has opened a new window of antitumor immunotherapy and some of them have gained FDA approval. The manipulation of immunogenetic regulators has opened a new interface for designing, implementation and interpretation of CRISPR/Cas9-based screening in immuno-oncology. Several cancers like lymphoma, melanoma, lung, and liver malignancies have been treated with this strategy, once thought to be impossible. The safe and efficient delivery of CRISPR/Cas9 system within the immune cells for the genome-editing strategy is a challenging task which needs to be sorted out for efficient immunotherapy. Several targeting approaches like virus-mediated, electroporation, microinjection and nanoformulation-based methods have been used, but each procedure offers some limitations. Here, we elaborate the recent updates of cancer management through immunotherapy in partnership with CRISPR/Cas9 technology. Further, some innovative methods of targeting this genome-editing system within the immune system cells for reprogramming them, as a novel strategy of anticancer immunotherapy is elaborated. In addition, future prospects and clinical trials are also discussed.",
			"category": 2,
			"name": "Allemailem Khaled S,2023"
		},
		{
			"PMID": 37790807,
			"title": "Crosstalk between endoplasmic reticulum stress and multidrug-resistant cancers: hope or frustration.",
			"journal": "Frontiers in pharmacology",
			"authorList": [
				"Qing Bowen",
				"Wang Song",
				"Du Yingan",
				"Liu Can",
				"Li Wei"
			],
			"DOI": "10.3389/fphar.2023.1273987",
			"date": "2023-10-05",
			"PMC": "",
			"citation": "",
			"abstract": "Endoplasmic reticulum stress (ERS) is a kind of cell response for coping with hypoxia and other stresses. Pieces of evidence show that continuous stress can promote the occurrence, development, and drug resistance of tumors through the unfolded protein response. Therefore, the abnormal ac-tivation of ERS and its downstream signaling pathways not only can regulate tumor growth and metastasis but also profoundly affect the efficacy of antitumor therapy. Therefore, revealing the molecular mechanism of ERS may be expected to solve the problem of tumor multidrug resistance (MDR) and become a novel strategy for the treatment of refractory and recurrent tumors. This re-view summarized the mechanism of ERS and tumor MDR, reviewed the relationship between ERS and tumor MDR, introduced the research status of tumor tissue and ERS, and previewed the prospect of targeting ERS to improve the therapeutic effect of tumor MDR. This article aims to provide researchers and clinicians with new ideas and inspiration for basic antitumor treatment.",
			"category": 2,
			"name": "Qing Bowen,2023"
		},
		{
			"PMID": 37754118,
			"title": "Advancing Healthcare: Synergizing Biosensors and Machine Learning for Early Cancer Diagnosis.",
			"journal": "Biosensors",
			"authorList": [
				"Kokabi Mahtab",
				"Tahir Muhammad Nabeel",
				"Singh Darshan",
				"Javanmard Mehdi"
			],
			"DOI": "10.3390/bios13090884",
			"date": "2023-10-03",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a fatal disease and a significant cause of millions of deaths. Traditional methods for cancer detection often have limitations in identifying the disease in its early stages, and they can be expensive and time-consuming. Since cancer typically lacks symptoms and is often only detected at advanced stages, it is crucial to use affordable technologies that can provide quick results at the point of care for early diagnosis. Biosensors that target specific biomarkers associated with different types of cancer offer an alternative diagnostic approach at the point of care. Recent advancements in manufacturing and design technologies have enabled the miniaturization and cost reduction of point-of-care devices, making them practical for diagnosing various cancer diseases. Furthermore, machine learning (ML) algorithms have been employed to analyze sensor data and extract valuable information through the use of statistical techniques. In this review paper, we provide details on how various machine learning algorithms contribute to the ongoing development of advanced data processing techniques for biosensors, which are continually emerging. We also provide information on the various technologies used in point-of-care cancer diagnostic biosensors, along with a comparison of the performance of different ML algorithms and sensing modalities in terms of classification accuracy.",
			"category": 2,
			"name": "Kokabi Mahtab,2023"
		},
		{
			"PMID": 37716438,
			"title": "Next-generation sequencing methodologies to detect low-frequency mutations: \"Catch me if you can\".",
			"journal": "Mutation research. Reviews in mutation research",
			"authorList": [
				"Menon Vijay",
				"Brash Douglas E"
			],
			"DOI": "10.1016/j.mrrev.2023.108471",
			"date": "2023-12-16",
			"PMC": "",
			"citation": "",
			"abstract": "Mutations, the irreversible changes in an organism's DNA sequence, are present in tissues at a variant allele frequency (VAF) ranging from \u223c10",
			"category": 2,
			"name": "Menon Vijay,2023"
		},
		{
			"PMID": 37680708,
			"title": "Trinity of inflammation, innate immune cells and cross-talk of signalling pathways in tumour microenvironment.",
			"journal": "Frontiers in pharmacology",
			"authorList": [
				"Attiq Ali",
				"Afzal Sheryar"
			],
			"DOI": "10.3389/fphar.2023.1255727",
			"date": "2023-09-10",
			"PMC": "",
			"citation": "",
			"abstract": "Unresolved inflammation is a pathological consequence of persistent inflammatory stimulus and perturbation in regulatory mechanisms. It increases the risk of tumour development and orchestrates all stages of tumorigenesis in selected organs. In certain cancers, inflammatory processes create the appropriate conditions for neoplastic transformation. While in other types, oncogenic changes pave the way for an inflammatory microenvironment that leads to tumour development. Of interest, hallmarks of tumour-promoting and cancer-associated inflammation are striking similar, sharing a complex network of stromal (fibroblasts and vascular cells) and inflammatory immune cells that collectively form the tumour microenvironment (TME). The cross-talks of signalling pathways initially developed to support homeostasis, change their role, and promote atypical proliferation, survival, angiogenesis, and subversion of adaptive immunity in TME. These transcriptional and regulatory pathways invariably contribute to cancer-promoting inflammation in chronic inflammatory disorders and foster \"smouldering\" inflammation in the microenvironment of various tumour types. Besides identifying common target sites of numerous cancer types, signalling programs and their cross-talks governing immune cells' plasticity and functional diversity can be used to develop new fate-mapping and lineage-tracing mechanisms. Here, we review the vital molecular mechanisms and pathways that establish the connection between inflammation and tumour development, progression, and metastasis. We also discussed the cross-talks between signalling pathways and devised strategies focusing on these interaction mechanisms to harness synthetic lethal drug combinations for targeted cancer therapy.",
			"category": 2,
			"name": "Attiq Ali,2023"
		},
		{
			"PMID": 37671310,
			"title": "Impact of Amplified Oncogenes on Salivary Gland Carcinomas.",
			"journal": "Cancer diagnosis & prognosis",
			"authorList": [
				"Papanikolaou Vasileios",
				"Chrysovergis Aristeidis",
				"Asimakopoulos Asimakis D",
				"Spyropoulou Despoina",
				"Ragos Vasileios",
				"Papanastasiou George",
				"Papouliakos Sotirios",
				"Mastronikoli Sofianiki",
				"Roukas Dimitrios",
				"Tsiambas Evangelos",
				"Pantos Pavlos",
				"Peschos Dimitrios",
				"Mastronikolis Nicholas",
				"Manaios Loukas",
				"Fotiades Panagiotis",
				"Vylliotis Antonis",
				"Kyrodimos Efthymios"
			],
			"DOI": "10.21873/cdp.10250",
			"date": "2023-09-07",
			"PMC": "",
			"citation": "",
			"abstract": "In normal epithelia, proto-oncogenes regulate critical intra- or intercellular functions, including cell growth and proliferation, apoptosis, and signaling transduction from the cell periphery (extracellular space) to the nucleus mediated by different pathways. Oncogenes are the mutated or amplified forms of the corresponding proto-oncogenes that are crucially involved in cell neoplastic and malignant transformation during carcinogenesis. Salivary gland carcinomas (SGCs) demonstrate a variety of histogenetic types. They are characterized by a broad spectrum of chromosomal and gene alterations. In particular, amplifications in specific genes [human epidermal growth factor receptor 2 (HER2), human epidermal growth factor receptor 4 (HER4), epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), Mouse double minute 2 homolog (MDM2), androgen receptor (AR), programmed death (ligand 1 (PD-L1), neurogenic differentiation factor 2 (NEUROD2), phosphatidylinositol 3,4,5-trisphosphate-dependent RAC exchanger 1 protein (PREX1), cyclin-dependent kinase4/6 (CDK4/6), proline-rich acidic protein 1 (PRAP1), kell antigen system (KEL), glutamate receptor subunit epsilon 2 (GRIN2D), Ewing sarcoma RNA-binding protein 1 (EWSR1), MYC proto-oncogene (MYC)] combined or not with chromosomal numerical imbalances (aneuploidy/ polysomy/monosomy) form different genetic signatures affecting the response to monoclonal antibody-based, oncologicaly targeted regimens. Different SGC histotypes demonstrate specific combinations of mutated/amplified genes that modify their clinicohistological features. In the current molecular review, we present the most important amplified oncogenes and their impact on the biological behavior of SGCS.",
			"category": 2,
			"name": "Papanikolaou Vasileios,2023"
		},
		{
			"PMID": 37667096,
			"title": "MYEOV with High Frequencies of Mutations in Head and Neck Cancers Facilitates Cancer Cell Malignant Behaviors.",
			"journal": "Biochemical genetics",
			"authorList": [
				"Ou Deming",
				"Wu Ying",
				"Zhang Jibin",
				"Liu Jun",
				"Liu Zeyu",
				"Shao Minfeng",
				"Guo Xiaoying",
				"Cui Shiman"
			],
			"DOI": "10.1007/s10528-023-10484-9",
			"date": "2024-06-19",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer driver genes (CDGs) and the driver mutations disrupt the homeostasis of numerous critical cell activities, thereby playing a critical role in tumor initiation and progression. In this study, integrative bioinformatics analyses were performed based on a series of online databases, aiming to identify driver genes with high frequencies of mutations in head and neck cancers. Higher myeloma overexpressed (MYEOV) genetic variation frequency and expression level were connected to a poorer prognosis in head and neck cancer patients. MYEOV was dramatically upregulated within head and neck tumor samples and cells. Consistently, MYEOV overexpression remarkably enhanced the aggressiveness of head and neck cancer cells by promoting colony formation, cell invasion, and cell migration. Conversely, MYEOV knockdown attenuated cancer cell aggressiveness and inhibited tumor growth and metastasis in the oral orthotopic tumor model. In conclusion, MYEOV is overexpressed in head and neck cancer, with greater mutation frequencies correlating to a poorer prognosis in head and neck cancer patients. MYEOV serves as an oncogene in head and neck cancer through the promotion of tumor cell colony formation, invasion, and migration, as well as promoting tumor growth and metastasis in the oral orthotopic tumor model.",
			"category": 2,
			"name": "Ou Deming,2024"
		},
		{
			"PMID": 37637038,
			"title": "Molecular mechanism of palmitic acid and its derivatives in tumor progression.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Wang Xitan",
				"Zhang Chaonan",
				"Bao Na"
			],
			"DOI": "10.3389/fonc.2023.1224125",
			"date": "2023-08-29",
			"PMC": "",
			"citation": "",
			"abstract": "Palmitic acid (PA) is a saturated fatty acid commonly found in coconut oil and palm oil. It serves as an energy source for the body and plays a role in the structure and function of cell membranes. Beyond its industrial applications, PA has gained attention for its potential therapeutic properties. Modern pharmacological studies have demonstrated that PA exhibits anti-inflammatory, antioxidant, and immune-enhancing effects. In recent years, PA has emerged as a promising anti-tumor agent with demonstrated efficacy against various malignancies including gastric cancer, liver cancer, cervical cancer, breast cancer, and colorectal cancer. Its anti-tumor effects encompass inducing apoptosis in tumor cells, inhibiting tumor cell proliferation, suppressing metastasis and invasion, enhancing sensitivity to chemotherapy, and improving immune function. The main anticancer mechanism of palmitic acid (PA) involves the induction of cell apoptosis through the mitochondrial pathway, facilitated by the promotion of intracellular reactive oxygen species (ROS) generation. PA also exhibits interference with the cancer cell cycle, leading to cell cycle arrest predominantly in the G1 phase. Moreover, PA induces programmed cell autophagy death, inhibits cell migration, invasion, and angiogenesis, and synergistically enhances the efficacy of chemotherapy drugs while reducing adverse reactions. PA acts on various intracellular and extracellular targets, modulating tumor cell signaling pathways, including the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), endoplasmic reticulum (ER), B Cell Lymphoma-2 (Bcl-2), P53, and other signaling pathways. Furthermore, derivatives of PA play a significant regulatory role in tumor resistance processes. This paper provides a comprehensive review of recent studies investigating the anti-tumor effects of PA. It summarizes the underlying mechanisms through which PA exerts its anti-tumor effects, aiming to inspire new perspectives for the treatment of malignant tumors in clinical settings and the development of novel anti-cancer drugs.",
			"category": 2,
			"name": "Wang Xitan,2023"
		},
		{
			"PMID": 37601684,
			"title": "Single-cell RNA sequencing identifies a novel proliferation cell type affecting clinical outcome of pancreatic ductal adenocarcinoma.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Ye Bicheng",
				"Wang Qi",
				"Zhu Xiaofeng",
				"Zeng Lingling",
				"Luo Huiyuan",
				"Xiong Yan",
				"Li Qin",
				"Zhu Qinmei",
				"Zhao Songyun",
				"Chen Ting",
				"Xie Jingen"
			],
			"DOI": "10.3389/fonc.2023.1236435",
			"date": "2023-08-23",
			"PMC": "",
			"citation": "",
			"abstract": "Pancreatic ductal adenocarcinoma (PDAC) is an extremely deadly neoplasm, with only a 5-year survival rate of around 9%. The tumor and its microenvironment are highly heterogeneous, and it is still unknown which cell types influence patient outcomes.",
			"category": 2,
			"name": "Ye Bicheng,2023"
		},
		{
			"PMID": 37592287,
			"title": "Sequence dependencies and mutation rates of localized mutational processes in cancer.",
			"journal": "Genome medicine",
			"authorList": [
				"Poulsgaard Gustav Alexander",
				"S\u00f8rensen Simon Grund",
				"Juul Randi Istrup",
				"Nielsen Morten Muhlig",
				"Pedersen Jakob Skou"
			],
			"DOI": "10.1186/s13073-023-01217-z",
			"date": "2023-08-21",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer mutations accumulate through replication errors and DNA damage coupled with incomplete repair. Individual mutational processes often show nucleotide sequence and functional region preferences. As a result, some sequence contexts mutate at much higher rates than others, with additional variation found between functional regions. Mutational hotspots, with recurrent mutations across cancer samples, represent genomic positions with elevated mutation rates, often caused by highly localized mutational processes.",
			"category": 2,
			"name": "Poulsgaard Gustav Alexander,2023"
		},
		{
			"PMID": 37540596,
			"title": "Topography of mutational signatures in human cancer.",
			"journal": "Cell reports",
			"authorList": [
				"Otlu Bur\u00e7ak",
				"D\u00edaz-Gay Marcos",
				"Vermes Ian",
				"Bergstrom Erik N",
				"Zhivagui Maria",
				"Barnes Mark",
				"Alexandrov Ludmil B"
			],
			"DOI": "10.1016/j.celrep.2023.112930",
			"date": "2023-09-13",
			"PMC": "",
			"citation": "",
			"abstract": "The somatic mutations found in a cancer genome are imprinted by different mutational processes. Each process exhibits a characteristic mutational signature, which can be affected by the genome architecture. However, the interplay between mutational signatures and topographical genomic features has not been extensively explored. Here, we integrate mutations from 5,120 whole-genome-sequenced tumors from 40 cancer types with 516 topographical features from ENCODE to evaluate the effect of nucleosome occupancy, histone modifications, CTCF binding, replication timing, and transcription/replication strand asymmetries on the cancer-specific accumulation of mutations from distinct mutagenic processes. Most mutational signatures are affected by topographical features, with signatures of related etiologies being similarly affected. Certain signatures exhibit periodic behaviors or cancer-type-specific enrichments/depletions near topographical features, revealing further information about the processes that imprinted them. Our findings, disseminated via the COSMIC (Catalog of Somatic Mutations in Cancer) signatures database, provide a comprehensive online resource for exploring the interactions between mutational signatures and topographical features across human cancer.",
			"category": 2,
			"name": "Otlu Bur\u00e7ak,2023"
		},
		{
			"PMID": 37516822,
			"title": "Network embedding framework for driver gene discovery by combining functional and structural information.",
			"journal": "BMC genomics",
			"authorList": [
				"Chu Xin",
				"Guan Boxin",
				"Dai Lingyun",
				"Liu Jin-Xing",
				"Li Feng",
				"Shang Junliang"
			],
			"DOI": "10.1186/s12864-023-09515-x",
			"date": "2023-09-25",
			"PMC": "",
			"citation": "",
			"abstract": "Comprehensive analysis of multiple data sets can identify potential driver genes for various cancers. In recent years, driver gene discovery based on massive mutation data and gene interaction networks has attracted increasing attention, but there is still a need to explore combining functional and structural information of genes in protein interaction networks to identify driver genes. Therefore, we propose a network embedding framework combining functional and structural information to identify driver genes. Firstly, we combine the mutation data and gene interaction networks to construct mutation integration network using network propagation algorithm. Secondly, the struc2vec model is used for extracting gene features from the mutation integration network, which contains both gene's functional and structural information. Finally, machine learning algorithms are utilized to identify the driver genes. Compared with the previous four excellent methods, our method can find gene pairs that are distant from each other through structural similarities and has better performance in identifying driver genes for 12 cancers in the cancer genome atlas. At the same time, we also conduct a comparative analysis of three gene interaction networks, three gene standard sets, and five machine learning algorithms. Our framework provides a new perspective for feature selection to identify novel driver genes.",
			"category": 2,
			"name": "Chu Xin,2023"
		},
		{
			"PMID": 37511629,
			"title": "SKAP1 Is a Novel Biomarker and Therapeutic Target for Gastric Cancer: Evidence from Expression, Functional, and Bioinformatic Analyses.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Zhu Lingqin",
				"Yu Qiongfang",
				"Li Yuanheng",
				"Zhang Meng",
				"Peng Zhiwei",
				"Wang Song",
				"Quan Ziyi",
				"Gao Dian"
			],
			"DOI": "10.3390/ijms241411870",
			"date": "2023-07-31",
			"PMC": "",
			"citation": "",
			"abstract": "Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Due to the lack of early symptoms, GC is often diagnosed at an advanced stage when treatment options are limited. There is an urgent need to identify biomarkers for early detection, prognosis evaluation, and targeted treatment of GC. Studies have shown that Src kinase-associated phosphoprotein 1 (SKAP1) promotes cell proliferation and invasion and is associated with poor prognosis in colorectal cancer, malignant fibrous histiocytoma, and breast cancer. However, the role and mechanism of SKAP1 in GC are unclear. Here, analyses of multiple databases and experiments revealed that SKAP1 expression was higher in GC than in adjacent normal tissues. The Cancer Genome Atlas data showed that high SKAP1 expression was associated with poor GC prognosis. SKAP1 expression was higher in GC than in normal gastric epithelial cells. SKAP1 silencing reduced the proliferation, migration and invasion of the GC cell lines MKN45 and HGC27. Rescue experiments suggest that SKAP1 may promote GC progression by activating JAK1/PI3K/AKT signaling and regulating GC cell proliferation, invasion, migration, and other functions. Bioinformatics analysis revealed that SKAP1 was associated with immune cell infiltration and checkpoint expression in GC. High SKAP1 expression was associated with poorer immunotherapy outcomes, suggesting its potential as a predictive biomarker of GC immunotherapy efficacy. In summary, SKAP1 is overexpressed in GC, where it promotes cell proliferation, invasion and migration and is associated with poor prognosis and poor immunotherapy outcomes. SKAP1 may represent a biomarker and therapeutic target in GC and regulates cellular functions through JAK1/PI3K/AKT signaling.",
			"category": 2,
			"name": "Zhu Lingqin,2023"
		},
		{
			"PMID": 37496999,
			"title": "SDC2 Stabilization by USP14 Promotes Gastric Cancer Progression through Co-option of PDK1.",
			"journal": "International journal of biological sciences",
			"authorList": [
				"You Li",
				"Dou Yi",
				"Zhang Yu",
				"Xiao Hongwei",
				"Lv Hong",
				"Wei Gong-Hong",
				"Xu Dazhi"
			],
			"DOI": "10.7150/ijbs.84331",
			"date": "2023-08-09",
			"PMC": "",
			"citation": "",
			"abstract": "Gastric cancer (GC) is a common malignancy and remains the fourth-leading cause of cancer-related deaths worldwide. Oncogenic potential of SDC2 has been implicated in multiple types of cancers, yet its role and underlying molecular mechanisms in GC remain unknown. Here, we found that SDC2 was highly expressed in GC and its upregulation correlated with poor prognosis in GC patients. Depletion of SDC2 significantly suppressed the growth and invasive capability of GC cells, while overexpressing SDC2 exerts opposite effects. Combined bioinformatics and experimental analyses substantiated that overexpression of SDC2 activated the AKT signaling pathway in GC, mechanistically through the interaction between SDC2 and PDK1-PH domain, thereby facilitating PDK1 membrane translocation to promote AKT activation. Moreover, SDC2 could also function as a co-receptor for FGF2 and was profoundly involved in the FGF2-AKT signaling axis in GC. Lastly, we revealed a mechanism on the USP14-mediated stabilization of SDC2 that is likely to contribute to SDC2 upregulation in GC tissues. Furthermore, we showed that IU1, a potent USP14 inhibitor, decreased the abundance of SDC2 in GC cells. Our findings indicate that SDC2 functions as a novel GC oncogene and has potential utility as a diagnostic marker and therapeutic target for GC.",
			"category": 2,
			"name": "You Li,2023"
		},
		{
			"PMID": 37489050,
			"title": "Inhibitors of phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase-related protein kinase family (PIKK).",
			"journal": "Journal of enzyme inhibition and medicinal chemistry",
			"authorList": [
				"Huang Xueqin",
				"You Li",
				"Nepovimova Eugenie",
				"Psotka Miroslav",
				"Malinak David",
				"Valko Marian",
				"Sivak Ladislav",
				"Korabecny Jan",
				"Heger Zbynek",
				"Adam Vojtech",
				"Wu Qinghua",
				"Kuca Kamil"
			],
			"DOI": "10.1080/14756366.2023.2237209",
			"date": "2023-08-03",
			"PMC": "",
			"citation": "",
			"abstract": "Phosphoinositide 3-kinases (PI3K) and phosphoinositide 3-kinase-related protein kinases (PIKK) are two structurally related families of kinases that play vital roles in cell growth and DNA damage repair. Dysfunction of PIKK members and aberrant stimulation of the PI3K/AKT/mTOR signalling pathway are linked to a plethora of diseases including cancer. In recent decades, numerous inhibitors related to the PI3K/AKT/mTOR signalling have made great strides in cancer treatment, like copanlisib and sirolimus. Notably, most of the PIKK inhibitors (such as VX-970 and M3814) related to DNA damage response have also shown good efficacy in clinical trials. However, these drugs still require a suitable combination therapy to overcome drug resistance or improve antitumor activity. Based on the aforementioned facts, we summarised the efficacy of PIKK, PI3K, and AKT inhibitors in the therapy of human malignancies and the resistance mechanisms of targeted therapy, in order to provide deeper insights into cancer treatment.",
			"category": 2,
			"name": "Huang Xueqin,2023"
		},
		{
			"PMID": 37484410,
			"title": "A novel tumor 4-driver gene signature for the prognosis of hepatocellular carcinoma.",
			"journal": "Heliyon",
			"authorList": [
				"Guo Houtian",
				"Lu Fei",
				"Lu Rongqi",
				"Huang Meiqi",
				"Li Xuejing",
				"Yuan Jianhui",
				"Wang Feng"
			],
			"DOI": "10.1016/j.heliyon.2023.e17054",
			"date": "2023-07-25",
			"PMC": "",
			"citation": "",
			"abstract": "Hepatocellular carcinoma (HCC), the main type of liver cancer, is the second most lethal tumor worldwide, with a 5-year survival rate of only 18%. Driver genes facilitate cancer cell growth and spread in the tumor microenvironment. Here, a comprehensive driver gene signature for the prognosis of HCC was developed.",
			"category": 2,
			"name": "Guo Houtian,2023"
		},
		{
			"PMID": 37482618,
			"title": "A systems biology approach to pathogenesis of gastric cancer: gene network modeling and pathway analysis.",
			"journal": "BMC gastroenterology",
			"authorList": [
				"Mottaghi-Dastjerdi Negar",
				"Ghorbani Abozar",
				"Montazeri Hamed",
				"Guzzi Pietro Hiram"
			],
			"DOI": "10.1186/s12876-023-02891-4",
			"date": "2023-07-26",
			"PMC": "",
			"citation": "",
			"abstract": "Gastric cancer (GC) ranks among the most common malignancies worldwide. This study aimed to find critical genes/pathways in GC pathogenesis.",
			"category": 2,
			"name": "Mottaghi-Dastjerdi Negar,2023"
		},
		{
			"PMID": 37469932,
			"title": "A computational model for the cancer field effect.",
			"journal": "Frontiers in artificial intelligence",
			"authorList": [
				"Deutscher Karl",
				"Hillen Thomas",
				"Newby Jay"
			],
			"DOI": "10.3389/frai.2023.1060879",
			"date": "2023-07-21",
			"PMC": "",
			"citation": "",
			"abstract": "The Cancer Field Effect describes an area of pre-cancerous cells that results from continued exposure to carcinogens. Cells in the cancer field can easily develop into cancer. Removal of the main tumor mass might leave the cancer field behind, increasing risk of recurrence.",
			"category": 2,
			"name": "Deutscher Karl,2023"
		},
		{
			"PMID": 37452161,
			"title": "Learning models for classifying Raman spectra of genomic DNA from tumor subtypes.",
			"journal": "Scientific reports",
			"authorList": [
				"Lancia Giacomo",
				"Durastanti Claudio",
				"Spitoni Cristian",
				"De Benedictis Ilaria",
				"Sciortino Antonio",
				"Cirillo Emilio N M",
				"Ledda Mario",
				"Lisi Antonella",
				"Convertino Annalisa",
				"Mussi Valentina"
			],
			"DOI": "10.1038/s41598-023-37303-w",
			"date": "2023-07-17",
			"PMC": "",
			"citation": "",
			"abstract": "An early and accurate detection of different subtypes of tumors is crucial for an effective guidance to personalized therapy and in predicting the ability of tumor to metastasize. Here we exploit the Surface Enhanced Raman Scattering (SERS) platform, based on disordered silver coated silicon nanowires (Ag/SiNWs), to efficiently discriminate genomic DNA of different subtypes of melanoma and colon tumors. The diagnostic information is obtained by performing label free Raman maps of the dried drops of DNA solutions onto the Ag/NWs mat and leveraging the classification ability of learning models to reveal the specific and distinct physico-chemical interaction of tumor DNA molecules with the Ag/NW, here supposed to be partly caused by a different DNA methylation degree.",
			"category": 2,
			"name": "Lancia Giacomo,2023"
		},
		{
			"PMID": 37449060,
			"title": "Antibody production and tolerance to the \u03b1-gal epitope as models for understanding and preventing the immune response to incompatible ABO carbohydrate antigens and for \u03b1-gal therapies.",
			"journal": "Frontiers in molecular biosciences",
			"authorList": [
				"Galili Uri"
			],
			"DOI": "10.3389/fmolb.2023.1209974",
			"date": "2023-07-18",
			"PMC": "",
			"citation": "",
			"abstract": "This review describes the significance of the \u03b1-gal epitope (Gal\u03b1-3Gal\u03b21-4GlcNAc-R) as the core of human blood-group A and B antigens (A and B antigens), determines in mouse models the principles underlying the immune response to these antigens, and suggests future strategies for the induction of immune tolerance to incompatible A and B antigens in human allografts. Carbohydrate antigens, such as ABO antigens and the \u03b1-gal epitope, differ from protein antigens in that they do not interact with T cells, but B cells interacting with them require T-cell help for their activation. The \u03b1-gal epitope is the core of both A and B antigens and is the ligand of the natural anti-Gal antibody, which is abundant in all humans. In A and O individuals, anti-Gal clones (called anti-Gal/B) comprise >85% of the so-called anti-B activity and bind to the B antigen in facets that do not include fucose-linked \u03b11-2 to the core \u03b1-gal. As many as 1% of B cells are anti-Gal B cells. Activation of quiescent anti-Gal B cells upon exposure to \u03b1-gal epitopes on xenografts and some protozoa can increase the titer of anti-Gal by 100-fold. \u03b11,3-Galactosyltransferase knockout (GT-KO) mice lack \u03b1-gal epitopes and can produce anti-Gal. These mice simulate human recipients of ABO-incompatible human allografts. Exposure for 2-4\u00a0weeks of na\u00efve and memory mouse anti-Gal B cells to \u03b1-gal epitopes in the heterotopically grafted wild-type (WT) mouse heart results in the elimination of these cells and immune tolerance to this epitope. Shorter exposures of 7\u00a0days of anti-Gal B cells to \u03b1-gal epitopes in the WT heart result in the production of accommodating anti-Gal antibodies that bind to \u03b1-gal epitopes but do not lyse cells or reject the graft. Tolerance to \u03b1-gal epitopes due to the elimination of na\u00efve and memory anti-Gal B cells can be further induced by 2 weeks ",
			"category": 2,
			"name": "Galili Uri,2023"
		},
		{
			"PMID": 37445850,
			"title": "Inhibition of Cancer Development by Natural Plant Polyphenols: Molecular Mechanisms.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Lyubitelev Alexander",
				"Studitsky Vasily"
			],
			"DOI": "10.3390/ijms241310663",
			"date": "2023-07-17",
			"PMC": "",
			"citation": "",
			"abstract": "Malignant tumors remain one of the main sources of morbidity and mortality around the world. A chemotherapeutic approach to cancer treatment poses a multitude of challenges, primarily due to the low selectivity and genotoxicity of the majority of chemotherapeutic drugs currently used in the clinical practice, often leading to treatment-induced tumors formation. Highly selective antitumor drugs can largely resolve this issue, but their high selectivity leads to significant drawbacks due to the intrinsic tumor heterogeneity. In contrast, plant polyphenols can simultaneously affect many processes that are involved in the acquiring and maintaining of hallmark properties of malignant cells, and their toxic dose is typically much higher than the therapeutic one. In the present work we describe the mechanisms of the action of polyphenols on cancer cells, including their effects on genetic and epigenetic instability, tumor-promoting inflammation, and altered microbiota.",
			"category": 2,
			"name": "Lyubitelev Alexander,2023"
		},
		{
			"PMID": 37444460,
			"title": "The Relationship between Telomere Length and Nucleoplasmic Bridges and Severity of Disease in Prostate Cancer Patients.",
			"journal": "Cancers",
			"authorList": [
				"Dhillon Varinderpal S",
				"Deo Permal",
				"Fenech Michael"
			],
			"DOI": "10.3390/cancers15133351",
			"date": "2023-07-18",
			"PMC": "",
			"citation": "",
			"abstract": "Telomeres are repetitive nucleotide (TTAGGG) sequences that stabilize the chromosome ends and play an important role in the prevention of cancer initiation and progression. Nucleoplasmic bridges (NPBs) are formed when chromatids remain joined together during mitotic anaphase either due to mis-repair of DNA breaks or due to chromatid end fusion as a result of telomere loss or telomere dysfunction. We tested the hypotheses that (i) telomere length (TL) is shorter in prostate cancer (PC) patients relative to healthy age-matched individuals, (ii) TL differs in different stages of PC and (iii) shorter TL is significantly correlated with NPBs formation in PC cases. TL was measured in whole blood by well-established quantitative PCR method and the frequency of NPBs was measured in lymphocytes using cytokinesis-block micronucleus cytome (CBMNcyt) assay. Our results indicate that TL is shorter and NPBs are increased in PC patients relative to age-matched healthy controls. Furthermore, TL was significantly shorter (",
			"category": 2,
			"name": "Dhillon Varinderpal S,2023"
		},
		{
			"PMID": 37428871,
			"title": "In\u00a0vivo CRISPR/Cas9 screening identifies Pbrm1 as a regulator of myeloid leukemia development in mice.",
			"journal": "Blood advances",
			"authorList": [
				"Li Bin E",
				"Li Grace Y",
				"Cai Wenqing",
				"Zhu Qian",
				"Seruggia Davide",
				"Fujiwara Yuko",
				"Vakoc Christopher R",
				"Orkin Stuart H"
			],
			"DOI": "10.1182/bloodadvances.2022009455",
			"date": "2023-09-15",
			"PMC": "",
			"citation": "",
			"abstract": "CRISPR/Cas9 screening approaches are powerful tool for identifying in\u00a0vivo cancer dependencies. Hematopoietic malignancies are genetically complex disorders in which the sequential acquisition of somatic mutations generates clonal diversity. Over time, additional cooperating mutations may drive disease progression. Using an in\u00a0vivo pooled gene editing screen of epigenetic factors in primary murine hematopoietic stem and progenitor cells (HSPCs), we sought to uncover unrecognized genes that contribute to leukemia progression. We, first, modeled myeloid leukemia in mice by functionally abrogating both Tet2 and Tet3 in HSPCs, followed by transplantation. We, then, performed pooled CRISPR/Cas9 editing of genes encoding epigenetic factors and identified Pbrm1/Baf180, a subunit of the polybromo BRG1/BRM-associated factor SWItch/Sucrose Non-Fermenting chromatin-remodeling complex, as a negative driver of disease progression. We found that Pbrm1 loss promoted leukemogenesis with a significantly shortened latency. Pbrm1-deficient leukemia cells were less immunogenic and were characterized by attenuated interferon signaling and reduced major histocompatibility complex class II (MHC II) expression. We explored the potential relevance to human leukemia by assessing the involvement of PBRM1 in the control of interferon pathway components and found that PBRM1 binds to the promoters of a subset of these genes, most notably IRF1, which in turn regulates MHC II expression. Our findings revealed a novel role for Pbrm1 in leukemia progression. More generally, CRISPR/Cas9 screening coupled with phenotypic readouts in\u00a0vivo has helped identify a pathway by which transcriptional control of interferon signaling influences leukemia cell interactions with the immune system.",
			"category": 2,
			"name": "Li Bin E,2023"
		},
		{
			"PMID": 37410227,
			"title": "Analysis of Mutational Signatures Using the mutSignatures R Library.",
			"journal": "Methods in molecular biology (Clifton, N.J.)",
			"authorList": [
				"Fantini Damiano",
				"Meeks Joshua J"
			],
			"DOI": "10.1007/978-1-0716-3291-8_3",
			"date": "2023-07-10",
			"PMC": "",
			"citation": "",
			"abstract": "Accumulation of somatic mutations is a hallmark of cancer. Defects in DNA metabolism and DNA repair and exposure to mutagens may result in characteristic nonrandom profiles of DNA mutations, also known as mutational signatures. Resolving mutational signatures can help identifying genetic instability processes active in human cancer samples, and there is an expectation that this information might be exploited in the future for drug discovery and personalized treatment.Here we show how to analyze bladder cancer mutation data using mutSignatures, an open-source R-based computational framework aimed at investigating DNA mutational signatures. We illustrate the typical steps of a mutational signature analysis. We start by importing and pre-processing mutation data from a list of Variant Call Format (VCF) files. Next, we show how to perform de novo mutational signature extraction and how to determine activity of previously resolved mutational signatures, including Catalogue of Somatic Mutations In Cancer (COSMIC) signatures. Finally, we provide insights into parameter selection, algorithm tuning, and data visualization.Overall, the chapter guides the reader through all steps of a mutational signature analysis using R and mutSignatures, a software that may help gathering insights into genetic instability and cancer biology.",
			"category": 2,
			"name": "Fantini Damiano,2023"
		},
		{
			"PMID": 37405215,
			"title": "Mutational Signatures in Salivary Gland Carcinomas.",
			"journal": "Cancer diagnosis & prognosis",
			"authorList": [
				"Chrysovergis Aristeidis",
				"Papanikolaou Vasileios",
				"Spyropoulou Despoina",
				"Roukas Dimitrios",
				"Asimakopoulos Asimakis D",
				"Papanastasiou George",
				"Mastronikoli Sofianiki",
				"Falidas Evangelos",
				"Papouliakos Sotirios",
				"Tsiambas Evangelos",
				"Pantos Pavlos",
				"Ragos Vasileios",
				"Peschos Dimitrios",
				"Mastronikolis Nicholas",
				"Kyrodimos Efthymios"
			],
			"DOI": "10.21873/cdp.10233",
			"date": "2023-07-18",
			"PMC": "",
			"citation": "",
			"abstract": "Salivary gland carcinomas belong to the head and neck carcinoma super category of malignancies. They are characterized by histopathological diversity and comprise a variety of entities and subtypes. Mucoepidermoid, adenoid cystic and salivary duct carcinomas represent the most prominent malignancies. Concerning their corresponding genetic background, a broad spectrum of gene and chromosomal imbalances has been detected. Point mutations and deletions, amplifications and translocations, combined or not with chromosomal aneuploidy/polysomy/monosomy, create a landscape of specific genetic signatures that affect the biological behavior of these tumors and modify response rates to potential targeted therapeutic strategies. In the current molecular review, we focused on the categorization and description of the most important mutational signatures in salivary gland carcinomas.",
			"category": 2,
			"name": "Chrysovergis Aristeidis,2023"
		},
		{
			"PMID": 37332013,
			"title": "Structure-based pathogenicity relationship identifier for predicting effects of single missense variants and discovery of higher-order cancer susceptibility clusters of mutations.",
			"journal": "Briefings in bioinformatics",
			"authorList": [
				"Wang Boshen",
				"Lei Xue",
				"Tian Wei",
				"Perez-Rathke Alan",
				"Tseng Yan-Yuan",
				"Liang Jie"
			],
			"DOI": "10.1093/bib/bbad206",
			"date": "2023-10-23",
			"PMC": "",
			"citation": "",
			"abstract": "We report the structure-based pathogenicity relationship identifier (SPRI), a novel computational tool for accurate evaluation of pathological effects of missense single mutations and prediction of higher-order spatially organized units of mutational clusters. SPRI can effectively extract properties determining pathogenicity encoded in protein structures, and can identify deleterious missense mutations of germ line origin associated with Mendelian diseases, as well as mutations of somatic origin associated with cancer drivers. It compares favorably to other methods in predicting deleterious mutations. Furthermore, SPRI can discover spatially organized pathogenic higher-order spatial clusters (patHOS) of deleterious mutations, including those of low recurrence, and can be used for discovery of candidate cancer driver genes and driver mutations. We further demonstrate that SPRI can take advantage of AlphaFold2 predicted structures and can be deployed for saturation mutation analysis of the whole human proteome.",
			"category": 2,
			"name": "Wang Boshen,2023"
		},
		{
			"PMID": 37328455,
			"title": "Cancer genomes tolerate deleterious coding mutations through somatic copy number amplifications of wild-type regions.",
			"journal": "Nature communications",
			"authorList": [
				"Alfieri Fabio",
				"Caravagna Giulio",
				"Schaefer Martin H"
			],
			"DOI": "10.1038/s41467-023-39313-8",
			"date": "2023-06-19",
			"PMC": "",
			"citation": "",
			"abstract": "Cancers evolve under the accumulation of thousands of somatic mutations and chromosomal aberrations. While most coding mutations are deleterious, almost all protein-coding genes lack detectable signals of negative selection. This raises the question of how tumors tolerate such large amounts of deleterious mutations. Using 8,690 tumor samples from The Cancer Genome Atlas, we demonstrate that copy number amplifications frequently cover haploinsufficient genes in mutation-prone regions. This could increase tolerance towards the deleterious impact of mutations by creating safe copies of wild-type regions and, hence, protecting the genes therein. Our findings demonstrate that these potential buffering events are highly influenced by gene functions, essentiality, and mutation impact and that they occur early during tumor evolution. We show how cancer type-specific mutation landscapes drive copy number alteration patterns across cancer types. Ultimately, our work paves the way for the detection of novel cancer vulnerabilities by revealing genes that fall within amplifications likely selected during evolution to mitigate the effect of mutations.",
			"category": 2,
			"name": "Alfieri Fabio,2023"
		},
		{
			"PMID": 37323536,
			"title": "Genetic association of mosaic loss of chromosome Y with prostate cancer in men of European and East Asian ancestries: a Mendelian randomization study.",
			"journal": "Frontiers in aging",
			"authorList": [
				"Kobayashi Takuro",
				"Hachiya Tsuyoshi",
				"Ikehata Yoshihiro",
				"Horie Shigeo"
			],
			"DOI": "10.3389/fragi.2023.1176451",
			"date": "2023-06-19",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "Kobayashi Takuro,2023"
		},
		{
			"PMID": 37253775,
			"title": "Deep learning model accurately classifies metastatic tumors from primary tumors based on mutational signatures.",
			"journal": "Scientific reports",
			"authorList": [
				"Zheng Weisheng",
				"Pu Mengchen",
				"Li Xiaorong",
				"Du Zhaolan",
				"Jin Sutong",
				"Li Xingshuai",
				"Zhou Jielong",
				"Zhang Yingsheng"
			],
			"DOI": "10.1038/s41598-023-35842-w",
			"date": "2023-06-01",
			"PMC": "",
			"citation": "",
			"abstract": "Metastatic propagation is the leading cause of death for most cancers. Prediction and elucidation of metastatic process is crucial for the treatment of cancer. Even though somatic mutations have been linked to tumorigenesis and metastasis, it is less explored whether metastatic events can be identified through genomic mutational signatures, which are concise descriptions of the mutational processes. Here, we developed MetaWise, a Deep Neural Network (DNN) model, by applying mutational signatures as input features calculated from Whole-Exome Sequencing (WES) data of TCGA and other metastatic cohorts. This model can accurately classify metastatic tumors from primary tumors and outperform traditional machine learning (ML) models and\u00a0a deep learning (DL) model, DiaDeL. Signatures of non-coding mutations also have a major impact on the model's performance. SHapley Additive exPlanations (SHAP) and Local Surrogate (LIME) analyses identify several mutational signatures which are directly correlated to metastatic spread in cancers, including APOBEC-mutagenesis, UV-induced signatures, and DNA damage response deficiency signatures.",
			"category": 2,
			"name": "Zheng Weisheng,2023"
		},
		{
			"PMID": 37242648,
			"title": "Dendrimers: Advancements and Potential Applications in Cancer Diagnosis and Treatment-An Overview.",
			"journal": "Pharmaceutics",
			"authorList": [
				"Crintea Andreea",
				"Motofelea Alexandru C\u0103t\u0103lin",
				"\u0218ovrea Alina Simona",
				"Constantin Anne-Marie",
				"Crivii Carmen-Bianca",
				"Carpa Rahela",
				"Du\u021bu Alina Gabriela"
			],
			"DOI": "10.3390/pharmaceutics15051406",
			"date": "2023-05-30",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a leading cause of death worldwide, and the main treatment methods for this condition are surgery, chemotherapy, and radiotherapy. These treatment methods are invasive and can cause severe adverse reactions among organisms, so nanomaterials are increasingly used as structures for anticancer therapies. Dendrimers are a type of nanomaterial with unique properties, and their production can be controlled to obtain compounds with the desired characteristics. These polymeric molecules are used in cancer diagnosis and treatment through the targeted distribution of some pharmacological substances. Dendrimers have the ability to fulfill several objectives in anticancer therapy simultaneously, such as targeting tumor cells so that healthy tissue is not affected, controlling the release of anticancer agents in the tumor microenvironment, and combining anticancer strategies based on the administration of anticancer molecules to potentiate their effect through photothermal therapy or photodynamic therapy. The purpose of this review is to summarize and highlight the possible uses of dendrimers regarding the diagnosis and treatment of oncological conditions.",
			"category": 2,
			"name": "Crintea Andreea,2023"
		},
		{
			"PMID": 37239381,
			"title": "The Genomic Landscape of Melanoma and Its Therapeutic Implications.",
			"journal": "Genes",
			"authorList": [
				"Yang Ting-Ting",
				"Yu Sebastian",
				"Ke Chiao-Li Khale",
				"Cheng Shih-Tsung"
			],
			"DOI": "10.3390/genes14051021",
			"date": "2023-05-29",
			"PMC": "",
			"citation": "",
			"abstract": "Melanoma is one of the most aggressive malignancies of the skin. The genetic composition of melanoma is complex and varies among different subtypes. With the aid of recent technologies such as next generation sequencing and single-cell sequencing, our understanding of the genomic landscape of melanoma and its tumor microenvironment has become increasingly clear. These advances may provide explanation to the heterogenic treatment outcomes of melanoma patients under current therapeutic guidelines and provide further insights to the development of potential new therapeutic targets. Here, we provide a comprehensive review on the genetics related to melanoma tumorigenesis, metastasis, and prognosis. We also review the genetics affecting the melanoma tumor microenvironment and its relation to tumor progression and treatment.",
			"category": 2,
			"name": "Yang Ting-Ting,2023"
		},
		{
			"PMID": 37213670,
			"title": "Synergistic Effect of Metformin and Lansoprazole Against Gastric Cancer through Growth Inhibition.",
			"journal": "International journal of medical sciences",
			"authorList": [
				"Kao Hsiao-Wei",
				"Tsai Kuo-Wang",
				"Lin Wen-Chang"
			],
			"DOI": "10.7150/ijms.82407",
			"date": "2023-05-24",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer has been linked to metabolic disorders and diverse gene mutations. Metformin, which is widely used to treat type 2 diabetes, inhibits the growth of cancer cells in animal models. Here we investigated the effects of metformin on human gastric cancer cell lines. We also investigated the synergistic anticancer effect of metformin and proton pump inhibitors. Lansoprazole, a proton pump inhibitor, is effective for treating gastroesophageal reflux disease. Our results revealed that metformin and lansoprazole can significantly inhibit cancer cell growth in a dose-dependent manner by suppressing cell cycle progression and inducing apoptosis. Low concentrations of metformin and lansoprazole have a synergistic effect on AGS cell growth inhibition. In summary, our findings suggest a new and safe treatment protocol for treating stomach cancers.",
			"category": 2,
			"name": "Kao Hsiao-Wei,2023"
		},
		{
			"PMID": 37188696,
			"title": "Mutational signatures association with replication timing in normal cells reveals similarities and differences with matched cancer tissues.",
			"journal": "Scientific reports",
			"authorList": [
				"Yaacov Adar",
				"Rosenberg Shai",
				"Simon Itamar"
			],
			"DOI": "10.1038/s41598-023-34631-9",
			"date": "2023-05-17",
			"PMC": "",
			"citation": "",
			"abstract": "Mutational signatures' association with replication timing (RT) has been studied in cancer samples, but the RT distribution of somatic mutations in non-cancerous cells was only minimally explored. Here, we performed comprehensive analyses of mutational signatures in 2.9\u00a0million somatic mutations across multiple non-cancerous tissues, stratified by early and late RT regions. We found that many mutational processes are active mainly or solely in early RT, such as SBS16 in hepatocytes and SBS88 in the colon, or in late RT, such as SBS4 in lung and hepatocytes, and SBS18 across many tissues. The two ubiquitous signatures, SBS1 and SBS5, showed late and early bias, respectively, across multiple tissues and in mutations representing germ cells. We also performed a direct comparison with cancer samples in 4 matched tissue-cancer types. Unexpectedly, while for most signatures the RT bias was consistent in normal tissue and in cancer, we found that SBS1's late RT bias is lost in cancer.",
			"category": 2,
			"name": "Yaacov Adar,2023"
		},
		{
			"PMID": 37179623,
			"title": "pH-Responsive Nano-transferosomes of Purpurin-18 Sodium Salt and Doxorubicin for Enhanced Anticancer Efficiency by Photodynamic and Chemo Combination Therapy.",
			"journal": "ACS omega",
			"authorList": [
				"Yeo Sooho",
				"Kim Min Je",
				"Yoon Il",
				"Lee Woo Kyoung"
			],
			"DOI": "10.1021/acsomega.3c01654",
			"date": "2023-05-16",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a devastating disease and a major human health concern. Various combination treatments have been developed to combat cancer. To obtain superior cancer therapy, the objective of this study was to synthesize purpurin-18 sodium salt (P18Na) and design P18Na- and doxorubicin hydrochloride (DOX)-loaded nano-transferosomes as a combination of photodynamic therapy (PDT) and chemotherapy for cancer. The characteristics of P18Na- and DOX-loaded nano-transferosomes were assessed, and the pharmacological efficacy of P18Na and DOX was determined using the HeLa and A549 cell lines. The nanodrug delivery system characteristics of the product were found to range from 98.38 to 217.50 nm and -23.63 to -41.10 mV, respectively. Further, the release of P18Na and DOX from nano-transferosomes exhibited a sustained pH-responsive behavior and burst in physiological and acidic environments, respectively. Accordingly, the nano-transferosomes effectively delivered P18Na and DOX into cancer cells, with less leakage in the body, and exhibited pH-responsive release in cancer cells. A photo-cytotoxicity study to HeLa and A549 cell lines revealed a size-dependent anti-cancer effect. These results suggest that the combined nano-transferosomes of P18Na and DOX are effective in the combination of PDT and chemotherapy for cancer.",
			"category": 2,
			"name": "Yeo Sooho,2023"
		},
		{
			"PMID": 37173324,
			"title": "Germline modifiers of the tumor immune microenvironment implicate drivers of cancer risk and immunotherapy response.",
			"journal": "Nature communications",
			"authorList": [
				"Pagadala Meghana",
				"Sears Timothy J",
				"Wu Victoria H",
				"P\u00e9rez-Guijarro Eva",
				"Kim Hyo",
				"Castro Andrea",
				"Talwar James V",
				"Gonzalez-Colin Cristian",
				"Cao Steven",
				"Schmiedel Benjamin J",
				"Goudarzi Shervin",
				"Kirani Divya",
				"Au Jessica",
				"Zhang Tongwu",
				"Landi Teresa",
				"Salem Rany M",
				"Morris Gerald P",
				"Harismendy Olivier",
				"Patel Sandip Pravin",
				"Alexandrov Ludmil B",
				"Mesirov Jill P",
				"Zanetti Maurizio",
				"Day Chi-Ping",
				"Fan Chun Chieh",
				"Thompson Wesley K",
				"Merlino Glenn",
				"Gutkind J Silvio",
				"Vijayanand Pandurangan",
				"Carter Hannah"
			],
			"DOI": "10.1038/s41467-023-38271-5",
			"date": "2023-05-15",
			"PMC": "",
			"citation": "",
			"abstract": "With the continued promise of immunotherapy for treating cancer, understanding how host genetics contributes to the tumor immune microenvironment (TIME) is essential to tailoring cancer screening and treatment strategies. Here, we study 1084 eQTLs affecting the TIME found through analysis of The Cancer Genome Atlas and literature curation. These TIME eQTLs are enriched in areas of active transcription, and associate with gene expression in specific immune cell subsets, such as macrophages and dendritic cells. Polygenic score models built with TIME eQTLs reproducibly stratify cancer risk, survival and immune checkpoint blockade (ICB) response across independent cohorts. To assess whether an eQTL-informed approach could reveal potential cancer immunotherapy targets, we inhibit CTSS, a gene implicated by cancer risk and ICB response-associated polygenic models; CTSS inhibition results in slowed tumor growth and extended survival in vivo. These results validate the potential of integrating germline variation and TIME characteristics for uncovering potential targets for immunotherapy.",
			"category": 2,
			"name": "Pagadala Meghana,2023"
		},
		{
			"PMID": 37168844,
			"title": "Variant biomarker discovery using mass spectrometry-based proteogenomics.",
			"journal": "Frontiers in aging",
			"authorList": [
				"Reilly Luke",
				"Seddighi Sahba",
				"Singleton Andrew B",
				"Cookson Mark R",
				"Ward Michael E",
				"Qi Yue A"
			],
			"DOI": "10.3389/fragi.2023.1191993",
			"date": "2023-11-12",
			"PMC": "",
			"citation": "",
			"abstract": "Genomic diversity plays critical roles in risk of disease pathogenesis and diagnosis. While genomic variants-including single nucleotide variants, frameshift variants, and mis-splicing isoforms-are commonly detected at the DNA or RNA level, their translated variant protein or polypeptide products are ultimately the functional units of the associated disease. These products are often released in biofluids and could be leveraged for clinical diagnosis and patient stratification. Recent emergence of integrated analysis of genomics with mass spectrometry-based proteomics for biomarker discovery, also known as proteogenomics, have significantly advanced the understanding disease risk variants, precise medicine, and biomarker discovery. In this review, we discuss variant proteins in the context of cancers and neurodegenerative diseases, outline current and emerging proteogenomic approaches for biomarker discovery, and provide a comprehensive proteogenomic strategy for detection of putative biomarker candidates in human biospecimens. This strategy can be implemented for proteogenomic studies in any field of enquiry. Our review timely addresses the need of biomarkers for aging related diseases.",
			"category": 2,
			"name": "Reilly Luke,2023"
		},
		{
			"PMID": 37165195,
			"title": "Widespread somatic L1 retrotransposition in normal colorectal epithelium.",
			"journal": "Nature",
			"authorList": [
				"Nam Chang Hyun",
				"Youk Jeonghwan",
				"Kim Jeong Yeon",
				"Lim Joonoh",
				"Park Jung Woo",
				"Oh Soo A",
				"Lee Hyun Jung",
				"Park Ji Won",
				"Won Hyein",
				"Lee Yunah",
				"Jeong Seung-Yong",
				"Lee Dong-Sung",
				"Oh Ji Won",
				"Han Jinju",
				"Lee Junehawk",
				"Kwon Hyun Woo",
				"Kim Min Jung",
				"Ju Young Seok"
			],
			"DOI": "10.1038/s41586-023-06046-z",
			"date": "2023-05-24",
			"PMC": "",
			"citation": "",
			"abstract": "Throughout an individual's lifetime, genomic alterations accumulate in somatic cells",
			"category": 2,
			"name": "Nam Chang Hyun,2023"
		},
		{
			"PMID": 37164759,
			"title": "Zebrafish imaging reveals hidden oncogenic-normal cell communication during primary tumorigenesis.",
			"journal": "Cell structure and function",
			"authorList": [
				"Haraoka Yukinari",
				"Miyake Mai",
				"Ishitani Tohru"
			],
			"DOI": "10.1247/csf.23026",
			"date": "2023-06-20",
			"PMC": "",
			"citation": "",
			"abstract": "Oncogenic mutations drive tumorigenesis, and single cells with oncogenic mutations act as the tumor seeds that gradually evolve into fully transformed tumors. However, oncogenic cell behavior and communication with neighboring cells during primary tumorigenesis remain poorly understood. We used the zebrafish, a small vertebrate model suitable for in vivo cell biology, to address these issues. We describe the cooperative and competitive communication between oncogenic cells and neighboring cells, as revealed by our recent zebrafish imaging studies. Newly generated oncogenic cells are actively eliminated by neighboring cells in healthy epithelia, whereas oncogenic cells cooperate with their neighbors to prime tumorigenesis in unhealthy epithelia via additional mutations or inflammation. In addition, we discuss the potential of zebrafish in vivo imaging to determine the initial steps of human tumorigenesis.Key words: zebrafish, imaging, cell-cell communication, cell competition, EDAC, senescence, primary tumorigenesis.",
			"category": 2,
			"name": "Haraoka Yukinari,2023"
		},
		{
			"PMID": 37122741,
			"title": "Exhausted T cells hijacking the cancer-immunity cycle: Assets and liabilities.",
			"journal": "Frontiers in immunology",
			"authorList": [
				"Brunell Anna E",
				"Lahesmaa Riitta",
				"Autio Anu",
				"Thotakura Anil K"
			],
			"DOI": "10.3389/fimmu.2023.1151632",
			"date": "2023-05-02",
			"PMC": "",
			"citation": "",
			"abstract": "T cell exhaustion is an alternative differentiation path of T cells, sometimes described as a dysfunction. During the last decade, insights of T cell exhaustion acting as a bottle neck in the field of cancer immunotherapy have undoubtedly provoked attention. One of the main drivers of T cell exhaustion is prolonged antigen presentation, a prerequisite in the cancer-immunity cycle. The umbrella term \"T cell exhaustion\" comprises various stages of T cell functionalities, describing the dynamic, one-way exhaustion process. Together these qualities of T cells at the exhaustion continuum can enable tumor clearance, but if the exhaustion acquired timeframe is exceeded, tumor cells have increased possibilities of escaping immune system surveillance. This could be considered a tipping point where exhausted T cells switch from an asset to a liability. In this review, the contrary role of exhausted T cells is discussed.",
			"category": 2,
			"name": "Brunell Anna E,2023"
		},
		{
			"PMID": 37122279,
			"title": "Editorial: Twenty Years On from Sequencing the Human Genome, Personalized/Precision Oncology Prepares to Meet the Challenges of Checkpoint Inhibitor Therapy.",
			"journal": "Medical science monitor : international medical journal of experimental and clinical research",
			"authorList": [
				"Parums Dinah V"
			],
			"DOI": "10.12659/MSM.940911",
			"date": "2023-05-02",
			"PMC": "",
			"citation": "",
			"abstract": "On April 14, 2003, the International Human Genome Project was declared complete after identifying, mapping, and sequencing approximately 92% of the human genome. Significant genetic alterations have now been identified in most human cancers. Personalized, or precision, oncology involves molecular profiling of tumors to identify targetable alterations for drug treatments. T-cell responses to antigens, including tumor-associated antigens, are mediated by the interaction between stimulatory and inhibitory signaling molecules, known as immune checkpoints. Targets of inhibitory checkpoints include programmed death 1 (PD-1), its ligand PD-L1, and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). Challenges of checkpoint inhibition therapy include the prevalence and severity of immune-related adverse events (irAEs) and the short duration of response. Also, the beneficial effects in patients with hematologic malignancies other than Hodgkin's lymphoma remain limited. Checkpoint inhibitors are now integrated into standard-of-care for patients with several types of cancer. This Editorial aims to highlight the impact and challenges of checkpoint inhibitors in personalized/precision oncology and how molecular technologies may begin to address these challenges.",
			"category": 2,
			"name": "Parums Dinah V,2023"
		},
		{
			"PMID": 37111291,
			"title": "Structure-Activity Relationship Studies Based on Quinazoline Derivatives as EGFR Kinase Inhibitors (2017-Present).",
			"journal": "Pharmaceuticals (Basel, Switzerland)",
			"authorList": [
				"\u0218andor Alexandru",
				"Ionu\u021b Ioana",
				"Marc Gabriel",
				"Oniga Ilioara",
				"Eniu Dan",
				"Oniga Ovidiu"
			],
			"DOI": "10.3390/ph16040534",
			"date": "2023-11-01",
			"PMC": "",
			"citation": "",
			"abstract": "The epidermal growth factor receptor (EGFR) plays a critical role in the tumorigenesis of various forms of cancer. Targeting the mutant forms of EGFR has been identified as an attractive therapeutic approach and led to the approval of three generations of inhibitors. The quinazoline core has emerged as a favorable scaffold for the development of novel EGFR inhibitors due to increased affinity for the active site of EGFR kinase. Currently, there are five first-generation (gefitinib, erlotinib, lapatinib, vandetanib, and icotinib) and two second-generation (afatinib and dacomitinib) quinazoline-based EGFR inhibitors approved for the treatment of various types of cancers. The aim of this review is to outline the structural modulations favorable for the inhibitory activity toward both common mutant (del19 and L858R) and resistance-conferring mutant (T790M and C797S) EGFR forms, and provide an overview of the newly synthesized quinazoline derivatives as potentially competitive, covalent or allosteric inhibitors of EGFR.",
			"category": 2,
			"name": "\u0218andor Alexandru,2023"
		},
		{
			"PMID": 37109525,
			"title": "The Role of Genetic Mutations in Mitochondrial-Driven Cancer Growth in Selected Tumors: Breast and Gynecological Malignancies.",
			"journal": "Life (Basel, Switzerland)",
			"authorList": [
				"Czegle Ibolya",
				"Huang Chelsea",
				"Soria Priscilla Geraldine",
				"Purkiss Dylan Wesley",
				"Shields Andrea",
				"Wappler-Guzzetta Edina Amalia"
			],
			"DOI": "10.3390/life13040996",
			"date": "2023-05-01",
			"PMC": "",
			"citation": "",
			"abstract": "There is an increasing understanding of the molecular and cytogenetic background of various tumors that helps us better conceptualize the pathogenesis of specific diseases. Additionally, in many cases, these molecular and cytogenetic alterations have diagnostic, prognostic, and/or therapeutic applications that are heavily used in clinical practice. Given that there is always room for improvement in cancer treatments and in cancer patient management, it is important to discover new therapeutic targets for affected individuals. In this review, we discuss mitochondrial changes in breast and gynecological (endometrial and ovarian) cancers. In addition, we review how the frequently altered genes in these diseases (",
			"category": 2,
			"name": "Czegle Ibolya,2023"
		},
		{
			"PMID": 37108214,
			"title": "Recent Advances in Genome-Editing Technology with CRISPR/Cas9 Variants and Stimuli-Responsive Targeting Approaches within Tumor Cells: A Future Perspective of Cancer Management.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Allemailem Khaled S",
				"Almatroodi Saleh A",
				"Almatroudi Ahmad",
				"Alrumaihi Faris",
				"Al Abdulmonem Waleed",
				"Al-Megrin Wafa Abdullah I",
				"Aljamaan Adel Nasser",
				"Rahmani Arshad Husain",
				"Khan Amjad Ali"
			],
			"DOI": "10.3390/ijms24087052",
			"date": "2023-05-01",
			"PMC": "",
			"citation": "",
			"abstract": "The innovative advances in transforming clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) into different variants have taken the art of genome-editing specificity to new heights. Allosteric modulation of Cas9-targeting specificity by sgRNA sequence alterations and protospacer adjacent motif (PAM) modifications have been a good lesson to learn about specificity and activity scores in different Cas9 variants. Some of the high-fidelity Cas9 variants have been ranked as Sniper-Cas9, eSpCas9 (1.1), SpCas9-HF1, HypaCas9, xCas9, and evoCas9. However, the selection of an ideal Cas9 variant for a given target sequence remains a challenging task. A safe and efficient delivery system for the CRISPR/Cas9 complex at tumor target sites faces considerable challenges, and nanotechnology-based stimuli-responsive delivery approaches have significantly contributed to cancer management. Recent innovations in nanoformulation design, such as pH, glutathione (GSH), photo, thermal, and magnetic responsive systems, have modernized the art of CRISPR/Cas9 delivery approaches. These nanoformulations possess enhanced cellular internalization, endosomal membrane disruption/bypass, and controlled release. In this review, we aim to elaborate on different CRISPR/Cas9 variants and advances in stimuli-responsive nanoformulations for the specific delivery of this endonuclease system. Furthermore, the critical constraints of this endonuclease system on clinical translations towards the management of cancer and prospects are described.",
			"category": 2,
			"name": "Allemailem Khaled S,2023"
		},
		{
			"PMID": 37057881,
			"title": "Adopted neoplastic cells and the consequences of their existence.",
			"journal": "Oncotarget",
			"authorList": [
				"Lazebnik Yuri"
			],
			"DOI": "10.18632/oncotarget.28408",
			"date": "2023-04-18",
			"PMC": "",
			"citation": "",
			"abstract": "A view that guides the bulk of cancer research and oncology posits that each neoplastic cell in a tumor is a genetic offspring of another neoplastic cell. Yet, analyzing tumors from transplant patients has revealed that some normal migratory cells adopt the phenotype of neoplastic cells without acquiring their genome, thus becoming what I suggest to call adopted neoplastic cells. This commentary reviews the evidence for the existence of adopted neoplastic cells, outlines the consequences of their presence, and discusses what kind of cells can be adopted, how, and why.",
			"category": 2,
			"name": "Lazebnik Yuri,2023"
		},
		{
			"PMID": 37051593,
			"title": "PredDSMC: A predictor for driver synonymous mutations in human cancers.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Wang Lihua",
				"Sun Jianhui",
				"Ma Shunshuai",
				"Xia Junfeng",
				"Li Xiaoyan"
			],
			"DOI": "10.3389/fgene.2023.1164593",
			"date": "2023-04-15",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "Wang Lihua,2023"
		},
		{
			"PMID": 37047684,
			"title": "The Efficacy of Tumor Mutation Burden as a Biomarker of Response to Immune Checkpoint Inhibitors.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Moeckel Camille",
				"Bakhl Katrina",
				"Georgakopoulos-Soares Ilias",
				"Zaravinos Apostolos"
			],
			"DOI": "10.3390/ijms24076710",
			"date": "2023-04-14",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is one of the leading causes of death in the world; therefore, extensive research has been dedicated to exploring potential therapeutics, including immune checkpoint inhibitors (ICIs). Initially, programmed-death ligand-1 was the biomarker utilized to predict the efficacy of ICIs. However, its heterogeneous expression in the tumor microenvironment, which is critical to cancer progression, promoted the exploration of the tumor mutation burden (TMB). Research in various cancers, such as melanoma and lung cancer, has shown an association between high TMB and response to ICIs, increasing its predictive value. However, the TMB has failed to predict ICI response in numerous other cancers. Therefore, future research is needed to analyze the variations between cancer types and establish TMB cutoffs in order to create a more standardized methodology for using the TMB clinically. In this review, we aim to explore current research on the efficacy of the TMB as a biomarker, discuss current approaches to overcoming immunoresistance to ICIs, and highlight new trends in the field such as liquid biopsies, next generation sequencing, chimeric antigen receptor T-cell therapy, and personalized tumor vaccines.",
			"category": 2,
			"name": "Moeckel Camille,2023"
		},
		{
			"PMID": 37012421,
			"title": "Best Practices in Microbial Experimental Evolution: Using Reporters and Long-Read Sequencing to Identify Copy Number Variation in Experimental Evolution.",
			"journal": "Journal of molecular evolution",
			"authorList": [
				"Spealman Pieter",
				"De Titir",
				"Chuong Julie N",
				"Gresham David"
			],
			"DOI": "10.1007/s00239-023-10102-7",
			"date": "2023-06-19",
			"PMC": "",
			"citation": "",
			"abstract": "Copy number variants (CNVs), comprising gene amplifications and deletions, are a pervasive class of heritable variation. CNVs play a key role in rapid adaptation in both natural, and experimental, evolution. However, despite the advent of new DNA sequencing technologies, detection and quantification of CNVs in heterogeneous populations has remained challenging. Here, we summarize recent advances in the use of CNV reporters that provide a facile means of quantifying de novo CNVs at a specific locus in the genome, and nanopore sequencing, for resolving the often complex structures of CNVs. We provide guidance for the engineering and analysis of CNV reporters and practical guidelines for single-cell analysis of CNVs using flow cytometry. We summarize recent advances in nanopore sequencing, discuss the utility of this technology, and provide guidance for the bioinformatic analysis of these data to define the molecular structure of CNVs. The combination of reporter systems for tracking and isolating CNV lineages and long-read DNA sequencing for characterizing CNV structures enables unprecedented resolution of\u00a0the mechanisms by which CNVs are generated and their evolutionary dynamics.",
			"category": 2,
			"name": "Spealman Pieter,2023"
		},
		{
			"PMID": 36968020,
			"title": "Strand asymmetries across genomic processes.",
			"journal": "Computational and structural biotechnology journal",
			"authorList": [
				"Moeckel Camille",
				"Zaravinos Apostolos",
				"Georgakopoulos-Soares Ilias"
			],
			"DOI": "10.1016/j.csbj.2023.03.007",
			"date": "2023-03-28",
			"PMC": "",
			"citation": "",
			"abstract": "Across biological systems, a number of genomic processes, including transcription, replication, DNA repair, and transcription factor binding, display intrinsic directionalities. These directionalities are reflected in the asymmetric distribution of nucleotides, motifs, genes, transposon integration sites, and other functional elements across the two complementary strands. Strand asymmetries, including GC skews and mutational biases, have shaped the nucleotide composition of diverse organisms. The investigation of strand asymmetries often serves as a method to understand underlying biological mechanisms, including protein binding preferences, transcription factor interactions, retrotransposition, DNA damage and repair preferences, transcription-replication collisions, and mutagenesis mechanisms. Research into this subject also enables the identification of functional genomic sites, such as replication origins and transcription start sites. Improvements in our ability to detect and quantify DNA strand asymmetries will provide insights into diverse functionalities of the genome, the contribution of different mutational mechanisms in germline and somatic mutagenesis, and our knowledge of genome instability and evolution, which all have significant clinical implications in human disease, including cancer. In this review, we describe key developments that have been made across the field of genomic strand asymmetries, as well as the discovery of associated mechanisms.",
			"category": 2,
			"name": "Moeckel Camille,2023"
		},
		{
			"PMID": 36950387,
			"title": null,
			"journal": "Cell genomics",
			"authorList": [
				"Fischer Anja",
				"Lersch Robert",
				"de Andrade Kr\u00e4tzig Niklas",
				"Strong Alexander",
				"Friedrich Mathias J",
				"Weber Julia",
				"Engleitner Thomas",
				"\u00d6llinger Rupert",
				"Yen Hsi-Yu",
				"Kohlhofer Ursula",
				"Gonzalez-Menendez Irene",
				"Sailer David",
				"Kogan Liz",
				"Lahnalampi Mari",
				"Laukkanen Saara",
				"Kaltenbacher Thorsten",
				"Klement Christine",
				"Rezaei Majdaddin",
				"Ammon Tim",
				"Montero Juan J",
				"Schneider G\u00fcnter",
				"Mayerle Julia",
				"Heikenw\u00e4lder Mathias",
				"Schmidt-Supprian Marc",
				"Quintanilla-Martinez Leticia",
				"Steiger Katja",
				"Liu Pentao",
				"Cadi\u00f1anos Juan",
				"Vassiliou George S",
				"Saur Dieter",
				"Lohi Olli",
				"Hein\u00e4niemi Merja",
				"Conte Nathalie",
				"Bradley Allan",
				"Rad Lena",
				"Rad Roland"
			],
			"DOI": "10.1016/j.xgen.2023.100276",
			"date": "2024-03-13",
			"PMC": "",
			"citation": "",
			"abstract": "In contrast to mono- or biallelic loss of tumor-suppressor function, effects of discrete gene dysregulations, as caused by non-coding (epi)genome alterations, are poorly understood. Here, by perturbing the regulatory genome in mice, we uncover pervasive roles of subtle gene expression variation in cancer evolution. Genome-wide screens characterizing 1,450 tumors revealed that such quasi-insufficiency is extensive across entities and displays diverse context dependencies, such as distinct cell-of-origin associations in T-ALL subtypes. We compile catalogs of non-coding regions linked to quasi-insufficiency, show their enrichment with human cancer risk variants, and provide functional insights by engineering regulatory alterations in mice. As such, kilo-/megabase deletions in a ",
			"category": 2,
			"name": "Fischer Anja,2024"
		},
		{
			"PMID": 36902227,
			"title": "Pan-Cancer Analysis Reveals Functional Similarity of Three lncRNAs across Multiple Tumors.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Khazaal Abir",
				"Zandavi Seid Miad",
				"Smolnikov Andrei",
				"Fatima Shadma",
				"Vafaee Fatemeh"
			],
			"DOI": "10.3390/ijms24054796",
			"date": "2023-03-14",
			"PMC": "",
			"citation": "",
			"abstract": "Long non-coding RNAs (lncRNAs) are emerging as key regulators in many biological processes. The dysregulation of lncRNA expression has been associated with many diseases, including cancer. Mounting evidence suggests lncRNAs to be involved in cancer initiation, progression, and metastasis. Thus, understanding the functional implications of lncRNAs in tumorigenesis can aid in developing novel biomarkers and therapeutic targets. Rich cancer datasets, documenting genomic and transcriptomic alterations together with advancement in bioinformatics tools, have presented an opportunity to perform pan-cancer analyses across different cancer types. This study is aimed at conducting a pan-cancer analysis of lncRNAs by performing differential expression and functional analyses between tumor and non-neoplastic adjacent samples across eight cancer types. Among dysregulated lncRNAs, seven were shared across all cancer types. We focused on three lncRNAs, found to be consistently dysregulated among tumors. It has been observed that these three lncRNAs of interest are interacting with a wide range of genes across different tissues, yet enriching substantially similar biological processes, found to be implicated in cancer progression and proliferation.",
			"category": 2,
			"name": "Khazaal Abir,2023"
		},
		{
			"PMID": 36900212,
			"title": "Genomics-Driven Precision Medicine in Pediatric Solid Tumors.",
			"journal": "Cancers",
			"authorList": [
				"Suthapot Praewa",
				"Chiangjong Wararat",
				"Chaiyawat Parunya",
				"Choochuen Pongsakorn",
				"Pruksakorn Dumnoensun",
				"Sangkhathat Surasak",
				"Hongeng Suradej",
				"Anurathapan Usanarat",
				"Chutipongtanate Somchai"
			],
			"DOI": "10.3390/cancers15051418",
			"date": "2023-03-13",
			"PMC": "",
			"citation": "",
			"abstract": "Over the past decades, several study programs have conducted genetic testing in cancer patients to identify potential genetic targets for the development of precision therapeutic strategies. These biomarker-driven trials have demonstrated improved clinical outcomes and progression-free survival rates in various types of cancers, especially for adult malignancies. However, similar progress in pediatric cancers has been slow due to their distinguished mutation profiles compared to adults and the low frequency of recurrent genomic alterations. Recently, increased efforts to develop precision medicine for childhood malignancies have led to the identification of genomic alterations and transcriptomic profiles of pediatric patients which presents promising opportunities to study rare and difficult-to-access neoplasms. This review summarizes the current state of known and potential genetic markers for pediatric solid tumors and provides perspectives on precise therapeutic strategies that warrant further investigations.",
			"category": 2,
			"name": "Suthapot Praewa,2023"
		},
		{
			"PMID": 36881401,
			"title": "High expression of TARS is associated with poor prognosis of endometrial cancer.",
			"journal": "Aging",
			"authorList": [
				"Si Lihui",
				"Liu Lianchang",
				"Yang Ruiqi",
				"Li Wenxin",
				"Xu Xiaohong"
			],
			"DOI": "10.18632/aging.204558",
			"date": "2023-03-23",
			"PMC": "",
			"citation": "",
			"abstract": "Endometrial cancer is the second largest and most common cancer in the world. It is urgent to explore novel biomarkers.",
			"category": 2,
			"name": "Si Lihui,2023"
		},
		{
			"PMID": 36845707,
			"title": "The cancer-risk variant frequency among Polish population reported by the first national whole-genome sequencing study.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Mroczek Magdalena",
				"Liu Jakub",
				"Sypniewski Mateusz",
				"Pie\u0144kowski Tadeusz",
				"Itrych Bartosz",
				"Stojak Joanna",
				"Pronobis-Szczylik Bartosz",
				"St\u0119pie\u0144 Maria",
				"Kaja El\u017cbieta",
				"D\u0105browski Maciej",
				"Suchocki Tomasz",
				"Wojtaszewska Marzena",
				"Zawadzki Pawe\u0142",
				"Mach Anna",
				"Sztromwasser Pawe\u0142",
				"Kr\u00f3l Zbigniew J",
				"Szyda Joanna",
				"Dobosz Paula"
			],
			"DOI": "10.3389/fonc.2023.1045817",
			"date": "2023-02-28",
			"PMC": "",
			"citation": "",
			"abstract": "Population-based cancer screening has raised many controversies in recent years, not only regarding the costs but also regarding the ethical nature and issues related to variant interpretation. Nowadays, genetic cancer screening standards are different in every country and usually encompass only individuals with a personal or family history of relevant cancer.",
			"category": 2,
			"name": "Mroczek Magdalena,2023"
		},
		{
			"PMID": 36829508,
			"title": "Overview of Optical Biosensors for Early Cancer Detection: Fundamentals, Applications and Future Perspectives.",
			"journal": "Biology",
			"authorList": [
				"Azab Mohammad Y",
				"Hameed Mohamed Farhat O",
				"Obayya Salah S A"
			],
			"DOI": "10.3390/biology12020232",
			"date": "2023-02-28",
			"PMC": "",
			"citation": "",
			"abstract": "Conventional cancer detection and treatment methodologies are based on surgical, chemical and radiational processes, which are expensive, time consuming and painful. Therefore, great interest has been directed toward developing sensitive, inexpensive and rapid techniques for early cancer detection. Optical biosensors have advantages in terms of high sensitivity and being label free with a compact size. In this review paper, the state of the art of optical biosensors for early cancer detection is presented in detail. The basic idea, sensitivity analysis, advantages and limitations of the optical biosensors are discussed. This includes optical biosensors based on plasmonic waveguides, photonic crystal fibers, slot waveguides and metamaterials. Further, the traditional optical methods, such as the colorimetric technique, optical coherence tomography, surface-enhanced Raman spectroscopy and reflectometric interference spectroscopy, are addressed.",
			"category": 2,
			"name": "Azab Mohammad Y,2023"
		},
		{
			"PMID": 36826055,
			"title": "Recurrent ",
			"journal": "Current issues in molecular biology",
			"authorList": [
				"Oh Kei Shing",
				"Bahmad Hisham F",
				"Stoyanov Kalin Veselinov",
				"Amjad Ibrahim H",
				"Brathwaite Carole"
			],
			"DOI": "10.3390/cimb45020110",
			"date": "2023-02-28",
			"PMC": "",
			"citation": "",
			"abstract": "Congenital infiltrating lipomatosis of the face (CILF) is a rare, congenital, nonhereditary facial overgrowth due to post-zygomatic activating mutations in ",
			"category": 2,
			"name": "Oh Kei Shing,2023"
		},
		{
			"PMID": 36808277,
			"title": "Venadaparib Is a Novel and Selective PARP Inhibitor with Improved Physicochemical Properties, Efficacy, and Safety.",
			"journal": "Molecular cancer therapeutics",
			"authorList": [
				"Lee Myongjae",
				"Je In-Gyu",
				"Kim Jeong Eun",
				"Yoo Yeongran",
				"Lim Jong-Ha",
				"Jang Eunhye",
				"Lee Yoonsuk",
				"Song Dong Keun",
				"Moon An-Na",
				"Kim Jeong-Ah",
				"Jeong Jinah",
				"Park Joon-Tae",
				"Lee Jung Woo",
				"Yang Ji-Hoon",
				"Hong Chang-Hee",
				"Park Sun-Young",
				"Park Young-Whan",
				"Baek Nam Seok",
				"Lee Sungsook",
				"Ha Kyoung Soo",
				"Choi SungKu",
				"Lee Won Sik"
			],
			"DOI": "10.1158/1535-7163.MCT-22-0068",
			"date": "2023-03-09",
			"PMC": "",
			"citation": "",
			"abstract": "PARP inhibitors have been approved by the FDA for use in the treatment of patients with ovarian, breast, pancreatic, and prostate cancers. PARP inhibitors show diverse suppressive effects on PARP family members and PARP-DNA trapping potency. These properties are associated with distinct safety/efficacy profiles. Here, we report the nonclinical characteristics of venadaparib (also known as IDX-1197 or NOV140101), a novel potent PARP inhibitor. The physiochemical properties of venadaparib were analyzed. Furthermore, the efficacy of venadaparib against PARP enzymes, PAR formation, and PARP trapping activities, and growth inhibition of cell lines with BRCA mutations were evaluated. Ex vivo and in vivo models were also established to study pharmacokinetics/pharmacodynamics, efficacy, and toxicity. Venadaparib specifically inhibits PARP-1 and -2 enzymes. Oral administration of venadaparib HCl at doses above 12.5 mg/kg significantly reduced tumor growth in the OV_065 patient-derived xenograft model. Intratumoral PARP inhibition remained at over 90% until 24 hours after dosing. Venadaparib had wider safety margins than olaparib. Notably, venadaparib showed favorable physicochemical properties and superior anticancer effects in homologous recombination-deficient in vitro and in vivo models with improved safety profiles. Our results suggest the possibility of venadaparib as a next-generation PARP inhibitor. On the basis of these findings, phase Ib/IIa studies on the efficacy and safety of venadaparib have been initiated.",
			"category": 2,
			"name": "Lee Myongjae,2023"
		},
		{
			"PMID": 36806386,
			"title": "The repertoire of copy number alteration signatures in human cancer.",
			"journal": "Briefings in bioinformatics",
			"authorList": [
				"Tao Ziyu",
				"Wang Shixiang",
				"Wu Chenxu",
				"Wu Tao",
				"Zhao Xiangyu",
				"Ning Wei",
				"Wang Guangshuai",
				"Wang Jinyu",
				"Chen Jing",
				"Diao Kaixuan",
				"Chen Fuxiang",
				"Liu Xue-Song"
			],
			"DOI": "10.1093/bib/bbad053",
			"date": "2023-03-21",
			"PMC": "",
			"citation": "",
			"abstract": "Copy number alterations (CNAs) are a predominant source of genetic alterations in human cancer and play an important role in cancer progression. However comprehensive understanding of the mutational processes and signatures of CNA is still lacking. Here we developed a mechanism-agnostic method to categorize CNA based on various fragment properties, which reflect the consequences of mutagenic processes and can be extracted from different types of data, including whole genome sequencing (WGS) and single nucleotide polymorphism (SNP) array. The 14 signatures of CNA have been extracted from 2778 pan-cancer analysis of whole genomes WGS samples, and further validated with 10\u00a0851 the cancer genome atlas SNP array dataset. Novel patterns of CNA have been revealed through this study. The activities of some CNA signatures consistently predict cancer patients' prognosis. This study provides a repertoire for understanding the signatures of CNA in cancer, with potential implications for cancer prognosis, evolution and etiology.",
			"category": 2,
			"name": "Tao Ziyu,2023"
		},
		{
			"PMID": 36791110,
			"title": "Gatekeeper mutations activate FGF receptor tyrosine kinases by destabilizing the autoinhibited state.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Besch Alida",
				"Marsiglia William M",
				"Mohammadi Moosa",
				"Zhang Yingkai",
				"Traaseth Nathaniel J"
			],
			"DOI": "10.1073/pnas.2213090120",
			"date": "2023-02-17",
			"PMC": "",
			"citation": "",
			"abstract": "Many types of human cancers are being treated with small molecule ATP-competitive inhibitors targeting the kinase domain of receptor tyrosine kinases. Despite initial successful remission, long-term treatment almost inevitably leads to the emergence of drug resistance mutations at the gatekeeper residue hindering the access of the inhibitor to a hydrophobic pocket at the back of the ATP-binding cleft. In addition to reducing drug efficacy, gatekeeper mutations elevate the intrinsic activity of the tyrosine kinase domain leading to more aggressive types of cancer. However, the mechanism of gain-of-function by gatekeeper mutations is poorly understood. Here, we characterized fibroblast growth factor receptor (FGFR) tyrosine kinases harboring two distinct gatekeeper mutations using kinase activity assays, NMR spectroscopy, bioinformatic analyses, and MD simulations. Our data show that gatekeeper mutations destabilize the autoinhibitory conformation of the DFG motif locally and of the kinase globally, suggesting they impart gain-of-function by facilitating the kinase's ability to populate the active state.",
			"category": 2,
			"name": "Besch Alida,2023"
		},
		{
			"PMID": 36774382,
			"title": "A cooperative nano-CRISPR scaffold potentiates immunotherapy via activation of tumour-intrinsic pyroptosis.",
			"journal": "Nature communications",
			"authorList": [
				"Wang Ning",
				"Liu Chao",
				"Li Yingjie",
				"Huang Dongxue",
				"Wu Xinyue",
				"Kou Xiaorong",
				"Wang Xiye",
				"Wu Qinjie",
				"Gong Changyang"
			],
			"DOI": "10.1038/s41467-023-36550-9",
			"date": "2023-02-14",
			"PMC": "",
			"citation": "",
			"abstract": "Efficient cancer immunotherapy depends on selective targeting of high bioactivity therapeutic agents to the tumours. However, delivering exogenous medication might prove difficult in clinical practice. Here we report a cooperative Nano-CRISPR scaffold (Nano-CD) that utilizes a specific sgRNA, selected from a functional screen for triggering endogenous GDSME expression, while releasing cisplatin to initiate immunologic cell death. Mechanistically, cascade-amplification of the antitumor immune response is prompted by the adjuvantic properties of the lytic intracellular content and enhanced by the heightened GDSME expression, resulting in pyroptosis and the release of tumor associated antigens. Neither of the single components provide efficient tumour control, while tumor growth is efficiently inhibited in primary and recurrent melanomas due to the combinatorial effect of cisplatin and self-supplied GSDME. Moreover, Nano-CD in combination with checkpoint blockade creates durable immune memory and strong systemic anti-tumor immune response, leading to disease relapse prevention, lung metastasis inhibition and increased survival in mouse melanomas. Taken together, our therapeutic approach utilizes CRISPR-technology to enable cell-intrinsic protein expression for immunotherapy, using GDSME as prototypic immune modulator. This nanoplatform thus can be applied to modulate further immunological processes for therapeutic benefit.",
			"category": 2,
			"name": "Wang Ning,2023"
		},
		{
			"PMID": 36769353,
			"title": "WGS Data Collections: How Do Genomic Databases Transform Medicine?",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Kr\u00f3l Zbigniew J",
				"Dobosz Paula",
				"\u015alubowska Antonina",
				"Mroczek Magdalena"
			],
			"DOI": "10.3390/ijms24033031",
			"date": "2023-02-14",
			"PMC": "",
			"citation": "",
			"abstract": "As a scientific community we assumed that exome sequencing will elucidate the basis of most heritable diseases. However, it turned out it was not the case; therefore, attention has been increasingly focused on the non-coding sequences that encompass 98% of the genome and may play an important regulatory function. The first WGS-based datasets have already been released including underrepresented populations. Although many databases contain pooled data from several cohorts, recently the importance of local databases has been highlighted. Genomic databases are not only collecting data but may also contribute to better diagnostics and therapies. They may find applications in population studies, rare diseases, oncology, pharmacogenetics, and infectious and inflammatory diseases. Further data may be analysed with Al technologies and in the context of other omics data. To exemplify their utility, we put a highlight on the Polish genome database and its practical application.",
			"category": 2,
			"name": "Kr\u00f3l Zbigniew J,2023"
		},
		{
			"PMID": 36769134,
			"title": "From the Catastrophic Objective Irreproducibility of Cancer Research and Unavoidable Failures of Molecular Targeted Therapies to the Sparkling Hope of Supramolecular Targeted Strategies.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Alekseenko Irina",
				"Kondratyeva Liya",
				"Chernov Igor",
				"Sverdlov Eugene"
			],
			"DOI": "10.3390/ijms24032796",
			"date": "2023-02-14",
			"PMC": "",
			"citation": "",
			"abstract": "The unprecedented non-reproducibility of the results published in the field of cancer research has recently come under the spotlight. In this short review, we try to highlight some general principles in the organization and evolution of cancerous tumors, which objectively lead to their enormous variability and, consequently, the irreproducibility of the results of their investigation. This heterogeneity is also extremely unfavorable for the effective use of molecularly targeted medicine. Against the seemingly comprehensive background of this heterogeneity, we single out two supramolecular characteristics common to all tumors: the clustered nature of tumor interactions with their microenvironment and the formation of biomolecular condensates with tumor-specific distinctive features. We suggest that these features can form the basis of strategies for tumor-specific supramolecular targeted therapies.",
			"category": 2,
			"name": "Alekseenko Irina,2023"
		},
		{
			"PMID": 36732636,
			"title": "The repertoire of mutational signatures in childhood cancer.",
			"journal": "Nature cancer",
			"authorList": [],
			"DOI": "10.1038/s43018-022-00512-9",
			"date": "2023-03-01",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "PMID:36732636;title:The repertoire of mutational signatures in childhood cancer.;journal:Nature cancer;DOI:10.1038/s43018-022-00512-9;date:2023-03-01;"
		},
		{
			"PMID": 36727489,
			"title": "WMDS.net: a network control framework for identifying key players in transcriptome programs.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Cheng Xiang",
				"Amanullah Md",
				"Liu Weigang",
				"Liu Yi",
				"Pan Xiaoqing",
				"Zhang Honghe",
				"Xu Haiming",
				"Liu Pengyuan",
				"Lu Yan"
			],
			"DOI": "10.1093/bioinformatics/btad071",
			"date": "2023-02-15",
			"PMC": "",
			"citation": "",
			"abstract": "Mammalian cells can be transcriptionally reprogramed to other cellular phenotypes. Controllability of such complex transitions in transcriptional networks underlying cellular phenotypes is an inherent biological characteristic. This network controllability can be interpreted by operating a few key regulators to guide the transcriptional program from one state to another. Finding the key regulators in the transcriptional program can provide key insights into the network state transition underlying cellular phenotypes.",
			"category": 2,
			"name": "Cheng Xiang,2023"
		},
		{
			"PMID": 36719112,
			"title": "SWEET: a single-sample network inference method for deciphering individual features in disease.",
			"journal": "Briefings in bioinformatics",
			"authorList": [
				"Chen Hsin-Hua",
				"Hsueh Chun-Wei",
				"Lee Chia-Hwa",
				"Hao Ting-Yi",
				"Tu Tzu-Ying",
				"Chang Lan-Yun",
				"Lee Jih-Chin",
				"Lin Chun-Yu"
			],
			"DOI": "10.1093/bib/bbad032",
			"date": "2023-03-21",
			"PMC": "",
			"citation": "",
			"abstract": "Recently, extracting inherent biological system information (e.g. cellular networks) from genome-wide expression profiles for developing personalized diagnostic and therapeutic strategies has become increasingly important. However, accurately constructing single-sample networks (SINs) to capture individual characteristics and heterogeneity in disease remains challenging. Here, we propose a sample-specific-weighted correlation network (SWEET) method to model SINs by integrating the genome-wide sample-to-sample correlation (i.e. sample weights) with the differential network between perturbed and aggregate networks. For a group of samples, the genome-wide sample weights can be assessed without prior knowledge of intrinsic subpopulations to address the network edge number bias caused by sample size differences. Compared with the state-of-the-art SIN inference methods, the SWEET SINs in 16 cancers more likely fit the scale-free property, display higher overlap with the human interactomes and perform better in identifying three types of cancer-related genes. Moreover, integrating SWEET SINs with a network proximity measure facilitates characterizing individual features and therapy in diseases, such as somatic mutation, mut-driver and essential genes. Biological experiments further validated two candidate repurposable drugs, albendazole for head and neck squamous cell carcinoma (HNSCC) and lung adenocarcinoma (LUAD) and encorafenib for HNSCC. By applying SWEET, we also identified two possible LUAD subtypes that exhibit distinct clinical features and molecular mechanisms. Overall, the SWEET method complements current SIN inference and analysis methods and presents a view of biological systems at the network level to offer numerous clues for further investigation and clinical translation in network medicine and precision medicine.",
			"category": 2,
			"name": "Chen Hsin-Hua,2023"
		},
		{
			"PMID": 36718360,
			"title": "Distinct but interchangeable subpopulations of colorectal cancer cells with different growth fates and drug sensitivity.",
			"journal": "iScience",
			"authorList": [
				"Coppo Roberto",
				"Kondo Jumpei",
				"Iida Keita",
				"Okada Mariko",
				"Onuma Kunishige",
				"Tanaka Yoshihisa",
				"Kamada Mayumi",
				"Ohue Masayuki",
				"Kawada Kenji",
				"Obama Kazutaka",
				"Inoue Masahiro"
			],
			"DOI": "10.1016/j.isci.2023.105962",
			"date": "2023-02-02",
			"PMC": "",
			"citation": "",
			"abstract": "Dynamic changes in cell properties lead to intratumor heterogeneity; however, the mechanisms of nongenetic cellular plasticity remain elusive. When the fate of each cell from colorectal cancer organoids was tracked through a clonogenic growth assay, the cells showed a wide range of growth ability even within the clonal organoids, consisting of distinct subpopulations; the cells generating large spheroids and the cells generating small spheroids. The cells from the small spheroids generated only small spheroids (S-pattern), while the cells from the large spheroids generated both small and large spheroids (D-pattern), both of which were tumorigenic. Transition from the S-pattern to the D-pattern occurred by various extrinsic triggers, in which Notch signaling and Musashi-1 played a key role. The S-pattern spheroids were resistant to chemotherapy and transited to the D-pattern upon drug treatment through Notch signaling. As the transition is linked to the drug resistance, it can be a therapeutic target.",
			"category": 2,
			"name": "Coppo Roberto,2023"
		},
		{
			"PMID": 36702998,
			"title": "APOBEC mutagenesis is a common process in normal human small intestine.",
			"journal": "Nature genetics",
			"authorList": [
				"Wang Yichen",
				"Robinson Philip S",
				"Coorens Tim H H",
				"Moore Luiza",
				"Lee-Six Henry",
				"Noorani Ayesha",
				"Sanders Mathijs A",
				"Jung Hyunchul",
				"Katainen Riku",
				"Heuschkel Robert",
				"Brunton-Sim Roxanne",
				"Weston Robyn",
				"Read Debbie",
				"Nobbs Beverley",
				"Fitzgerald Rebecca C",
				"Saeb-Parsy Kourosh",
				"Martincorena I\u00f1igo",
				"Campbell Peter J",
				"Rushbrook Simon",
				"Zilbauer Matthias",
				"Buczacki Simon James Alexander",
				"Stratton Michael R"
			],
			"DOI": "10.1038/s41588-022-01296-5",
			"date": "2023-02-15",
			"PMC": "",
			"citation": "",
			"abstract": "APOBEC mutational signatures SBS2 and SBS13 are common in many human cancer types. However, there is an incomplete understanding of its stimulus, when it occurs in the progression from normal to cancer cell and the APOBEC enzymes responsible. Here we whole-genome sequenced 342 microdissected normal epithelial crypts from the small intestines of 39 individuals and found that SBS2/SBS13 mutations were present in 17% of crypts, more frequent than most other normal tissues. Crypts with SBS2/SBS13 often had immediate crypt neighbors without SBS2/SBS13, suggesting that the underlying cause of SBS2/SBS13 is cell-intrinsic. APOBEC mutagenesis occurred in an episodic manner throughout the human lifespan, including in young children. APOBEC1 mRNA levels were very high in the small intestine epithelium, but low in the large intestine epithelium and other tissues. The results suggest that the high levels of SBS2/SBS13 in the small intestine are collateral damage from APOBEC1 fulfilling its physiological function of editing APOB mRNA.",
			"category": 2,
			"name": "Wang Yichen,2023"
		},
		{
			"PMID": 36702933,
			"title": "Comprehensive analysis of mutational signatures reveals distinct patterns and molecular processes across 27 pediatric cancers.",
			"journal": "Nature cancer",
			"authorList": [
				"Thatikonda Venu",
				"Islam S M Ashiqul",
				"Autry Robert J",
				"Jones Barbara C",
				"Gr\u00f6bner Susanne N",
				"Warsow Gregor",
				"Hutter Barbara",
				"Huebschmann Daniel",
				"Fr\u00f6hling Stefan",
				"Kool Marcel",
				"Blattner-Johnson Mirjam",
				"Jones David T W",
				"Alexandrov Ludmil B",
				"Pfister Stefan M",
				"J\u00e4ger Natalie"
			],
			"DOI": "10.1038/s43018-022-00509-4",
			"date": "2023-03-01",
			"PMC": "",
			"citation": "",
			"abstract": "Analysis of mutational signatures can reveal underlying molecular mechanisms of the processes that have imprinted the somatic mutations found in cancer genomes. Here, we analyze single base substitutions and small insertions and deletions in pediatric cancers encompassing 785 whole-genome sequenced tumors from 27 molecularly defined cancer subtypes. We identified only a small number of mutational signatures active in pediatric cancers, compared with previously analyzed adult cancers. Further, we report a significant difference in the proportion of pediatric tumors showing homologous recombination repair defect signatures compared with previous analyses. In pediatric leukemias, we identified an indel signature, not previously reported, characterized by long insertions in nonrepeat regions, affecting mainly intronic and intergenic regions, but also exons of known cancer genes. We provide a systematic overview of COSMIC v.3 mutational signatures active across pediatric cancers, which is highly relevant for understanding tumor biology and enabling future research in defining biomarkers of treatment response.",
			"category": 2,
			"name": "Thatikonda Venu,2023"
		},
		{
			"PMID": 36699399,
			"title": "MAST: a hybrid Multi-Agent Spatio-Temporal model of tumor microenvironment informed using a data-driven approach.",
			"journal": "Bioinformatics advances",
			"authorList": [
				"Cesaro Giulia",
				"Milia Mikele",
				"Baruzzo Giacomo",
				"Finco Giovanni",
				"Morandini Francesco",
				"Lazzarini Alessio",
				"Alotto Piergiorgio",
				"da Cunha Carvalho de Miranda Noel Filipe",
				"Trajanoski Zlatko",
				"Finotello Francesca",
				"Di Camillo Barbara"
			],
			"DOI": "10.1093/bioadv/vbac092",
			"date": "2023-02-02",
			"PMC": "",
			"citation": "",
			"abstract": "Recently, several computational modeling approaches, such as agent-based models, have been applied to study the interaction dynamics between immune and tumor cells in human cancer. However, each tumor is characterized by a specific and unique tumor microenvironment, emphasizing the need for specialized and personalized studies of each cancer scenario.",
			"category": 2,
			"name": "Cesaro Giulia,2023"
		},
		{
			"PMID": 36689556,
			"title": "PANACEA: network-based methods for pharmacotherapy prioritization in personalized oncology.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Ulgen Ege",
				"Ozisik Ozan",
				"Sezerman Osman Ugur"
			],
			"DOI": "10.1093/bioinformatics/btad022",
			"date": "2023-01-25",
			"PMC": "",
			"citation": "",
			"abstract": "Identifying appropriate pharmacotherapy options from genomics results is a significant challenge in personalized oncology. However, computational methods for prioritizing drugs are underdeveloped. With the hypothesis that network-based approaches can improve the performance by extending the use of potential drug targets beyond direct interactions, we devised two network-based methods for personalized pharmacotherapy prioritization in cancer.",
			"category": 2,
			"name": "Ulgen Ege,2023"
		},
		{
			"PMID": 36687219,
			"title": "Anti-cancer Activity of Chrysin in Cancer Therapy: a Systematic Review.",
			"journal": "Indian journal of surgical oncology",
			"authorList": [
				"Salari Nader",
				"Faraji Farahnaz",
				"Jafarpour Sima",
				"Faraji Fatemeh",
				"Rasoulpoor Shna",
				"Dokaneheifard Sadat",
				"Mohammadi Masoud"
			],
			"DOI": "10.1007/s13193-022-01550-6",
			"date": "2023-12-02",
			"PMC": "",
			"citation": "",
			"abstract": "Chrysin is a natural bioactive compound that is extracted from many trees, honey, and propolis. Chrysin has several pharmacological activities such as anti-inflammatory, anti-cancer, and antioxidant properties. This study was performed to evaluate the anti-cancer activities of chrysin in cancer therapy. The present study was conducted by systematic review of studies published up to August 2021. Related studies were identified by searching Web of Science (WoS), PubMed, Science Direct, SID, MagIran, Scopus, and Google Scholar databases. The keywords of chrysin, cancer, anti-cancer, and cancer therapy were used for searching. The quality of the studies was assessed by the CONSORT checklist. A total of 21 studies were identified. The results of studies showed that chrysin has an anticancer effect by stimulating apoptosis in a wide range of human cells and rats. Chrysin is also an important factor in inhibiting tumor growth and neoplasticity. Chrysin inhibits the growth and proliferation of cancer cells by inducing cytotoxic effects. Therefore, due to the antitumor effects of chrysin and its safety and non-toxicity towards normal cells, this compound can be considered as an adjuvant along with chemotherapeutic agents in cancer treatment.",
			"category": 2,
			"name": "Salari Nader,2023"
		},
		{
			"PMID": 36675137,
			"title": "Mining TCGA Database for Genes with Prognostic Value in Breast Cancer.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Filippi Alexandru",
				"Mocanu Maria-Magdalena"
			],
			"DOI": "10.3390/ijms24021622",
			"date": "2023-01-24",
			"PMC": "",
			"citation": "",
			"abstract": "The aim of the study was to use transcriptomics data to identify genes associated with advanced/aggressive breast cancer and their effect on survival outcomes. We used the publicly available The Cancer Genome Atlas (TCGA) database to obtain RNA sequence data from patients with less than five years survival (Poor Prognosis, ",
			"category": 2,
			"name": "Filippi Alexandru,2023"
		},
		{
			"PMID": 36662868,
			"title": "Cullin-5 deficiency orchestrates the tumor microenvironment to promote mammary tumor development through CREB1-CCL2 signaling.",
			"journal": "Science advances",
			"authorList": [
				"Chen Si",
				"Shao Fangyuan",
				"Zeng Jianming",
				"Guo Sen",
				"Wang Lijian",
				"Sun Heng",
				"Lei Josh Haipeng",
				"Lyu Xueying",
				"Gao Shuai",
				"Chen Qiang",
				"Miao Kai",
				"Xu Xiaoling",
				"Deng Chu-Xia"
			],
			"DOI": "10.1126/sciadv.abq1395",
			"date": "2023-01-31",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer-associated gene 1 (",
			"category": 2,
			"name": "Chen Si,2023"
		},
		{
			"PMID": 36632887,
			"title": "Antisense-oligonucleotide co-micelles with tumor targeting peptides elicit therapeutic effects by inhibiting microRNA-21 in the glioblastoma animal models.",
			"journal": "Journal of advanced research",
			"authorList": [
				"Lee Youngki",
				"Ha Junkyu",
				"Kim Minkyung",
				"Kang Subin",
				"Kang Minji",
				"Lee Minhyung"
			],
			"DOI": "10.1016/j.jare.2023.01.005",
			"date": "2023-11-03",
			"PMC": "",
			"citation": "",
			"abstract": "miRNA-21 (miR-21) is highly expressed in glioblastoma, facilitating tumor growth by blocking the expression of apoptosis-related genes. Therefore, an antisense microRNA oligonucleotide (AMO) against miR-21 was suggested as a therapeutic nucleic acid for glioblastoma.",
			"category": 2,
			"name": "Lee Youngki,2023"
		},
		{
			"PMID": 36632585,
			"title": "The Landscape of Single Nucleotide Polymorphisms in Papillary Thyroid Carcinoma.",
			"journal": "Cancer diagnosis & prognosis",
			"authorList": [
				"Kyrodimos Efthymios",
				"Chrysovergis Aristeidis",
				"Mastronikolis Nicholas",
				"Papanastasiou George",
				"Tsiambas Evangelos",
				"Spyropoulou Despoina",
				"Katsinis Spyros",
				"Manoli Arezina",
				"Papouliakos Sotirios",
				"Pantos Pavlos",
				"Ragos Vasileios",
				"Peschos Dimitrios",
				"Papanikolaou Vasileios"
			],
			"DOI": "10.21873/cdp.10175",
			"date": "2023-01-13",
			"PMC": "",
			"citation": "",
			"abstract": "Thyroid carcinoma represents a leading malignancy among those derived from human endocrine systems. It comprises a variety of different histological subtypes, including mainly papillary carcinoma, follicular carcinoma, anaplastic carcinoma, and medullar carcinoma. A broad spectrum of genetic imbalances, comprising gross chromosomal (polysomy/aneuploidy) and specific gene (mutations, amplifications, deletions) alterations, has been reported. Interestingly, the role of isolated, specific gene polymorphisms, especially of the single nucleotide polymorphism (SNP) type, in thyroid carcinoma is under investigation. SNPs are the most common genetic variations in the genome. The current molecular review focuses on the impact of specific SNPs on the biological behavior of papillary thyroid carcinoma in their carriers.",
			"category": 2,
			"name": "Kyrodimos Efthymios,2023"
		},
		{
			"PMID": 36618380,
			"title": "Frequent somatic mosaicism in T lymphocyte subsets in individuals with and without multiple sclerosis.",
			"journal": "Frontiers in immunology",
			"authorList": [
				"Van Horebeek Lies",
				"Dedoncker Nina",
				"Dubois B\u00e9n\u00e9dicte",
				"Goris An"
			],
			"DOI": "10.3389/fimmu.2022.993178",
			"date": "2023-01-10",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic variants are variations in an individual's genome acquired after the zygotic stadium and result from mitotic errors or not (fully) repaired DNA damage.",
			"category": 2,
			"name": "Van Horebeek Lies,2023"
		},
		{
			"PMID": 36617985,
			"title": "Transmicron: accurate prediction of insertion probabilities improves detection of cancer driver genes from transposon mutagenesis screens.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Bredthauer Carl",
				"Fischer Anja",
				"Ahari Ata Jadid",
				"Cao Xueqi",
				"Weber Julia",
				"Rad Lena",
				"Rad Roland",
				"Wachutka Leonhard",
				"Gagneur Julien"
			],
			"DOI": "10.1093/nar/gkac1215",
			"date": "2023-03-07",
			"PMC": "",
			"citation": "",
			"abstract": "Transposon screens are powerful in vivo assays used to identify loci driving carcinogenesis. These loci are identified as Common Insertion Sites (CISs), i.e. regions with more transposon insertions than expected by chance. However, the identification of CISs is affected by biases in the insertion behaviour of transposon systems. Here, we introduce Transmicron, a novel method that differs from previous methods by (i) modelling neutral insertion rates based on chromatin accessibility, transcriptional activity\u00a0and sequence context and (ii) estimating oncogenic selection for each genomic region using Poisson regression to model insertion counts while controlling for neutral insertion rates. To assess the benefits of our approach, we generated a dataset applying two different transposon systems under comparable conditions. Benchmarking for enrichment of known cancer genes showed improved performance of Transmicron against state-of-the-art methods. Modelling neutral insertion rates allowed for better control of false positives and stronger agreement of the results between transposon systems. Moreover, using Poisson regression to consider intra-sample and inter-sample information proved beneficial in small and moderately-sized datasets. Transmicron is open-source and freely available. Overall, this study contributes to the understanding of transposon biology and introduces a novel approach to use this knowledge for discovering cancer driver genes.",
			"category": 2,
			"name": "Bredthauer Carl,2023"
		},
		{
			"PMID": 36612087,
			"title": "Immunodeficiencies Push Readmissions in Malignant Tumor Patients: A Retrospective Cohort Study Based on the Nationwide Readmission Database.",
			"journal": "Cancers",
			"authorList": [
				"Wang Wenchen",
				"Meng Qingyu",
				"Cheng Yiping",
				"Han Yalin",
				"Xue Yonggan",
				"Kuang Yanshen",
				"Wang Xuning",
				"Ning Bobin",
				"Ke Mu",
				"Teng Zhipeng",
				"Li Sen",
				"Li Peng",
				"Liu Hongyi",
				"Fan Xiude",
				"Jia Baoqing"
			],
			"DOI": "10.3390/cancers15010088",
			"date": "2023-01-11",
			"PMC": "",
			"citation": "",
			"abstract": "Immunodeficiency diseases (IDDs) are associated with an increased proportion of cancer-related morbidity. However, the relationship between IDDs and malignancy readmissions has not been well described. Understanding this relationship could help us to develop a more reasonable discharge plan in the special tumor population.",
			"category": 2,
			"name": "Wang Wenchen,2023"
		},
		{
			"PMID": 36544004,
			"title": "A mechanism for inheriting radiation-induced DNA damage.",
			"journal": "Nature",
			"authorList": [
				"Cutler Ronald",
				"Vijg Jan"
			],
			"DOI": "10.1038/d41586-022-04449-y",
			"date": "2023-01-12",
			"PMC": "",
			"citation": "",
			"abstract": "Radiation-damaged paternal DNA has been found to cause embryos of the second generation of nematode worms, but not the first, to die. The proposed mechanisms help to explain the observed lack of such an effect in humans.",
			"category": 2,
			"name": "Cutler Ronald,2023"
		},
		{
			"PMID": 36536253,
			"title": "Ultrafast prediction of somatic structural variations by filtering out reads matched to pan-genome k-mer sets.",
			"journal": "Nature biomedical engineering",
			"authorList": [
				"Sohn Jang-Il",
				"Choi Min-Hak",
				"Yi Dohun",
				"Menon Vipin A",
				"Kim Yeon Jeong",
				"Lee Junehawk",
				"Park Jung Woo",
				"Kyung Sungkyu",
				"Shin Seung-Ho",
				"Na Byunggook",
				"Joung Je-Gun",
				"Ju Young Seok",
				"Yeom Min Sun",
				"Koh Youngil",
				"Yoon Sung-Soo",
				"Baek Daehyun",
				"Kim Tae-Min",
				"Nam Jin-Wu"
			],
			"DOI": "10.1038/s41551-022-00980-5",
			"date": "2023-07-26",
			"PMC": "",
			"citation": "",
			"abstract": "Variant callers typically produce massive numbers of false positives for structural variations, such as cancer-relevant copy-number alterations and fusion genes resulting from genome rearrangements. Here we describe an ultrafast and accurate detector of somatic structural variations that reduces read-mapping costs by filtering out reads matched to pan-genome k-mer sets. The detector, which we named ETCHING (for efficient detection of chromosomal rearrangements and fusion genes), reduces the number of false positives by leveraging machine-learning classifiers trained with six breakend-related features (clipped-read count, split-reads count, supporting paired-end read count, average mapping quality, depth difference and total length of clipped bases). When benchmarked against six callers on reference cell-free DNA, validated biomarkers of structural variants, matched tumour and normal whole genomes, and tumour-only targeted sequencing datasets, ETCHING was 11-fold faster than the second-fastest structural-variant caller at comparable performance and memory use. The speed and accuracy of ETCHING may aid large-scale genome projects and facilitate practical implementations in precision medicine.",
			"category": 2,
			"name": "Sohn Jang-Il,2023"
		},
		{
			"PMID": 36524129,
			"title": "Prognosis stratification in breast cancer and characterization of immunosuppressive microenvironment through a pyrimidine metabolism-related signature.",
			"journal": "Frontiers in immunology",
			"authorList": [
				"Luo Yongzhou",
				"Tian Wenwen",
				"Lu Xiuqing",
				"Zhang Chao",
				"Xie Jindong",
				"Deng Xinpei",
				"Xie Yi",
				"Yang Shuhui",
				"Du Wei",
				"He Rongfang",
				"Wei Weidong"
			],
			"DOI": "10.3389/fimmu.2022.1056680",
			"date": "2022-12-19",
			"PMC": "",
			"citation": "",
			"abstract": "Pyrimidine metabolism is a hallmark of cancer and will soon become an essential part of cancer therapy. In the tumor microenvironment, cells reprogram pyrimidine metabolism intrinsically and extracellularly, thereby promoting tumorigenesis. Metabolites in pyrimidine metabolism have a significant impact on promoting cancer advancement and modulating immune system responses. In preclinical studies and practical clinical applications, critical targets in pyrimidine metabolism are acted upon by drugs to exert promising therapeutic effects on tumors. However, the pyrimidine metabolism in breast cancer (BC) is still largely underexplored. In this study, 163 credible pyrimidine metabolism-related genes (PMGs) were retrieved, and their somatic mutations and expression levels were determined. In addition, by using The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases, 12 PMGs related to the overall survival (OS) were determined using the univariate Cox regression analysis. Subsequently, by performing the LASSO Cox hazards regression analysis in the 12 PMGs in TCGA-BRCA dataset, we developed a prognosis nomogram using eight OS-related PMGs and then verified the same in the METABRIC, GSE96058, GSE20685, GSE42568 and GSE86166 data. Moreover, we validated relationships between the pyrimidine metabolism index (PMI) and the survival probability of patients, essential clinical parameters, including the TNM stage and the PAM50 subtypes. Next, we verified the predictive capability of the optimum model, including the signature, the PAM50 subtype, and age, using ROC analysis and calibration curve, and compared it with other single clinical factors for the predictive power of benefit using decision curve analysis. Finally, we investigated the potential effects of pyrimidine metabolism on immune checkpoints, tumor-infiltrating immune cells, and cytokine levels and determined the potential implications of pyrimidine metabolism in BC immunotherapy. In conclusion, our findings suggest that pyrimidine metabolism has underlying prognostic significance in BC and can facilitate a new management approach for patients with different prognoses and more precise immunotherapy.",
			"category": 2,
			"name": "Luo Yongzhou,2022"
		},
		{
			"PMID": 36505462,
			"title": "Tumor immunomodulatory effects of polyphenols.",
			"journal": "Frontiers in immunology",
			"authorList": [
				"Wang Qin",
				"Yang Bin",
				"Wang Nan",
				"Gu Jian"
			],
			"DOI": "10.3389/fimmu.2022.1041138",
			"date": "2022-12-16",
			"PMC": "",
			"citation": "",
			"abstract": "Polyphenols, commonly found in various plants, have attracted enormous attention due to their potential pharmacological activity, especially antitumor activity dependent on immune function. In recent years, the development of nanomedicine can counteract the low bioavailability of polyphenols and improve the effect of tumor treatment. Among them, metal-phenolic networks (MPNs), which utilize various metal ions and phenolic ligands for coordination binding, have now become candidates for polyphenol-based nanomedicine treatment of tumors. In this mini-review, we described the classification of polyphenols and their mechanisms in antitumor immune responses, and provided suggestions for the next steps of treating tumors with polyphenols.",
			"category": 2,
			"name": "Wang Qin,2022"
		},
		{
			"PMID": 36497297,
			"title": "Computational Analysis Reveals the Temporal Acquisition of Pathway Alterations during the Evolution of Cancer.",
			"journal": "Cancers",
			"authorList": [
				"Ahrenfeldt Johanne",
				"Christensen Ditte S",
				"Soka\u010d Mateo",
				"Kisist\u00f3k Judit",
				"McGranahan Nicholas",
				"Birkbak Nicolai J"
			],
			"DOI": "10.3390/cancers14235817",
			"date": "2022-12-21",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer metastasis is the lethal developmental step in cancer, responsible for the majority of cancer deaths. To metastasise, cancer cells must acquire the ability to disseminate systemically and to escape an activated immune response. Here, we endeavoured to investigate if metastatic dissemination reflects acquisition of genomic traits that are selected for. We acquired mutation and copy number data from 8332 tumours representing 19 cancer types acquired from The Cancer Genome Atlas and the Hartwig Medical Foundation. A total of 827,344 non-synonymous mutations across 8332 tumour samples representing 19 cancer types were timed as early or late relative to copy number alterations, and potential driver events were annotated. We found that metastatic cancers had a significantly higher proportion of clonal mutations and a general enrichment of early mutations in p53 and RTK/KRAS pathways. However, while individual pathways demonstrated a clear time-separated preference for specific events, the relative timing did not vary between primary and metastatic cancers. These results indicate that the selective pressure that drives cancer development does not change dramatically between primary and metastatic cancer on a genomic level, and is mainly focused on alterations that increase proliferation.",
			"category": 2,
			"name": "Ahrenfeldt Johanne,2022"
		},
		{
			"PMID": 36478991,
			"title": "Development and Clinical Validation of a Novel 5 Gene Signature Based on Fatty Acid Metabolism-Related Genes in Oral Squamous Cell Carcinoma.",
			"journal": "Oxidative medicine and cellular longevity",
			"authorList": [
				"Fan Yi",
				"Wang Jing",
				"Wang Yaping",
				"Li Yanni",
				"Wang Sijie",
				"Weng Yanfeng",
				"Yang Qiujiao",
				"Chen Chen",
				"Lin Lisong",
				"Qiu Yu",
				"Wang Jing",
				"Chen Fa",
				"He Baochang",
				"Liu Fengqiong"
			],
			"DOI": "10.1155/2022/3285393",
			"date": "2022-12-15",
			"PMC": "",
			"citation": "",
			"abstract": "Lipid metabolism disorders play a crucial role in tumor development and progression. The aim of the study focused on constructing a novel prognostic model of oral squamous cell carcinoma (OSCC) patients using fatty acid metabolism-related genes.",
			"category": 2,
			"name": "Fan Yi,2022"
		},
		{
			"PMID": 36478203,
			"title": "bmVAE: a variational autoencoder method for clustering single-cell mutation data.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Yan Jiaqian",
				"Ma Ming",
				"Yu Zhenhua"
			],
			"DOI": "10.1093/bioinformatics/btac790",
			"date": "2023-01-10",
			"PMC": "",
			"citation": "",
			"abstract": "Genetic intra-tumor heterogeneity (ITH) characterizes the differences in genomic variations between tumor clones, and accurately unmasking ITH is important for personalized cancer therapy. Single-cell DNA sequencing now emerges as a powerful means for deciphering underlying ITH based on point mutations of single cells. However, detecting tumor clones from single-cell mutation data remains challenging due to the error-prone and discrete nature of the data.",
			"category": 2,
			"name": "Yan Jiaqian,2023"
		},
		{
			"PMID": 36428799,
			"title": "The Somatic Mutation Landscape of UDP-Glycosyltransferase (",
			"journal": "Cancers",
			"authorList": [
				"Hu Dong Gui",
				"Marri Shashikanth",
				"Hulin Julie-Ann",
				"McKinnon Ross A",
				"Mackenzie Peter I",
				"Meech Robyn"
			],
			"DOI": "10.3390/cancers14225708",
			"date": "2022-12-13",
			"PMC": "",
			"citation": "",
			"abstract": "The human UDP-glycosyltransferase (UGTs) superfamily has a critical role in the metabolism of anticancer drugs and numerous pro/anti-cancer molecules (e.g., steroids, lipids, fatty acids, bile acids and carcinogens). Recent studies have shown wide and abundant expression of ",
			"category": 2,
			"name": "Hu Dong Gui,2022"
		},
		{
			"PMID": 36421850,
			"title": "Prevalence and Genotype-Phenotype Correlation of Lynch Syndrome in a Selected High-Risk Cohort from Qatar's Population.",
			"journal": "Genes",
			"authorList": [
				"Sidenna Mariem",
				"Khodjet-El-Khil Houssein",
				"Al Mulla Hajar",
				"Al-Shafai Mashael",
				"Habish Hind Hassan",
				"Al-Sulaiman Reem",
				"Al-Bader Salha Bujassoum"
			],
			"DOI": "10.3390/genes13112176",
			"date": "2022-11-28",
			"PMC": "",
			"citation": "",
			"abstract": "Lynch syndrome (LS) is the most common cause of hereditary colorectal cancers (CRC) and is associated with an increased risk for ovarian and endometrial cancers. There is lack of knowledge on the epidemiology of LS in the non-Caucasian populations especially in Qatar. The aim of this retrospective study is to explore the prevalence of LS in a selected high-risk cohort in the State of Qatar in addition to investigating the frequency and genotype-phenotype correlation associated with mismatch repair genes pathogenic variants. Retrospective review of medical records of 31 individuals with LS, 20 affected with colorectal cancer and 11 unaffected with family history of cancers, referred from January 2017 until August 2020. The prevalence of LS among affected and unaffected patients is 22% (20/92) and 2.2% respectively. Among affected individuals, ",
			"category": 2,
			"name": "Sidenna Mariem,2022"
		},
		{
			"PMID": 36396655,
			"title": "Somatic mutation distribution across tumour cohorts provides a signal for positive selection in cancer.",
			"journal": "Nature communications",
			"authorList": [
				"Bostr\u00f6m Martin",
				"Larsson Erik"
			],
			"DOI": "10.1038/s41467-022-34746-z",
			"date": "2022-11-21",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer gene discovery is reliant on distinguishing driver mutations from a multitude of passenger mutations in tumour genomes. While driver genes may be revealed based on excess mutation recurrence or clustering, there is a need for orthogonal principles. Here, we take advantage of the fact that non-cancer genes, containing only passenger mutations under neutral selection, exhibit a likelihood of mutagenesis in a given tumour determined by the tumour's mutational signature and burden. This relationship can be disrupted by positive selection, leading to a difference in the distribution of mutated cases across a cohort for driver and passenger genes. We apply this principle to detect cancer drivers independently of recurrence in large pan-cancer cohorts, and show that our method (SEISMIC) performs comparably to traditional approaches and can provide resistance to known confounding mutational phenomena. Being based on a different principle, the approach provides a much-needed complement to existing methods for detecting signals of selection.",
			"category": 2,
			"name": "Bostr\u00f6m Martin,2022"
		},
		{
			"PMID": 36395362,
			"title": "Treasures from trash in cancer research.",
			"journal": "Oncotarget",
			"authorList": [
				"Moreira Fabiano Cordeiro",
				"Sarquis Dionison Pereira",
				"Souza Jorge Estefano Santana de",
				"Avelar Daniel de Souza",
				"Ara\u00fajo Ta\u00edssa Maria Thomaz",
				"Khayat Andr\u00e9 Salim",
				"Santos Sidney Emanuel Batista Dos",
				"de Assump\u00e7\u00e3o Paulo Pimentel"
			],
			"DOI": "10.18632/oncotarget.28308",
			"date": "2022-11-21",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer research has significantly improved in recent years, primarily due to next-generation sequencing (NGS) technology. Consequently, an enormous amount of genomic and transcriptomic data has been generated. In most cases, the data needed for research goals are used, and unwanted reads are discarded. However, these eliminated data contain relevant information. Aiming to test this hypothesis, genomic and transcriptomic data were acquired from public datasets.",
			"category": 2,
			"name": "Moreira Fabiano Cordeiro,2022"
		},
		{
			"PMID": 36388765,
			"title": "Uncovering novel mutational signatures by ",
			"journal": "Cell genomics",
			"authorList": [
				"Islam S M Ashiqul",
				"D\u00edaz-Gay Marcos",
				"Wu Yang",
				"Barnes Mark",
				"Vangara Raviteja",
				"Bergstrom Erik N",
				"He Yudou",
				"Vella Mike",
				"Wang Jingwei",
				"Teague Jon W",
				"Clapham Peter",
				"Moody Sarah",
				"Senkin Sergey",
				"Li Yun Rose",
				"Riva Laura",
				"Zhang Tongwu",
				"Gruber Andreas J",
				"Steele Christopher D",
				"Otlu Bur\u00e7ak",
				"Khandekar Azhar",
				"Abbasi Ammal",
				"Humphreys Laura",
				"Syulyukina Natalia",
				"Brady Samuel W",
				"Alexandrov Boian S",
				"Pillay Nischalan",
				"Zhang Jinghui",
				"Adams David J",
				"Martincorena I\u00f1igo",
				"Wedge David C",
				"Landi Maria Teresa",
				"Brennan Paul",
				"Stratton Michael R",
				"Rozen Steven G",
				"Alexandrov Ludmil B"
			],
			"DOI": "10.1016/j.xgen.2022.100179",
			"date": "2024-07-17",
			"PMC": "",
			"citation": "",
			"abstract": "Mutational signature analysis is commonly performed in cancer genomic studies. Here, we present SigProfilerExtractor, an automated tool for ",
			"category": 2,
			"name": "Islam S M Ashiqul,2024"
		},
		{
			"PMID": 36358834,
			"title": "Organoids for Modeling (Colorectal) Cancer in a Dish.",
			"journal": "Cancers",
			"authorList": [
				"Rathje Florian",
				"Klingler Stefan",
				"Aberger Fritz"
			],
			"DOI": "10.3390/cancers14215416",
			"date": "2022-11-17",
			"PMC": "",
			"citation": "",
			"abstract": "Functional studies of primary cancer have been limited to animal models for a long time making it difficult to study aspects specific to human cancer biology. The development of organoid technology enabled us to culture human healthy and tumor cells as three-dimensional self-organizing structures in vitro for a prolonged time. Organoid cultures conserve the heterogeneity of the originating epithelium regarding cell types and tumor clonality. Therefore, organoids are considered an invaluable tool to study and genetically dissect various aspects of human cancer biology. In this review, we describe the applications, advantages, and limitations of organoids as human cancer models with the main emphasis on colorectal cancer.",
			"category": 2,
			"name": "Rathje Florian,2022"
		},
		{
			"PMID": 36357424,
			"title": "Single cell profiling of primary and paired metastatic lymph node tumors in breast cancer patients.",
			"journal": "Nature communications",
			"authorList": [
				"Liu Tong",
				"Liu Cheng",
				"Yan Meisi",
				"Zhang Lei",
				"Zhang Jing",
				"Xiao Min",
				"Li Zhigao",
				"Wei Xiaofan",
				"Zhang Hongquan"
			],
			"DOI": "10.1038/s41467-022-34581-2",
			"date": "2022-11-14",
			"PMC": "",
			"citation": "",
			"abstract": "The microenvironment of lymph node metastasized tumors (LNMT) determines tumor progression and response to therapy, but a systematic study of LNMT is lacking. Here, we generate single-cell maps of primary tumors (PTs) and paired LNMTs in 8 breast cancer patients. We demonstrate that the activation, cytotoxicity, and proliferation of T cells are suppressed in LNMT compared with PT. CD4",
			"category": 2,
			"name": "Liu Tong,2022"
		},
		{
			"PMID": 36344707,
			"title": "MACHETE identifies interferon-encompassing chromosome 9p21.3 deletions as mediators of immune evasion and metastasis.",
			"journal": "Nature cancer",
			"authorList": [
				"Barriga Francisco M",
				"Tsanov Kaloyan M",
				"Ho Yu-Jui",
				"Sohail Noor",
				"Zhang Amy",
				"Baslan Timour",
				"Wuest Alexandra N",
				"Del Priore Isabella",
				"Me\u0161kauskait\u0117 Brigita",
				"Livshits Geulah",
				"Alonso-Curbelo Direna",
				"Simon Janelle",
				"Chaves-Perez Almudena",
				"Bar-Sagi Dafna",
				"Iacobuzio-Donahue Christine A",
				"Notta Faiyaz",
				"Chaligne Ronan",
				"Sharma Roshan",
				"Pe'er Dana",
				"Lowe Scott W"
			],
			"DOI": "10.1038/s43018-022-00443-5",
			"date": "2022-12-06",
			"PMC": "",
			"citation": "",
			"abstract": "The most prominent homozygous deletions in cancer affect chromosome 9p21.3 and eliminate CDKN2A/B tumor suppressors, disabling a cell-intrinsic barrier to tumorigenesis. Half of 9p21.3 deletions, however, also encompass a type I interferon (IFN) gene cluster; the consequences of this co-deletion remain unexplored. To functionally dissect 9p21.3 and other large genomic deletions, we developed a flexible deletion engineering strategy, MACHETE (molecular alteration of chromosomes with engineered tandem elements). Applying MACHETE to a syngeneic mouse model of pancreatic cancer, we found that co-deletion of the IFN cluster promoted immune evasion, metastasis and immunotherapy resistance. Mechanistically, IFN co-deletion disrupted type I IFN signaling in the tumor microenvironment, leading to marked changes in infiltrating immune cells and escape from CD8",
			"category": 2,
			"name": "Barriga Francisco M,2022"
		},
		{
			"PMID": 36340455,
			"title": "Epigenetic Mechanisms in Breast Adenocarcinoma: Novel DNA Methylation Patterns.",
			"journal": "Cancer diagnosis & prognosis",
			"authorList": [
				"Metaxas Georgios I",
				"Tsiambas Evangelos",
				"Marinopoulos Spyridon",
				"Spyropoulou Despoina",
				"Manaios Loukas",
				"Adamopoulou Maria",
				"Falidas Evangelos",
				"Peschos Dimitrios",
				"Kalkani Helen",
				"Dimitrakakis Constantine"
			],
			"DOI": "10.21873/cdp.10149",
			"date": "2022-11-08",
			"PMC": "",
			"citation": "",
			"abstract": "Breast adenocarcinoma is a leading cause of death in females worldwide. A broad spectrum of genetic and epigenetic alterations has been already identified and reported in millions of examined cancerous substrates, evidence of a high-level genomic heterogeneity that characterizes these malignancies. Concerning epigenetic changes and imbalances that critically affect progression and prognosis in the corresponding patients, DNA methylation, histone modifications (acetylation), micro-RNAs (miRs) alterations and chromatin re-organization represent the main mechanisms. Referring to DNA methylation, promoter hyper-hypo methylation in critical tumour suppressor and oncogenes is implicated in normal epithelia transformation to their neoplastic and finally malignant cyto-phenotypes. The current review is focused on the different methylation patterns and mechanisms detected in breast adenocarcinoma and their impact on the corresponding groups of patient response to specific chemotherapeutic regimens and life span prognosis.",
			"category": 2,
			"name": "Metaxas Georgios I,2022"
		},
		{
			"PMID": 36325153,
			"title": "Potential Therapeutic Strategy for ",
			"journal": "JTO clinical and research reports",
			"authorList": [
				"Huang Ming-Hung",
				"Lee Jih-Hsiang",
				"Hung Pei-Shan",
				"Chih-Hsin Yang James"
			],
			"DOI": "10.1016/j.jtocrr.2022.100405",
			"date": "2022-11-04",
			"PMC": "",
			"citation": "",
			"abstract": "Although driver gene mutations have been believed to be mutually exclusive, some patients with NSCLC and concomitant ",
			"category": 2,
			"name": "Huang Ming-Hung,2022"
		},
		{
			"PMID": 36294788,
			"title": "Cancer Genetics and Clinical Research.",
			"journal": "Journal of personalized medicine",
			"authorList": [
				"Allegra Sarah"
			],
			"DOI": "10.3390/jpm12101649",
			"date": "2022-10-30",
			"PMC": "",
			"citation": "",
			"abstract": "Understanding how complex diseases as well as cancers arise is one of the great challenges of modern medicine [...].",
			"category": 2,
			"name": "Allegra Sarah,2022"
		},
		{
			"PMID": 36291918,
			"title": "The Emerging Roles of Protein Interactions with O-GlcNAc Cycling Enzymes in Cancer.",
			"journal": "Cancers",
			"authorList": [
				"Hu Chia-Wei",
				"Xie Jinshan",
				"Jiang Jiaoyang"
			],
			"DOI": "10.3390/cancers14205135",
			"date": "2024-02-12",
			"PMC": "",
			"citation": "",
			"abstract": "The dynamic O-GlcNAc modification of intracellular proteins is an important nutrient sensor for integrating metabolic signals into vast networks of highly coordinated cellular activities. Dysregulation of the sole enzymes responsible for O-GlcNAc cycling, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), and the associated cellular O-GlcNAc profile is a common feature across nearly every cancer type. Many studies have investigated the effects of aberrant OGT/OGA expression on global O-GlcNAcylation activity in cancer cells. However, recent studies have begun to elucidate the roles of protein-protein interactions (PPIs), potentially through regions outside of the immediate catalytic site of OGT/OGA, that regulate greater protein networks to facilitate substrate-specific modification, protein translocalization, and the assembly of larger biomolecular complexes. Perturbation of OGT/OGA PPI networks makes profound changes in the cell and may directly contribute to cancer malignancies. Herein, we highlight recent studies on the structural features of OGT and OGA, as well as the emerging roles and molecular mechanisms of their aberrant PPIs in rewiring cancer networks. By integrating complementary approaches, the research in this area will aid in the identification of key protein contacts and functional modules derived from OGT/OGA that drive oncogenesis and will illuminate new directions for anti-cancer drug development.",
			"category": 2,
			"name": "Hu Chia-Wei,2024"
		},
		{
			"PMID": 36289620,
			"title": "Exploiting the Molecular Basis of Oesophageal Cancer for Targeted Therapies and Biomarkers for Drug Response: Guiding Clinical Decision-Making.",
			"journal": "Biomedicines",
			"authorList": [
				"Mbatha Sikhumbuzo",
				"Hull Rodney",
				"Dlamini Zodwa"
			],
			"DOI": "10.3390/biomedicines10102359",
			"date": "2022-10-30",
			"PMC": "",
			"citation": "",
			"abstract": "Worldwide, oesophageal cancer is the sixth leading cause of deaths related to cancer and represents a major health concern. Sub-Saharan Africa is one of the regions of the world with the highest incidence and mortality rates for oesophageal cancer and most of the cases of oesophageal cancer in this region are oesophageal squamous cell carcinoma (OSCC). The development and progression of OSCC is characterized by genomic changes which can be utilized as diagnostic or prognostic markers. These include changes in the expression of various genes involved in signaling pathways that regulate pathways that regulate processes that are related to the hallmarks of cancer, changes in the tumor mutational burden, changes in alternate splicing and changes in the expression of non-coding RNAs such as miRNA. These genomic changes give rise to characteristic profiles of altered proteins, transcriptomes, spliceosomes and genomes which can be used in clinical applications to monitor specific disease related parameters. Some of these profiles are characteristic of more aggressive forms of cancer or are indicative of treatment resistance or tumors that will be difficult to treat or require more specialized specific treatments. In Sub-Saharan region of Africa there is a high incidence of viral infections such as HPV and HIV, which are both risk factors for OSCC. The genomic changes that occur due to these infections can serve as diagnostic markers for OSCC related to viral infection. Clinically this is an important distinction as it influences treatment as well as disease progression and treatment monitoring practices. This underlines the importance of the characterization of the molecular landscape of OSCC in order to provide the best treatment, care, diagnosis and screening options for the management of OSCC.",
			"category": 2,
			"name": "Mbatha Sikhumbuzo,2022"
		},
		{
			"PMID": 36289336,
			"title": "Phenotypic plasticity and genetic control in colorectal cancer evolution.",
			"journal": "Nature",
			"authorList": [
				"Househam Jacob",
				"Heide Timon",
				"Cresswell George D",
				"Spiteri Inmaculada",
				"Kimberley Chris",
				"Zapata Luis",
				"Lynn Claire",
				"James Chela",
				"Mossner Maximilian",
				"Fernandez-Mateos Javier",
				"Vinceti Alessandro",
				"Baker Ann-Marie",
				"Gabbutt Calum",
				"Berner Alison",
				"Schmidt Melissa",
				"Chen Bingjie",
				"Lakatos Eszter",
				"Gunasri Vinaya",
				"Nichol Daniel",
				"Costa Helena",
				"Mitchinson Miriam",
				"Ramazzotti Daniele",
				"Werner Benjamin",
				"Iorio Francesco",
				"Jansen Marnix",
				"Caravagna Giulio",
				"Barnes Chris P",
				"Shibata Darryl",
				"Bridgewater John",
				"Rodriguez-Justo Manuel",
				"Magnani Luca",
				"Sottoriva Andrea",
				"Graham Trevor A"
			],
			"DOI": "10.1038/s41586-022-05311-x",
			"date": "2022-11-30",
			"PMC": "",
			"citation": "",
			"abstract": "Genetic and epigenetic variation, together with transcriptional plasticity, contribute to intratumour heterogeneity",
			"category": 2,
			"name": "Househam Jacob,2022"
		},
		{
			"PMID": 36266635,
			"title": "Construction and analysis of sample-specific driver modules for breast cancer.",
			"journal": "BMC genomics",
			"authorList": [
				"Chen Yuanyuan",
				"Li Haitao",
				"Sun Xiao"
			],
			"DOI": "10.1186/s12864-022-08928-4",
			"date": "2022-10-24",
			"PMC": "",
			"citation": "",
			"abstract": "It is important to understand the functional impact of somatic mutation and methylation aberration at an individual level to implement precision medicine. Recent studies have demonstrated that the\u00a0perturbation of gene interaction networks can provide a fundamental link between genotype (or epigenotype) and phenotype. However, it is unclear how individual mutations affect the function of biological networks, especially for individual methylation aberration. To solve this, we provided a sample-specific driver module construction method using the 2-order network theory and hub-gene theory to identify individual perturbation networks driven by mutations or methylation aberrations.",
			"category": 2,
			"name": "Chen Yuanyuan,2022"
		},
		{
			"PMID": 36251535,
			"title": "Clinical decisions by the molecular tumor board on comprehensive genomic profiling tests in Japan: A retrospective observational study.",
			"journal": "Cancer medicine",
			"authorList": [
				"Shirota Hidekazu",
				"Komine Keigo",
				"Takahashi Masanobu",
				"Takahashi Shin",
				"Miyauchi Eisaku",
				"Niizuma Hidetaka",
				"Tada Hiroshi",
				"Shimada Muneaki",
				"Niihori Tetsuya",
				"Aoki Yoko",
				"Sugiyama Ikuko",
				"Kawamura Maako",
				"Yasuda Jun",
				"Suzuki Shuhei",
				"Iwaya Takeshi",
				"Saito Motonobu",
				"Saito Tsuyoshi",
				"Shibata Hiroyuki",
				"Furukawa Toru",
				"Ishioka Chikashi"
			],
			"DOI": "10.1002/cam4.5349",
			"date": "2023-03-23",
			"PMC": "",
			"citation": "",
			"abstract": "A paradigm shift has occurred in cancer chemotherapy from tumor-specific treatment with cytotoxic agents to personalized medicine with molecular-targeted drugs. Thus, it is essential to identify genomic alterations and molecular features to recommend effective targeted molecular medicines regardless of the tumor site. Nevertheless, it takes considerable expertise to identify treatment targets from primary-sequencing data in order to provide drug recommendations. The Molecular Tumor Board (MTB) denotes a platform that integrates clinical and molecular features for clinical decisions.",
			"category": 2,
			"name": "Shirota Hidekazu,2023"
		},
		{
			"PMID": 36246660,
			"title": "DETexT: An SNV detection enhancement for low read depth by integrating mutational signatures into TextCNN.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Zheng Tian"
			],
			"DOI": "10.3389/fgene.2022.943972",
			"date": "2022-10-19",
			"PMC": "",
			"citation": "",
			"abstract": "Detecting SNV at very low read depths helps to reduce sequencing requirements, lowers sequencing costs, and aids in the early screening, diagnosis, and treatment of cancer. However, the accuracy of SNV detection is significantly reduced at read depths below \u00d734 due to the lack of a sufficient number of read pairs to help filter out false positives. Many recent studies have revealed the potential of mutational signature (MS) in detecting true SNV, understanding the mutational processes that lead to the development of human cancers, and analyzing the endogenous and exogenous causes. Here, we present DETexT, an SNV detection method better suited to low read depths, which classifies false positive variants by combining MS with deep learning algorithms to mine correlation information around bases in individual reads without relying on the support of duplicate read pairs. We have validated the effectiveness of DETexT on simulated and real datasets and conducted comparative experiments. The source code has been uploaded to https://github.com/TrinaZ/extra-lowRD for academic use only.",
			"category": 2,
			"name": "Zheng Tian,2022"
		},
		{
			"PMID": 36246650,
			"title": "Two subtypes of cutaneous melanoma with distinct mutational signatures and clinico-genomic characteristics.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Kim Yoon-Seob",
				"Lee Minho",
				"Chung Yeun-Jun"
			],
			"DOI": "10.3389/fgene.2022.987205",
			"date": "2022-10-19",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "Kim Yoon-Seob,2022"
		},
		{
			"PMID": 36232840,
			"title": "Deep Learning Approaches for Detection of Breast Adenocarcinoma Causing Carcinogenic Mutations.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Shah Asghar Ali",
				"Alturise Fahad",
				"Alkhalifah Tamim",
				"Khan Yaser Daanial"
			],
			"DOI": "10.3390/ijms231911539",
			"date": "2022-10-17",
			"PMC": "",
			"citation": "",
			"abstract": "Genes are composed of DNA and each gene has a specific sequence. Recombination or replication within the gene base ends in a permanent change in the nucleotide collection in a DNA called mutation and some mutations can lead to cancer. Breast adenocarcinoma starts in secretary cells. Breast adenocarcinoma is the most common of all cancers that occur in women. According to a survey within the United States of America, there are more than 282,000 breast adenocarcinoma patients registered each 12 months, and most of them are women. Recognition of cancer in its early stages saves many lives. A proposed framework is developed for the early detection of breast adenocarcinoma using an ensemble learning technique with multiple deep learning algorithms, specifically: Long Short-Term Memory (LSTM), Gated Recurrent Units (GRU), and Bi-directional LSTM. There are 99 types of driver genes involved in breast adenocarcinoma. This study uses a dataset of 4127 samples including men and women taken from more than 12 cohorts of cancer detection institutes. The dataset encompasses a total of 6170 mutations that occur in 99 genes. On these gene sequences, different algorithms are applied for feature extraction. Three types of testing techniques including independent set testing, self-consistency testing, and a 10-fold cross-validation test is applied to validate and test the learning approaches. Subsequently, multiple deep learning approaches such as LSTM, GRU, and bi-directional LSTM algorithms are applied. Several evaluation metrics are enumerated for the validation of results including accuracy, sensitivity, specificity, Mathew's correlation coefficient, area under the curve, training loss, precision, recall, F1 score, and Cohen's kappa while the values obtained are 99.57, 99.50, 99.63, 0.99, 1.0, 0.2027, 99.57, 99.57, 99.57, and 99.14 respectively.",
			"category": 2,
			"name": "Shah Asghar Ali,2022"
		},
		{
			"PMID": 36175592,
			"title": "Association between cancer genes and germ layer specificity.",
			"journal": "Medical oncology (Northwood, London, England)",
			"authorList": [
				"Lee Hwayeong",
				"Lee Sungwhan",
				"Cho Woo Jong",
				"Shin Minjung",
				"Park Leeyoung"
			],
			"DOI": "10.1007/s12032-022-01823-8",
			"date": "2022-10-03",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer signaling pathways defining cell fates are related to differentiation. During the developmental process, three germ layers (endoderm, mesoderm, and ectoderm) are formed during embryonic development that differentiate into organs via the epigenetic regulation of specific genes. To examine the relationship, the specificities of cancer gene mutations that depend on the germ layers are studied. The major organs affected by cancer were determined based on statistics from the National Cancer Information Center of Korea, and were grouped according to their germ layer origins. Then, the gene mutation frequencies were evaluated to identify any bias based on the differentiation group using the Catalogue of Somatic Mutations in Cancer (COSMIC) database. The chi-square test showed that the p-value of 152 of 166 genes was less than 0.05, and 151 genes showed p-values of less than 0.05 even after adjusting for the false discovery rate (FDR). The germ layer-specific genes were evaluated using visualization based on basic statistics, and the results matched the top ranking genes depending on organs in the COSMIC database.The current study confirmed the germ layer specificity of major cancer genes. The germ layer specificity of mutated driver genes is possibly important in cancer treatments because each mutated gene may react differently depending on the germ layer of origin. By understanding the mechanism of gene mutation in the development and progression of cancer in the context of cell-fate pathways, a more effective therapeutic strategy for cancer can be established.",
			"category": 2,
			"name": "Lee Hwayeong,2022"
		},
		{
			"PMID": 36159778,
			"title": "A novel anti-B7-H3 chimeric antigen receptor from a single-chain antibody library for immunotherapy of solid cancers.",
			"journal": "Molecular therapy oncolytics",
			"authorList": [
				"Birley Kathleen",
				"Leboreiro-Babe Clara",
				"Rota Enrique Miranda",
				"Buschhaus Magdalena",
				"Gavriil Artemis",
				"Vitali Alice",
				"Alonso-Ferrero Maria",
				"Hopwood Lee",
				"Parienti Lara",
				"Ferry Gabrielle",
				"Flutter Barry",
				"Himoudi Nourredine",
				"Chester Kerry",
				"Anderson John"
			],
			"DOI": "10.1016/j.omto.2022.08.008",
			"date": "2022-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "B7-H3 (CD276) has emerged as a target for cancer immunotherapy by virtue of consistent expression in many malignancies, relative absence from healthy tissues, and an emerging role as a\u00a0driver of tumor immune inhibition. Recent studies have reported B7-H3 to be a suitable target for chimeric antigen receptor-modified T\u00a0cell (CAR-T) therapy using CARs constructed from established anti-B7-H3 antibodies converted into single-chain Fv format (scFv). We constructed and screened binders in an scFv library to generate a new anti-B7-H3 CAR-T with favorable properties. This allowed access to numerous specificities ready formatted for CAR evaluation. Selected anti-human B7-H3 scFvs were readily cloned into CAR-T and evaluated for anti-tumor reactivity in cytotoxicity, cytokine, and proliferation assays. Two binders with divergent complementarity determining regions were found to show optimal antigen-specific cytotoxicity and cytokine secretion. One binder in second-generation CD28-CD3\u03b6 CAR format induced sustained ",
			"category": 2,
			"name": "Birley Kathleen,2022"
		},
		{
			"PMID": 36144012,
			"title": "Statistical Classification for Raman Spectra of Tumoral Genomic DNA.",
			"journal": "Micromachines",
			"authorList": [
				"Durastanti Claudio",
				"Cirillo Emilio N M",
				"De Benedictis Ilaria",
				"Ledda Mario",
				"Sciortino Antonio",
				"Lisi Antonella",
				"Convertino Annalisa",
				"Mussi Valentina"
			],
			"DOI": "10.3390/mi13091388",
			"date": "2022-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "We exploit Surface-Enhanced Raman Scattering (SERS) to investigate aqueous droplets of genomic DNA deposited onto silver-coated silicon nanowires, and we show that it is possible to efficiently discriminate between spectra of tumoral and healthy cells. To assess the robustness of the proposed technique, we develop two different statistical approaches, one based on the Principal Components Analysis of spectral data and one based on the computation of the \u21132 distance between spectra. Both methods prove to be highly efficient, and we test their accuracy via the Cohen's \u03ba statistics. We show that the synergistic combination of the SERS spectroscopy and the statistical analysis methods leads to efficient and fast cancer diagnostic applications allowing rapid and unexpansive discrimination between healthy and tumoral genomic DNA alternative to the more complex and expensive DNA sequencing.",
			"category": 2,
			"name": "Durastanti Claudio,2022"
		},
		{
			"PMID": 36140723,
			"title": "The Multi-Omic Landscape of Primary Breast Tumors and Their Metastases: Expanding the Efficacy of Actionable Therapeutic Targets.",
			"journal": "Genes",
			"authorList": [
				"Yang Guang",
				"Lu Tao",
				"Weisenberger Daniel J",
				"Liang Gangning"
			],
			"DOI": "10.3390/genes13091555",
			"date": "2022-09-26",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer (BC) mortality is almost exclusively due to metastasis, which is the least understood aspect of cancer biology and represents a significant clinical challenge. Although we have witnessed tremendous advancements in the treatment for metastatic breast cancer (mBC), treatment resistance inevitably occurs in most patients. Recently, efforts in characterizing mBC revealed distinctive genomic, epigenomic and transcriptomic (multi-omic) landscapes to that of the primary tumor. Understanding of the molecular underpinnings of mBC is key to understanding resistance to therapy and the development of novel treatment options. This review summarizes the differential molecular landscapes of BC and mBC, provides insights into the genomic heterogeneity of mBC and highlights the therapeutically relevant, multi-omic features that may serve as novel therapeutic targets for mBC patients.",
			"category": 2,
			"name": "Yang Guang,2022"
		},
		{
			"PMID": 36139078,
			"title": "Research Progress on Nanoparticles-Based CRISPR/Cas9 System for Targeted Therapy of Tumors.",
			"journal": "Biomolecules",
			"authorList": [
				"Nie Dengyun",
				"Guo Ting",
				"Yue Miao",
				"Li Wenya",
				"Zong Xinyu",
				"Zhu Yinxing",
				"Huang Junxing",
				"Lin Mei"
			],
			"DOI": "10.3390/biom12091239",
			"date": "2022-09-26",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a genetic mutation disease that seriously endangers the health and life of all human beings. As one of the most amazing academic achievements in the past decade, CRISPR/Cas9 technology has been sought after by many researchers due to its powerful gene editing capability. CRISPR/Cas9 technology shows great potential in oncology, and has become one of the most promising technologies for cancer genome-editing therapeutics. However, its efficiency and the safety issues of in vivo gene editing severely limit its widespread application. Therefore, developing a suitable delivery method for the CRISPR/Cas9 system is an urgent problem to be solved at present. Rapid advances in nanomedicine suggest nanoparticles could be a viable option. In this review, we summarize the latest research on the potential use of nanoparticle-based CRISPR/Cas9 systems in cancer therapeutics, in order to further their clinical application. We hope that this review will provide a novel insight into the CRISPR/Cas9 system and offer guidance for nanocarrier designs that will enable its use in cancer clinical applications.",
			"category": 2,
			"name": "Nie Dengyun,2022"
		},
		{
			"PMID": 36114670,
			"title": "Targeted genomic translocations and inversions generated using a paired prime editing strategy.",
			"journal": "Molecular therapy : the journal of the American Society of Gene Therapy",
			"authorList": [
				"Kweon Jiyeon",
				"Hwang Hye-Yeon",
				"Ryu Haesun",
				"Jang An-Hee",
				"Kim Daesik",
				"Kim Yongsub"
			],
			"DOI": "10.1016/j.ymthe.2022.09.008",
			"date": "2023-01-09",
			"PMC": "",
			"citation": "",
			"abstract": "A variety of cancers have been found to have chromosomal rearrangements, and the genomic abnormalities often induced expression of fusion oncogenes. To date, a pair of engineered nucleases including ZFNs, TALENs, and CRISPR-Cas9 nucleases have been used to generate chromosomal rearrangement in living cells and organisms for disease modeling. However, these methods induce unwanted indel mutations at the DNA break junctions, resulting in incomplete disease modeling. Here, we developed prime editor nuclease-mediated translocation and inversion (PETI), a method for programmable chromosomal translocation and inversion using prime editor 2 nuclease (PE2 nuclease) and paired pegRNA. Using PETI method, we successfully introduced DNA recombination in episomal fluorescence reporters as well as precise chromosomal translocations in human cells. We applied PETI to create cancer-associated translocations and inversions such as NPM1-ALK and EML4-ALK in human cells. Our findings show that PETI generated chromosomal translocation and inversion in a programmable manner with efficiencies comparable of Cas9. PETI methods, we believe, could be used to create disease models or for gene therapy.",
			"category": 2,
			"name": "Kweon Jiyeon,2023"
		},
		{
			"PMID": 36110544,
			"title": "Therapeutic and prognostic potential of GPCRs in prostate cancer from multi-omics landscape.",
			"journal": "Frontiers in pharmacology",
			"authorList": [
				"Li Shiqi",
				"Chen Jianfang",
				"Chen Xin",
				"Yu Jin",
				"Guo Yanzhi",
				"Li Menglong",
				"Pu Xuemei"
			],
			"DOI": "10.3389/fphar.2022.997664",
			"date": "2022-09-17",
			"PMC": "",
			"citation": "",
			"abstract": "Prostate cancer (PRAD) is a common and fatal malignancy. It is difficult to manage clinically due to drug resistance and poor prognosis, thus creating an urgent need for novel therapeutic targets and prognostic biomarkers. Although G protein-coupled receptors (GPCRs) have been most attractive for drug development, there have been lack of an exhaustive assessment on GPCRs in PRAD like their molecular features, prognostic and therapeutic values. To close this gap, we herein systematically investigate multi-omics profiling for GPCRs in the primary PRAD by analyzing somatic mutations, somatic copy-number alterations (SCNAs), DNA methylation and mRNA expression. GPCRs exhibit low expression levels and mutation frequencies while SCNAs are more prevalent. 46 and 255 disease-related GPCRs are identified by the mRNA expression and DNA methylation analysis, respectively, complementing information lack in the genome analysis. In addition, the genomic alterations do not exhibit an observable correlation with the GPCR expression, reflecting the complex regulatory processes from DNA to RNA. Conversely, a tight association is observed between the DNA methylation and mRNA expression. The virtual screening and molecular dynamics simulation further identify four potential drugs in repositioning to PRAD. The combination of 3 clinical characteristics and 26 GPCR molecular features revealed by the transcriptome and genome exhibit good performance in predicting progression-free survival in patients with the primary PRAD, providing candidates as new biomarkers. These observations from the multi-omics analysis on GPCRs provide new insights into the underlying mechanism of primary PRAD and potential of GPCRs in developing therapeutic strategies on PRAD.",
			"category": 2,
			"name": "Li Shiqi,2022"
		},
		{
			"PMID": 36110223,
			"title": "Construction and validation of a necroptosis-related lncRNAs prognosis signature of hepatocellular carcinoma.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Peng YunZhen",
				"Wu GuoJing",
				"Qiu Xin",
				"Luo Yue",
				"Zou YiShu",
				"Wei XueYan",
				"Li Aimin"
			],
			"DOI": "10.3389/fgene.2022.916024",
			"date": "2022-09-17",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "Peng YunZhen,2022"
		},
		{
			"PMID": 36083242,
			"title": "Carcinogenesis resistance in the longest-lived rodent, the naked mole-rat.",
			"journal": "Cancer science",
			"authorList": [
				"Yamamura Yuki",
				"Kawamura Yoshimi",
				"Oka Kaori",
				"Miura Kyoko"
			],
			"DOI": "10.1111/cas.15570",
			"date": "2022-12-14",
			"PMC": "",
			"citation": "",
			"abstract": "Certain mammalian species are resistant to cancer, and a better understanding of how this cancer resistance arises could provide valuable insights for basic cancer research. Recent technological innovations in molecular biology have allowed the study of cancer-resistant mammals, despite the fact that they are not the classical model animals, which are easily studied using genetic approaches. Naked mole-rats (NMRs; Heterocephalus glaber) are the longest-lived rodent, with a maximum lifespan of more than 37\u2009years, and almost never show spontaneous carcinogenesis. NMRs are currently attracting much attention from aging and cancer researchers, and published studies on NMR have continued to increase over the past decade. Cancer development occurs via multiple steps and involves many biological processes. Recent research on the NMR as a model for cancer resistance suggests that they possess various unique carcinogenesis-resistance mechanisms, including efficient DNA repair pathways, cell-autonomous resistance to transformation, and dampened inflammatory response. Here, we summarize the molecular mechanisms of carcinogenesis resistance in NMR, which have been uncovered over the past two decades, and discuss future perspectives.",
			"category": 2,
			"name": "Yamamura Yuki,2022"
		},
		{
			"PMID": 36078884,
			"title": "Investigation of the Effect of Imatinib and Hydroxyurea Combination Therapy on Hematological Parameters and Gene Expression in Chronic Myeloid Leukemia (CML) Patients.",
			"journal": "Journal of clinical medicine",
			"authorList": [
				"Al-Amleh Esraa K",
				"Al-Sanabra Ola M",
				"Alqaisi Khalid M",
				"Alqaraleh Moath",
				"Al-Nahal Jumana",
				"Hamadneh Lama",
				"Malki Mohammed Imad",
				"Alhmoud Jehad F"
			],
			"DOI": "10.3390/jcm11174954",
			"date": "2022-09-13",
			"PMC": "",
			"citation": "",
			"abstract": "(1) Background: Chronic myeloid leukemia is defined as the neoplastic development of mostly myeloid cells in the bone marrow. Several treatments, including chemotherapy, radiation, hormone treatment, and immunological therapy, can be used to control this condition. The therapeutic impact on leukemic individuals varies, and the response to therapy varies between patients due to disease heterogeneity. The primary goal of this study is to compare the effects of single and Imatinib (IM) and Hydroxyurea (HU) combined treatment on hematological parameters and gene expression in CML patients. (2) Methods: This study was conducted on 51 patients, with chronic myeloid leukemia, who were admitted to Al-Basher hospital in Amman, Jordan, for follow-up. Their hematological parameters were checked and gene expression was measured for (BCL2, PP2A, CIP2A, and WT1). (3) Results: The BCL2 gene was found to be less expressed in both IM and (HU + IM) treatments as compared to the HU group alone, while PP2A gene expression was raised. Such a thing indicates that the outcome of the combined therapy method is not ideal, since PP2A activation causes CML cells to move toward the blast crisis stage. Furthermore, CIP2A gene expression revealed that IM and (HU + IM) had the same therapeutic effect and were more successful in CML patients than HU alone. With regards to the treatment effect on hematological parameters, notably in CML patients in later stages, the combination therapy (HU + IM) raised lymphocyte count, indicating a greater response to the treatment. When compared to single medicines, the combination treatment reduced the proportion of neutrophils to normal reference ranges. Platelet counts, on the other hand, dramatically decreased in both IM and (HU + IM). (4) Conclusion: Because the studied genes (BCL2, PP2A, CIP2A, and WT1) are participating in cell proliferation and death, the findings show that the examined genes are significant to understand the efficacy of various therapies. Furthermore, it was found that there was a clear effect of the clinic-based strategic treatment on hematological indicators such as WBCs, lymphocytes, neutrophils, and platelet counts.",
			"category": 2,
			"name": "Al-Amleh Esraa K,2022"
		},
		{
			"PMID": 36069825,
			"title": "A New View of Activating Mutations in Cancer.",
			"journal": "Cancer research",
			"authorList": [
				"Nussinov Ruth",
				"Tsai Chung-Jung",
				"Jang Hyunbum"
			],
			"DOI": "10.1158/0008-5472.CAN-22-2125",
			"date": "2022-11-16",
			"PMC": "",
			"citation": "",
			"abstract": "A vast effort has been invested in the identification of driver mutations of cancer. However, recent studies and observations call into question whether the activating mutations or the signal strength are the major determinant of tumor development. The data argue that signal strength determines cell fate, not the mutation that initiated it. In addition to activating mutations, factors that can impact signaling strength include (i) homeostatic mechanisms that can block or enhance the signal, (ii) the types and locations of additional mutations, and (iii) the expression levels of specific isoforms of genes and regulators of proteins in the pathway. Because signal levels are largely decided by chromatin structure, they vary across cell types, states, and time windows. A strong activating mutation can be restricted by low expression, whereas a weaker mutation can be strengthened by high expression. Strong signals can be associated with cell proliferation, but too strong a signal may result in oncogene-induced senescence. Beyond cancer, moderate signal strength in embryonic neural cells may be associated with neurodevelopmental disorders, and moderate signals in aging may be associated with neurodegenerative diseases, like Alzheimer's disease. The challenge for improving patient outcomes therefore lies in determining signaling thresholds and predicting signal strength.",
			"category": 2,
			"name": "Nussinov Ruth,2022"
		},
		{
			"PMID": 36035123,
			"title": "CCAS: One-stop and comprehensive annotation system for individual cancer genome at multi-omics level.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Zheng Xinchang",
				"Zong Wenting",
				"Li Zhaohua",
				"Ma Yingke",
				"Sun Yanling",
				"Xiong Zhuang",
				"Wu Song",
				"Yang Fei",
				"Zhao Wei",
				"Bu Congfan",
				"Du Zhenglin",
				"Xiao Jingfa",
				"Bao Yiming"
			],
			"DOI": "10.3389/fgene.2022.956781",
			"date": "2022-08-30",
			"PMC": "",
			"citation": "",
			"abstract": "Due to the explosion of cancer genome data and the urgent needs for cancer treatment, it is becoming increasingly important and necessary to easily and timely analyze and annotate cancer genomes. However, tumor heterogeneity is recognized as a serious barrier to annotate cancer genomes at the individual patient level. In addition, the interpretation and analysis of cancer multi-omics data rely heavily on existing database resources that are often located in different data centers or research institutions, which poses a huge challenge for data parsing. Here we present CCAS (Cancer genome Consensus Annotation System, https://ngdc.cncb.ac.cn/ccas/#/home), a one-stop and comprehensive annotation system for the individual patient at multi-omics level. CCAS integrates 20 widely recognized resources in the field to support data annotation of 10 categories of cancers covering 395 subtypes. Data from each resource are manually curated and standardized by using ontology frameworks. CCAS accepts data on single nucleotide variant/insertion or deletion, expression, copy number variation, and methylation level as input files to build a consensus annotation. Outputs are arranged in the forms of tables or figures and can be searched, sorted, and downloaded. Expanded panels with additional information are used for conciseness, and most figures are interactive to show additional information. Moreover, CCAS offers multidimensional annotation information, including mutation signature pattern, gene set enrichment analysis, pathways and clinical trial related information. These are helpful for intuitively understanding the molecular mechanisms of tumors and discovering key functional genes.",
			"category": 2,
			"name": "Zheng Xinchang,2022"
		},
		{
			"PMID": 35999207,
			"title": "Genome-wide mutational signatures in low-coverage whole genome sequencing of cell-free DNA.",
			"journal": "Nature communications",
			"authorList": [
				"Wan Jonathan C M",
				"Stephens Dennis",
				"Luo Lingqi",
				"White James R",
				"Stewart Caitlin M",
				"Rousseau Beno\u00eet",
				"Tsui Dana W Y",
				"Diaz Luis A"
			],
			"DOI": "10.1038/s41467-022-32598-1",
			"date": "2022-08-25",
			"PMC": "",
			"citation": "",
			"abstract": "Mutational signatures accumulate in somatic cells as an admixture of endogenous and exogenous processes that occur during an individual's lifetime. Since dividing cells release cell-free DNA (cfDNA) fragments into the circulation, we hypothesize that plasma cfDNA might reflect mutational signatures. Point mutations in plasma whole genome sequencing (WGS) are challenging to identify through conventional mutation calling due to low sequencing coverage and low mutant allele fractions. In this proof of concept study of plasma WGS at 0.3-1.5x coverage from 215 patients and 227 healthy individuals, we show that both pathological and physiological mutational signatures may be identified in plasma. By applying machine learning to mutation profiles, patients with stage I-IV cancer can be distinguished from healthy individuals with an Area Under the Curve of 0.96. Interrogating mutational processes in plasma may enable earlier cancer detection, and might enable the assessment of cancer risk and etiology.",
			"category": 2,
			"name": "Wan Jonathan C M,2022"
		},
		{
			"PMID": 35949260,
			"title": "Substitution mutational signatures in whole-genome-sequenced cancers in the UK population.",
			"journal": "Science (New York, N.Y.)",
			"authorList": [
				"Degasperi Andrea",
				"Zou Xueqing",
				"Amarante Tauanne Dias",
				"Martinez-Martinez Andrea",
				"Koh Gene Ching Chiek",
				"Dias Jo\u00e3o M L",
				"Heskin Laura",
				"Chmelova Lucia",
				"Rinaldi Giuseppe",
				"Wang Valerie Ya Wen",
				"Nanda Arjun S",
				"Bernstein Aaron",
				"Momen Sophie E",
				"Young Jamie",
				"Perez-Gil Daniel",
				"Memari Yasin",
				"Badja Cherif",
				"Shooter Scott",
				"Czarnecki Jan",
				"Brown Matthew A",
				"Davies Helen R",
				"Genomics England Research Consortium",
				"Nik-Zainal Serena"
			],
			"DOI": "10.1126/science.abl9283",
			"date": "2022-08-12",
			"PMC": "",
			"citation": "",
			"abstract": "Whole-genome sequencing (WGS) permits comprehensive cancer genome analyses, revealing mutational signatures, imprints of DNA damage and repair processes that have arisen in each patient's cancer. We performed mutational signature analyses on 12,222 WGS tumor-normal matched pairs, from patients recruited via the UK National Health Service. We contrasted our results to two independent cancer WGS datasets, the International Cancer Genome Consortium (ICGC) and Hartwig Foundation, involving 18,640 WGS cancers in total. Our analyses add 40 single and 18 double substitution signatures to the current mutational signature tally. Critically, we show for each organ, that cancers have a limited number of 'common' signatures and a long tail of 'rare' signatures. We provide a practical solution for utilizing this concept of common versus rare signatures in future analyses.",
			"category": 2,
			"name": "Degasperi Andrea,2022"
		},
		{
			"PMID": 35936888,
			"title": "3D Cell Cultures: Evolution of an Ancient Tool for New Applications.",
			"journal": "Frontiers in physiology",
			"authorList": [
				"Cacciamali Andrea",
				"Villa Riccardo",
				"Dotti Silvia"
			],
			"DOI": "10.3389/fphys.2022.836480",
			"date": "2022-08-09",
			"PMC": "",
			"citation": "",
			"abstract": "Recently, research is undergoing a drastic change in the application of the animal model as a unique investigation strategy, considering an alternative approach for the development of science for the future. Although conventional monolayer cell cultures represent an established and widely used ",
			"category": 2,
			"name": "Cacciamali Andrea,2022"
		},
		{
			"PMID": 35935942,
			"title": "Human Variation in DNA Repair, Immune Function, and Cancer Risk.",
			"journal": "Frontiers in immunology",
			"authorList": [
				"Cheong Ana",
				"Nagel Zachary D"
			],
			"DOI": "10.3389/fimmu.2022.899574",
			"date": "2022-08-09",
			"PMC": "",
			"citation": "",
			"abstract": "DNA damage constantly threatens genome integrity, and DNA repair deficiency is associated with increased cancer risk. An intuitive and widely accepted explanation for this relationship is that unrepaired DNA damage leads to carcinogenesis due to the accumulation of mutations in somatic cells. But DNA repair also plays key roles in the function of immune cells, and immunodeficiency is an important risk factor for many cancers. Thus, it is possible that emerging links between inter-individual variation in DNA repair capacity and cancer risk are driven, at least in part, by variation in immune function, but this idea is underexplored. In this review we present an overview of the current understanding of the links between cancer risk and both inter-individual variation in DNA repair capacity and inter-individual variation in immune function. We discuss factors that play a role in both types of variability, including age, lifestyle, and environmental exposures. In conclusion, we propose a research paradigm that incorporates functional studies of both genome integrity and the immune system to predict cancer risk and lay the groundwork for personalized prevention.",
			"category": 2,
			"name": "Cheong Ana,2022"
		},
		{
			"PMID": 35932013,
			"title": "Distinct non-clock-like signatures of the basal cell carcinomas from three sisters with a lethal Gorlin-Goltz syndrome.",
			"journal": "BMC medical genomics",
			"authorList": [
				"Ye Lihua",
				"Wang Li",
				"Peng Kexin",
				"Fang Ou",
				"Tian Zhen",
				"Li Caihua",
				"Fu Xiaopeng",
				"Chen Qingdong",
				"Chen Jia",
				"Luan Jing",
				"Zhang Zhenghua",
				"Zhang Qiaoan"
			],
			"DOI": "10.1186/s12920-022-01324-7",
			"date": "2022-08-09",
			"PMC": "",
			"citation": "",
			"abstract": "Gorlin-Goltz syndrome (GS) is an inherited disease characterized by predisposition to basal cell carcinomas (BCCs) and various developmental defects, whose numerous disease-causing PTCH1 mutations have been identified in the hedgehog (Hh) signaling pathway.",
			"category": 2,
			"name": "Ye Lihua,2022"
		},
		{
			"PMID": 35920867,
			"title": "d",
			"journal": "Journal of molecular evolution",
			"authorList": [
				"Gu Xun"
			],
			"DOI": "10.1007/s00239-022-10064-2",
			"date": "2022-09-19",
			"PMC": "",
			"citation": "",
			"abstract": "One of the most popular measures in the analysis of protein sequence evolution is the ratio of nonsynonymous distance (d",
			"category": 2,
			"name": "Gu Xun,2022"
		},
		{
			"PMID": 35907861,
			"title": "Deficient DNA base-excision repair in the forebrain leads to a sex-specific anxiety-like phenotype in mice.",
			"journal": "BMC biology",
			"authorList": [
				"Mueller Flavia S",
				"Amport Ren\u00e9",
				"Notter Tina",
				"Schalbetter Sina M",
				"Lin Han-Yu",
				"Garajova Zuzana",
				"Amini Parisa",
				"Weber-Stadlbauer Ulrike",
				"Markkanen Enni"
			],
			"DOI": "10.1186/s12915-022-01377-1",
			"date": "2022-08-02",
			"PMC": "",
			"citation": "",
			"abstract": "Neuropsychiatric disorders, such as schizophrenia (SZ) and autism spectrum disorder (ASD), are common, multi-factorial and multi-symptomatic disorders. Ample evidence implicates oxidative stress, deficient repair of oxidative DNA lesions and DNA damage in the development of these disorders. However, it remains unclear whether insufficient DNA repair and resulting DNA damage are causally connected to their aetiopathology, or if increased levels of DNA damage observed in patient tissues merely accumulate as a consequence of cellular dysfunction. To assess a potential causal role for deficient DNA repair in the development of these disorders, we behaviourally characterized a mouse model in which CaMKIIa-Cre-driven postnatal conditional knockout (KO) of the core base-excision repair (BER) protein XRCC1 leads to accumulation of unrepaired DNA damage in the forebrain.",
			"category": 2,
			"name": "Mueller Flavia S,2022"
		},
		{
			"PMID": 35903677,
			"title": "Case Report: Malignant Brain Tumors in Siblings With ",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Wu Di",
				"Chen Qingshan",
				"Chen Jian"
			],
			"DOI": "10.3389/fonc.2022.920305",
			"date": "2022-07-31",
			"PMC": "",
			"citation": "",
			"abstract": "Familial brain tumor incidences are low. Identifying the genetic alterations of familial brain tumors can help better understand the pathogenesis and make therapy regimens for these tumors.",
			"category": 2,
			"name": "Wu Di,2022"
		},
		{
			"PMID": 35900151,
			"title": "SECEDO: SNV-based subclone detection using ultra-low coverage single-cell DNA sequencing.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Rozho\u0148ov\u00e1 Hana",
				"Danciu Daniel",
				"Stark Stefan",
				"R\u00e4tsch Gunnar",
				"Kahles Andr\u00e9",
				"Lehmann Kjong-Van"
			],
			"DOI": "10.1093/bioinformatics/btac510",
			"date": "2022-11-14",
			"PMC": "",
			"citation": "",
			"abstract": "Several recently developed single-cell DNA sequencing technologies enable whole-genome sequencing of thousands of cells. However, the ultra-low coverage of the sequenced data (<0.05\u00d7 per cell) mostly limits their usage to the identification of copy number alterations in multi-megabase segments. Many tumors are not copy number-driven, and thus single-nucleotide variant (SNV)-based subclone detection may contribute to a more comprehensive view on intra-tumor heterogeneity. Due to the low coverage of the data, the identification of SNVs is only possible when superimposing the sequenced genomes of hundreds of genetically similar cells. Thus, we have developed a new approach to efficiently cluster tumor cells based on a Bayesian filtering approach of relevant loci and exploiting read overlap and phasing.",
			"category": 2,
			"name": "Rozho\u0148ov\u00e1 Hana,2022"
		},
		{
			"PMID": 35891790,
			"title": null,
			"journal": "Computational and structural biotechnology journal",
			"authorList": [
				"Mazzocchetti G",
				"Poletti A",
				"Solli V",
				"Borsi E",
				"Martello M",
				"Vigliotta I",
				"Armuzzi S",
				"Taurisano B",
				"Zamagni E",
				"Cavo M",
				"Terragna C"
			],
			"DOI": "10.1016/j.csbj.2022.06.062",
			"date": "2022-07-29",
			"PMC": "",
			"citation": "",
			"abstract": "Human cancer arises from a population of cells that have acquired a wide range of genetic alterations, most of which are targets of therapeutic treatments or are used as prognostic factors for patient's risk stratification. Among these, copy number alterations (CNAs) are quite frequent. Currently, several molecular biology technologies, such as microarrays, NGS and single-cell approaches are used to define the genomic profile of tumor samples. Output data need to be analyzed with bioinformatic approaches and particularly by employing computational algorithms. Molecular biology tools estimate the baseline region by comparing either the mean probe signals, or the number of reads to the reference genome. However, when tumors display complex karyotypes, this type of approach could fail the baseline region estimation and consequently cause errors in the CNAs call. To overcome this issue, we designed an R-package, ",
			"category": 2,
			"name": "Mazzocchetti G,2022"
		},
		{
			"PMID": 35883434,
			"title": "Target-Based Small Molecule Drug Discovery for Colorectal Cancer: A Review of Molecular Pathways and In Silico Studies.",
			"journal": "Biomolecules",
			"authorList": [
				"Moshawih Said",
				"Lim Ai Fern",
				"Ardianto Chrismawan",
				"Goh Khang Wen",
				"Kifli Nurolaini",
				"Goh Hui Poh",
				"Jarrar Qais",
				"Ming Long Chiau"
			],
			"DOI": "10.3390/biom12070878",
			"date": "2022-07-28",
			"PMC": "",
			"citation": "",
			"abstract": "Colorectal cancer is one of the most prevalent cancer types. Although there have been breakthroughs in its treatments, a better understanding of the molecular mechanisms and genetic involvement in colorectal cancer will have a substantial role in producing novel and targeted treatments with better safety profiles. In this review, the main molecular pathways and driver genes that are responsible for initiating and propagating the cascade of signaling molecules reaching carcinoma and the aggressive metastatic stages of colorectal cancer were presented. Protein kinases involved in colorectal cancer, as much as other cancers, have seen much focus and committed efforts due to their crucial role in subsidizing, inhibiting, or changing the disease course. Moreover, notable improvements in colorectal cancer treatments with in silico studies and the enhanced selectivity on specific macromolecular targets were discussed. Besides, the selective multi-target agents have been made easier by employing in silico methods in molecular de novo synthesis or target identification and drug repurposing.",
			"category": 2,
			"name": "Moshawih Said,2022"
		},
		{
			"PMID": 35873035,
			"title": "Cancer genes and cancer stem cells in tumorigenesis: Evolutionary deep homology and controversies.",
			"journal": "Genes & diseases",
			"authorList": [
				"Niculescu Vladimir F"
			],
			"DOI": "10.1016/j.gendis.2022.03.010",
			"date": "2022-07-26",
			"PMC": "",
			"citation": "",
			"abstract": "In the past, contradictory statements have been made about the age of cancer genes. While phylostratigraphic studies suggest that cancer genes emerged during the transitional period from unicellularians (UC) to early metazoans (EM), life cycle studies suggest that they arose earlier. This controversy could not be resolved. Phylostratigraphic methods use data from somatic tumor gene collections containing or lacking polyploidy genes (PGCC genes) and compare them to genes from evolutionary node taxa. I analyze whether the selected taxa are suitable to resolve the above contradiction or not. Both cancer and amoebae life cycles have a reproductive asexual germline that produces germline stem cells (GSCs) and somatic cell lines that cannot. When the germline loses its reproductive function, the soma-to-germ transition forms a new reproductive germline. The reproductive polyploidy of cancer is homologous to the reproductive polyploidy of unicellular cysts. PGCCs repair DNA defects, reorganize the involved genome architecture and produce new GSCs. The present study refutes the dogma of the early metazoan origin of cancer. Cancer has a unicellular life cycle that was adopted by early metazoans to rescue themselves from evolutionary dead ends. Early metazoans controlled the unicellular life cycle through suppressor and anti-suppressor genes that could suspend or reactivate it. They are the archetypes of tumor suppressor genes and oncogenes. Cells of mammalians and humans that reach a similar impasse as early metazoans can reactivate the conserved life cycle of unicellularians.",
			"category": 2,
			"name": "Niculescu Vladimir F,2022"
		},
		{
			"PMID": 35850404,
			"title": "Game of clones: Battles in the field of carcinogenesis.",
			"journal": "Pharmacology & therapeutics",
			"authorList": [
				"Rahal Zahraa",
				"Sinjab Ansam",
				"Wistuba Ignacio I",
				"Kadara Humam"
			],
			"DOI": "10.1016/j.pharmthera.2022.108251",
			"date": "2022-08-16",
			"PMC": "",
			"citation": "",
			"abstract": "Recent advances in bulk sequencing approaches as well as genomic decoding at the single-cell level have revealed surprisingly high somatic mutational burdens in normal tissues, as well as increased our understanding of the landscape of \"field cancerization\", that is, molecular and immune alterations in mutagen-exposed normal-appearing tissues that recapitulated those present in tumors. Charting the somatic mutational landscapes in normal tissues can have strong implications on our understanding of how tumors arise from mutagenized epithelium. Making sense of those mutations to understand the progression along the pathologic continuum of normal epithelia, preneoplasias, up to malignant tissues will help pave way for identification of ideal targets that can guide new strategies for preventing or eliminating cancers at their earliest stages of development. In this review, we will provide a brief history of field cancerization and its implications on understanding early stages of cancer pathogenesis and deviation from the pathologically \"normal\" state. The review will provide an overview of how mutations accumulating in normal tissues can lead to a patchwork of mutated cell clones that compete while maintaining an overall state of functional homeostasis. The review also explores the role of clonal competition in directing the fate of normal tissues and summarizes multiple mechanisms elicited in this phenomenon and which have been linked to cancer development. Finally, we highlight the importance of understanding mutations in normal tissues, as well as clonal competition dynamics (in both the epithelium and the microenvironment) and their significance in exploring new approaches to combatting cancer.",
			"category": 2,
			"name": "Rahal Zahraa,2022"
		},
		{
			"PMID": 35842644,
			"title": "Transcriptome profiling and co-expression network analysis of lncRNAs and mRNAs in colorectal cancer by RNA sequencing.",
			"journal": "BMC cancer",
			"authorList": [
				"Li Mingjie",
				"Guo Dandan",
				"Chen Xijun",
				"Lu Xinxin",
				"Huang Xiaoli",
				"Wu Yan'an"
			],
			"DOI": "10.1186/s12885-022-09878-6",
			"date": "2022-07-19",
			"PMC": "",
			"citation": "",
			"abstract": "Long non-coding RNAs (lncRNAs) are widely involved in the pathogenesis of cancers. However, biological roles of lncRNAs in occurrence and progression of colorectal cancer (CRC) remain unclear. The current study aimed to evaluate the expression pattern of lncRNAs and messenger RNAs (mRNAs).",
			"category": 2,
			"name": "Li Mingjie,2022"
		},
		{
			"PMID": 35831792,
			"title": "DriverRWH: discovering cancer driver genes by random walk on a gene mutation hypergraph.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"Wang Chenye",
				"Shi Junhan",
				"Cai Jiansheng",
				"Zhang Yusen",
				"Zheng Xiaoqi",
				"Zhang Naiqian"
			],
			"DOI": "10.1186/s12859-022-04788-7",
			"date": "2022-07-15",
			"PMC": "",
			"citation": "",
			"abstract": "Recent advances in next-generation sequencing technologies have helped investigators generate massive amounts of cancer genomic data. A critical challenge in cancer genomics is identification of a few cancer driver genes whose mutations cause tumor growth. However, the majority of existing computational approaches underuse the co-occurrence mutation information of the individuals, which are deemed to be important in tumorigenesis and tumor progression, resulting in high rate of false positive.",
			"category": 2,
			"name": "Wang Chenye,2022"
		},
		{
			"PMID": 35804819,
			"title": "Breast Cancer Genomics: Primary and Most Common Metastases.",
			"journal": "Cancers",
			"authorList": [
				"Bennett Caroline",
				"Carroll Caleb",
				"Wright Cooper",
				"Awad Barbara",
				"Park Jeong Mi",
				"Farmer Meagan",
				"Brown Elizabeth Bryce",
				"Heatherly Alexis",
				"Woodard Stefanie"
			],
			"DOI": "10.3390/cancers14133046",
			"date": "2022-07-16",
			"PMC": "",
			"citation": "",
			"abstract": "Specific genomic alterations have been found in primary breast cancer involving driver mutations that result in tumorigenesis. Metastatic breast cancer, which is uncommon at the time of disease onset, variably impacts patients throughout the course of their disease. Both the molecular profiles and diverse genomic pathways vary in the development and progression of metastatic breast cancer. From the most common metastatic site (bone), to the rare sites such as orbital, gynecologic, or pancreatic metastases, different levels of gene expression indicate the potential involvement of numerous genes in the development and spread of breast cancer. Knowledge of these alterations can, not only help predict future disease, but also lead to advancement in breast cancer treatments. This review discusses the somatic landscape of breast primary and metastatic tumors.",
			"category": 2,
			"name": "Bennett Caroline,2022"
		},
		{
			"PMID": 35804437,
			"title": "SYSMut: decoding the functional significance of rare somatic mutations in cancer.",
			"journal": "Briefings in bioinformatics",
			"authorList": [
				"Khalighi Sirvan",
				"Joseph Peronne",
				"Babu Deepak",
				"Singh Salendra",
				"LaFramboise Thomas",
				"Guda Kishore",
				"Varadan Vinay"
			],
			"DOI": "10.1093/bib/bbac280",
			"date": "2022-07-20",
			"PMC": "",
			"citation": "",
			"abstract": "Current tailored-therapy efforts in cancer are largely focused on a small number of highly recurrently mutated driver genes but therapeutic targeting of these oncogenes remains challenging. However, the vast number of genes mutated infrequently across cancers has received less attention, in part, due to a lack of understanding of their biological significance. We present SYSMut, an extendable systems biology platform that can robustly infer the biologic consequences of somatic mutations by integrating routine multiomics profiles in primary tumors. We establish SYSMut's improved performance vis-\u00e0-vis state-of-the-art driver gene identification methodologies by recapitulating the functional impact of known driver genes, while additionally identifying novel functionally impactful mutated genes across 29 cancers. Subsequent application of SYSMut on low-frequency gene mutations in head and neck squamous cell (HNSC) cancers, followed by molecular and pharmacogenetic validation, revealed the lipidogenic network as a novel therapeutic vulnerability in aggressive HNSC cancers. SYSMut is thus a robust scalable framework that enables the discovery of new targetable avenues in cancer.",
			"category": 2,
			"name": "Khalighi Sirvan,2022"
		},
		{
			"PMID": 35764888,
			"title": "Structural variations in cancer and the 3D genome.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Dubois Frank",
				"Sidiropoulos Nikos",
				"Weischenfeldt Joachim",
				"Beroukhim Rameen"
			],
			"DOI": "10.1038/s41568-022-00488-9",
			"date": "2022-08-29",
			"PMC": "",
			"citation": "",
			"abstract": "Structural variations (SVs) affect more of the cancer genome than any other type of somatic genetic alteration but difficulties in detecting and interpreting them have limited our understanding. Clinical cancer sequencing also increasingly aims to detect SVs, leading to a widespread necessity to interpret their biological and clinical relevance. Recently, analyses of large whole-genome sequencing data sets revealed features that impact rates of SVs across the genome in different cancers. A striking feature has been the extent to which, in both their generation and their influence on the selective fitness of cancer cells, SVs are more specific to individual cancer types than other genetic alterations such as single-nucleotide variants. This Perspective discusses how the folding of the 3D genome, and differences in its folding across cell types, affect observed SV rates in different cancer types as well as how SVs can impact cancer cell fitness.",
			"category": 2,
			"name": "Dubois Frank,2022"
		},
		{
			"PMID": 35764656,
			"title": "The impact of rare germline variants on human somatic mutation processes.",
			"journal": "Nature communications",
			"authorList": [
				"Vali-Pour Mischan",
				"Park Solip",
				"Espinosa-Carrasco Jose",
				"Ortiz-Mart\u00ednez Daniel",
				"Lehner Ben",
				"Supek Fran"
			],
			"DOI": "10.1038/s41467-022-31483-1",
			"date": "2022-06-30",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic mutations are an inevitable component of ageing and the most important cause of cancer. The rates and types of somatic mutation vary across individuals, but relatively few inherited influences on mutation processes are known. We perform a gene-based rare variant association study with diverse mutational processes, using human cancer genomes from over 11,000 individuals of European ancestry. By combining burden and variance tests, we identify 207 associations involving 15 somatic mutational phenotypes and 42 genes that replicated in an independent data set at a false discovery rate of 1%. We associate rare inherited deleterious variants in genes such as MSH3, EXO1, SETD2, and MTOR with two phenotypically different forms of DNA mismatch repair deficiency, and variants in genes such as EXO1, PAXIP1, RIF1, and WRN with deficiency in homologous recombination repair. In addition, we identify associations with other mutational processes, such as APEX1 with APOBEC-signature mutagenesis. Many of the genes interact with each other and with known mutator genes within cellular sub-networks. Considered collectively, damaging variants in the identified genes are prevalent in the population. We suggest that rare germline variation in diverse genes commonly impacts mutational processes in somatic cells.",
			"category": 2,
			"name": "Vali-Pour Mischan,2022"
		},
		{
			"PMID": 35741808,
			"title": "miRNAs Copy Number Variations Repertoire as Hallmark Indicator of Cancer Species Predisposition.",
			"journal": "Genes",
			"authorList": [
				"Vischioni Chiara",
				"Bove Fabio",
				"De Chiara Matteo",
				"Mandreoli Federica",
				"Martoglia Riccardo",
				"Pisi Valentino",
				"Liti Gianni",
				"Taccioli Cristian"
			],
			"DOI": "10.3390/genes13061046",
			"date": "2022-06-27",
			"PMC": "",
			"citation": "",
			"abstract": "Aging is one of the hallmarks of multiple human diseases, including cancer. We hypothesized that variations in the number of copies (CNVs) of specific genes may protect some long-living organisms theoretically more susceptible to tumorigenesis from the onset of cancer. Based on the statistical comparison of gene copy numbers within the genomes of both cancer-prone and -resistant species, we identified novel gene targets linked to tumor predisposition, such as CD52, SAT1 and SUMO. Moreover, considering their genome-wide copy number landscape, we discovered that microRNAs (miRNAs) are among the most significant gene families enriched for cancer progression and predisposition. Through bioinformatics analyses, we identified several alterations in miRNAs copy number patterns, involving miR-221, miR-222, miR-21, miR-372, miR-30b, miR-30d and miR-31, among others. Therefore, our analyses provide the first evidence that an altered miRNAs copy number signature can statistically discriminate species more susceptible to cancer from those that are tumor resistant, paving the way for further investigations.",
			"category": 2,
			"name": "Vischioni Chiara,2022"
		},
		{
			"PMID": 35740438,
			"title": "Current Developments of ",
			"journal": "Biomedicines",
			"authorList": [
				"Tialiou Alexia",
				"Chin Jiamin",
				"Keppler Bernhard K",
				"Reithofer Michael R"
			],
			"DOI": "10.3390/biomedicines10061417",
			"date": "2022-07-16",
			"PMC": "",
			"citation": "",
			"abstract": "Since their first discovery, ",
			"category": 2,
			"name": "Tialiou Alexia,2022"
		},
		{
			"PMID": 35737245,
			"title": "Using CRISPR-Cas9 to Dissect Cancer Mutations in Cell Lines.",
			"journal": "Methods in molecular biology (Clifton, N.J.)",
			"authorList": [
				"Sayed Shady",
				"S\u00fcr\u00fcn Duran",
				"Mircetic Jovan",
				"Sidorova Olga Alexandra",
				"Buchholz Frank"
			],
			"DOI": "10.1007/978-1-0716-2376-3_18",
			"date": "2022-06-27",
			"PMC": "",
			"citation": "",
			"abstract": "The CRISPR-Cas9 technology has revolutionized the scope and pace of biomedical research, enabling the targeting of specific genomic sequences for a wide spectrum of applications. Here we describe assays to functionally interrogate mutations identified in cancer cells utilizing both CRISPR-Cas9 nuclease and base editors. We provide guidelines to interrogate known cancer driver mutations or functionally screen for novel vulnerability mutations with these systems in characterized human cancer cell lines. The proposed platform should be transferable to primary cancer cells, opening up a path for precision oncology on a functional level.",
			"category": 2,
			"name": "Sayed Shady,2022"
		},
		{
			"PMID": 35731312,
			"title": "BRCA1, BRCA2, TP53, PIK3CA, PTEN and AKT1 genes mutations in Burkina Faso breast cancer patients: prevalence, spectrum and novel variant.",
			"journal": "Molecular genetics and genomics : MGG",
			"authorList": [
				"Ouedraogo Serge Yannick",
				"Zoure Abdou Azaque",
				"Zeye Moutanou Modeste Judes",
				"Kiendrebeogo Touwendpoulimd\u00e9 Isabelle",
				"Zhou Xi",
				"Sawadogo Alexis Yobi",
				"Simpore Jacques",
				"Chen Hanchun"
			],
			"DOI": "10.1007/s00438-022-01914-1",
			"date": "2022-08-30",
			"PMC": "",
			"citation": "",
			"abstract": "BRCA1 and BRCA2 are the two most commonly mutated tumor suppressor genes associated with hereditary breast cancer (BC). Also, mutations in TP53, PIK3CA, PTEN and AKT1 were observed at a high frequency in BC with their mutation spectrum exhibiting a subgroup particularity with enormous clinical significance in the prevention, classification and treatment of cancers. Unfortunately, the mutation spectrum of these genes is still unknown in most Sub-Saharan African population. Therefore, using samples from 133 unselected BC patients, we aimed to assess the contribution of these mutations by direct Sanger sequencing. The analysis revealed pathogenic germline variants on BRCA1 exon 11 (c.3331C\u2009>\u2009T, 0.75%) and BRCA2 exon 11 (c.5635G\u2009>\u2009T, c.6211delA; 1.5%). Five other pathogenic variants were identified in 61 of the 133 subjects (45.86%), with 39.09% for PIK3CA, 12.78% for TP53. Interestingly, a variant in PIK3CA found in high frequency in our population was different from the one usually found in other populations (c.1634A\u2009>\u2009C, 38.34%), and four patients carried mutations linked to Cowen Syndrome 5 c.[1634A\u2009>\u2009C;1658_1659delGTinsC]. A novel variant (c.312G\u2009>\u2009T) was found in TP53 gene at 12.78%. Overall, mutation carriers were found more in Her2 negative and in patients that underwent surgery and chemotherapy. No pathogenic variant was found in PTEN and AKT1. Our population displayed a high frequency of PIK3CA mutations with an unusual distribution and spectrum as well as a relatively low prevalence of BRCA mutations. Our results provided novel data on an unstudied population and may help in prevention, and the establishment of suitable therapeutic approaches for our population.",
			"category": 2,
			"name": "Ouedraogo Serge Yannick,2022"
		},
		{
			"PMID": 35726091,
			"title": "Genome-wide mapping of somatic mutation rates uncovers drivers of cancer.",
			"journal": "Nature biotechnology",
			"authorList": [
				"Sherman Maxwell A",
				"Yaari Adam U",
				"Priebe Oliver",
				"Dietlein Felix",
				"Loh Po-Ru",
				"Berger Bonnie"
			],
			"DOI": "10.1038/s41587-022-01353-8",
			"date": "2022-11-11",
			"PMC": "",
			"citation": "",
			"abstract": "Identification of cancer driver mutations that confer a proliferative advantage is central to understanding cancer; however, searches have often been limited to protein-coding sequences and specific non-coding elements (for example, promoters) because of the challenge of modeling the highly variable somatic mutation rates observed across tumor genomes. Here we present Dig, a method to search for driver elements and mutations anywhere in the genome. We use deep neural networks to map cancer-specific mutation rates genome-wide at kilobase-scale resolution. These estimates are then refined to search for evidence of driver mutations under positive selection throughout the genome by comparing observed to expected mutation counts. We mapped mutation rates for 37 cancer types and applied these maps to identify putative drivers within intronic cryptic splice regions, 5' untranslated regions and infrequently mutated genes. Our high-resolution mutation rate maps, available for web-based exploration, are a resource to enable driver discovery genome-wide.",
			"category": 2,
			"name": "Sherman Maxwell A,2022"
		},
		{
			"PMID": 35707123,
			"title": "The DNA methylation landscape of five pediatric-tumor types.",
			"journal": "PeerJ",
			"authorList": [
				"Parker Alyssa C",
				"Quinteros Bad\u00ed I",
				"Piccolo Stephen R"
			],
			"DOI": "10.7717/peerj.13516",
			"date": "2023-01-16",
			"PMC": "",
			"citation": "",
			"abstract": "Fewer DNA mutations have been identified in pediatric tumors than in adult tumors, suggesting that alternative tumorigenic mechanisms, including aberrant DNA methylation, may play a prominent role. In one epigenetic process of regulating gene expression, methyl groups are attached at the 5-carbon of the cytosine ring, leading to 5-methylcytosine (5mC). In somatic cells, 5mC occurs mostly in CpG islands, which are often within promoter regions. In Wilms tumors and acute myeloid leukemias, increased levels of epigenetic silencing have been associated with worse patient outcomes. However, to date, researchers have studied methylation primarily in adult tumors and for specific genes-but not on a pan-pediatric cancer scale. We addressed these gaps first by aggregating methylation data from 309 noncancerous samples, establishing baseline expectations for each probe and gene. Even though these samples represent diverse, noncancerous tissue types and population ancestral groups, methylation levels were consistent for most genes. Second, we compared tumor methylation levels against the baseline values for 489 pediatric tumors representing five cancer types: Wilms tumors, clear cell sarcomas of the kidney, rhabdoid tumors, neuroblastomas, and osteosarcomas. Tumor hypomethylation was more common than hypermethylation, and as many as 41.7% of genes were hypomethylated in a given tumor, compared to a maximum of 34.2% for hypermethylated genes. However, in known oncogenes, hypermethylation was more than twice as common as in other genes. We identified 139 probes (31 genes) that were differentially methylated between at least one tumor type and baseline levels, and 32 genes that were differentially methylated across the pediatric tumor types. We evaluated whether genomic events and aberrant methylation were mutually exclusive but did not find evidence of this phenomenon.",
			"category": 2,
			"name": "Parker Alyssa C,2023"
		},
		{
			"PMID": 35682953,
			"title": "Beyond Genetics: Metastasis as an Adaptive Response in Breast Cancer.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Ruscitto Federica",
				"Roda Niccol\u00f2",
				"Priami Chiara",
				"Migliaccio Enrica",
				"Pelicci Pier Giuseppe"
			],
			"DOI": "10.3390/ijms23116271",
			"date": "2022-06-13",
			"PMC": "",
			"citation": "",
			"abstract": "Metastatic disease represents the primary cause of breast cancer (BC) mortality, yet it is still one of the most enigmatic processes in the biology of this tumor. Metastatic progression includes distinct phases: invasion, intravasation, hematogenous dissemination, extravasation and seeding at distant sites, micro-metastasis formation and metastatic outgrowth. Whole-genome sequencing analyses of primary BC and metastases revealed that BC metastatization is a non-genetically selected trait, rather the result of transcriptional and metabolic adaptation to the unfavorable microenvironmental conditions which cancer cells are exposed to (e.g., hypoxia, low nutrients, endoplasmic reticulum stress and chemotherapy administration). In this regard, the latest multi-omics analyses unveiled intra-tumor phenotypic heterogeneity, which determines the polyclonal nature of breast tumors and constitutes a challenge for clinicians, correlating with patient poor prognosis. The present work reviews BC classification and epidemiology, focusing on the impact of metastatic disease on patient prognosis and survival, while describing general principles and current in vitro/in vivo models of the BC metastatic cascade. The authors address here both genetic and phenotypic intrinsic heterogeneity of breast tumors, reporting the latest studies that support the role of the latter in metastatic spreading. Finally, the review illustrates the mechanisms underlying adaptive stress responses during BC metastatic progression.",
			"category": 2,
			"name": "Ruscitto Federica,2022"
		},
		{
			"PMID": 35682769,
			"title": "Proteomic Profiling and Biomarker Discovery in Colorectal Liver Metastases.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Wong Geoffrey Yuet Mun",
				"Diakos Connie",
				"Hugh Thomas J",
				"Molloy Mark P"
			],
			"DOI": "10.3390/ijms23116091",
			"date": "2022-06-13",
			"PMC": "",
			"citation": "",
			"abstract": "Colorectal liver metastases (CRLM) are the leading cause of death among patients with metastatic colorectal cancer (CRC). As part of multimodal therapy, liver resection is the mainstay of curative-intent treatment for select patients with CRLM. However, effective treatment of CRLM remains challenging as recurrence occurs in most patients after liver resection. Proposed clinicopathologic factors for predicting recurrence are inconsistent and lose prognostic significance over time. The rapid development of next-generation sequencing technologies and decreasing DNA sequencing costs have accelerated the genomic profiling of various cancers. The characterisation of genomic alterations in CRC has significantly improved our understanding of its carcinogenesis. However, the functional context at the protein level has not been established for most of this genomic information. Furthermore, genomic alterations do not always result in predicted changes in the corresponding proteins and cancer phenotype, while post-transcriptional and post-translational regulation may alter synthesised protein levels, affecting phenotypes. More recent advancements in mass spectrometry-based technology enable accurate protein quantitation and comprehensive proteomic profiling of cancers. Several studies have explored proteomic biomarkers for predicting CRLM after oncologic resection of primary CRC and recurrence after curative-intent resection of CRLM. The current review aims to rationalise the proteomic complexity of CRC and explore the potential applications of proteomic biomarkers in CRLM.",
			"category": 2,
			"name": "Wong Geoffrey Yuet Mun,2022"
		},
		{
			"PMID": 35668934,
			"title": "Ferroptosis and Tumor Drug Resistance: Current Status and Major Challenges.",
			"journal": "Frontiers in pharmacology",
			"authorList": [
				"Nie Zhenyu",
				"Chen Mei",
				"Gao Yuanhui",
				"Huang Denggao",
				"Cao Hui",
				"Peng Yanling",
				"Guo Na",
				"Wang Fei",
				"Zhang Shufang"
			],
			"DOI": "10.3389/fphar.2022.879317",
			"date": "2022-07-16",
			"PMC": "",
			"citation": "",
			"abstract": "Ferroptosis is a novel type of regulated cell death, whose unique metabolic characteristics are commonly used to evaluate the conditions of various diseases especially in tumors. Accumulating evidence supports that ferroptosis can regulate tumor development, metastasis, and therapeutic responses. Considering to the important role of chemotherapy in tumor treatment, drug resistance has become the most serious challenge. Revealing the molecular mechanism of ferroptosis is expected to solve tumor drug resistance and find new therapies to treat cancers. In this review, we discuss the relationship between ferroptosis and tumor drug resistance, summarize the abnormal ferroptosis in tissues of different cancer types and current research progress and challenges in overcoming treatment resistance, and explore the concept of targeting ferroptosis to improve tumor treatment outcomes.",
			"category": 2,
			"name": "Nie Zhenyu,2022"
		},
		{
			"PMID": 35665491,
			"title": "Hepatobiliary Tumor Organoids Reveal HLA Class I Neoantigen Landscape and Antitumoral Activity of Neoantigen Peptide Enhanced with Immune Checkpoint Inhibitors.",
			"journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)",
			"authorList": [
				"Wang Wenwen",
				"Yuan Tinggan",
				"Ma Lili",
				"Zhu Yanjing",
				"Bao Jinxia",
				"Zhao Xiaofang",
				"Zhao Yan",
				"Zong Yali",
				"Zhang Yani",
				"Yang Shuai",
				"Qiu Xinyao",
				"Shen Siyun",
				"Wu Rui",
				"Wu Tong",
				"Wang Hongyang",
				"Gao Dong",
				"Wang Peng",
				"Chen Lei"
			],
			"DOI": "10.1002/advs.202105810",
			"date": "2022-08-08",
			"PMC": "",
			"citation": "",
			"abstract": "Neoantigen-directed therapy lacks preclinical models recapitulating neoantigen characteristics of original tumors. It is urgent to develop a platform to assess T cell response for neoantigen screening. Here, immunogenic potential of neoantigen-peptides of tumor tissues and matched organoids (n = 27 pairs) are analyzed by Score tools with whole genome sequencing (WGS)-based human leukocyte antigen (HLA)-class-I algorithms. The comparisons between 9203 predicted neoantigen-peptides from 2449 mutations of tumor tissues and 9991 ones from 2637 mutations of matched organoids demonstrate that organoids preserved majority of genetic features, HLA alleles, and similar neoantigen landscape of original tumors. Higher neoantigen load is observed in tumors with early stage. Multiomics analysis combining WGS, RNA-seq, single-cell RNA-seq, mass spectrometry filters out 93 candidate neoantigen-peptides with strong immunogenic potential for functional validation in five organoids. Immunogenic peptides are defined by inducing increased CD107aCD137IFN-\u03b3 expressions and IFN-\u03b3 secretion of CD8 cells in flow cytometry and enzyme-linked immunosorbent assay assays. Nine immunogenic peptides shared by at least two individuals are validated, including peptide from TP53",
			"category": 2,
			"name": "Wang Wenwen,2022"
		},
		{
			"PMID": 35665374,
			"title": "Cancer Epigenomics and Beyond: Advancing the Precision Oncology Paradigm.",
			"journal": "Journal of immunotherapy and precision oncology",
			"authorList": [
				"Lee Daniel Y"
			],
			"DOI": "10.36401/JIPO-20-18",
			"date": "2022-12-09",
			"PMC": "",
			"citation": "",
			"abstract": "How cancers are characterized and treated has evolved over the past few decades. Major advances in genomics tools and techniques have revealed interlinked regulatory pathways of cancers with unprecedented detail. Early discoveries led to success with rationally targeted small molecules and more recently with immunomodulatory agents, setting the stage for precision oncology. However, drug resistance to every agent has thus far proven intractable, sending us back to fill the gaps in our rudimentary knowledge of tumor biology. Epigenetics is emerging as a fundamental process in every hallmark of cancer. Large-scale interrogation of the cancer epigenome continues to reveal new mechanisms of astounding complexity. In this review, I present selected experimental and clinical examples that have shaped our understanding of cancer at the molecular level. Translation of our collective erudition into revolutionary diagnostic and treatment strategies will advance the precision oncology paradigm.",
			"category": 2,
			"name": "Lee Daniel Y,2022"
		},
		{
			"PMID": 35650238,
			"title": "The genomic landscape of cholangiocarcinoma reveals the disruption of post-transcriptional modifiers.",
			"journal": "Nature communications",
			"authorList": [
				"Zhang Yaodong",
				"Ma Zijian",
				"Li Changxian",
				"Wang Cheng",
				"Jiang Wangjie",
				"Chang Jiang",
				"Han Sheng",
				"Lu Zefa",
				"Shao Zicheng",
				"Wang Yirui",
				"Wang Hongwei",
				"Jiao Chenyu",
				"Wang Dong",
				"Wu Xiaofeng",
				"Shen Hongbing",
				"Wang Xuehao",
				"Hu Zhibin",
				"Li Xiangcheng"
			],
			"DOI": "10.1038/s41467-022-30708-7",
			"date": "2022-06-03",
			"PMC": "",
			"citation": "",
			"abstract": "Molecular variation between geographical populations and subtypes indicate potential genomic heterogeneity and novel genomic features within CCA. Here, we analyze exome-sequencing data of 87 perihilar cholangiocarcinoma (pCCA) and 261 intrahepatic cholangiocarcinoma (iCCA) cases from 3 Asian centers (including 43 pCCAs and 24 iCCAs from our center). iCCA tumours demonstrate a higher tumor mutation burden and copy number alteration burden (CNAB) than pCCA tumours, and high CNAB indicates a poorer pCCA prognosis. We identify 12 significantly mutated genes and 5 focal CNA regions, and demonstrate common mutations in post-transcriptional modification-related potential driver genes METTL14 and RBM10 in pCCA tumours. Finally we demonstrate the tumour-suppressive role of METTL14, a major RNA N6-adenosine methyltransferase (m6A), and illustrate that its loss-of-function mutation R298H may act through m6A modification on potential driver gene MACF1. Our results may be valuable for better understanding of how post-transcriptional modification can affect CCA development, and highlight both similarities and differences between pCCA and iCCA.",
			"category": 2,
			"name": "Zhang Yaodong,2022"
		},
		{
			"PMID": 35637532,
			"title": "Heritable genomic diversity in breast cancer driver genes and associations with risk in a Chilean population.",
			"journal": "Biological research",
			"authorList": [
				"Morales-Pison Sebastian",
				"Gonzalez-Hormazabal Patricio",
				"Tapia Julio C",
				"Salas-Burgos Alexis",
				"Ampuero Sandra",
				"G\u00f3mez Fernando",
				"Waugh Enrique",
				"Reyes Jos\u00e9 Miguel",
				"Jara Lilian"
			],
			"DOI": "10.1186/s40659-022-00384-4",
			"date": "2022-06-02",
			"PMC": "",
			"citation": "",
			"abstract": "Driver mutations are the genetic components responsible for tumor initiation and progression. These variants, which may be inherited, influence cancer risk and therefore underlie many familial cancers. The present study examines the potential association between SNPs in driver genes SF3B1 (rs4685), TBX3 (rs12366395, rs8853, and rs1061651) and MAP3K1 (rs72758040) and BC in BRCA1/2-negative Chilean families.",
			"category": 2,
			"name": "Morales-Pison Sebastian,2022"
		},
		{
			"PMID": 35627162,
			"title": "Inferring Potential Cancer Driving Synonymous Variants.",
			"journal": "Genes",
			"authorList": [
				"Zeng Zishuo",
				"Bromberg Yana"
			],
			"DOI": "10.3390/genes13050778",
			"date": "2022-05-31",
			"PMC": "",
			"citation": "",
			"abstract": "Synonymous single nucleotide variants (sSNVs) are often considered functionally silent, but a few cases of cancer-causing sSNVs have been reported. From available databases, we collected four categories of sSNVs: germline, somatic in normal tissues, somatic in cancerous tissues, and putative cancer drivers. We found that screening sSNVs for recurrence among patients, conservation of the affected genomic position, and synVep prediction (synVep is a machine learning-based sSNV effect predictor) recovers cancer driver variants (termed ",
			"category": 2,
			"name": "Zeng Zishuo,2022"
		},
		{
			"PMID": 35627101,
			"title": "Effects of Multi-Omics Characteristics on Identification of Driver Genes Using Machine Learning Algorithms.",
			"journal": "Genes",
			"authorList": [
				"Li Feng",
				"Chu Xin",
				"Dai Lingyun",
				"Wang Juan",
				"Liu Jinxing",
				"Shang Junliang"
			],
			"DOI": "10.3390/genes13050716",
			"date": "2022-05-31",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a complex disease caused by genomic and epigenetic alterations; hence, identifying meaningful cancer drivers is an important and challenging task. Most studies have detected cancer drivers with mutated traits, while few studies consider multiple omics characteristics as important factors. In this study, we present a framework to analyze the effects of multi-omics characteristics on the identification of driver genes. We utilize four machine learning algorithms within this framework to detect cancer driver genes in pan-cancer data, including 75 characteristics among 19,636 genes. The 75 features are divided into four types and analyzed using Kullback-Leibler divergence based on CGC genes and non-CGC genes. We detect cancer driver genes in two different ways. One is to detect driver genes from a single feature type, while the other is from the top N features. The first analysis denotes that the mutational features are the best characteristics. The second analysis reveals that the top 45 features are the most effective feature combinations and superior to the mutational features. The top 45 features not only contain mutational features but also three other types of features. Therefore, our study extends the detection of cancer driver genes and provides a more comprehensive understanding of cancer mechanisms.",
			"category": 2,
			"name": "Li Feng,2022"
		},
		{
			"PMID": 35622868,
			"title": "Neural networks enable efficient and accurate simulation-based inference of evolutionary parameters from adaptation dynamics.",
			"journal": "PLoS biology",
			"authorList": [
				"Avecilla Grace",
				"Chuong Julie N",
				"Li Fangfei",
				"Sherlock Gavin",
				"Gresham David",
				"Ram Yoav"
			],
			"DOI": "10.1371/journal.pbio.3001633",
			"date": "2022-05-31",
			"PMC": "",
			"citation": "",
			"abstract": "The rate of adaptive evolution depends on the rate at which beneficial mutations are introduced into a population and the fitness effects of those mutations. The rate of beneficial mutations and their expected fitness effects is often difficult to empirically quantify. As these 2 parameters determine the pace of evolutionary change in a population, the dynamics of adaptive evolution may enable inference of their values. Copy number variants (CNVs) are a pervasive source of heritable variation that can facilitate rapid adaptive evolution. Previously, we developed a locus-specific fluorescent CNV reporter to quantify CNV dynamics in evolving populations maintained in nutrient-limiting conditions using chemostats. Here, we use CNV adaptation dynamics to estimate the rate at which beneficial CNVs are introduced through de novo mutation and their fitness effects using simulation-based likelihood-free inference approaches. We tested the suitability of 2 evolutionary models: a standard Wright-Fisher model and a chemostat model. We evaluated 2 likelihood-free inference algorithms: the well-established Approximate Bayesian Computation with Sequential Monte Carlo (ABC-SMC) algorithm, and the recently developed Neural Posterior Estimation (NPE) algorithm, which applies an artificial neural network to directly estimate the posterior distribution. By systematically evaluating the suitability of different inference methods and models, we show that NPE has several advantages over ABC-SMC and that a Wright-Fisher evolutionary model suffices in most cases. Using our validated inference framework, we estimate the CNV formation rate at the GAP1 locus in the yeast Saccharomyces cerevisiae to be 10-4.7 to 10-4 CNVs per cell division and a fitness coefficient of 0.04 to 0.1 per generation for GAP1 CNVs in glutamine-limited chemostats. We experimentally validated our inference-based estimates using 2 distinct experimental methods-barcode lineage tracking and pairwise fitness assays-which provide independent confirmation of the accuracy of our approach. Our results are consistent with a beneficial CNV supply rate that is 10-fold greater than the estimated rates of beneficial single-nucleotide mutations, explaining the outsized importance of CNVs in rapid adaptive evolution. More generally, our study demonstrates the utility of novel neural network-based likelihood-free inference methods for inferring the rates and effects of evolutionary processes from empirical data with possible applications ranging from tumor to viral evolution.",
			"category": 2,
			"name": "Avecilla Grace,2022"
		},
		{
			"PMID": 35620468,
			"title": "Multi-Omic Data Improve Prediction of Personalized Tumor Suppressors and Oncogenes.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Sudhakar Malvika",
				"Rengaswamy Raghunathan",
				"Raman Karthik"
			],
			"DOI": "10.3389/fgene.2022.854190",
			"date": "2022-07-16",
			"PMC": "",
			"citation": "",
			"abstract": "The progression of tumorigenesis starts with a few mutational and structural driver events in the cell. Various cohort-based computational tools exist to identify driver genes but require multiple samples to identify less frequently mutated driver genes. Many studies use different methods to identify driver mutations/genes from mutations that have no impact on tumor progression; however, a small fraction of patients show no mutational events in any known driver genes. Current unsupervised methods map somatic and expression data onto a network to identify personalized driver genes based on changes in expression. Our method is the first machine learning model to classify genes as tumor suppressor gene (TSG), oncogene (OG), or neutral, thus assigning the functional impact of the gene in the patient. In this study, we develop a multi-omic approach, PIVOT (Personalized Identification of driVer OGs and TSGs), to train on experimentally or computationally validated mutational and structural driver events. Given the lack of any gold standards for the identification of personalized driver genes, we label the data using four strategies and, based on classification metrics, show gene-based labeling strategies perform best. We build different models using SNV, RNA, and multi-omic features to be used based on the data available. Our models trained on multi-omic data improved predictions compared with mutation and expression data, achieving an accuracy ",
			"category": 2,
			"name": "Sudhakar Malvika,2022"
		},
		{
			"PMID": 35595234,
			"title": "Examining clustered somatic mutations with SigProfilerClusters.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Bergstrom Erik N",
				"Kundu Mousumy",
				"Tbeileh Noura",
				"Alexandrov Ludmil B"
			],
			"DOI": "10.1093/bioinformatics/btac335",
			"date": "2022-11-14",
			"PMC": "",
			"citation": "",
			"abstract": "Clustered mutations are found in the human germline as well as in the genomes of cancer and normal somatic cells. Clustered events can be imprinted by a multitude of mutational processes, and they have been implicated in both cancer evolution and development disorders. Existing tools for identifying clustered mutations have been optimized for a particular subtype of clustered event and, in most cases, relied on a predefined inter-mutational distance (IMD) cutoff combined with a piecewise linear regression analysis.",
			"category": 2,
			"name": "Bergstrom Erik N,2022"
		},
		{
			"PMID": 35575002,
			"title": "A practical framework RNMF for exploring the association between mutational signatures and genes using gene cumulative contribution abundance.",
			"journal": "Cancer medicine",
			"authorList": [
				"Li Zhenzhang",
				"Liang Haihua",
				"Zhang Shaoan",
				"Luo Wen"
			],
			"DOI": "10.1002/cam4.4717",
			"date": "2022-11-08",
			"PMC": "",
			"citation": "",
			"abstract": "Mutational signatures are somatic mutation patterns enriching operational mutational processes, which can provide abundant information about the mechanism of cancer. However, understanding of the pathogenic biological processes is still limited, such as the association between mutational signatures and genes.",
			"category": 2,
			"name": "Li Zhenzhang,2022"
		},
		{
			"PMID": 35558225,
			"title": "Effect of double mutations T790M/L858R on conformation and drug-resistant mechanism of epidermal growth factor receptor explored by molecular dynamics simulations.",
			"journal": "RSC advances",
			"authorList": [
				"Yan Fangfang",
				"Liu Xinguo",
				"Zhang Shaolong",
				"Su Jing",
				"Zhang Qinggang",
				"Chen Jianzhong"
			],
			"DOI": "10.1039/c8ra06844e",
			"date": "2023-11-03",
			"PMC": "",
			"citation": "",
			"abstract": "Epidermal growth factor receptor (EGFR) is one of the most promising targets for the treatment of cancers. Double mutations T790M/L858R lead to different degrees of drug resistance toward inhibitors. In this study, molecular dynamics (MD) simulations followed by principal component analysis are performed to study the conformational changes of EGFR induced by T790M/L858R. The results suggest that T790M/L858R cause obvious disturbance of the structural stability of EGFR. Molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) and residue-based free energy decomposition methods are integrated to explore the drug-resistant mechanism of T790M/L858R toward inhibitors. The results show that the decrease in van der Waals interactions of inhibitors with the mutated EFGR relative to the wild-type (WT) one is the main force inducing drug resistance of T790M/L858R toward inhibitors TAK-285, while drug resistance toward W2P and HKI-272 is dominated by the decrease in van der Waals interactions and the increase in polar interactions. We expect that the information obtained from this study can aid rational design of effective drugs to relieve drug resistance of EGFR induced by T790M/L858R.",
			"category": 2,
			"name": "Yan Fangfang,2023"
		},
		{
			"PMID": 35545669,
			"title": "Genetic and chemotherapeutic influences on germline hypermutation.",
			"journal": "Nature",
			"authorList": [
				"Kaplanis Joanna",
				"Ide Benjamin",
				"Sanghvi Rashesh",
				"Neville Matthew",
				"Danecek Petr",
				"Coorens Tim",
				"Prigmore Elena",
				"Short Patrick",
				"Gallone Giuseppe",
				"McRae Jeremy",
				"Genomics England Research Consortium",
				"Carmichael Jenny",
				"Barnicoat Angela",
				"Firth Helen",
				"O'Brien Patrick",
				"Rahbari Raheleh",
				"Hurles Matthew"
			],
			"DOI": "10.1038/s41586-022-04712-2",
			"date": "2022-05-20",
			"PMC": "",
			"citation": "",
			"abstract": "Mutations in the germline generates all evolutionary genetic variation and is a cause of genetic disease. Parental age is the primary determinant of the number of new germline mutations in an individual's genome",
			"category": 2,
			"name": "Kaplanis Joanna,2022"
		},
		{
			"PMID": 35531214,
			"title": "Mutational pattern of PIK3CA exon 20 in circulating DNA in breast cancer.",
			"journal": "Saudi journal of biological sciences",
			"authorList": [
				"Ibrahim Iman Hassan",
				"Abd El-Aziz Heba Gamal",
				"Amer Noha Nagah Labib",
				"Abd El-Sameea Hesham Samir"
			],
			"DOI": "10.1016/j.sjbs.2022.01.002",
			"date": "2022-07-16",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer (BC) is one of the most common cancers with diverse mutations, etiology and causes. Mutational signature of the driver genes could allow for better understanding disease etiology and progression. This study aims to assess PIK3CA Exon 20 somatic mutational signature in relation to potential underlying etiology. Circulating DNA of 71 Egyptian BC patients was isolated, amplified for PIK3CA Exon 20, and sequenced. Mutational signature was determined according to COSMIC v2 signature. Public BC dataset was analysed to assess PIK3CA mutations effect on the transcriptomic profile. Somatic mutations of PIK3CA exon 20 were found in 66.2% of the study cohort. Nucleotide substitution patterns were similar to general nucleotide substitution patterns in BC. Signature 3 and 9 were the most common signatures in the studied BC patients. Signature of Aristolochic acid exposure was found in some cases. The most common nucleotide substitution was T\u00a0>\u00a0A transversion, but substitutions T\u00a0>\u00a0G and T\u00a0>\u00a0C were correlated to each other and to the total mutation number. PIK3CA mutations were found to disrupt several pathways including RAC1, PDGF, Wnt, and integrin signalling. PIK3CA exon 20 mutational signatures in Egyptian BC patients could suggest a disease etiology involving homologous recombination deficiency (HRD) and polymerase eta (Pol \u03b7). Nucleotide substitution patterns could indicate the role of exposure to oxidative stress and some carcinogens such as 4-aminobiphenyl and Aristolochic acid.",
			"category": 2,
			"name": "Ibrahim Iman Hassan,2022"
		},
		{
			"PMID": 35521545,
			"title": "Noncoding RNAs endogenously rule the cancerous regulatory realm while proteins govern the normal.",
			"journal": "Computational and structural biotechnology journal",
			"authorList": [
				"Wang Anyou"
			],
			"DOI": "10.1016/j.csbj.2022.04.015",
			"date": "2022-07-16",
			"PMC": "",
			"citation": "",
			"abstract": "Cancers evolve from normal tissues and share an endogenous regulatory realm distinctive from that of normal human tissues. Unearthing such an endogenous realm faces challenges due to heterogeneous biology data. This study computes petabyte level data and reveals the endogenous regulatory networks of normal and cancers and then unearths the most important endogenous regulators for normal and cancerous realm. In normal, proteins dominate the entire realm and ",
			"category": 2,
			"name": "Wang Anyou,2022"
		},
		{
			"PMID": 35515712,
			"title": "A semiparametric kernel independence test with application to mutational signatures.",
			"journal": "Journal of the American Statistical Association",
			"authorList": [
				"Lee DongHyuk",
				"Zhu Bin"
			],
			"DOI": "10.1080/01621459.2020.1871357",
			"date": "2022-07-16",
			"PMC": "",
			"citation": "",
			"abstract": "Cancers arise owing to somatic mutations, and the characteristic combinations of somatic mutations form mutational signatures. Despite many mutational signatures being identified, mutational processes underlying a number of mutational signatures remain unknown, which hinders the identification of interventions that may reduce somatic mutation burdens and prevent the development of cancer. We demonstrate that the unknown cause of a mutational signature can be inferred by the associated signatures with known etiology. However, existing association tests are not statistically powerful due to excess zeros in mutational signatures data. To address this limitation, we propose a semiparametric kernel independence test (SKIT). The SKIT statistic is defined as the integrated squared distance between mixed probability distributions and is decomposed into four disjoint components to pinpoint the source of dependency. We derive the asymptotic null distribution and prove the asymptotic convergence of power. Due to slow convergence to the asymptotic null distribution, a bootstrap method is employed to compute ",
			"category": 2,
			"name": "Lee DongHyuk,2022"
		},
		{
			"PMID": 35488922,
			"title": "Genome interpretation using in silico predictors of variant impact.",
			"journal": "Human genetics",
			"authorList": [
				"Katsonis Panagiotis",
				"Wilhelm Kevin",
				"Williams Amanda",
				"Lichtarge Olivier"
			],
			"DOI": "10.1007/s00439-022-02457-6",
			"date": "2022-10-03",
			"PMC": "",
			"citation": "",
			"abstract": "Estimating the effects of variants found in disease driver genes opens the door to personalized therapeutic opportunities. Clinical associations and laboratory experiments can only characterize a tiny fraction of all the available variants, leaving the majority as variants of unknown significance (VUS). In silico methods bridge this gap by providing instant estimates on a large scale, most often based on the numerous genetic differences between species. Despite concerns that these methods may lack reliability in individual subjects, their numerous practical applications over cohorts suggest they are already helpful and have a role to play in genome interpretation when used at the proper scale and context. In this review, we aim to gain insights into the training and validation of these variant effect predicting methods and illustrate representative types of experimental and clinical applications. Objective performance assessments using various datasets that are not yet published indicate the strengths and limitations of each method. These show that cautious use of in silico variant impact predictors is essential for addressing genome interpretation challenges.",
			"category": 2,
			"name": "Katsonis Panagiotis,2022"
		},
		{
			"PMID": 35482859,
			"title": "Stepwise-edited, human melanoma models reveal mutations' effect on tumor and microenvironment.",
			"journal": "Science (New York, N.Y.)",
			"authorList": [
				"Hodis Eran",
				"Torlai Triglia Elena",
				"Kwon John Y H",
				"Biancalani Tommaso",
				"Zakka Labib R",
				"Parkar Saurabh",
				"H\u00fctter Jan-Christian",
				"Buffoni Lorenzo",
				"Delorey Toni M",
				"Phillips Devan",
				"Dionne Danielle",
				"Nguyen Lan T",
				"Schapiro Denis",
				"Maliga Zoltan",
				"Jacobson Connor A",
				"Hendel Ayal",
				"Rozenblatt-Rosen Orit",
				"Mihm Martin C",
				"Garraway Levi A",
				"Regev Aviv"
			],
			"DOI": "10.1126/science.abi8175",
			"date": "2022-05-02",
			"PMC": "",
			"citation": "",
			"abstract": "Establishing causal relationships between genetic alterations of human cancers and specific phenotypes of malignancy remains a challenge. We sequentially introduced mutations into healthy human melanocytes in up to five genes spanning six commonly disrupted melanoma pathways, forming nine genetically distinct cellular models of melanoma. We connected mutant melanocyte genotypes to malignant cell expression programs in vitro and in vivo, replicative immortality, malignancy, rapid tumor growth, pigmentation, metastasis, and histopathology. Mutations in malignant cells also affected tumor microenvironment composition and cell states. Our melanoma models shared genotype-associated expression programs with patient melanomas, and a deep learning model showed that these models partially recapitulated genotype-associated histopathological features as well. Thus, a progressive series of genome-edited human cancer models can causally connect genotypes carrying multiple mutations to phenotype.",
			"category": 2,
			"name": "Hodis Eran,2022"
		},
		{
			"PMID": 35478149,
			"title": "ALK Protein Expression Patterns in Squamous Cell Carcinoma of the Oral Cavity.",
			"journal": "In vivo (Athens, Greece)",
			"authorList": [
				"Chrysovergis Aristeidis",
				"Papanikolaou Vasileios",
				"Mastronikolis Nicholas",
				"Tsiambas Evangelos",
				"Katsinis Spyros",
				"Manoli Arezina",
				"Papouliakos Sotirios",
				"Ragos Vasileios",
				"Pantos Pavlos",
				"Peschos Dimitrios",
				"Mastronikolis Stylianos",
				"Fotiades Panagiotis",
				"Mamoulidis Panagiotis",
				"Spyropoulou Despoina",
				"Kyrodimos Efthymios"
			],
			"DOI": "10.21873/invivo.12813",
			"date": "2022-04-29",
			"PMC": "",
			"citation": "",
			"abstract": "Oral squamous cell carcinoma (OSCC) is characterized by a broad spectrum of genomic imbalances, including gross chromosomal (polysomy/aneuploidy) ones as well as specific gene alterations. Aberrant expression of anaplastic lymphoma kinase (ALK) seems to be a useful molecular marker for discriminating patients based on genetic signatures in a variety of solid malignancies, such as lung carcinoma. Our aim was to analyze ALK protein expression patterns in a series of OSCCs.",
			"category": 2,
			"name": "Chrysovergis Aristeidis,2022"
		},
		{
			"PMID": 35463310,
			"title": "LncRNA HCG11 Facilitates Nasopharyngeal Carcinoma Progression Through Regulating miRNA-490-3p/MAP3K9 Axis.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Zheng Jian",
				"Zhao Zhuochen",
				"Ren Huijun",
				"Wang Yongfeng",
				"Meng Xianchun",
				"Zhang Wenjing",
				"Zhang Cai",
				"Ming Liang",
				"Lu Xiubo"
			],
			"DOI": "10.3389/fonc.2022.872033",
			"date": "2022-07-16",
			"PMC": "",
			"citation": "",
			"abstract": "Long noncoding RNAs (LncRNAs) play complex but important roles in the progression of various tumors. This study aimed to elucidate the functional mechanisms of the HLA complex group 11 (HCG11) in nasopharyngeal carcinoma (NPC).",
			"category": 2,
			"name": "Zheng Jian,2022"
		},
		{
			"PMID": 35418684,
			"title": "Somatic mutation rates scale with lifespan across mammals.",
			"journal": "Nature",
			"authorList": [
				"Cagan Alex",
				"Baez-Ortega Adrian",
				"Brzozowska Natalia",
				"Abascal Federico",
				"Coorens Tim H H",
				"Sanders Mathijs A",
				"Lawson Andrew R J",
				"Harvey Luke M R",
				"Bhosle Shriram",
				"Jones David",
				"Alcantara Raul E",
				"Butler Timothy M",
				"Hooks Yvette",
				"Roberts Kirsty",
				"Anderson Elizabeth",
				"Lunn Sharna",
				"Flach Edmund",
				"Spiro Simon",
				"Januszczak Inez",
				"Wrigglesworth Ethan",
				"Jenkins Hannah",
				"Dallas Tilly",
				"Masters Nic",
				"Perkins Matthew W",
				"Deaville Robert",
				"Druce Megan",
				"Bogeska Ruzhica",
				"Milsom Michael D",
				"Neumann Bj\u00f6rn",
				"Gorman Frank",
				"Constantino-Casas Fernando",
				"Peachey Laura",
				"Bochynska Diana",
				"Smith Ewan St John",
				"Gerstung Moritz",
				"Campbell Peter J",
				"Murchison Elizabeth P",
				"Stratton Michael R",
				"Martincorena I\u00f1igo"
			],
			"DOI": "10.1038/s41586-022-04618-z",
			"date": "2022-04-22",
			"PMC": "",
			"citation": "",
			"abstract": "The rates and patterns of somatic mutation in normal tissues are largely unknown outside of humans",
			"category": 2,
			"name": "Cagan Alex,2022"
		},
		{
			"PMID": 35413944,
			"title": "TE Density: a tool to investigate the biology of transposable elements.",
			"journal": "Mobile DNA",
			"authorList": [
				"Teresi Scott J",
				"Teresi Michael B",
				"Edger Patrick P"
			],
			"DOI": "10.1186/s13100-022-00264-4",
			"date": "2023-11-01",
			"PMC": "",
			"citation": "",
			"abstract": "Transposable elements (TEs) are powerful creators of genotypic and phenotypic diversity due to their inherent mutagenic capabilities and in this way they serve as a deep reservoir of sequences for genomic variation. As agents of genetic disruption, a TE's potential to impact phenotype is partially a factor of its location in the genome. Previous research has shown TEs' ability to impact the expression of neighboring genes, however our understanding of this trend is hampered by the exceptional amount of diversity in the TE world, and a lack of publicly available computational methods that quantify the presence of TEs relative to genes.",
			"category": 2,
			"name": "Teresi Scott J,2023"
		},
		{
			"PMID": 35411116,
			"title": "High-throughput functional evaluation of human cancer-associated mutations using base editors.",
			"journal": "Nature biotechnology",
			"authorList": [
				"Kim Younggwang",
				"Lee Seungho",
				"Cho Soohyuk",
				"Park Jinman",
				"Chae Dongwoo",
				"Park Taeyoung",
				"Minna John D",
				"Kim Hyongbum Henry"
			],
			"DOI": "10.1038/s41587-022-01276-4",
			"date": "2022-06-17",
			"PMC": "",
			"citation": "",
			"abstract": "Comprehensive phenotypic characterization of the many mutations found in cancer tissues is one of the biggest challenges in cancer genomics. In this study, we evaluated the functional effects of 29,060 cancer-related transition mutations that result in protein variants on the survival and proliferation of non-tumorigenic lung cells using cytosine and adenine base editors and single guide RNA (sgRNA) libraries. By monitoring base editing efficiencies and outcomes using surrogate target sequences paired with sgRNA-encoding sequences on the lentiviral delivery construct, we identified sgRNAs that induced a single primary protein variant per sgRNA, enabling linking those mutations to the cellular phenotypes caused by base editing. The functions of the vast majority of the protein variants (28,458 variants, 98%) were classified as neutral or likely neutral; only 18 (0.06%) and 157 (0.5%) variants caused outgrowing and likely outgrowing phenotypes, respectively. We expect that our approach can be extended to more variants of unknown significance and other tumor types.",
			"category": 2,
			"name": "Kim Younggwang,2022"
		},
		{
			"PMID": 35406690,
			"title": "Single-Cell Molecular Characterization to Partition the Human Glioblastoma Tumor Microenvironment Genetic Background.",
			"journal": "Cells",
			"authorList": [
				"Lessi Francesca",
				"Franceschi Sara",
				"Morelli Mariangela",
				"Menicagli Michele",
				"Pasqualetti Francesco",
				"Santonocito Orazio",
				"Gambacciani Carlo",
				"Pieri Francesco",
				"Aquila Filippo",
				"Aretini Paolo",
				"Mazzanti Chiara Maria"
			],
			"DOI": "10.3390/cells11071127",
			"date": "2022-04-13",
			"PMC": "",
			"citation": "",
			"abstract": "Glioblastoma (GB) is a devastating primary brain malignancy. The recurrence of GB is inevitable despite the standard treatment of surgery, chemotherapy, and radiation, and the median survival is limited to around 15 months. The barriers to treatment include the complex interactions among the different cellular components inhabiting the tumor microenvironment. The complex heterogeneous nature of GB cells is helped by the local inflammatory tumor microenvironment, which mostly induces tumor aggressiveness and drug resistance.",
			"category": 2,
			"name": "Lessi Francesca,2022"
		},
		{
			"PMID": 35389777,
			"title": "Genome-wide analysis of somatic noncoding mutation patterns in cancer.",
			"journal": "Science (New York, N.Y.)",
			"authorList": [
				"Dietlein Felix",
				"Wang Alex B",
				"Fagre Christian",
				"Tang Anran",
				"Besselink Nicolle J M",
				"Cuppen Edwin",
				"Li Chunliang",
				"Sunyaev Shamil R",
				"Neal James T",
				"Van Allen Eliezer M"
			],
			"DOI": "10.1126/science.abg5601",
			"date": "2022-04-15",
			"PMC": "",
			"citation": "",
			"abstract": "We established a genome-wide compendium of somatic mutation events in 3949 whole cancer genomes representing 19 tumor types. Protein-coding events captured well-established drivers. Noncoding events near tissue-specific genes, such as ",
			"category": 2,
			"name": "Dietlein Felix,2022"
		},
		{
			"PMID": 35378785,
			"title": "The Valuable Role of ARMC1 in Invasive Breast Cancer as a Novel Biomarker.",
			"journal": "BioMed research international",
			"authorList": [
				"Gan Yunhao",
				"Zhong Fuxin",
				"Wang Hao",
				"Li Lingyu"
			],
			"DOI": "10.1155/2022/1740295",
			"date": "2022-04-07",
			"PMC": "",
			"citation": "",
			"abstract": "Invasive breast carcinoma (BRCA) is a common type of breast cancer with a high clinical incidence. Thus, it is significant to find effective biomarkers for BRCA diagnosis and treatment. Although some members of armadillo (ARM) repeat family of proteins are confirmed to be biomarkers in cancers, the role of armadillo repeat-containing 1 (ARMC1) in BRCA remains unknown.",
			"category": 2,
			"name": "Gan Yunhao,2022"
		},
		{
			"PMID": 35373283,
			"title": "Patchwork Cancer Predisposition.",
			"journal": "Cancer discovery",
			"authorList": [
				"Liggett L Alexander",
				"Sankaran Vijay G"
			],
			"DOI": "10.1158/2159-8290.CD-22-0025",
			"date": "2022-04-05",
			"PMC": "",
			"citation": "",
			"abstract": "Inherited genetic variation is increasingly identified as an important predisposing factor to a variety of cancers. In this issue of Cancer Discovery, Pareja and colleagues developed a method of reliably detecting mosaic cancer susceptibility mutations in patients who have been sequenced as part of the MSK-IMPACT tumor profiling platform. This led to the identification of a number of mosaic mutations in cancer susceptibility alleles that are generally found in the germline, suggesting that many predisposition variants may be missed through conventional testing. See related article by Pareja et al., p. 949 (6).",
			"category": 2,
			"name": "Liggett L Alexander,2022"
		},
		{
			"PMID": 35366242,
			"title": "Mechanisms of action of triptolide against colorectal cancer: insights from proteomic and phosphoproteomic analyses.",
			"journal": "Aging",
			"authorList": [
				"Song Xinqiang",
				"He Huanhuan",
				"Zhang Yu",
				"Fan Jinke",
				"Wang Lei"
			],
			"DOI": "10.18632/aging.203992",
			"date": "2022-04-22",
			"PMC": "",
			"citation": "",
			"abstract": "Triptolide is a potent anti-inflammatory agent that also possesses anticancer activity, including against colorectal cancer (CRC), one of the most frequent cancers around the world. In order to clarify how triptolide may be effective against CRC, we analyzed the proteome and phosphoproteome of CRC cell line HCT116 after incubation for 48 h with the drug (40 nM) or vehicle. Tandem mass tagging led to the identification of 403 proteins whose levels increased and 559 whose levels decreased in the presence of triptolide. We also identified 3,110 sites in proteins that were phosphorylated at higher levels and 3,161 sites phosphorylated at lower levels in the presence of the drug. Analysis of these differentially expressed and/or phosphorylated proteins showed that they were enriched in pathways involving ribosome biogenesis, PI3K-Akt signaling, MAPK signaling, nucleic acid binding as well as other pathways. Protein-protein interactions were explored using the STRING database, and we identified nine protein modules and 15 hub proteins. Finally, we identified 57 motifs using motif analysis of phosphosites and found 16 motifs were experimentally verified for known protein kinases, while 41 appear to be novel. These findings may help clarify how triptolide works against CRC and may guide the development of novel treatments.",
			"category": 2,
			"name": "Song Xinqiang,2022"
		},
		{
			"PMID": 35326534,
			"title": "Deciphering Tumour Heterogeneity: From Tissue to Liquid Biopsy.",
			"journal": "Cancers",
			"authorList": [
				"Gilson Pauline",
				"Merlin Jean-Louis",
				"Harl\u00e9 Alexandre"
			],
			"DOI": "10.3390/cancers14061384",
			"date": "2022-03-29",
			"PMC": "",
			"citation": "",
			"abstract": "Human solid malignancies harbour a heterogeneous set of cells with distinct genotypes and phenotypes. This heterogeneity is installed at multiple levels. A biological diversity is commonly observed between tumours from different patients (inter-tumour heterogeneity) and cannot be fully captured by the current consensus molecular classifications for specific cancers. To extend the complexity in cancer, there are substantial differences from cell to cell within an individual tumour (intra-tumour heterogeneity, ITH) and the features of cancer cells evolve in space and time. Currently, treatment-decision making usually relies on the molecular characteristics of a limited tumour tissue sample at the time of diagnosis or disease progression but does not take into account the complexity of the bulk tumours and their constant evolution over time. In this review, we explore the extent of tumour heterogeneity with an emphasis on ITH and report the mechanisms that promote and sustain this diversity in cancers. We summarise the clinical strikes of ITH in the management of patients with cancer. Finally, we discuss the current material and technological approaches that are relevant to adequately appreciate ITH.",
			"category": 2,
			"name": "Gilson Pauline,2022"
		},
		{
			"PMID": 35311113,
			"title": "Comprehensive Analysis Identified Mutation-Gene Signature Impacts the Prognosis Through Immune Function in Hepatocellular Carcinoma.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Lin Zhuo",
				"Xu Qian",
				"Song Xian",
				"Zeng Yuan",
				"Zeng Liuwei",
				"Zhao Luying",
				"Xu Jun",
				"Miao Dan",
				"Chen Zhuoyan",
				"Yu Fujun"
			],
			"DOI": "10.3389/fonc.2022.748557",
			"date": "2022-03-22",
			"PMC": "",
			"citation": "",
			"abstract": "Hepatocellular carcinoma (HCC) is a life-threatening and refractory malignancy with poor outcome. Genetic mutations are the hallmark of cancer. Thus far, there is no comprehensive prognostic model constructed by mutation-gene transcriptome in HCC. The prognostic value of mutation-gene signature in HCC remains elusive.",
			"category": 2,
			"name": "Lin Zhuo,2022"
		},
		{
			"PMID": 35309357,
			"title": "Cancer Therapy With TCR-Engineered T Cells: Current Strategies, Challenges, and Prospects.",
			"journal": "Frontiers in immunology",
			"authorList": [
				"Shafer Paul",
				"Kelly Lauren M",
				"Hoyos Valentina"
			],
			"DOI": "10.3389/fimmu.2022.835762",
			"date": "2022-05-02",
			"PMC": "",
			"citation": "",
			"abstract": "To redirect T cells against tumor cells, T cells can be engineered ",
			"category": 2,
			"name": "Shafer Paul,2022"
		},
		{
			"PMID": 35304872,
			"title": "Zebrafish imaging reveals TP53 mutation switching oncogene-induced senescence from suppressor to driver in primary tumorigenesis.",
			"journal": "Nature communications",
			"authorList": [
				"Haraoka Yukinari",
				"Akieda Yuki",
				"Nagai Yuri",
				"Mogi Chihiro",
				"Ishitani Tohru"
			],
			"DOI": "10.1038/s41467-022-29061-6",
			"date": "2022-04-05",
			"PMC": "",
			"citation": "",
			"abstract": "Most tumours are thought to arise through oncogenic cell generation followed by additional mutations. How a new oncogenic cell primes tumorigenesis by acquiring additional mutations remains unclear. We show that an additional TP53 mutation stimulates primary tumorigenesis by switching oncogene-induced senescence from a tumour suppressor to a driver. Zebrafish imaging reveals that a newly emerged oncogenic cell with the Ras",
			"category": 2,
			"name": "Haraoka Yukinari,2022"
		},
		{
			"PMID": 35273398,
			"title": "Organoid screening reveals epigenetic vulnerabilities in human colorectal cancer.",
			"journal": "Nature chemical biology",
			"authorList": [
				"Toshimitsu Kohta",
				"Takano Ai",
				"Fujii Masayuki",
				"Togasaki Kazuhiro",
				"Matano Mami",
				"Takahashi Sirirat",
				"Kanai Takanori",
				"Sato Toshiro"
			],
			"DOI": "10.1038/s41589-022-00984-x",
			"date": "2022-05-30",
			"PMC": "",
			"citation": "",
			"abstract": "Precision oncology presumes an accurate prediction of drug response on the basis of the molecular profile of tumors. However, the extent to which patient-derived tumor organoids recapitulate the response of in vivo tumors to a given drug remains obscure. To gain insights into the pharmacobiology of human colorectal cancer (CRC), we here created a robust drug screening platform for patient-derived colorectal organoids. Application of suspension culture increased organoid scalability, and a refinement of the culture condition enabled incorporation of normal and precursor organoids to high-throughput drug screening. Drug screening identified bromodomain and extra-terminal (BET) bromodomain protein inhibitor as a cancer-selective growth suppressor that targets genes aberrantly activated in CRC. A multi-omics analysis identified an association between checkpoint with forkhead and ring finger domaines (CHFR) silencing and paclitaxel sensitivity, which was further validated by gene engineering of organoids and in xenografts. Our findings highlight the utility of multiparametric validation in enhancing the biological and clinical fidelity of a drug screening system.",
			"category": 2,
			"name": "Toshimitsu Kohta,2022"
		},
		{
			"PMID": 35263369,
			"title": "Characterisation of breast cancer molecular signature and treatment assessment with vibrational spectroscopy and chemometric approach.",
			"journal": "PloS one",
			"authorList": [
				"Ko\u0142odziej Magdalena",
				"Kaznowska Ewa",
				"Paszek Sylwia",
				"Cebulski J\u00f3zef",
				"Barna\u015b Edyta",
				"Cholewa Marian",
				"Vongsvivut Jitraporn",
				"Zawlik Izabela"
			],
			"DOI": "10.1371/journal.pone.0264347",
			"date": "2022-04-21",
			"PMC": "",
			"citation": "",
			"abstract": "Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. The insight into the detailed biochemical composition of TNBC would help develop dedicated treatments. Thus, in this study Fourier Transform Infrared microspectroscopy combined with chemometrics and absorbance ratios investigation was employed to compare healthy controls with TNBC tissue before and after chemotherapy within the same patient. The primary spectral differences between control and cancer tissues were found in proteins, polysaccharides, and nucleic acids. Amide I/Amide II ratio decrease before and increase after chemotherapy, whereas DNA, RNA, and glycogen contents increase before and decrease after the treatment. The chemometric results revealed discriminatory features reflecting a clinical response scheme and proved the chemotherapy efficacy assessment with infrared spectroscopy is possible.",
			"category": 2,
			"name": "Ko\u0142odziej Magdalena,2022"
		},
		{
			"PMID": 35230683,
			"title": "Identification of Copy Number Alterations from Next-Generation Sequencing Data.",
			"journal": "Advances in experimental medicine and biology",
			"authorList": [
				"Nabavi Sheida",
				"Zare Fatima"
			],
			"DOI": "10.1007/978-3-030-91836-1_4",
			"date": "2022-03-03",
			"PMC": "",
			"citation": "",
			"abstract": "Copy number variation (CNV), which is deletion and multiplication of segments of a genome, is an important genomic alteration that has been associated with many diseases including cancer. In cancer, CNVs are mostly somatic aberrations that occur during cancer evolution. Advances in sequencing technologies and arrival of next-generation sequencing data (whole-genome sequencing and whole-exome sequencing or targeted sequencing) have opened up an opportunity to detect CNVs with higher accuracy and resolution. Many computational methods have been developed for somatic CNV detection, which is a challenging task due to complexity of cancer sequencing data, high level of noise and biases in the sequencing process, and big data nature of sequencing data. Nevertheless, computational detection of CNV in sequencing data has resulted in the discovery of actionable cancer-specific CNVs to be used to guide cancer therapeutics, contributing to significant progress in precision oncology. In this chapter, we start by introducing CNVs. Then, we discuss the main approaches and methods developed for detecting somatic CNV for next-generation sequencing data, along with its challenges. Finally, we describe the overall workflow for CNV detection and introduce the most common publicly available software tools developed for somatic CNV detection and analysis.",
			"category": 2,
			"name": "Nabavi Sheida,2022"
		},
		{
			"PMID": 35222422,
			"title": "T Cell Recognition of Tumor Neoantigens and Insights Into T Cell Immunotherapy.",
			"journal": "Frontiers in immunology",
			"authorList": [
				"Sim Malcolm J W",
				"Sun Peter D"
			],
			"DOI": "10.3389/fimmu.2022.833017",
			"date": "2022-04-08",
			"PMC": "",
			"citation": "",
			"abstract": "In cancer, non-synonymous DNA base changes alter protein sequence and produce neoantigens that are detected by the immune system. For immune detection, neoantigens must first be presented on class I or II human leukocyte antigens (HLA) followed by recognition by peptide-specific receptors, exemplified by the T-cell receptor (TCR). Detection of neoantigens represents a unique challenge to the immune system due to their high similarity with endogenous 'self' proteins. Here, we review insights into how TCRs detect neoantigens from structural studies and delineate two broad mechanistic categories: 1) recognition of mutated 'self' peptides and 2) recognition of novel 'non-self' peptides generated through anchor residue modifications. While mutated 'self' peptides differ only by a single amino acid from an existing 'self' epitope, mutations that form anchor residues generate an entirely new epitope, hitherto unknown to the immune system. We review recent structural studies that highlight these structurally distinct mechanisms and discuss how they may lead to differential anti-tumor immune responses. We discuss how T cells specific for neoantigens derived from anchor mutations can be of high affinity and provide insights to their use in adoptive T cell transfer-based immunotherapy.",
			"category": 2,
			"name": "Sim Malcolm J W,2022"
		},
		{
			"PMID": 35215689,
			"title": "Polymeric Nanostructures Containing Proteins and Peptides for Pharmaceutical Applications.",
			"journal": "Polymers",
			"authorList": [
				"Vardaxi Antiopi",
				"Kafetzi Martha",
				"Pispas Stergios"
			],
			"DOI": "10.3390/polym14040777",
			"date": "2022-03-01",
			"PMC": "",
			"citation": "",
			"abstract": "Over the last three decades, proteins and peptides have attracted great interest as drugs of choice for combating a broad spectrum of diseases, including diabetes mellitus, cancer, and infectious and neurological diseases. However, the delivery of therapeutic proteins to target sites should take into account the obstacles and limitations related to their intrinsic sensitivity to different environmental conditions, fragile tertiary structures, and short half-life. Polymeric nanostructures have emerged as competent vehicles for protein delivery, as they are multifunctional and can be tailored according to their peculiarities. Thus, the enhanced bioavailability and biocompatibility, the adjustable control of physicochemical features, and the colloidal stability of polymer-based nanostructures further enable either the embedding or conjugation of hydrophobic or hydrophilic bioactive molecules, which are some of the features of paramount importance that they possess and which contribute to their selection as vehicles. The present review aims to discuss the prevalent nanostructures composed of block copolymers from the viewpoint of efficient protein hospitality and administration, as well as the up-to-date scientific publications and anticipated applications of polymeric nanovehicles containing proteins and peptides.",
			"category": 2,
			"name": "Vardaxi Antiopi,2022"
		},
		{
			"PMID": 35177608,
			"title": "Spatiotemporal dynamics of clonal selection and diversification in normal endometrial epithelium.",
			"journal": "Nature communications",
			"authorList": [
				"Yamaguchi Manako",
				"Nakaoka Hirofumi",
				"Suda Kazuaki",
				"Yoshihara Kosuke",
				"Ishiguro Tatsuya",
				"Yachida Nozomi",
				"Saito Kyota",
				"Ueda Haruka",
				"Sugino Kentaro",
				"Mori Yutaro",
				"Yamawaki Kaoru",
				"Tamura Ryo",
				"Revathidevi Sundaramoorthy",
				"Motoyama Teiichi",
				"Tainaka Kazuki",
				"Verhaak Roel G W",
				"Inoue Ituro",
				"Enomoto Takayuki"
			],
			"DOI": "10.1038/s41467-022-28568-2",
			"date": "2022-03-03",
			"PMC": "",
			"citation": "",
			"abstract": "It has become evident that somatic mutations in cancer-associated genes accumulate in the normal endometrium, but spatiotemporal understanding of the evolution and expansion of mutant clones is limited. To elucidate the timing and mechanism of the clonal expansion of somatic mutations in cancer-associated genes in the normal endometrium, we sequence 1311 endometrial glands from 37 women. By collecting endometrial glands from different parts of the endometrium, we show that multiple glands with the same somatic mutations occupy substantial areas of the endometrium. We demonstrate that \"rhizome structures\", in which the basal glands run horizontally along the muscular layer and multiple vertical glands rise from the basal gland, originate from the same ancestral clone. Moreover, mutant clones detected in the vertical glands diversify by acquiring additional mutations. These results suggest that clonal expansions through the rhizome structures are involved in the mechanism by which mutant clones extend their territories. Furthermore, we show clonal expansions and copy neutral loss-of-heterozygosity events occur early in life, suggesting such events can be tolerated many years in the normal endometrium. Our results of the evolutionary dynamics of mutant clones in the human endometrium will lead to a better understanding of the mechanisms of endometrial regeneration during the menstrual cycle and the development of therapies for the prevention and treatment of endometrium-related diseases.",
			"category": 2,
			"name": "Yamaguchi Manako,2022"
		},
		{
			"PMID": 35169688,
			"title": "Machine learning for multi-omics data integration in cancer.",
			"journal": "iScience",
			"authorList": [
				"Cai Zhaoxiang",
				"Poulos Rebecca C",
				"Liu Jia",
				"Zhong Qing"
			],
			"DOI": "10.1016/j.isci.2022.103798",
			"date": "2022-02-18",
			"PMC": "",
			"citation": "",
			"abstract": "Multi-omics data analysis is an important aspect of cancer molecular biology studies and has led to ground-breaking discoveries. Many efforts have been made to develop machine learning methods that automatically integrate omics data. Here, we review machine learning tools categorized as either general-purpose or task-specific, covering both supervised and unsupervised learning for integrative analysis of multi-omics data. We benchmark the performance of five machine learning approaches using data from the Cancer Cell Line Encyclopedia, reporting accuracy on cancer type classification and mean absolute error on drug response prediction, and evaluating runtime efficiency. This review provides recommendations to researchers regarding suitable machine learning method selection for their specific applications. It should also promote the development of novel machine learning methodologies for data integration, which will be essential for drug discovery, clinical trial design, and personalized treatments.",
			"category": 2,
			"name": "Cai Zhaoxiang,2022"
		},
		{
			"PMID": 35158934,
			"title": "Targeting Oncogenic Pathways in the Era of Personalized Oncology: A Systemic Analysis Reveals Highly Mutated Signaling Pathways in Cancer Patients and Potential Therapeutic Targets.",
			"journal": "Cancers",
			"authorList": [
				"Karagiannakos Alexandros",
				"Adamaki Maria",
				"Tsintarakis Antonis",
				"Vojtesek Borek",
				"F\u00e5hraeus Robin",
				"Zoumpourlis Vassilis",
				"Karakostis Konstantinos"
			],
			"DOI": "10.3390/cancers14030664",
			"date": "2022-02-19",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is the second leading cause of death globally. One of the main hallmarks in cancer is the functional deregulation of crucial molecular pathways via driver genetic events that lead to abnormal gene expression, giving cells a selective growth advantage. Driver events are defined as mutations, fusions and copy number alterations that are causally implicated in oncogenesis. Molecular analysis on tissues that have originated from a wide range of anatomical areas has shown that mutations in different members of several pathways are implicated in different cancer types. In recent decades, significant efforts have been made to incorporate this knowledge into daily medical practice, providing substantial insight towards clinical diagnosis and personalized therapies. However, since there is still a strong need for more effective drug development, a deep understanding of the involved signaling mechanisms and the interconnections between these pathways is highly anticipated. Here, we perform a systemic analysis on cancer patients included in the Pan-Cancer Atlas project, with the aim to select the ten most highly mutated signaling pathways (p53, RTK-RAS, lipids metabolism, PI-3-Kinase/Akt, ubiquitination, b-catenin/Wnt, Notch, cell cycle, homology directed repair (HDR) and splicing) and to provide a detailed description of each pathway, along with the corresponding therapeutic applications currently being developed or applied. The ultimate scope is to review the current knowledge on highly mutated pathways and to address the attractive perspectives arising from ongoing experimental studies for the clinical implementation of personalized medicine.",
			"category": 2,
			"name": "Karagiannakos Alexandros,2022"
		},
		{
			"PMID": 35158828,
			"title": "Alternative Splicing, Epigenetic Modifications and Cancer: A Dangerous Triangle, or a Hopeful One?",
			"journal": "Cancers",
			"authorList": [
				"Gimeno-Valiente Francisco",
				"L\u00f3pez-Rodas Gerardo",
				"Castillo Josefa",
				"Franco Luis"
			],
			"DOI": "10.3390/cancers14030560",
			"date": "2022-02-19",
			"PMC": "",
			"citation": "",
			"abstract": "The alteration of epigenetic modifications often causes cancer onset and development. In a similar way, aberrant alternative splicing may result in oncogenic products. These issues have often been individually reviewed, but there is a growing body of evidence for the interconnection of both causes of cancer. Actually, aberrant splicing may result from abnormal epigenetic signalization and epigenetic factors may be altered by alternative splicing. In this way, the interrelation between epigenetic marks and alternative splicing form the base of a triangle, while cancer may be placed at the vertex. The present review centers on the interconnections at the triangle base, i.e., between alternative splicing and epigenetic modifications, which may result in neoplastic transformations. The effects of different epigenetic factors, including DNA and histone modifications, the binding of non-coding RNAs and the alterations of chromatin organization on alternative splicing resulting in cancer are first considered. Other less-frequently considered questions, such as the epigenetic regulation of the splicing machinery, the aberrant splicing of epigenetic writers, readers and erasers, etc., are next reviewed in their connection with cancer. The knowledge of the above-mentioned relationships has allowed increasing the collection of biomarkers potentially useful as cancer diagnostic and/or prognostic tools. Finally, taking into account on one hand that epigenetic changes are reversible, and some epigenetic drugs already exist and, on the other hand, that drugs intended for reversing aberrations in alternative splicing, therapeutic possibilities for breaking the mentioned cancer-related triangle are discussed.",
			"category": 2,
			"name": "Gimeno-Valiente Francisco,2022"
		},
		{
			"PMID": 35155216,
			"title": "Role of Long Non-Coding RNA LINC00641 in Cancer.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Han Xue",
				"Zhang Shitai"
			],
			"DOI": "10.3389/fonc.2021.829137",
			"date": "2022-02-16",
			"PMC": "",
			"citation": "",
			"abstract": "Long non-coding RNAs (lncRNAs) are non-protein coding RNAs with more than 200 nucleic acids in length. When lncRNAs are located in the nucleus, they regulate chromosome structure, participate in chromatin remodeling, and act as transcription regulators. When lncRNAs are exported to the cytoplasm, they regulate mRNA stability, regulate translation, and interfere with post-translational modification. In recent years, more and more evidences have shown that lncRNA can regulate the biological processes of tumor proliferation, apoptosis, invasion and metastasis, and can participate in a variety of tumor signaling pathways. Long-gene non-protein coding RNA641 (LINC00641), located on human chromosome 14q11.2, is differentially expressed in a variety of tumors and is related to overall survival and prognosis, etc. Interfering the expression of LINC00641 can lead to changes in tumor cell proliferation, invasion, metastasis, apoptosis and other biological behaviors. Therefore, LINC00641 is a promising new biomarker and potential clinical therapeutic target. In this review, the biological functions, related mechanisms and clinical significance of LINC00641 in many human cancers are described in detail.",
			"category": 2,
			"name": "Han Xue,2022"
		},
		{
			"PMID": 35153470,
			"title": "Liquid Biopsy: A Distinctive Approach to the Diagnosis and Prognosis of Cancer.",
			"journal": "Cancer informatics",
			"authorList": [
				"Hirahata Tetsuyuki",
				"Ul Quraish Reeshan",
				"Quraish Afraz Ul",
				"Ul Quraish Shahan",
				"Naz Munazzah",
				"Razzaq Mohammad Abdul"
			],
			"DOI": "10.1177/11769351221076062",
			"date": "2022-02-16",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a leading cause of morbidity and mortality worldwide. Over the past decades, the concept of precision cancer medicine has emerged as a novel approach in the field of oncology that aims to tailor the most effective treatment options to each individual cancer patient based on the genetic profile of the tumor of each individual patient. Recently, tissue biopsy has become an essential part of cancer care and is widely used to characterize the tumor. However, tissue biopsy techniques face different challenges due to their invasiveness, cost, time, and adversity in potential sampling due to tissue heterogeneity. To overcome these issues, a non-invasive approach has developed, which is known as liquid biopsy. It is a simple, fast, and worthwhile technique based on the analysis of circulating tumor DNA (which is a fraction of cfDNA), circulating tumor cells (CTCs), and other tumor-derived material in blood plasma. This review provides an overview of the concept of liquid biopsy and briefly discusses the role of ctDNA and CTC analysis as tools for early diagnosis and prognosis of cancer. In this review, we also speculate on the advantages of liquid biopsy as opposed to tissue biopsy and postulate that liquid biopsy may be a comprehensive approach to overcome the current limitations associated with costly, invasive, and time-consuming tissue biopsy.",
			"category": 2,
			"name": "Hirahata Tetsuyuki,2022"
		},
		{
			"PMID": 35145111,
			"title": "Copy number amplification of ENSA promotes the progression of triple-negative breast cancer via cholesterol biosynthesis.",
			"journal": "Nature communications",
			"authorList": [
				"Chen Yi-Yu",
				"Ge Jing-Yu",
				"Zhu Si-Yuan",
				"Shao Zhi-Ming",
				"Yu Ke-Da"
			],
			"DOI": "10.1038/s41467-022-28452-z",
			"date": "2022-03-03",
			"PMC": "",
			"citation": "",
			"abstract": "Copy number alterations (CNAs) are pivotal genetic events in triple-negative breast cancer (TNBC). Here, our integrated copy number and transcriptome analysis of 302 TNBC patients reveals that gene alpha-endosulfine (ENSA) exhibits recurrent amplification at the 1q21.3 region and is highly expressed in TNBC. ENSA promotes tumor growth and indicates poor patient survival in TNBC. Mechanistically, we identify ENSA as an essential regulator of cholesterol biosynthesis in TNBC that upregulates the expression of sterol regulatory element-binding transcription factor 2 (SREBP2), a pivotal transcription factor in cholesterol biosynthesis. We confirm that ENSA can increase the level of p-STAT3 (Tyr705) and activated STAT3 binds to the promoter of SREBP2 to promote its transcription. Furthermore, we reveal the efficacy of STAT3 inhibitor Stattic in TNBC with high ENSA expression. In conclusion, the amplification of ENSA at the 1q21.3 region promotes TNBC progression and indicates sensitivity to STAT3 inhibitors.",
			"category": 2,
			"name": "Chen Yi-Yu,2022"
		},
		{
			"PMID": 35144655,
			"title": "Somatic mutational profiles and germline polygenic risk scores in human cancer.",
			"journal": "Genome medicine",
			"authorList": [
				"Liu Yuxi",
				"Gusev Alexander",
				"Heng Yujing J",
				"Alexandrov Ludmil B",
				"Kraft Peter"
			],
			"DOI": "10.1186/s13073-022-01016-y",
			"date": "2022-03-16",
			"PMC": "",
			"citation": "",
			"abstract": "The mutational profile of cancer reflects the activity of the mutagenic processes which have been operative throughout the lineage of the cancer cell. These processes leave characteristic profiles of somatic mutations called mutational signatures. Mutational signatures, including single-base substitution (SBS) signatures, may reflect the effects of exogenous or endogenous exposures.",
			"category": 2,
			"name": "Liu Yuxi,2022"
		},
		{
			"PMID": 35132182,
			"title": "Phase separation drives tumor pathogenesis and evolution: all roads lead to Rome.",
			"journal": "Oncogene",
			"authorList": [
				"Gu Xiang",
				"Zhuang Ai",
				"Yu Jie",
				"Chai Peiwei",
				"Jia Renbing",
				"Ruan Jing"
			],
			"DOI": "10.1038/s41388-022-02195-z",
			"date": "2022-04-18",
			"PMC": "",
			"citation": "",
			"abstract": "Cells coordinate numerous biochemical reactions in space and time, depending on the subdivision of the intracellular space into functional compartments. Compelling evidence has demonstrated that phase separation induces the formation of membrane-less compartments to partition intracellular substances in a strictly regulated manner and participates in various biological processes. Based on the strong association of cancer with the dysregulation of intracellular physiological processes and the occurrence of phase separation in cancer-associated condensates, phase separation undoubtedly plays a significant role in tumorigenesis. In this review, we summarize the drivers and functions of phase separation, elaborate on the roles of phase separation in tumor pathogenesis and evolution, and propose substantial research and therapeutic prospects for phase separation in cancer.",
			"category": 2,
			"name": "Gu Xiang,2022"
		},
		{
			"PMID": 35121724,
			"title": "A Review of Emerging Biomarkers for Immune Checkpoint Inhibitors in Tumors of the Gastrointestinal Tract.",
			"journal": "Medical science monitor : international medical journal of experimental and clinical research",
			"authorList": [
				"Liao Xuqiang",
				"Li Gao",
				"Cai Renzhong",
				"Chen Ru"
			],
			"DOI": "10.12659/MSM.935348",
			"date": "2022-03-14",
			"PMC": "",
			"citation": "",
			"abstract": "In recent years, immune checkpoint inhibition (ICI) therapy has made a tremendous improvement in the treatment of malignant tumors of gastrointestinal tract, especially for those with metastatic or recurrent lesions. However, while some patients benefit from ICI, others do not. In fact, predictive biomarkers can play a crucial role in screening patients who may benefit from a selected or targeted treatment, including immunotherapies such as programmed death-1/programmed death-1 ligand 1 (PD-1/PD-L1) inhibitors. A variety of techniques can be used to detect and quantify tumor biomarkers, each of which has a specific clinical application scenario and limitations. Cancer biomarkers in the gastrointestinal system involve an extremely complex network that requires careful interpretation and analysis. Different prognostic or predictive biomarkers are playing important roles in various tumor types, stages, and pathology/molecular subgroups, sometimes overlapping. Expression levels of biomarkers vary between different tumor types and even between the different lesions in the same tumor, depending on the heterogeneity of the patient, the tumor types, and the techniques of detection. The present systematic review comprehensively summarizes the potential biomarkers of immunotherapy, such as PD-1/PD-L1, total mutation burden (TMB), and tumor-infiltrating lymphocytes (TILs) in various gastrointestinal tumors, including tumors of the colon, stomach, esophagus, liver, and pancreas, to assist future application of immunotherapy and patient selection in clinical practice.",
			"category": 2,
			"name": "Liao Xuqiang,2022"
		},
		{
			"PMID": 35096611,
			"title": "Comprehensive Comparative Molecular Characterization of Young and Old Lung Cancer Patients.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Hu Mingming",
				"Tan Jinjing",
				"Liu Zhentian",
				"Li Lifeng",
				"Zhang Hongmei",
				"Zhao Dan",
				"Li Baolan",
				"Gao Xuan",
				"Che Nanying",
				"Zhang Tongmei"
			],
			"DOI": "10.3389/fonc.2021.806845",
			"date": "2022-04-30",
			"PMC": "",
			"citation": "",
			"abstract": "Young lung cancer as a small subgroup of lung cancer has not been fully studied. Most of the previous studies focused on the clinicopathological features, but studies of molecular characteristics are still few and limited. Here, we explore the characteristics of prognosis and variation in young lung cancer patients with NSCLC.",
			"category": 2,
			"name": "Hu Mingming,2022"
		},
		{
			"PMID": 35083160,
			"title": "The Development of Single-Cell Metabolism and Its Role in Studying Cancer Emergent Properties.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Wei Dingju",
				"Xu Meng",
				"Wang Zhihua",
				"Tong Jingjing"
			],
			"DOI": "10.3389/fonc.2021.814085",
			"date": "2022-01-28",
			"PMC": "",
			"citation": "",
			"abstract": "Metabolic reprogramming is one of the hallmarks of malignant tumors, which provides energy and material basis for tumor rapid proliferation, immune escape, as well as extensive invasion and metastasis. Blocking the energy and material supply of tumor cells is one of the strategies to treat tumor, however tumor cell metabolic heterogeneity prevents metabolic-based anti-cancer treatment. Therefore, searching for the key metabolic factors that regulate cell cancerous change and tumor recurrence has become a major challenge. Emerging technology--single-cell metabolomics is different from the traditional metabolomics that obtains average information of a group of cells. Single-cell metabolomics identifies the metabolites of single cells in different states by mass spectrometry, and captures the molecular biological information of the energy and substances synthesized in single cells, which provides more detailed information for tumor treatment metabolic target screening. This review will combine the current research status of tumor cell metabolism with the advantages of single-cell metabolomics technology, and explore the role of single-cell sequencing technology in searching key factors regulating tumor metabolism. The addition of single-cell technology will accelerate the development of metabolism-based anti-cancer strategies, which may greatly improve the prognostic survival rate of cancer patients.",
			"category": 2,
			"name": "Wei Dingju,2022"
		},
		{
			"PMID": 35081118,
			"title": "KLF3 and PAX6 are candidate driver genes in late-stage, MSI-hypermutated endometrioid endometrial carcinomas.",
			"journal": "PloS one",
			"authorList": [
				"Rudd Meghan L",
				"Hansen Nancy F",
				"Zhang Xiaolu",
				"Urick Mary Ellen",
				"Zhang Suiyuan",
				"Merino Maria J",
				"National Institutes of Health Intramural Sequencing Center Comparative Sequencing Program",
				"Mullikin James C",
				"Brody Lawrence C",
				"Bell Daphne W"
			],
			"DOI": "10.1371/journal.pone.0251286",
			"date": "2022-02-14",
			"PMC": "",
			"citation": "",
			"abstract": "Endometrioid endometrial carcinomas (EECs) are the most common histological subtype of uterine cancer. Late-stage disease is an adverse prognosticator for EEC. The purpose of this study was to analyze EEC exome mutation data to identify late-stage-specific statistically significantly mutated genes (SMGs), which represent candidate driver genes potentially associated with disease progression. We exome sequenced 15 late-stage (stage III or IV) non-ultramutated EECs and paired non-tumor DNAs; somatic variants were called using Strelka, Shimmer, SomaticSniper and MuTect. Additionally, somatic mutation calls were extracted from The Cancer Genome Atlas (TCGA) data for 66 late-stage and 270 early-stage (stage I or II) non-ultramutated EECs. MutSigCV (v1.4) was used to annotate SMGs in the two late-stage cohorts and to derive p-values for all mutated genes in the early-stage cohort. To test whether late-stage SMGs are statistically significantly mutated in early-stage tumors, q-values for late-stage SMGs were re-calculated from the MutSigCV (v1.4) early-stage p-values, adjusting for the number of late-stage SMGs tested. We identified 14 SMGs in the combined late-stage EEC cohorts. When the 14 late-stage SMGs were examined in the TCGA early-stage data, only Kr\u00fcppel-like factor 3 (KLF3) and Paired box 6 (PAX6) failed to reach significance as early-stage SMGs, despite the inclusion of enough early-stage cases to ensure adequate statistical power. Within TCGA, nonsynonymous mutations in KLF3 and PAX6 were, respectively, exclusive or nearly exclusive to the microsatellite instability (MSI)-hypermutated molecular subgroup and were dominated by insertions-deletions at homopolymer tracts. In conclusion, our findings are hypothesis-generating and suggest that KLF3 and PAX6, which encode transcription factors, are MSI target genes and late-stage-specific SMGs in EEC.",
			"category": 2,
			"name": "Rudd Meghan L,2022"
		},
		{
			"PMID": 35057729,
			"title": "Multi-view manifold regularized compact low-rank representation for cancer samples clustering on multi-omics data.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"Wang Juan",
				"Lu Cong-Hai",
				"Kong Xiang-Zhen",
				"Dai Ling-Yun",
				"Yuan Shasha",
				"Zhang Xiaofeng"
			],
			"DOI": "10.1186/s12859-021-04220-6",
			"date": "2022-01-24",
			"PMC": "",
			"citation": "",
			"abstract": "The identification of cancer types is of great significance for early diagnosis and clinical treatment of cancer. Clustering cancer samples is an important means to identify cancer types, which has been paid much attention in the field of bioinformatics. The purpose of cancer clustering is to find expression patterns of different cancer types, so that the samples with similar expression patterns can be gathered into the same type. In order to improve the accuracy and reliability of cancer clustering, many clustering methods begin to focus on the integration analysis of cancer multi-omics data. Obviously, the methods based on multi-omics data have more advantages than those using single omics data. However, the high heterogeneity and noise of cancer multi-omics data pose a great challenge to the multi-omics analysis method.",
			"category": 2,
			"name": "Wang Juan,2022"
		},
		{
			"PMID": 35040778,
			"title": "Mitochondrial genome sequencing of marine leukaemias reveals cancer contagion between clam species in the Seas of Southern Europe.",
			"journal": "eLife",
			"authorList": [
				"Garcia-Souto Daniel",
				"Bruzos Alicia L",
				"Diaz Seila",
				"Rocha Sara",
				"Peque\u00f1o-Valtierra Ana",
				"Roman-Lewis Camila F",
				"Alonso Juana",
				"Rodriguez Rosana",
				"Costas Damian",
				"Rodriguez-Castro Jorge",
				"Villanueva Antonio",
				"Silva Luis",
				"Valencia Jose Maria",
				"Annona Giovanni",
				"Tarallo Andrea",
				"Ricardo Fernando",
				"Brato\u0161 Cetini\u0107 Ana",
				"Posada David",
				"Pasantes Juan Jose",
				"Tubio Jose Mc"
			],
			"DOI": "10.7554/eLife.66946",
			"date": "2022-03-15",
			"PMC": "",
			"citation": "",
			"abstract": "Clonally transmissible cancers are tumour lineages that are transmitted between individuals via the transfer of living cancer cells. In marine bivalves, leukaemia-like transmissible cancers, called hemic neoplasia (HN), have demonstrated the ability to infect individuals from different species. We performed whole-genome sequencing in eight warty venus clams that were diagnosed with HN, from two sampling points located more than 1000 nautical miles away in the Atlantic Ocean and the Mediterranean Sea Coasts of Spain. Mitochondrial genome sequencing analysis from neoplastic animals revealed the coexistence of haplotypes from two different clam species. Phylogenies estimated from mitochondrial and nuclear markers confirmed this leukaemia originated in striped venus clams and later transmitted to clams of the species warty venus, in which it survives as a contagious cancer. The analysis of mitochondrial and nuclear gene sequences supports all studied tumours belong to a single neoplastic lineage that spreads in the Seas of Southern Europe.",
			"category": 2,
			"name": "Garcia-Souto Daniel,2022"
		},
		{
			"PMID": 35037014,
			"title": "Comprehensive evaluation of computational methods for predicting cancer driver genes.",
			"journal": "Briefings in bioinformatics",
			"authorList": [
				"Shi Xiaohui",
				"Teng Huajing",
				"Shi Leisheng",
				"Bi Wenjian",
				"Wei Wenqing",
				"Mao Fengbiao",
				"Sun Zhongsheng"
			],
			"DOI": "10.1093/bib/bbab548",
			"date": "2022-04-22",
			"PMC": "",
			"citation": "",
			"abstract": "Optimal methods could effectively improve the accuracy of predicting and identifying candidate driver genes. Various computational methods based on mutational frequency, network and function approaches have been developed to identify mutation driver genes in cancer genomes. However, a comprehensive evaluation of the performance levels of network-, function- and frequency-based methods is lacking. In the present study, we assessed and compared eight performance criteria for eight network-based, one function-based and three frequency-based algorithms using eight benchmark datasets. Under different conditions, the performance of approaches varied in terms of network, measurement and sample size. The frequency-based driverMAPS and network-based HotNet2 methods showed the best overall performance. Network-based algorithms using protein-protein interaction networks outperformed the function- and the frequency-based approaches. Precision, F1 score and Matthews correlation coefficient were low for most approaches. Thus, most of these algorithms require stringent cutoffs to correctly distinguish driver and non-driver genes. We constructed a website named Cancer Driver Catalog (http://159.226.67.237/sun/cancer_driver/), wherein we integrated the gene scores predicted by the foregoing software programs. This resource provides valuable guidance for cancer researchers and clinical oncologists prioritizing cancer driver gene candidates by using an optimal tool.",
			"category": 2,
			"name": "Shi Xiaohui,2022"
		},
		{
			"PMID": 35030014,
			"title": "How can same-gene mutations promote both cancer and developmental disorders?",
			"journal": "Science advances",
			"authorList": [
				"Nussinov Ruth",
				"Tsai Chung-Jung",
				"Jang Hyunbum"
			],
			"DOI": "10.1126/sciadv.abm2059",
			"date": "2024-02-14",
			"PMC": "",
			"citation": "",
			"abstract": "The question of how same-gene mutations can drive both cancer and neurodevelopmental disorders has been puzzling. It has also been puzzling why those with neurodevelopmental disorders have a high risk of cancer. Ras, MEK, PI3K, PTEN, and SHP2 are among the oncogenic proteins that can harbor mutations that encode diseases other than cancer. Understanding why some of their mutations can promote cancer, whereas others promote neurodevelopmental diseases, and why even the same mutations may promote both phenotypes, has important clinical ramifications. Here, we review the literature and address these tantalizing questions. We propose that cell type\u2013specific expression of the mutant protein, and of other proteins in the respective pathway, timing of activation (during embryonic development or sporadic emergence), and the absolute number of molecules that the mutations activate, alone or in combination, are pivotal in determining the pathological phenotypes\u2014cancer and (or) developmental disorders.",
			"category": 2,
			"name": "Nussinov Ruth,2024"
		},
		{
			"PMID": 34999837,
			"title": "Clinical reliability of genomic data obtained from spinal metastatic tumor samples.",
			"journal": "Neuro-oncology",
			"authorList": [
				"Barzilai Ori",
				"Martin Axel",
				"Reiner Anne S",
				"Laufer Ilya",
				"Schmitt Adam",
				"Bilsky Mark H"
			],
			"DOI": "10.1093/neuonc/noac009",
			"date": "2022-07-06",
			"PMC": "",
			"citation": "",
			"abstract": "The role of tumor genomic profiling is rapidly growing as it results in targeted, personalized, cancer therapy. Though routinely used in clinical practice, there are no data exploring the reliability of genomic data obtained from spine metastases samples often leading to multiple biopsies in clinical practice. This study compares the genomic tumor landscape between spinal metastases and the corresponding primary tumors as well as between spinal metastases and visceral metastases.",
			"category": 2,
			"name": "Barzilai Ori,2022"
		},
		{
			"PMID": 34997044,
			"title": "Novel ratio-metric features enable the identification of new driver genes across cancer types.",
			"journal": "Scientific reports",
			"authorList": [
				"Sudhakar Malvika",
				"Rengaswamy Raghunathan",
				"Raman Karthik"
			],
			"DOI": "10.1038/s41598-021-04015-y",
			"date": "2022-02-23",
			"PMC": "",
			"citation": "",
			"abstract": "An emergent area of cancer genomics is the identification of driver genes. Driver genes confer a selective growth advantage to the cell. While several driver genes have been discovered, many remain undiscovered, especially those mutated at a low frequency across samples. This study defines new features and builds a pan-cancer model, cTaG, to identify new driver genes. The features capture the functional impact of the mutations as well as their recurrence across samples, which helps build a model unbiased to genes with low frequency. The model classifies genes into the functional categories of driver genes, tumour suppressor genes (TSGs) and oncogenes (OGs), having distinct mutation type profiles. We overcome overfitting and show that certain mutation types, such as nonsense mutations, are more important for classification. Further, cTaG was employed to identify tissue-specific driver genes. Some known cancer driver genes predicted by cTaG as TSGs with high probability are ARID1A, TP53, and RB1. In addition to these known genes, potential driver genes predicted are CD36, ZNF750 and ARHGAP35 as TSGs and TAB3 as an oncogene. Overall, our approach surmounts the issue of low recall and bias towards genes with high mutation rates and predicts potential new driver genes for further experimental screening. cTaG is available at https://github.com/RamanLab/cTaG .",
			"category": 2,
			"name": "Sudhakar Malvika,2022"
		},
		{
			"PMID": 34976841,
			"title": "Predictive Biomarkers for Checkpoint Inhibitor-Based Immunotherapy in Hepatocellular Carcinoma: Where Do We Stand?",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Rizzo Alessandro",
				"Ricci Angela Dalia",
				"Di Federico Alessandro",
				"Frega Giorgio",
				"Palloni Andrea",
				"Tavolari Simona",
				"Brandi Giovanni"
			],
			"DOI": "10.3389/fonc.2021.803133",
			"date": "2022-01-04",
			"PMC": "",
			"citation": "",
			"abstract": "Hepatocellular carcinoma (HCC) remains the sixth most commonly diagnosed malignancy worldwide, still representing an important cause of cancer-related death. Over the next few years, novel systemic treatment options have emerged. Among these, immune checkpoint inhibitors (ICIs) have been widely evaluated and are under assessment, as monotherapy or in combination with other anticancer agents in treatment-na\u00efve and previously treated patients. In particular, the approval of the PD-L1 inhibitor atezolizumab plus the antiangiogenic agent bevacizumab as front-line treatment for advanced HCC has led to the adoption of this combination in this setting, and the IMbrave 150 phase III trial has established a novel standard of care. However, several questions remain unanswered, including the identification of reliable predictors of response to ICIs in HCC patients. In the current paper, we will provide an updated overview of potentially useful predictive biomarkers of response to immunotherapy in advanced HCC. A literature search was conducted in September 2021 of Pubmed/Medline, Cochrane library and Scopus databases.",
			"category": 2,
			"name": "Rizzo Alessandro,2022"
		},
		{
			"PMID": 34971383,
			"title": "Positive Selection and Enhancer Evolution Shaped Lifespan and Body Mass in Great Apes.",
			"journal": "Molecular biology and evolution",
			"authorList": [
				"Tejada-Martinez Daniela",
				"Avelar Roberto A",
				"Lopes In\u00eas",
				"Zhang Bruce",
				"Novoa Guy",
				"de Magalh\u00e3es Jo\u00e3o Pedro",
				"Trizzino Marco"
			],
			"DOI": "10.1093/molbev/msab369",
			"date": "2022-03-31",
			"PMC": "",
			"citation": "",
			"abstract": "Within primates, the great apes are outliers both in terms of body size and lifespan, since they include the largest and longest-lived species in the order. Yet, the molecular bases underlying such features are poorly understood. Here, we leveraged an integrated approach to investigate multiple sources of molecular variation across primates, focusing on over 10,000 genes, including approximately 1,500 previously associated with lifespan, and additional approximately 9,000 for which an association with longevity has never been suggested. We analyzed dN/dS rates, positive selection, gene expression (RNA-seq), and gene regulation (ChIP-seq). By analyzing the correlation between dN/dS, maximum lifespan, and body mass, we identified 276 genes whose rate of evolution positively correlates with maximum lifespan in primates. Further, we identified five genes, important for tumor suppression, adaptive immunity, metastasis, and inflammation, under positive selection exclusively in the great ape lineage. RNA-seq data, generated from the liver of six species representing all the primate lineages, revealed that 8% of approximately 1,500 genes previously associated with longevity are differentially expressed in apes relative to other primates. Importantly, by integrating RNA-seq with ChIP-seq for H3K27ac (which marks active enhancers), we show that the differentially expressed longevity genes are significantly more likely than expected to be located near a novel \"ape-specific\" enhancer. Moreover, these particular ape-specific enhancers are enriched for young transposable elements, and specifically SINE-Vntr-Alus. In summary, we demonstrate that multiple evolutionary forces have contributed to the evolution of lifespan and body size in primates.",
			"category": 2,
			"name": "Tejada-Martinez Daniela,2022"
		},
		{
			"PMID": 34968247,
			"title": "One Omics Approach Does Not Rule Them All: The Metabolome and the Epigenome Join Forces in Haematological Malignancies.",
			"journal": "Epigenomes",
			"authorList": [
				"Kalushkova Antonia",
				"Nylund Patrick",
				"P\u00e1rraga Alba Atienza",
				"Lennartsson Andreas",
				"Jernberg-Wiklund Helena"
			],
			"DOI": "10.3390/epigenomes5040022",
			"date": "2022-01-01",
			"PMC": "",
			"citation": "",
			"abstract": "Aberrant DNA methylation, dysregulation of chromatin-modifying enzymes, and microRNAs (miRNAs) play a crucial role in haematological malignancies. These epimutations, with an impact on chromatin accessibility and transcriptional output, are often associated with genomic instability and the emergence of drug resistance, disease progression, and poor survival. In order to exert their functions, epigenetic enzymes utilize cellular metabolites as co-factors and are highly dependent on their availability. By affecting the expression of metabolic enzymes, epigenetic modifiers may aid the generation of metabolite signatures that could be utilized as targets and biomarkers in cancer. This interdependency remains often neglected and poorly represented in studies, despite well-established methods to study the cellular metabolome. This review critically summarizes the current knowledge in the field to provide an integral picture of the interplay between epigenomic alterations and the cellular metabolome in haematological malignancies. Our recent findings defining a distinct metabolic signature upon response to enhancer of zeste homolog 2 (EZH2) inhibition in multiple myeloma (MM) highlight how a shift of preferred metabolic pathways may potentiate novel treatments. The suggested link between the epigenome and the metabolome in haematopoietic tumours holds promise for the use of metabolic signatures as possible biomarkers of response to treatment.",
			"category": 2,
			"name": "Kalushkova Antonia,2022"
		},
		{
			"PMID": 34963661,
			"title": "A full-proteome, interaction-specific characterization of mutational hotspots across human cancers.",
			"journal": "Genome research",
			"authorList": [
				"Chen Siwei",
				"Liu Yuan",
				"Zhang Yingying",
				"Wierbowski Shayne D",
				"Lipkin Steven M",
				"Wei Xiaomu",
				"Yu Haiyuan"
			],
			"DOI": "10.1101/gr.275437.121",
			"date": "2022-03-10",
			"PMC": "",
			"citation": "",
			"abstract": "Rapid accumulation of cancer genomic data has led to the identification of an increasing number of mutational hotspots with uncharacterized significance. Here we present a biologically informed computational framework that characterizes the functional relevance of all 1107 published mutational hotspots identified in approximately 25,000 tumor samples across 41 cancer types in the context of a human 3D interactome network, in which the interface of each interaction is mapped at residue resolution. Hotspots reside in network hub proteins and are enriched on protein interaction interfaces, suggesting that alteration of specific protein-protein interactions is critical for the oncogenicity of many hotspot mutations. Our framework enables, for the first time, systematic identification of specific protein interactions affected by hotspot mutations at the full proteome scale. Furthermore, by constructing a hotspot-affected network that connects all hotspot-affected interactions throughout the whole-human interactome, we uncover genome-wide relationships among hotspots and implicate novel cancer proteins that do not harbor hotspot mutations themselves. Moreover, applying our network-based framework to specific cancer types identifies clinically significant hotspots that can be used for prognosis and therapy targets. Overall, we show that our framework bridges the gap between the statistical significance of mutational hotspots and their biological and clinical significance in human cancers.",
			"category": 2,
			"name": "Chen Siwei,2022"
		},
		{
			"PMID": 34960018,
			"title": "Effects of a 3-Week Hospital-Controlled Very-Low-Calorie Diet in Severely Obese Patients.",
			"journal": "Nutrients",
			"authorList": [
				"O\u017evald Ivan",
				"Bo\u017ei\u010devi\u0107 Dragan",
				"Duh Lidija",
				"Vinkovi\u0107 Vr\u010dek Ivana",
				"Pavi\u010di\u0107 Ivan",
				"Domijan Ana-Marija",
				"Mili\u0107 Mirta"
			],
			"DOI": "10.3390/nu13124468",
			"date": "2022-01-12",
			"PMC": "",
			"citation": "",
			"abstract": "Although a very-low-calorie diet (VLCD) is considered safe and has demonstrated benefits among other types of diets, data are scarce concerning its effects on improving health and weight loss in severely obese patients. As part of the personalized weight loss program developed at the Duga Resa Special Hospital for Extended Treatment, Croatia, we evaluated anthropometric, biochemical, and permanent DNA damage parameters (assessed with the cytochalasin B-blocked micronucleus ",
			"category": 2,
			"name": "O\u017evald Ivan,2022"
		},
		{
			"PMID": 34944094,
			"title": "Somatic Mutational Profile of High-Grade Serous Ovarian Carcinoma and Triple-Negative Breast Carcinoma in Young and Elderly Patients: Similarities and Divergences.",
			"journal": "Cells",
			"authorList": [
				"Serio Pedro Adolpho de Menezes Pacheco",
				"de Lima Pereira Gl\u00e1ucia Fernanda",
				"Katayama Maria Lucia Hirata",
				"Roela Rosimeire Aparecida",
				"Maistro Simone",
				"Folgueira Maria Aparecida Azevedo Koike"
			],
			"DOI": "10.3390/cells10123586",
			"date": "2022-01-05",
			"PMC": "",
			"citation": "",
			"abstract": "Triple-negative breast cancer (TNBC) and High-Grade Serous Ovarian Cancer (HGSOC) are aggressive malignancies that share similarities; however, different ages of onset may reflect distinct tumor behaviors. Thus, our aim was to compare somatic mutations in potential driver genes in 109 TNBC and 81 HGSOC from young (Y \u2264 40 years) and elderly (E \u2265 75 years) patients.",
			"category": 2,
			"name": "Serio Pedro Adolpho de Menezes Pacheco,2022"
		},
		{
			"PMID": 34930241,
			"title": "Clinical feature-related single-base substitution sequence signatures identified with an unsupervised machine learning approach.",
			"journal": "BMC medical genomics",
			"authorList": [
				"Ji Hongchen",
				"Li Junjie",
				"Zhang Qiong",
				"Yang Jingyue",
				"Duan Juanli",
				"Wang Xiaowen",
				"Ma Ben",
				"Zhang Zhuochao",
				"Pan Wei",
				"Zhang Hongmei"
			],
			"DOI": "10.1186/s12920-021-01144-1",
			"date": "2022-04-07",
			"PMC": "",
			"citation": "",
			"abstract": "Mutation processes leave different signatures in genes. For single-base substitutions, previous studies have suggested that mutation signatures are not only reflected in mutation bases but also in neighboring bases. However, because of the lack of a method to identify features of long sequences next to mutation bases, the understanding of how flanking sequences influence mutation signatures is limited.",
			"category": 2,
			"name": "Ji Hongchen,2022"
		},
		{
			"PMID": 34916293,
			"title": "Recurrent high-impact mutations at cognate structural positions in class A G protein-coupled receptors expressed in tumors.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Huh Eunna",
				"Gallion Jonathan",
				"Agosto Melina A",
				"Wright Sara J",
				"Wensel Theodore G",
				"Lichtarge Olivier"
			],
			"DOI": "10.1073/pnas.2113373118",
			"date": "2022-01-12",
			"PMC": "",
			"citation": "",
			"abstract": "G protein-coupled receptors (GPCRs) are the largest family of human proteins. They have a common structure and, signaling through a much smaller set of G proteins, arrestins, and effectors, activate downstream pathways that often modulate hallmark mechanisms of cancer. Because there are many more GPCRs than effectors, mutations in different receptors could perturb signaling similarly so as to favor a tumor. We hypothesized that somatic mutations in tumor samples may not be enriched within a single gene but rather that cognate mutations with similar effects on GPCR function are distributed across many receptors. To test this possibility, we systematically aggregated somatic cancer mutations across class A GPCRs and found a nonrandom distribution of positions with variant amino acid residues. Individual cancer types were enriched for highly impactful, recurrent mutations at selected cognate positions of known functional motifs. We also discovered that no single receptor drives this pattern, but rather multiple receptors contain amino acid substitutions at a few cognate positions. Phenotypic characterization suggests these mutations induce perturbation of G protein activation and/or \u03b2-arrestin recruitment. These data suggest that recurrent impactful oncogenic mutations perturb different GPCRs to subvert signaling and promote tumor growth or survival. The possibility that multiple different GPCRs could moonlight as drivers or enablers of a given cancer through mutations located at cognate positions across GPCR paralogs opens a window into cancer mechanisms and potential approaches to therapeutics.",
			"category": 2,
			"name": "Huh Eunna,2022"
		},
		{
			"PMID": 34912705,
			"title": "Precise Identification of Recurrent Somatic Mutations in Oral Cancer Through Whole-Exome Sequencing Using Multiple Mutation Calling Pipelines.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Lin Li-Han",
				"Chou Chung-Hsien",
				"Cheng Hui-Wen",
				"Chang Kuo-Wei",
				"Liu Chung-Ji"
			],
			"DOI": "10.3389/fonc.2021.741626",
			"date": "2021-12-17",
			"PMC": "",
			"citation": "",
			"abstract": "Understanding the genomic alterations in oral carcinogenesis remains crucial for the appropriate diagnosis and treatment of oral squamous cell carcinoma (OSCC). To unveil the mutational spectrum, in this study, we conducted whole-exome sequencing (WES), using six mutation calling pipelines and multiple filtering criteria applied to 50 paired OSCC samples. The tumor mutation burden extracted from the data set of somatic variations was significantly associated with age, tumor staging, and survival. Several genes (",
			"category": 2,
			"name": "Lin Li-Han,2021"
		},
		{
			"PMID": 34884820,
			"title": "Integration of Mutational Signature Analysis with 3D Chromatin Data Unveils Differential AID-Related Mutagenesis in Indolent Lymphomas.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Sepulveda-Yanez Julieta H",
				"Alvarez-Saravia Diego",
				"Fernandez-Goycoolea Jose",
				"Aldridge Jacqueline",
				"van Bergen Cornelis A M",
				"Posthuma Ward",
				"Uribe-Paredes Roberto",
				"Veelken Hendrik",
				"Navarrete Marcelo A"
			],
			"DOI": "10.3390/ijms222313015",
			"date": "2021-12-22",
			"PMC": "",
			"citation": "",
			"abstract": "Activation-induced deaminase (AID) is required for somatic hypermutation in immunoglobulin genes, but also induces off-target mutations. Follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL), the most frequent types of indolent B-cell tumors, are exposed to AID activity during lymphomagenesis. We designed a workflow integrating de novo mutational signatures extraction and fitting of COSMIC (Catalogue Of Somatic Mutations In Cancer) signatures, with tridimensional chromatin conformation data (Hi-C). We applied the workflow to exome sequencing data from lymphoma samples. In 33 FL and 30 CLL samples, 42% and 34% of the contextual mutations could be traced to a known AID motif. We demonstrate that both CLL and FL share mutational processes dominated by spontaneous deamination, failures in DNA repair, and AID activity. The processes had equiproportional distribution across active and nonactive chromatin compartments in CLL. In contrast, canonical AID activity and failures in DNA repair pathways in FL were significantly higher within the active chromatin compartment. Analysis of DNA repair genes revealed a higher prevalence of base excision repair gene mutations (",
			"category": 2,
			"name": "Sepulveda-Yanez Julieta H,2021"
		},
		{
			"PMID": 34880864,
			"title": "Cancer ",
			"journal": "Frontiers in immunology",
			"authorList": [
				"Liu Wenbin",
				"Deng Yang",
				"Li Zishuai",
				"Chen Yifan",
				"Zhu Xiaoqiong",
				"Tan Xiaojie",
				"Cao Guangwen"
			],
			"DOI": "10.3389/fimmu.2021.768098",
			"date": "2022-02-14",
			"PMC": "",
			"citation": "",
			"abstract": "Chronic inflammation is a prerequisite for the development of cancers. Here, we present the framework of a novel theory termed as Cancer Evolution-Development (",
			"category": 2,
			"name": "Liu Wenbin,2022"
		},
		{
			"PMID": 34876593,
			"title": "A computational approach for the discovery of significant cancer genes by weighted mutation and asymmetric spreading strength in networks.",
			"journal": "Scientific reports",
			"authorList": [
				"Cutigi Jorge Francisco",
				"Evangelista Adriane Feijo",
				"Reis Rui Manuel",
				"Simao Adenilso"
			],
			"DOI": "10.1038/s41598-021-02671-8",
			"date": "2022-01-27",
			"PMC": "",
			"citation": "",
			"abstract": "Identifying significantly mutated genes in cancer is essential for understanding the mechanisms of tumor initiation and progression. This task is a key challenge since large-scale genomic studies have reported an endless number of genes mutated at a shallow frequency. Towards uncovering infrequently mutated genes, gene interaction networks combined with mutation data have been explored. This work proposes Discovering Significant Cancer Genes (DiSCaGe), a computational method for discovering significant genes for cancer. DiSCaGe computes a mutation score for the genes based on the type of mutations they have. The influence received for their neighbors in the network is also considered and obtained through an asymmetric spreading strength applied to a consensus gene network. DiSCaGe produces a ranking of prioritized possible cancer genes. An experimental evaluation with six types of cancer revealed the potential of DiSCaGe for discovering known and possible novel significant cancer genes.",
			"category": 2,
			"name": "Cutigi Jorge Francisco,2022"
		},
		{
			"PMID": 34858165,
			"title": "Identifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification.",
			"journal": "Frontiers in pharmacology",
			"authorList": [
				"Zhang Yubao",
				"Ma Xiaoran",
				"Li Huayao",
				"Zhuang Jing",
				"Feng Fubin",
				"Liu Lijuan",
				"Liu Cun",
				"Sun Changgang"
			],
			"DOI": "10.3389/fphar.2021.685773",
			"date": "2021-12-04",
			"PMC": "",
			"citation": "",
			"abstract": "Triple negative breast cancer (TNBC) is a subtype of breast cancer with complex heterogeneity, high invasiveness, and long-term poor prognosis. With the development of molecular pathology and molecular genetics, the gene map of TNBC with distinctive biological characteristics has been outlined more clearly. Natural plant extracts such as paclitaxel, vinblastine, colchicine etc., have occupied an important position in the treatment of hormone-independent breast cancer. Ursolic acid (UA), a triterpenoid acid compound derived from apple, pear, loquat leaves, etc., has been reported to be effective in a variety of cancer treatments, but there are few reports on the treatment of TNBC. This study performed comprehensive bioinformatics analysis and ",
			"category": 2,
			"name": "Zhang Yubao,2021"
		},
		{
			"PMID": 34850320,
			"title": "What do cellular responses to acidity tell us about cancer?",
			"journal": "Cancer metastasis reviews",
			"authorList": [
				"Blaszczak Wiktoria",
				"Swietach Pawel"
			],
			"DOI": "10.1007/s10555-021-10005-3",
			"date": "2022-05-02",
			"PMC": "",
			"citation": "",
			"abstract": "The notion that invasive cancer is a product of somatic evolution is a well-established theory that can be modelled mathematically and demonstrated empirically from therapeutic responses. Somatic evolution is by no means deterministic, and ample opportunities exist to steer its trajectory towards cancer cell extinction. One such strategy is to alter the chemical microenvironment shared between host and cancer cells in a way that no longer favours the latter. Ever since the first description of the Warburg effect, acidosis has been recognised as a key chemical signature of the tumour microenvironment. Recent findings have suggested that responses to acidosis, arising through a process of selection and adaptation, give cancer cells a competitive advantage over the host. A surge of research efforts has attempted to understand the basis of this advantage and seek ways of exploiting it therapeutically. Here, we review key findings and place these in the context of a mathematical framework. Looking ahead, we highlight areas relating to cellular adaptation, selection, and heterogeneity that merit more research efforts in order to close in on the goal of exploiting tumour acidity in future therapies.",
			"category": 2,
			"name": "Blaszczak Wiktoria,2022"
		},
		{
			"PMID": 34830107,
			"title": "Aging, Bone Marrow and Next-Generation Sequencing (NGS): Recent Advances and Future Perspectives.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Ganguly Payal",
				"Toghill Bradley",
				"Pathak Shelly"
			],
			"DOI": "10.3390/ijms222212225",
			"date": "2021-12-17",
			"PMC": "",
			"citation": "",
			"abstract": "The aging of bone marrow (BM) remains a very imperative and alluring subject, with an ever-increasing interest among fellow scientists. A considerable amount of progress has been made in this field with the established 'hallmarks of aging' and continued efforts to investigate the age-related changes observed within the BM. Inflammaging is considered as a low-grade state of inflammation associated with aging, and whilst the possible mechanisms by which aging occurs are now largely understood, the processes leading to the underlying changes within aged BM remain elusive. The ability to identify these changes and detect such alterations at the genetic level are key to broadening the knowledgebase of aging BM. Next-generation sequencing (NGS) is an important molecular-level application presenting the ability to not only determine genomic base changes but provide transcriptional profiling (RNA-seq), as well as a high-throughput analysis of DNA-protein interactions (ChIP-seq). Utilising NGS to explore the genetic alterations occurring over the aging process within alterative cell types facilitates the comprehension of the molecular and cellular changes influencing the dynamics of aging BM. Thus, this review prospects the current landscape of BM aging and explores how NGS technology is currently being applied within this ever-expanding field of research.",
			"category": 2,
			"name": "Ganguly Payal,2021"
		},
		{
			"PMID": 34824211,
			"title": "Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture.",
			"journal": "Nature communications",
			"authorList": [
				"\u00c1lvarez Eva G",
				"Demeulemeester Jonas",
				"Otero Paula",
				"Jolly Clemency",
				"Garc\u00eda-Souto Daniel",
				"Peque\u00f1o-Valtierra Ana",
				"Zamora Jorge",
				"Tojo Marta",
				"Temes Javier",
				"Baez-Ortega Adrian",
				"Rodriguez-Martin Bernardo",
				"Oitaben Ana",
				"Bruzos Alicia L",
				"Mart\u00ednez-Fern\u00e1ndez M\u00f3nica",
				"Haase Kerstin",
				"Zumalave Sonia",
				"Abal Rosanna",
				"Rodr\u00edguez-Castro Jorge",
				"Rodriguez-Casanova Aitor",
				"Diaz-Lagares Angel",
				"Li Yilong",
				"Raine Keiran M",
				"Butler Adam P",
				"Otero Iago",
				"Ono Atsushi",
				"Aikata Hiroshi",
				"Chayama Kazuaki",
				"Ueno Masaki",
				"Hayami Shinya",
				"Yamaue Hiroki",
				"Maejima Kazuhiro",
				"Blanco Miguel G",
				"Forns Xavier",
				"Rivas Carmen",
				"Ruiz-Ba\u00f1obre Juan",
				"P\u00e9rez-Del-Pulgar Sof\u00eda",
				"Torres-Ruiz Ra\u00fal",
				"Rodriguez-Perales Sandra",
				"Garaigorta Urtzi",
				"Campbell Peter J",
				"Nakagawa Hidewaki",
				"Van Loo Peter",
				"Tubio Jose M C"
			],
			"DOI": "10.1038/s41467-021-26805-8",
			"date": "2022-01-03",
			"PMC": "",
			"citation": "",
			"abstract": "Most cancers are characterized by the somatic acquisition of genomic rearrangements during tumour evolution that eventually drive the oncogenesis. Here, using multiplatform sequencing technologies, we identify and characterize a remarkable mutational mechanism in human hepatocellular carcinoma caused by Hepatitis B virus, by which DNA molecules from the virus are inserted into the tumour genome causing dramatic changes in its configuration, including non-homologous chromosomal fusions, dicentric chromosomes and megabase-size telomeric deletions. This aberrant mutational mechanism, present in at least 8% of all HCC tumours, can provide the driver rearrangements that a cancer clone requires to survive and grow, including loss of relevant tumour suppressor genes. Most of these events are clonal and occur early during liver cancer evolution. Real-time timing estimation reveals some HBV-mediated rearrangements occur as early as two decades before cancer diagnosis. Overall, these data underscore the importance of characterising liver cancer genomes for patterns of HBV integration.",
			"category": 2,
			"name": "\u00c1lvarez Eva G,2022"
		},
		{
			"PMID": 34805272,
			"title": "Biosynthesis of \u03b1-Gal Epitopes (Gal\u03b11-3Gal\u03b21-4GlcNAc-R) and Their Unique Potential in Future \u03b1-Gal Therapies.",
			"journal": "Frontiers in molecular biosciences",
			"authorList": [
				"Galili Uri"
			],
			"DOI": "10.3389/fmolb.2021.746883",
			"date": "2021-11-23",
			"PMC": "",
			"citation": "",
			"abstract": "The \u03b1-gal epitope is a carbohydrate antigen which appeared early in mammalian evolution and is synthesized in large amounts by the glycosylation enzyme \u03b11,3galactosyltransferase (\u03b11,3GT) in non-primate mammals, lemurs, and New-World monkeys. Ancestral Old-World monkeys and apes synthesizing \u03b1-gal epitopes underwent complete extinction 20-30\u00a0million years ago, and their mutated progeny lacking \u03b1-gal epitopes survived. Humans, apes, and Old-World monkeys which evolved from the surviving progeny lack \u03b1-gal epitopes and produce the natural anti-Gal antibody which binds specifically to \u03b1-gal epitopes. Because of this reciprocal distribution of the \u03b1-gal epitope and anti-Gal in mammals, transplantation of organs from non-primate mammals (e.g., pig xenografts) into Old-World monkeys or humans results in hyperacute rejection following anti-Gal binding to \u03b1-gal epitopes on xenograft cells. The ",
			"category": 2,
			"name": "Galili Uri,2021"
		},
		{
			"PMID": 34804850,
			"title": "Systemic treatment of penile squamous cell carcinoma-hurdles and hopes of preclinical models and clinical regimens: a narrative review.",
			"journal": "Translational andrology and urology",
			"authorList": [
				"Thomas Anita",
				"do Canto Alvim Luisa Matos",
				"Rainho Claudia Aparecida",
				"Juengel Eva",
				"Blaheta Roman Alexander",
				"Spiess Philippe E",
				"Rogatto Silvia Regina",
				"Tsaur Igor"
			],
			"DOI": "10.21037/tau-20-945",
			"date": "2022-09-10",
			"PMC": "",
			"citation": "",
			"abstract": "Despite contemporary research efforts, the prognosis of penile squamous cell carcinoma (PeSCC) has not significantly improved over the past decade. Despite frequently encountered patient-related delayed medical consultations impairing outcomes, several other aspects contribute to the lack of advancement in the treatment of this condition. One essential reason is that translational research, a prerequisite for the clinically successful disease management, is still at an early stage in PeSCC as compared to many other malignancies. Preclinical experimental models are indispensable for the evaluation of tumor biology and identification of genomic alterations. However, since neither commercial PeSCC cell lines are available nor xenograft models sustainably established, such analyses are challenging in this field of research. In addition, systemic therapies are less effective and toxic without decisive breakthroughs over recent years. Current systemic management of PeSCC is based on protocols that have been investigated in small series of only up to 30 patients. Thus, there is an unmet medical need for new approaches necessitating research efforts to develop more efficacious systemic strategies. This review aims to highlight the current state of knowledge in the molecular alterations involved in the etiology and ensuing steps for cancer progression, existing preclinical models of translational research, clinically relevant systemic protocols, and ongoing clinical trials.",
			"category": 2,
			"name": "Thomas Anita,2022"
		},
		{
			"PMID": 34772924,
			"title": "MRPS31 loss is a key driver of mitochondrial deregulation and hepatocellular carcinoma aggressiveness.",
			"journal": "Cell death & disease",
			"authorList": [
				"Min Seongki",
				"Lee Young-Kyoung",
				"Hong Jiwon",
				"Park Tae Jun",
				"Woo Hyun Goo",
				"Kwon So Mee",
				"Yoon Gyesoon"
			],
			"DOI": "10.1038/s41419-021-04370-8",
			"date": "2022-03-24",
			"PMC": "",
			"citation": "",
			"abstract": "Deregulated mitochondrial energetics is a metabolic hallmark of cancer cells. However, the causative mechanism of the bioenergetic deregulation is not clear. In this study, we show that somatic copy number alteration (SCNA) of mitoribosomal protein (MRP) genes is a key mechanism of bioenergetic deregulation in hepatocellular carcinoma (HCC). Association analysis between the genomic and transcriptomic profiles of 82 MRPs using The Cancer Genome Atlas-Liver HCC database identified eight key SCNA-dependent MRPs: MRPS31, MRPL10, MRPL21, MRPL15, MRPL13, MRPL55, and DAP3. MRPS31 was the only downregulated MRP harboring a DNA copy number (DCN) loss. MRPS31 loss was associated specifically with the DCN losses of many genes on chromosome 13q. Survival analysis revealed a unique dependency of HCC on the MRPS31 deficiency, showing poor clinical outcome. Subclass prediction analysis using several public classifiers indicated that MRPS31 loss is linked to aggressive HCC phenotypes. By employing hepatoma cell lines with SCNA-dependent MRPS31 expression (JHH5, HepG2, Hep3B, and SNU449), we demonstrated that MRPS31 deficiency is the key mechanism, disturbing the whole mitoribosome assembly. MRPS31 suppression enhanced hepatoma cell invasiveness by augmenting MMP7 and COL1A1 expression. Unlike the action of MMP7 on extracellular matrix destruction, COL1A1 modulated invasiveness via the ZEB1-mediated epithelial-to-mesenchymal transition. Finally, MRPS31 expression further stratified the high COL1A1/DDR1-expressing HCC groups into high and low overall survival, indicating that MRPS31 loss is a promising prognostic marker. SIGNIFICANCE: Our results provide new mechanistic insight for mitochondrial deregulation in HCC and present MRPS31 as a novel biomarker of HCC malignancy.",
			"category": 2,
			"name": "Min Seongki,2022"
		},
		{
			"PMID": 34745228,
			"title": "The Mutagenic Impact of Environmental Exposures in Human Cells and Cancer: Imprints Through Time.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Rosendahl Huber Axel",
				"Van Hoeck Arne",
				"Van Boxtel Ruben"
			],
			"DOI": "10.3389/fgene.2021.760039",
			"date": "2023-09-21",
			"PMC": "",
			"citation": "",
			"abstract": "During life, the DNA of our cells is continuously exposed to external damaging processes. Despite the activity of various repair mechanisms, DNA damage eventually results in the accumulation of mutations in the genomes of our cells. Oncogenic mutations are at the root of carcinogenesis, and carcinogenic agents are often highly mutagenic. Over the past decade, whole genome sequencing data of healthy and tumor tissues have revealed how cells in our body gradually accumulate mutations because of exposure to various mutagenic processes. Dissection of mutation profiles based on the type and context specificities of the altered bases has revealed a variety of signatures that reflect past exposure to environmental mutagens, ranging from chemotherapeutic drugs to genotoxic gut bacteria. In this review, we discuss the latest knowledge on somatic mutation accumulation in human cells, and how environmental mutagenic factors further shape the mutation landscapes of tissues. In addition, not all carcinogenic agents induce mutations, which may point to alternative tumor-promoting mechanisms, such as altered clonal selection dynamics. In short, we provide an overview of how environmental factors induce mutations in the DNA of our healthy cells and how this contributes to carcinogenesis. A better understanding of how environmental mutagens shape the genomes of our cells can help to identify potential preventable causes of cancer.",
			"category": 2,
			"name": "Rosendahl Huber Axel,2023"
		},
		{
			"PMID": 34729943,
			"title": "Discovery of a novel potentially transforming somatic mutation in CSF2RB gene in breast cancer.",
			"journal": "Cancer medicine",
			"authorList": [
				"Rashid Mamoon",
				"Ali Rizwan",
				"Almuzzaini Bader",
				"Song Hao",
				"AlHallaj Alshaimaa",
				"Abdulkarim Al Abdulrahman",
				"Mohamed Baz Omar",
				"Al Zahrani Hajar",
				"Mustafa Sabeena Muhammed",
				"Alharbi Wardah",
				"Hussein Mohamed",
				"Boudjelal Mohamed"
			],
			"DOI": "10.1002/cam4.4106",
			"date": "2022-03-18",
			"PMC": "",
			"citation": "",
			"abstract": "The colony stimulating factor 2 receptor subunit beta (CSF2RB) is the common signaling subunit of the cytokine receptors for IL-3, IL-5, and GM-CSF. Several studies have shown that spontaneous and random mutants of CSF2RB can lead to ligand independence in vitro. To date, no report(s) have been shown for the presence of potentially transforming and oncogenic CSF2RB mutation(s) clinically in cancer patients until the first reported case of a leukemia patient in 2016 harboring a germline-activating mutation (R461C). We combined exome sequencing, pathway analyses, and functional assays to identify novel somatic mutations in KAIMRC1 cells and breast tumor specimen. The patient's peripheral blood mononuclear cell (PBMC) exome served as a germline control in the identification of somatic mutations. Here, we report the discovery of a novel potentially transforming and oncogenic somatic mutation (S230I) in the CSF2RB gene of a breast cancer patient and the cell line, KAIMRC1 established from her breast tumor tissue. KAIMRC1 cells are immortalized and shown to survive and proliferate in ligand starvation condition. Immunoblot analysis showed that mutant CSF2RB signals through JAK2/STAT and PI3K/mTOR pathways in ligand starvation conditions. Screening a small molecule kinase inhibitor library revealed potent JAK2 inhibitors against KAIMRC1 cells. We, for the first time, identified a somatic, potentially transforming, and oncogenic CSF2RB mutation (S230I) in breast cancer patients that seem to be an actionable mutation leading to the development of new therapeutics for breast cancer.",
			"category": 2,
			"name": "Rashid Mamoon,2022"
		},
		{
			"PMID": 34689757,
			"title": "Deep learning for cancer type classification and driver gene identification.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"Zeng Zexian",
				"Mao Chengsheng",
				"Vo Andy",
				"Li Xiaoyu",
				"Nugent Janna Ore",
				"Khan Seema A",
				"Clare Susan E",
				"Luo Yuan"
			],
			"DOI": "10.1186/s12859-021-04400-4",
			"date": "2021-10-26",
			"PMC": "",
			"citation": "",
			"abstract": "Genetic information is becoming more readily available and is increasingly being used to predict patient cancer types as well as their subtypes. Most classification methods thus far utilize somatic mutations as independent features for classification and are limited by study power. We aim to develop a novel method to effectively explore the landscape of genetic variants, including germline variants, and small insertions and deletions for cancer type prediction.",
			"category": 2,
			"name": "Zeng Zexian,2021"
		},
		{
			"PMID": 34683090,
			"title": "Integrated Molecular Characterization to Reveal the Association between Kynurenine 3-Monooxygenase Expression and Tumorigenesis in Human Breast Cancers.",
			"journal": "Journal of personalized medicine",
			"authorList": [
				"Tsang Yuk-Wah",
				"Liao Chi-Hsun",
				"Ke Chiao-Hsu",
				"Tu Chi-Wen",
				"Lin Chen-Si"
			],
			"DOI": "10.3390/jpm11100948",
			"date": "2021-10-26",
			"PMC": "",
			"citation": "",
			"abstract": "Kynurenine 3-monooxygenase (KMO) is overexpressed in several tumors and participates in the progression of breast cancer tumorigenesis, including cancer types such as triple-negative breast cancer (TNBC). This malignant gene is an enzyme in the kynurenine pathway, which is involved in the carcinogenesis of cancer through immune function manipulation. However, it remains unclear whether the role of the KMO contributes to tumorigenesis and immune functions in human breast cancer. In this study, we found that KMO was highly expressed in different types of tumors, especially in invasive ductal breast carcinoma. In addition, KMO expression was positively correlated with the malignant clinical features of patients with breast cancer, such as TNBC and a nodal-positive status, along with patients with a higher Nottingham prognostic index (NPI). Furthermore, the top ten KMO-correlated genes were the chemokines and pro-inflammatory cytokines known to be involved in the progression of various cancers, therefore, KMO may facilitate breast cancers via synergistically regulating inflammatory responses in tumors with these hub genes. Taken together, these findings highlight the tumor-promotion role of KMO in breast cancers and suggest that KMO can serve as a biomarker for prognosis prediction in breast cancer patients.",
			"category": 2,
			"name": "Tsang Yuk-Wah,2021"
		},
		{
			"PMID": 34680378,
			"title": "Oncomine\u2122 Comprehensive Assay v3 vs. Oncomine\u2122 Comprehensive Assay Plus.",
			"journal": "Cancers",
			"authorList": [
				"Vestergaard Lau K",
				"Oliveira Douglas N P",
				"Poulsen Tim S",
				"H\u00f8gdall Claus K",
				"H\u00f8gdall Estrid V"
			],
			"DOI": "10.3390/cancers13205230",
			"date": "2021-10-26",
			"PMC": "",
			"citation": "",
			"abstract": "The usage of next generation sequencing in combination with targeted gene panels has enforced a better understanding of tumor compositions. The identification of key genomic biomarkers underlying a disease are crucial for diagnosis, prognosis, treatment and therapeutic responses. The Oncomine\u2122 Comprehensive Assay v3 (OCAv3) covers 161 cancer-associated genes and is routinely employed to support clinical decision making for a therapeutic course. An improved version, Oncomine\u2122 Comprehensive Assay Plus (OCA-Plus), has been recently developed, covering 501 genes (144 overlapping with OCAv3) in addition to microsatellite instability (MSI) and tumor mutational burden (TMB) assays in one workflow. The validation of MSI and TMB was not addressed in the present study. However, the implementation of new assays must be validated and confirmed across multiple samples before it can be introduced into a clinical setting. Here, we report the comparison of DNA sequencing results from 50 ovarian cancer formalin-fixed, paraffin-embedded samples subjected to OCAv3 and OCA-Plus. A validation assessment of gene mutations identified using OCA-Plus was performed on the 144 overlapping genes and 313,769 intersecting nucleotide positions of the OCAv3 and the OCA-Plus. Our results showed a 91% concordance within variants classified as likely-pathogenic or pathogenic. Moreover, results showed that a region of ",
			"category": 2,
			"name": "Vestergaard Lau K,2021"
		},
		{
			"PMID": 34680347,
			"title": "No Need to Stick Together to Be Connected: Multiple Types of Enhancers' Networking.",
			"journal": "Cancers",
			"authorList": [
				"Vitale Emanuele",
				"Gugnoni Mila",
				"Ciarrocchi Alessia"
			],
			"DOI": "10.3390/cancers13205201",
			"date": "2021-10-26",
			"PMC": "",
			"citation": "",
			"abstract": "The control of gene expression at a transcriptional level requires a widespread landscape of regulatory elements. Central to these regulatory circuits are enhancers (ENHs), which are defined as cis-acting DNA elements able to increase the transcription of a target gene in a distance- and orientation-independent manner. ENHs are not independent functional elements but work in a complex and dynamic cooperative network, constituting the building blocks of multimodular domains of gene expression regulation. The information from each of these elements converges on the target promoter, contributing to improving the precision and sharpness of gene modulation. ENHs' interplay varies in its nature and extent, ranging from an additive to redundant effect depending on contexts. Moving from super-enhancers that drive the high expression levels of identity genes, to shadow-enhancers, whose redundant functions contribute to buffering the variation in gene expression, this review aims to describe the different modalities of ENHs' interaction and their role in the regulation of complex biological processes like cancer development.",
			"category": 2,
			"name": "Vitale Emanuele,2021"
		},
		{
			"PMID": 34663940,
			"title": "Dissecting single-cell genomes through the clonal organoid technique.",
			"journal": "Experimental & molecular medicine",
			"authorList": [
				"Youk Jeonghwan",
				"Kwon Hyun Woo",
				"Kim Ryul",
				"Ju Young Seok"
			],
			"DOI": "10.1038/s12276-021-00680-1",
			"date": "2022-04-04",
			"PMC": "",
			"citation": "",
			"abstract": "The revolution in genome sequencing technologies has enabled the comprehensive detection of genomic variations in human cells, including inherited germline polymorphisms, de novo mutations, and postzygotic mutations. When these technologies are combined with techniques for isolating and expanding single-cell DNA, the landscape of somatic mosaicism in an individual body can be systematically revealed at a single-cell resolution. Here, we summarize three strategies (whole-genome amplification, microdissection of clonal patches in the tissue, and in vitro clonal expansion of single cells) that are currently applied for single-cell mutational analyses. Among these approaches, in vitro clonal expansion, particularly via adult stem cell-derived organoid culture technologies, yields the most sensitive and precise catalog of somatic mutations in single cells. Moreover, because it produces living mutant cells, downstream validation experiments and multiomics profiling are possible. Through the synergistic combination of organoid culture and genome sequencing, researchers can track genome changes at a single-cell resolution, which will lead to new discoveries that were previously impossible.",
			"category": 2,
			"name": "Youk Jeonghwan,2022"
		},
		{
			"PMID": 34642306,
			"title": "Genomic comparison between cerebrospinal fluid and primary tumor revealed the genetic events associated with brain metastasis in lung adenocarcinoma.",
			"journal": "Cell death & disease",
			"authorList": [
				"Deng Zhiyong",
				"Cui Liang",
				"Li Pansong",
				"Ren Nianjun",
				"Zhong Zhe",
				"Tang Zhi",
				"Wang Lei",
				"Gong Jianwu",
				"Cheng Haofeng",
				"Guan Yanfang",
				"Yi Xin",
				"Xia Xuefeng",
				"Zhou Rongrong",
				"He Zhengwen"
			],
			"DOI": "10.1038/s41419-021-04223-4",
			"date": "2022-02-02",
			"PMC": "",
			"citation": "",
			"abstract": "Lung adenocarcinoma (LUAD) is most common pathological type of lung cancer. LUAD with brain metastases (BMs) usually have poor prognosis. To identify the potential genetic factors associated with BM, a genomic comparison for BM cerebrospinal fluid (CSF) and primary lung tumor samples obtained from 1082 early- and late-stage LUAD patients was performed. We found that single nucleotide variation (SNV) of EGFR was highly enriched in CSF (87% of samples). Compared with the other primary lung tissues, copy number gain of EGFR (27%), CDK4 (11%), PMS2 (11%), MET (10%), IL7R (8%), RICTOR (7%), FLT4 (5%), and FGFR4 (4%), and copy number loss of CDKN2A (28%) and CDKN2B (18%) were remarkably more frequent in CSF samples. CSF had significantly lower tumor mutation burden (TMB) level but more abundant copy number variant. It was also found that the relationships among co-occurrent and mutually exclusive genes were dynamically changing with LUAD development. Additionally, CSF (97% of samples) harbored more abundant targeted drugs related driver and fusion genes. The signature 15 associated with defective DNA mismatch repair (dMMR) was only identified in the CSF group. Cancer associated pathway analysis further revealed that ErbB (95%) and cell cycle (84%) were unique pathways in CSF samples. The tumor evolution analysis showed that CSF carried significantly fewer clusters, but subclonal proportion of EGFR was remarkably increased with tumor progression. Collectively, CSF sequencing showed unique genomic characteristics and the intense copy number instability associated with cell cycle disorder and dMMR might be the crucial genetic factors in BM of LUAD.",
			"category": 2,
			"name": "Deng Zhiyong,2022"
		},
		{
			"PMID": 34641463,
			"title": "Comparative Study of Bioactivity and Safety Evaluation of Ethanolic Extracts of ",
			"journal": "Molecules (Basel, Switzerland)",
			"authorList": [
				"Kim Jun Gu",
				"Lim Jae Jung",
				"You Ji Sang",
				"Kwon Hyeok Jun",
				"Lim Heung Bin"
			],
			"DOI": "10.3390/molecules26195919",
			"date": "2021-11-15",
			"PMC": "",
			"citation": "",
			"abstract": "The fruit and pericarp of ",
			"category": 2,
			"name": "Kim Jun Gu,2021"
		},
		{
			"PMID": 34637327,
			"title": "Somatic Mosaicism in Biology and Disease.",
			"journal": "Annual review of physiology",
			"authorList": [
				"Ogawa Hayato",
				"Horitani Keita",
				"Izumiya Yasuhiro",
				"Sano Soichi"
			],
			"DOI": "10.1146/annurev-physiol-061121-040048",
			"date": "2022-03-23",
			"PMC": "",
			"citation": "",
			"abstract": "Contrary to earlier beliefs, every cell in the individual is genetically different due to somatic mutations. Consequently, tissues become a mixture of cells with distinct genomes, a phenomenon termed somatic mosaicism. Recent advances in genome sequencing technology have unveiled possible causes of mutations and how they shape the unique mutational landscape of the tissues. Moreover, the analysis of sequencing data in combination with clinical information has revealed the impacts of somatic mosaicism on disease processes. In this review, we discuss somatic mosaicism in various tissues and its clinical implications for human disease.",
			"category": 2,
			"name": "Ogawa Hayato,2022"
		},
		{
			"PMID": 34629898,
			"title": "The Mutation and Expression Level of LRP1B are Associated with Immune Infiltration and Prognosis in Hepatocellular Carcinoma.",
			"journal": "International journal of general medicine",
			"authorList": [
				"Wang Mengmeng",
				"Xiong Zhifan"
			],
			"DOI": "10.2147/IJGM.S333390",
			"date": "2022-04-27",
			"PMC": "",
			"citation": "",
			"abstract": "This study aimed to explore the expression level and mutation of LRP1B in hepatocellular carcinoma (HCC) and to analyse the relationship between its prognostic value and immune invasion.",
			"category": 2,
			"name": "Wang Mengmeng,2022"
		},
		{
			"PMID": 34624550,
			"title": "Common Postzygotic Mutational Signatures in Healthy Adult Tissues Related to Embryonic Hypoxia.",
			"journal": "Genomics, proteomics & bioinformatics",
			"authorList": [
				"Hong Yaqiang",
				"Zhang Dake",
				"Zhou Xiangtian",
				"Chen Aili",
				"Abliz Amir",
				"Bai Jian",
				"Wang Liang",
				"Hu Qingtao",
				"Gong Kenan",
				"Guan Xiaonan",
				"Liu Mengfei",
				"Zheng Xinchang",
				"Lai Shujuan",
				"Qu Hongzhu",
				"Zhao Fuxin",
				"Hao Shuang",
				"Wu Zhen",
				"Cai Hong",
				"Hu Shaoyan",
				"Ma Yue",
				"Zhang Junting",
				"Ke Yang",
				"Wang Qian-Fei",
				"Chen Wei",
				"Zeng Changqing"
			],
			"DOI": "10.1016/j.gpb.2021.09.005",
			"date": "2022-09-26",
			"PMC": "",
			"citation": "",
			"abstract": "Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors. Here, we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals. In blood, sperm, and muscle cells, we resolved three common types of mutational signatures. Signatures A and B represent clock-like mutational processes, and the polymorphisms of epigenetic regulation genes influence the proportion of signature B in mutation profiles. Notably, signature C, characterized by C>T transitions at GpCpN sites, tends to be a feature of diverse normal tissues. Mutations of this type are likely to occur early during embryonic development, supported by their relatively high allelic frequencies, presence in multiple tissues, and decrease in occurrence with age. Almost none of the public datasets for tumors feature this signature, except for 19.6% of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1 (HIF-1) signaling pathway. Moreover, the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1\u03b1. Thus, embryonic hypoxia may explain this novel signature across multiple normal tissues. Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C>T transitions at GpCpN sites; and individuals' genetic background may also influence their postzygotic mutation profiles.",
			"category": 2,
			"name": "Hong Yaqiang,2022"
		},
		{
			"PMID": 34598711,
			"title": "Comprehensive characterization and clinical relevance of the SWI/SNF copy number aberrations across human cancers.",
			"journal": "Hereditas",
			"authorList": [
				"Xing Zhiwei",
				"Ma Buhuan",
				"Sun Weiting",
				"Sun Yimin",
				"Liu Caixia"
			],
			"DOI": "10.1186/s41065-021-00203-y",
			"date": "2022-01-13",
			"PMC": "",
			"citation": "",
			"abstract": "Alterations in genes encoding chromatin regulatory proteins are prevalent in cancers and may confer oncogenic properties and molecular changes linked to therapy resistance. However, the impact of copy number alterations (CNAs) of the SWItch/Sucrose NonFermentable (SWI/SNF) complex on the oncogenic and immunologic properties has not been systematically explored across human cancer types.",
			"category": 2,
			"name": "Xing Zhiwei,2022"
		},
		{
			"PMID": 34561899,
			"title": "Bioengineering Approaches for the Advanced Organoid Research.",
			"journal": "Advanced materials (Deerfield Beach, Fla.)",
			"authorList": [
				"Yi Sang Ah",
				"Zhang Yixiao",
				"Rathnam Christopher",
				"Pongkulapa Thanapat",
				"Lee Ki-Bum"
			],
			"DOI": "10.1002/adma.202007949",
			"date": "2022-02-23",
			"PMC": "",
			"citation": "",
			"abstract": "Recent advances in 3D cell culture technology have enabled scientists to generate stem cell derived organoids that recapitulate the structural and functional characteristics of native organs. Current organoid technologies have been striding toward identifying the essential factors for controlling the processes involved in organoid development, including physical cues and biochemical signaling. There is a growing demand for engineering dynamic niches characterized by conditions that resemble in vivo organogenesis to generate reproducible and reliable organoids for various applications. Innovative biomaterial-based and advanced engineering-based approaches have been incorporated into conventional organoid culture methods to facilitate the development of organoid research. The recent advances in organoid engineering, including extracellular matrices and genetic modulation, are comprehensively summarized to pinpoint the parameters critical for organ-specific patterning. Moreover, perspective trends in developing tunable organoids in response to exogenous and endogenous cues are discussed for next-generation developmental studies, disease modeling, and therapeutics.",
			"category": 2,
			"name": "Yi Sang Ah,2022"
		},
		{
			"PMID": 34560840,
			"title": "Identification of driver genes based on gene mutational effects and network centrality.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"Tang Yun-Yun",
				"Wei Pi-Jing",
				"Zhao Jian-Ping",
				"Xia Junfeng",
				"Cao Rui-Fen",
				"Zheng Chun-Hou"
			],
			"DOI": "10.1186/s12859-021-04377-0",
			"date": "2021-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "As one of the deadliest diseases in the world, cancer is driven by a few somatic mutations that disrupt the normal growth of cells, and leads to abnormal proliferation and tumor development. The vast majority of somatic mutations did not affect the occurrence and development of cancer; thus, identifying the mutations responsible for tumor occurrence and development is one of the main targets of current cancer treatments.",
			"category": 2,
			"name": "Tang Yun-Yun,2021"
		},
		{
			"PMID": 34522461,
			"title": "DNA damage in cancer development: special implications in viral oncogenesis.",
			"journal": "American journal of cancer research",
			"authorList": [
				"Katerji Meghri",
				"Duerksen-Hughes Penelope J"
			],
			"DOI": "",
			"date": "2024-04-03",
			"PMC": "",
			"citation": "",
			"abstract": "DNA lesions arise from a combination of physiological/metabolic sources and exogenous environmental influences. When left unrepaired, these alterations accumulate in the cells and can give rise to mutations that change the function of important proteins (i.e. tumor suppressors, oncoproteins), or cause chromosomal rearrangements (i.e. gene fusions) that also result in the deregulation of key cellular molecules. Progressive acquisition of such genetic changes promotes uncontrolled cell proliferation and evasion of cell death, and hence plays a key role in carcinogenesis. Another less-studied consequence of DNA damage accumulating in the host genome is the integration of oncogenic DNA viruses such as Human papillomavirus, Merkel cell polyomavirus, and Hepatitis B virus. This critical step of viral-induced carcinogenesis is thought to be particularly facilitated by DNA breaks in both viral and host genomes. Therefore, the impact of DNA damage on carcinogenesis is magnified in the case of such oncoviruses via the additional effect of increasing integration frequency. In this review, we briefly present the various endogenous and exogenous factors that cause different types of DNA damage. Next, we discuss the contribution of these lesions in cancer development. Finally, we examine the amplified effect of DNA damage in viral-induced oncogenesis and summarize the limited data existing in the literature related to DNA damage-induced viral integration. To conclude, additional research is needed to assess the DNA damage pathways involved in the transition from viral infection to cancer. Discovering that a certain DNA damaging agent increases the likelihood of viral integration will enable the development of prophylactic and therapeutic strategies designed specifically to prevent such integration, with an ultimate goal of reducing or eliminating these viral-induced malignancies.",
			"category": 2,
			"name": "Katerji Meghri,2024"
		},
		{
			"PMID": 34512722,
			"title": "Tumor Expression Profile Analysis Developed and Validated a Prognostic Model Based on Immune-Related Genes in Bladder Cancer.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Dong Bingqi",
				"Liang Jiaming",
				"Li Ding",
				"Song Wenping",
				"Zhao Shiming",
				"Ma Yongkang",
				"Song Jinbo",
				"Zhu Mingkai",
				"Yang Tiejun"
			],
			"DOI": "10.3389/fgene.2021.696912",
			"date": "2021-09-14",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "Dong Bingqi,2021"
		},
		{
			"PMID": 34512202,
			"title": "Clear Cell Papillary Renal Cell Carcinoma Shares Distinct Molecular Characteristics and may be Significantly Associated With Higher Risk of Developing Second Primary Malignancy.",
			"journal": "Pathology oncology research : POR",
			"authorList": [
				"Tian Xi",
				"Xu Wen-Hao",
				"Wu Jun-Long",
				"Gan Hua-Lei",
				"Wang Hong-Kai",
				"Gu Wei-Jie",
				"Qu Yuan-Yuan",
				"Zhang Hai-Liang",
				"Ye Ding-Wei"
			],
			"DOI": "10.3389/pore.2021.1609809",
			"date": "2022-02-10",
			"PMC": "",
			"citation": "",
			"abstract": "Traditionally, clear cell papillary renal cell carcinoma (ccpRCC) was considered to share similar molecular and histological characteristics with clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC). Here we aimed to identify somatic and germline variants of ccpRCC. For this purpose, we conducted whole-exome sequencing to detect somatic variants in the tissues of 18 patients with pathologically confirmed ccpRCC, who underwent surgical treatment at Fudan University Shanghai Cancer Center. Targeted sequencing was conducted to detect germline variants in paired tumor or normal tissues or blood. Somatic and germline variants of ccRCC and Renal cell carcinoma included in The Cancer Genome Atlas data and other published data were analyzed as well. The molecular profiles of ccpRCC, ccRCC and pRCC were compared. Among the 387 somatic variants identified, ",
			"category": 2,
			"name": "Tian Xi,2022"
		},
		{
			"PMID": 34504716,
			"title": "Identification of Common Driver Gene Modules and Associations between Cancers through Integrated Network Analysis.",
			"journal": "Global challenges (Hoboken, NJ)",
			"authorList": [
				"Gao Bo",
				"Zhao Yue",
				"Gao Yonghang",
				"Li Guojun",
				"Wu Ling-Yun"
			],
			"DOI": "10.1002/gch2.202100006",
			"date": "2023-09-20",
			"PMC": "",
			"citation": "",
			"abstract": "High-throughput biological data has created an unprecedented opportunity for illuminating the mechanisms of tumor emergence and evolution. An important and challenging problem in deciphering cancers is to investigate the commonalities of driver genes and pathways and the associations between cancers. Aiming at this problem, a tool ComCovEx is developed to identify common cancer driver gene modules between two cancers by searching for the candidates in local signaling networks using an exclusivity-coverage iteration strategy and outputting those with significant coverage and exclusivity for both cancers. The associations of the cancer pairs are further evaluated by Fisher's exact test. Being applied to 11 TCGA cancer datasets, ComCovEx identifies 13 significantly associated cancer pairs with plenty of biologically significant common gene modules. The novel results of cancer relationship and common gene modules reveal the relevant pathological basis of different cancer types and provide new clues to diagnosis and drug treatment in associated cancers.",
			"category": 2,
			"name": "Gao Bo,2023"
		},
		{
			"PMID": 34485698,
			"title": "Novel insights into the pathogenesis and treatment of NRAS mutant melanoma.",
			"journal": "Expert review of precision medicine and drug development",
			"authorList": [
				"Zhao Jeffrey",
				"Galvez Carlos",
				"Beckermann Kathryn Eby",
				"Johnson Douglas B",
				"Sosman Jeffrey A"
			],
			"DOI": "10.1080/23808993.2021.1938545",
			"date": "2024-06-07",
			"PMC": "",
			"citation": "",
			"abstract": "NRAS was the first mutated oncogene identified in melanoma and is currently the second most common driver mutation in this malignancy. For patients with NRAS",
			"category": 2,
			"name": "Zhao Jeffrey,2024"
		},
		{
			"PMID": 34439360,
			"title": "Nanotechnology in Tumor Biomarker Detection: The Potential of Liganded Nanoclusters as Nonlinear Optical Contrast Agents for Molecular Diagnostics of Cancer.",
			"journal": "Cancers",
			"authorList": [
				"Combes Guillaume F",
				"Vu\u010dkovi\u0107 Ana-Marija",
				"Peri\u0107 Bakuli\u0107 Martina",
				"Antoine Rodolphe",
				"Bona\u010di\u0107-Koutecky Vlasta",
				"Trajkovi\u0107 Katarina"
			],
			"DOI": "10.3390/cancers13164206",
			"date": "2023-11-07",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is one of the leading causes of premature death, and, as such, it can be prevented by developing strategies for early and accurate diagnosis. Cancer diagnostics has evolved from the macroscopic detection of malignant tissues to the fine analysis of tumor biomarkers using personalized medicine approaches. Recently, various nanomaterials have been introduced into the molecular diagnostics of cancer. This has resulted in a number of tumor biomarkers that have been detected in vitro and in vivo using nanodevices and corresponding imaging techniques. Atomically precise ligand-protected noble metal quantum nanoclusters represent an interesting class of nanomaterials with a great potential for the detection of tumor biomarkers. They are characterized by high biocompatibility, low toxicity, and suitability for controlled functionalization with moieties specifically recognizing tumor biomarkers. Their non-linear optical properties are of particular importance as they enable the visualization of nanocluster-labeled tumor biomarkers using non-linear optical techniques such as two-photon-excited fluorescence and second harmonic generation. This article reviews liganded nanoclusters among the different nanomaterials used for molecular cancer diagnosis and the relevance of this new class of nanomaterials as non-linear optical probe and contrast agents.",
			"category": 2,
			"name": "Combes Guillaume F,2023"
		},
		{
			"PMID": 34439334,
			"title": "Insights into the Evolving Roles of Circular RNAs in Cancer.",
			"journal": "Cancers",
			"authorList": [
				"Harper Katherine Louise",
				"Mottram Timothy James",
				"Whitehouse Adrian"
			],
			"DOI": "10.3390/cancers13164180",
			"date": "2024-02-14",
			"PMC": "",
			"citation": "",
			"abstract": "The majority of RNAs transcribed from the human genome have no coding capacity and are termed non-coding RNAs (ncRNAs). It is now widely accepted that ncRNAs play key roles in cell regulation and disease. Circular RNAs (circRNAs) are a form of ncRNA, characterised by a closed loop structure with roles as competing endogenous RNAs (ceRNAs), protein interactors and transcriptional regulators. Functioning as key cellular regulators, dysregulated circRNAs have a significant impact on disease progression, particularly in cancer. Evidence is emerging of specific circRNAs having oncogenic or tumour suppressive properties. The multifaceted nature of circRNA function may additionally have merit as a novel therapeutic target, either in treatment or as a novel biomarker, due to their cell-and disease-state specific expression and long-term stability. This review aims to summarise current findings on how circRNAs are dysregulated in cancer, the effects this has on disease progression, and how circRNAs may be targeted or utilised as future potential therapeutic options.",
			"category": 2,
			"name": "Harper Katherine Louise,2024"
		},
		{
			"PMID": 34433967,
			"title": "Clonal dynamics in early human embryogenesis inferred from somatic mutation.",
			"journal": "Nature",
			"authorList": [
				"Park Seongyeol",
				"Mali Nanda Maya",
				"Kim Ryul",
				"Choi Jeong-Woo",
				"Lee Junehawk",
				"Lim Joonoh",
				"Park Jung Min",
				"Park Jung Woo",
				"Kim Donghyun",
				"Kim Taewoo",
				"Yi Kijong",
				"Choi June Hyug",
				"Kwon Seong Gyu",
				"Hong Joo Hee",
				"Youk Jeonghwan",
				"An Yohan",
				"Kim Su Yeon",
				"Oh Soo A",
				"Kwon Youngoh",
				"Hong Dongwan",
				"Kim Moonkyu",
				"Kim Dong Sun",
				"Park Ji Young",
				"Oh Ji Won",
				"Ju Young Seok"
			],
			"DOI": "10.1038/s41586-021-03786-8",
			"date": "2021-10-22",
			"PMC": "",
			"citation": "",
			"abstract": "Cellular dynamics and fate decision in early human embryogenesis remain largely unknown owing to the challenges of performing studies in human embryos",
			"category": 2,
			"name": "Park Seongyeol,2021"
		},
		{
			"PMID": 34433963,
			"title": "Extensive phylogenies of human development inferred from somatic mutations.",
			"journal": "Nature",
			"authorList": [
				"Coorens Tim H H",
				"Moore Luiza",
				"Robinson Philip S",
				"Sanghvi Rashesh",
				"Christopher Joseph",
				"Hewinson James",
				"Przybilla Moritz J",
				"Lawson Andrew R J",
				"Spencer Chapman Michael",
				"Cagan Alex",
				"Oliver Thomas R W",
				"Neville Matthew D C",
				"Hooks Yvette",
				"Noorani Ayesha",
				"Mitchell Thomas J",
				"Fitzgerald Rebecca C",
				"Campbell Peter J",
				"Martincorena I\u00f1igo",
				"Rahbari Raheleh",
				"Stratton Michael R"
			],
			"DOI": "10.1038/s41586-021-03790-y",
			"date": "2021-11-04",
			"PMC": "",
			"citation": "",
			"abstract": "Starting from the zygote, all cells in the human body continuously acquire mutations. Mutations shared between different cells imply a common progenitor and are thus naturally occurring markers for lineage tracing",
			"category": 2,
			"name": "Coorens Tim H H,2021"
		},
		{
			"PMID": 34411908,
			"title": "Significance and limitations of the use of next-generation sequencing technologies for detecting mutational signatures.",
			"journal": "DNA repair",
			"authorList": [
				"Abbasi Ammal",
				"Alexandrov Ludmil B"
			],
			"DOI": "10.1016/j.dnarep.2021.103200",
			"date": "2022-02-04",
			"PMC": "",
			"citation": "",
			"abstract": "Next generation sequencing technologies (NGS) have been critical in characterizing the genomic landscape and untangling the genetic heterogeneity of human cancer. Since its advent, NGS has played a pivotal role in identifying the patterns of somatic mutations imprinted on cancer genomes and in deciphering the signatures of the mutational processes that have generated these patterns. Mutational signatures serve as phenotypic molecular footprints of exposures to environmental factors as well as deficiency and infidelity of DNA replication and repair pathways. Since the first roadmap of mutational signatures in human cancer was generated from whole-genome and whole-exome sequencing data, there has been a growing interest to extract mutational signatures from other NGS technologies such as targeted panel sequencing, RNA sequencing, single-cell sequencing, duplex sequencing, reduced representation sequencing, and long-read sequencing. Many of these technologies have their inherent sequencing biases and produce technical artifacts that can confound the extraction of reliable and interpretable mutational signatures. In this review, we highlight the relevance, limitations, and prospects of using different NGS technologies for examining mutational patterns and for deciphering mutational signatures.",
			"category": 2,
			"name": "Abbasi Ammal,2022"
		},
		{
			"PMID": 34409036,
			"title": "Application of Ovarian Cancer Organoids in Precision Medicine: Key Challenges and Current Opportunities.",
			"journal": "Frontiers in cell and developmental biology",
			"authorList": [
				"Yang Jiani",
				"Huang Shan",
				"Cheng Shanshan",
				"Jin Yue",
				"Zhang Nan",
				"Wang Yu"
			],
			"DOI": "10.3389/fcell.2021.701429",
			"date": "2021-08-20",
			"PMC": "",
			"citation": "",
			"abstract": "Ovarian cancer (OC) is the leading cause of death among gynecologic malignances. Over the past decades, human-derived models have advanced from monolayer cell cultures to three-dimensional (3D) organoids that could faithfully recapitulate biological characteristics and tumor heterogeneity of primary tissues. As a complement of previous studies based on cell lines or xenografts, organoids provide a 3D platform for mutation-carcinogenesis modeling, high-throughput drug screening, genetic engineering, and biobanking, which might fulfill the gap between basic research and clinical practice. Stepwise, cutting-edge bioengineering techniques of organoid-on-a-chip and 3D bioprinting might converge current challenges and contribute to personalized therapy. We comprehensively reviewed the advantages, challenges, and translational potential of OC organoids. Undeniably, organoids represent an excellent near-physiological platform for OC, paving the way for precision medicine implementation. Future efforts will doubtlessly bring this innovative technique from bench to bedside.",
			"category": 2,
			"name": "Yang Jiani,2021"
		},
		{
			"PMID": 34406439,
			"title": "[The molecular tumor board].",
			"journal": "Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen",
			"authorList": [
				"Missios Pavlos",
				"Beha Janina",
				"Bitzer Michael",
				"Malek Nisar P"
			],
			"DOI": "10.1007/s00104-021-01487-6",
			"date": "2021-10-26",
			"PMC": "",
			"citation": "",
			"abstract": "New diagnostic tools in the field of oncology that became available with introduction of the next generation sequencing call for adjustments in the current clinical workflow. To ensure correct interpretation, newly collected data need to be processed and categorized properly. Thus, current experts in oncology need to be trained and new experts from other fields need to be recruited.",
			"category": 2,
			"name": "Missios Pavlos,2021"
		},
		{
			"PMID": 34372868,
			"title": "Impact of DNA double-strand breaks on pancreaticobiliary maljunction carcinogenesis.",
			"journal": "Diagnostic pathology",
			"authorList": [
				"Kuraishi Yasuhiro",
				"Uehara Takeshi",
				"Muraki Takashi",
				"Iwaya Mai",
				"Kinugawa Yasuhiro",
				"Nakajima Tomoyuki",
				"Watanabe Takayuki",
				"Miyagawa Yusuke",
				"Umemura Takeji"
			],
			"DOI": "10.1186/s13000-021-01132-0",
			"date": "2022-01-10",
			"PMC": "",
			"citation": "",
			"abstract": "Pancreaticobiliary maljunction (PBM) is a condition characterized by chronic inflammation due to refluxed pancreatic juice into the biliary tract that is associated with an elevated risk of biliary tract cancer. DNA double-strand breaks (DSBs) are considered the most serious form of DNA damage. DSBs are provoked by inflammatory cell damage and are recognized as an important oncogenic event in several cancers. This study used \u03b3-H2AX, an established marker of DSB formation, to evaluate the impact of DNA damage on carcinogenesis in PBM.",
			"category": 2,
			"name": "Kuraishi Yasuhiro,2022"
		},
		{
			"PMID": 34359827,
			"title": "Transcending toward Advanced 3D-Cell Culture Modalities: A Review about an Emerging Paradigm in Translational Oncology.",
			"journal": "Cells",
			"authorList": [
				"Farhat Joviana",
				"Pandey Ishan",
				"AlWahsh Mohammad"
			],
			"DOI": "10.3390/cells10071657",
			"date": "2021-10-26",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a disorder characterized by an uncontrollable overgrowth and a fast-moving spread of cells from a localized tissue to multiple organs of the body, reaching a metastatic state. Throughout years, complexity of cancer progression and invasion, high prevalence and incidence, as well as the high rise in treatment failure cases leading to a poor patient prognosis accounted for continuous experimental investigations on animals and cellular models, mainly with 2D- and 3D-cell culture. Nowadays, these research models are considered a main asset to reflect the physiological events in many cancer types in terms of cellular characteristics and features, replication and metastatic mechanisms, metabolic pathways, biomarkers expression, and chemotherapeutic agent resistance. In practice, based on research perspective and hypothesis, scientists aim to choose the best model to approach their understanding and to prove their hypothesis. Recently, 3D-cell models are seen to be highly incorporated as a crucial tool for reflecting the true cancer cell microenvironment in pharmacokinetic and pharmacodynamics studies, in addition to the intensity of anticancer drug response in pharmacogenomics trials. Hence, in this review, we shed light on the unique characteristics of 3D cells favoring its promising usage through a comparative approach with other research models, specifically 2D-cell culture. Plus, we will discuss the importance of 3D models as a direct reflector of the intrinsic cancer cell environment with the newest multiple methods and types available for 3D-cells implementation.",
			"category": 2,
			"name": "Farhat Joviana,2021"
		},
		{
			"PMID": 34359771,
			"title": "Glutamatergic Signaling a Therapeutic Vulnerability in Melanoma.",
			"journal": "Cancers",
			"authorList": [
				"Eddy Kevinn",
				"Chen Suzie"
			],
			"DOI": "10.3390/cancers13153874",
			"date": "2023-09-20",
			"PMC": "",
			"citation": "",
			"abstract": "Like other cancers, melanomas are associated with the hyperactivation of two major cell signaling cascades, the MAPK and PI3K/AKT pathways. Both pathways are activated by numerous genes implicated in the development and progression of melanomas such as mutated ",
			"category": 2,
			"name": "Eddy Kevinn,2023"
		},
		{
			"PMID": 34339016,
			"title": "Current Trends of Immunotherapy in the Treatment of Cutaneous Melanoma: A Review.",
			"journal": "Dermatology and therapy",
			"authorList": [
				"Naik Piyu Parth"
			],
			"DOI": "10.1007/s13555-021-00583-z",
			"date": "2023-11-07",
			"PMC": "",
			"citation": "",
			"abstract": "Cutaneous melanoma remains a severe public health threat, with annual incidence increasing slowly but steadily over 4 decades. While early-stage melanomas can typically be treated with complete surgical excision with favorable results, the development of metastatic cancer, which is related to a lower survival rate, is linked to the primary tumor's rising stage and other high-risk features. Even though the first discoveries of an immunological anti-tumor response were published about a century ago, immunotherapy has only been a feasible therapeutic option for cutaneous melanoma in the last 30\u00a0years. Nonetheless, for the treatment of various cancers, including metastatic melanoma, the area of cancer immunotherapy has made significant progress in the last decade. As a result, melanoma continues to be the subject of several preclinical and clinical investigations to further understand cancer immunobiology and test different tumor immunotherapies. Immunotherapy's resistance to radiation and cytotoxic chemotherapy is one of its most distinguishing features. Furthermore, the discovery of biomarkers will aid in patient stratification and management during immunotherapy treatment.\u00a0In this article, we discuss current knowledge and recent developments in immune-mediated therapy of melanoma.",
			"category": 2,
			"name": "Naik Piyu Parth,2023"
		},
		{
			"PMID": 34307451,
			"title": "Comprehensive Molecular Analyses of a Novel Mutational Signature Classification System with Regard to Prognosis, Genomic Alterations, and Immune Landscape in Glioma.",
			"journal": "Frontiers in molecular biosciences",
			"authorList": [
				"Liu Zaoqu",
				"Lu Taoyuan",
				"Wang Libo",
				"Liu Long",
				"Li Lifeng",
				"Han Xinwei"
			],
			"DOI": "10.3389/fmolb.2021.682084",
			"date": "2021-07-27",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "Liu Zaoqu,2021"
		},
		{
			"PMID": 34306573,
			"title": "Using bioinformatics approaches to investigate driver genes and identify BCL7A as a prognostic gene in colorectal cancer.",
			"journal": "Computational and structural biotechnology journal",
			"authorList": [
				"Chao Jeffrey Yung-Chuan",
				"Chang Hsin-Chuan",
				"Jiang Jeng-Kai",
				"Yang Chih-Yung",
				"Chen Fang-Hsin",
				"Lai Yo-Liang",
				"Lin Wen-Jen",
				"Li Chia-Yang",
				"Wang Shu-Chi",
				"Yang Muh-Hwa",
				"Lin Yu-Feng",
				"Cheng Wei-Chung"
			],
			"DOI": "10.1016/j.csbj.2021.06.044",
			"date": "2021-07-27",
			"PMC": "",
			"citation": "",
			"abstract": "Colorectal cancer (CRC) results from the uncontrolled growth of cells in the colon, rectum, or appendix. The 5-year relative survival rate for patients with CRC is 65% and is correlated with the stage at diagnosis (being 91% for stage I at diagnosis versus 12% for stage IV). This study aimed to identify CRC driver genes to assist in the design of a cancer panel to detect gene mutations during clinical early-stage screening and identify genes for use in prognostic assessments and the evaluation of appropriate treatment options. First, we utilized bioinformatics approaches to analyze 354 paired sequencing profiles from The Cancer Genome Atlas (TCGA) to identify CRC driver genes and analyzed the sequencing profiles of 38 patients with >5\u00a0years of follow-up data to search for prognostic genes. The results revealed eight driver genes and ten prognostic genes. Next, the presence of the identified gene mutations was verified using tissue and blood samples from Taiwanese CRC patients. The results showed that the set identified gene mutations provide high coverage for driver gene screening, and ",
			"category": 2,
			"name": "Chao Jeffrey Yung-Chuan,2021"
		},
		{
			"PMID": 34296799,
			"title": "Loss of smarcad1a accelerates tumorigenesis of malignant peripheral nerve sheath tumors in zebrafish.",
			"journal": "Genes, chromosomes & cancer",
			"authorList": [
				"Han Han",
				"Jiang Guangzhen",
				"Kumari Rashmi",
				"Silic Martin R",
				"Owens Jake L",
				"Hu Chang-Deng",
				"Mittal Suresh K",
				"Zhang GuangJun"
			],
			"DOI": "10.1002/gcc.22983",
			"date": "2022-02-24",
			"PMC": "",
			"citation": "",
			"abstract": "Malignant peripheral nerve sheath tumors (MPNSTs) are a type of sarcoma that generally originates from Schwann cells. The prognosis for this type of malignancy is relatively poor due to complicated genetic alterations and the lack of specific targeted therapy. Chromosome fragment 4q22-23 is frequently deleted in MPNSTs and other human tumors, suggesting tumor suppressor genes may reside in this region. Here, we provide evidence that SMARCAD1, a known chromatin remodeler, is a novel tumor suppressor gene located in 4q22-23. We identified two human homologous smarcad1 genes (smarcad1a and smarcad1b) in zebrafish, and both genes share overlapping expression patterns during embryonic development. We demonstrated that two smarcad1a loss-of-function mutants, sa1299 and p403, can accelerate MPNST tumorigenesis in the tp53 mutant background, suggesting smarcad1a is a bona fide tumor suppressor gene for MPNSTs. Moreover, we found that DNA double-strand break (DSB) repair might be compromised in both mutants compared to wildtype zebrafish, as indicated by pH2AX, a DNA DSB marker. In addition, both SMARCAD1 gene knockdown and overexpression in human cells were able to inhibit tumor growth and displayed similar DSB repair responses, suggesting proper SMARCAD1 gene expression level or gene dosage is critical for cell growth. Given that mutations of SMARCAD1 sensitize cells to poly ADP ribose polymerase inhibitors in yeast and the human U2OS osteosarcoma cell line, the identification of SMARCAD1 as a novel tumor suppressor gene might contribute to the development of new cancer therapies for MPNSTs.",
			"category": 2,
			"name": "Han Han,2022"
		},
		{
			"PMID": 34287479,
			"title": "Germline and Somatic mutations in postmenopausal breast cancer patients.",
			"journal": "Clinics (Sao Paulo, Brazil)",
			"authorList": [
				"Nagy Tauana Rodrigues",
				"Maistro Simone",
				"Encinas Giselly",
				"Katayama Maria Lucia Hirata",
				"Pereira Glaucia Fernanda de Lima",
				"Gaburo-J\u00fanior Nelson",
				"Franco Lucas Augusto Moyses",
				"Gouv\u00eaa Ana Carolina Ribeiro Chaves de",
				"Diz Maria Del Pilar Estevez",
				"Leite Luiz Antonio Senna",
				"Folgueira Maria Aparecida Azevedo Koike"
			],
			"DOI": "10.6061/clinics/2021/e2837",
			"date": "2021-08-03",
			"PMC": "",
			"citation": "",
			"abstract": "In breast cancer (BC) patients, the frequency of germline BRCA mutations (gBRCA) may vary according to the ethnic background, age, and family history of cancer. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the second most common somatic mutated gene in BC; however, the association of mutations in both genes with cancer has not been thoroughly investigated. Thus, our aims were to investigate gBRCA mutation frequency in a cohort of postmenopausal Brazilian BC patients and the association of gBRCA1/BRCA2 and PIK3CA somatic mutations.",
			"category": 2,
			"name": "Nagy Tauana Rodrigues,2021"
		},
		{
			"PMID": 34277640,
			"title": "HFS-SLPEE: A Novel Hierarchical Feature Selection and Second Learning Probability Error Ensemble Model for Precision Cancer Diagnosis.",
			"journal": "Frontiers in cell and developmental biology",
			"authorList": [
				"Meng Yajie",
				"Jin Min"
			],
			"DOI": "10.3389/fcell.2021.696359",
			"date": "2023-09-20",
			"PMC": "",
			"citation": "",
			"abstract": "The emergence of high-throughput RNA-seq data has offered unprecedented opportunities for cancer diagnosis. However, capturing biological data with highly nonlinear and complex associations by most existing approaches for cancer diagnosis has been challenging. In this study, we propose a novel hierarchical feature selection and second learning probability error ensemble model (named HFS-SLPEE) for precision cancer diagnosis. Specifically, we first integrated protein-coding gene expression profiles, non-coding RNA expression profiles, and DNA methylation data to provide rich information; afterward, we designed a novel hierarchical feature selection method, which takes the CpG-gene biological associations into account and can select a compact set of superior features; next, we used four individual classifiers with significant differences and apparent complementary to build the heterogeneous classifiers; lastly, we developed a second learning probability error ensemble model called SLPEE to thoroughly learn the new data consisting of classifiers-predicted class probability values and the actual label, further realizing the self-correction of the diagnosis errors. Benchmarking comparisons on TCGA showed that HFS-SLPEE performs better than the state-of-the-art approaches. Moreover, we analyzed in-depth 10 groups of selected features and found several novel HFS-SLPEE-predicted epigenomics and epigenetics biomarkers for breast invasive carcinoma (BRCA) (e.g., TSLP and ADAMTS9-AS2), lung adenocarcinoma (LUAD) (e.g., HBA1 and CTB-43E15.1), and kidney renal clear cell carcinoma (KIRC) (e.g., IRX2 and BMPR1B-AS1).",
			"category": 2,
			"name": "Meng Yajie,2023"
		},
		{
			"PMID": 34262633,
			"title": "A BAYESIAN NONPARAMETRIC MODEL FOR INFERRING SUBCLONAL POPULATIONS FROM STRUCTURED DNA SEQUENCING DATA.",
			"journal": "The annals of applied statistics",
			"authorList": [
				"He Shai",
				"Schein Aaron",
				"Sarsani Vishal",
				"Flaherty Patrick"
			],
			"DOI": "10.1214/20-aoas1434",
			"date": "2021-07-16",
			"PMC": "",
			"citation": "",
			"abstract": "There are distinguishing features or \"hallmarks\" of cancer that are found across tumors, individuals, and types of cancer, and these hallmarks can be driven by specific genetic mutations. Yet, within a single tumor there is often extensive genetic heterogeneity as evidenced by single-cell and bulk DNA sequencing data. The goal of this work is to jointly infer the underlying genotypes of tumor subpopulations and the distribution of those subpopulations in individual tumors by integrating single-cell and bulk sequencing data. Understanding the genetic composition of the tumor at the time of treatment is important in the personalized design of targeted therapeutic combinations and monitoring for possible recurrence after treatment. We propose a hierarchical Dirichlet process mixture model that incorporates the correlation structure induced by a structured sampling arrangement and we show that this model improves the quality of inference. We develop a representation of the hierarchical Dirichlet process prior as a Gamma-Poisson hierarchy and we use this representation to derive a fast Gibbs sampling inference algorithm using the augment-and-marginalize method. Experiments with simulation data show that our model outperforms standard numerical and statistical methods for decomposing admixed count data. Analyses of real acute lymphoblastic leukemia cancer sequencing dataset shows that our model improves upon state-of-the-art bioinformatic methods. An interpretation of the results of our model on this real dataset reveals co-mutated loci across samples.",
			"category": 2,
			"name": "He Shai,2021"
		},
		{
			"PMID": 34262604,
			"title": "A Cluster-Based Approach for the Discovery of Copy Number Variations From Next-Generation Sequencing Data.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Liu Guojun",
				"Zhang Junying"
			],
			"DOI": "10.3389/fgene.2021.699510",
			"date": "2024-04-02",
			"PMC": "",
			"citation": "",
			"abstract": "The next-generation sequencing technology offers a wealth of data resources for the detection of copy number variations (CNVs) at a high resolution. However, it is still challenging to correctly detect CNVs of different lengths. It is necessary to develop new CNV detection tools to meet this demand. In this work, we propose a new CNV detection method, called CBCNV, for the detection of CNVs of different lengths from whole genome sequencing data. CBCNV uses a clustering algorithm to divide the read depth segment profile, and assigns an abnormal score to each read depth segment. Based on the abnormal score profile, Tukey's fences method is adopted in CBCNV to forecast CNVs. The performance of the proposed method is evaluated on simulated data sets, and is compared with those of several existing methods. The experimental results prove that the performance of CBCNV is better than those of several existing methods. The proposed method is further tested and verified on real data sets, and the experimental results are found to be consistent with the simulation results. Therefore, the proposed method can be expected to become a routine tool in the analysis of CNVs from tumor-normal matched samples.",
			"category": 2,
			"name": "Liu Guojun,2024"
		},
		{
			"PMID": 34257550,
			"title": "EGFR and KRAS Mutations in Lung Parenchyma of Subjects With EGFR/KRAS Wild-Type Lung Adenocarcinoma.",
			"journal": "Pathology oncology research : POR",
			"authorList": [
				"Chalela Roberto",
				"Gonz\u00e1lez-Garc\u00eda Jose Gregorio",
				"Khilzi Karys",
				"Curull V\u00edctor",
				"S\u00e1nchez-Font Albert",
				"Longar\u00f3n Raquel",
				"Rodrigo-Calvo Mar\u00eda Teresa",
				"Mart\u00edn-Ontiyuelo Clara",
				"Gea Joaquim",
				"Bellosillo Beatr\u00edz"
			],
			"DOI": "10.3389/pore.2021.598292",
			"date": "2022-01-03",
			"PMC": "",
			"citation": "",
			"abstract": "The acquisition of driver mutations in non-tumoral cells appears to be very important during the carcinogenesis of adenocarcinoma (ADC). Recent studies suggest that cancer-related mutations may not necessarily be present only in malignant cells, but also in histologically \"healthy cells\". ",
			"category": 2,
			"name": "Chalela Roberto,2022"
		},
		{
			"PMID": 34250385,
			"title": "Global Implementation of Precision Oncology.",
			"journal": "JCO precision oncology",
			"authorList": [
				"Yam Clinton",
				"Ma Brigette B Y",
				"Yap Timothy A"
			],
			"DOI": "10.1200/PO.21.00001",
			"date": "2022-03-02",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Yam Clinton,2022"
		},
		{
			"PMID": 34230647,
			"title": "Non-coding driver mutations in human cancer.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Elliott Kerryn",
				"Larsson Erik"
			],
			"DOI": "10.1038/s41568-021-00371-z",
			"date": "2021-09-23",
			"PMC": "",
			"citation": "",
			"abstract": "Tumour formation involves random mutagenic events and positive evolutionary selection acting on a subset of such events, referred to as driver mutations. A decade of careful surveying of tumour DNA using exome-based analyses has revealed a multitude of protein-coding somatic driver mutations, some of which are clinically actionable. Today, a transition towards whole-genome analysis is well under way, technically enabling the discovery of potential driver mutations occurring outside protein-coding sequences. Mutations are abundant in this vast non-coding space, which is more than 50 times larger than the coding exome, but reliable identification of selection signals in non-coding DNA remains a challenge. In this Review, we discuss recent findings in the field, where the emerging landscape is one in which non-coding driver mutations appear to be relatively infrequent. Nevertheless, we highlight several notable discoveries. We consider possible reasons for the relative absence of non-coding driver events, as well as the difficulties associated with detecting signals of positive selection in non-coding DNA.",
			"category": 2,
			"name": "Elliott Kerryn,2021"
		},
		{
			"PMID": 34205004,
			"title": "Identifying Cancer Drivers Using DRIVE: A Feature-Based Machine Learning Model for a Pan-Cancer Assessment of Somatic Missense Mutations.",
			"journal": "Cancers",
			"authorList": [
				"Dragomir Ionut",
				"Akbar Adnan",
				"Cassidy John W",
				"Patel Nirmesh",
				"Clifford Harry W",
				"Contino Gianmarco"
			],
			"DOI": "10.3390/cancers13112779",
			"date": "2021-07-05",
			"PMC": "",
			"citation": "",
			"abstract": "Sporadic cancer develops from the accrual of somatic mutations. Out of all small-scale somatic aberrations in coding regions, 95% are base substitutions, with 90% being missense mutations. While multiple studies focused on the importance of this mutation type, a machine learning method based on the number of protein-protein interactions (PPIs) has not been fully explored. This study aims to develop an improved computational method for driver identification, validation and evaluation (DRIVE), which is compared to other methods for assessing its performance. DRIVE aims at distinguishing between driver and passenger mutations using a feature-based learning approach comprising two levels of biological classification for a pan-cancer assessment of somatic mutations. Gene-level features include the maximum number of protein-protein interactions, the biological process and the type of post-translational modifications (PTMs) while mutation-level features are based on pathogenicity scores. Multiple supervised classification algorithms were trained on Genomics Evidence Neoplasia Information Exchange (GENIE) project data and then tested on an independent dataset from The Cancer Genome Atlas (TCGA) study. Finally, the most powerful classifier using DRIVE was evaluated on a benchmark dataset, which showed a better overall performance compared to other state-of-the-art methodologies, however, considerable care must be taken due to the reduced size of the dataset. DRIVE outlines the outstanding potential that multiple levels of a feature-based learning model will play in the future of oncology-based precision medicine.",
			"category": 2,
			"name": "Dragomir Ionut,2021"
		},
		{
			"PMID": 34204917,
			"title": "Evaluation of Somatic Mutations in Solid Metastatic Pan-Cancer Patients.",
			"journal": "Cancers",
			"authorList": [
				"Roosan Moom R",
				"Mambetsariev Isa",
				"Pharaon Rebecca",
				"Fricke Jeremy",
				"Baroz Angel R",
				"Chao Joseph",
				"Chen Chen",
				"Nasser Mohd W",
				"Chirravuri-Venkata Ramakanth",
				"Jain Maneesh",
				"Smith Lynette",
				"Yost Susan E",
				"Reckamp Karen L",
				"Pillai Raju",
				"Arvanitis Leonidas",
				"Afkhami Michelle",
				"Wang Edward W",
				"Chung Vincent",
				"Cristea Mihaela",
				"Fakih Marwan",
				"Koczywas Marianna",
				"Massarelli Erminia",
				"Mortimer Joanne",
				"Yuan Yuan",
				"Batra Surinder K",
				"Pal Sumanta",
				"Salgia Ravi"
			],
			"DOI": "10.3390/cancers13112776",
			"date": "2023-09-20",
			"PMC": "",
			"citation": "",
			"abstract": "Metastasis continues to be the primary cause of all cancer-related deaths despite the recent advancements in cancer treatments. To evaluate the role of mutations in overall survival (OS) and treatment outcomes, we analyzed 957 metastatic patients with seven major cancer types who had available molecular testing results with a FoundationOne CDx",
			"category": 2,
			"name": "Roosan Moom R,2023"
		},
		{
			"PMID": 34193169,
			"title": "The underlying molecular mechanisms and prognostic factors of RNA binding protein in colorectal cancer: a study based on multiple online databases.",
			"journal": "Cancer cell international",
			"authorList": [
				"He Qinglian",
				"Li Ziqi",
				"Lei Xue",
				"Zou Qian",
				"Yu Haibing",
				"Ding Yuanlin",
				"Xu Guangxian",
				"Zhu Wei"
			],
			"DOI": "10.1186/s12935-021-02031-6",
			"date": "2021-07-04",
			"PMC": "",
			"citation": "",
			"abstract": "RNA binding protein (RBP) is an active factor involved in the occurrence and development of colorectal cancer (CRC). Therefore, the potential mechanism of RBP in CRC needs to be clarified by dry-lab analyses or wet-lab experiments.",
			"category": 2,
			"name": "He Qinglian,2021"
		},
		{
			"PMID": 34158745,
			"title": "Landscape of cell heterogeneity and evolutionary trajectory in ulcerative colitis-associated colon cancer revealed by single-cell RNA sequencing.",
			"journal": "Chinese journal of cancer research = Chung-kuo yen cheng yen chiu",
			"authorList": [
				"Wang Quan",
				"Wang Zhu",
				"Zhang Zhen",
				"Zhang Wei",
				"Zhang Mengmeng",
				"Shen Zhanlong",
				"Ye Yingjiang",
				"Jiang Kewei",
				"Wang Shan"
			],
			"DOI": "10.21147/j.issn.1000-9604.2021.02.13",
			"date": "2022-04-24",
			"PMC": "",
			"citation": "",
			"abstract": "The goal of this study was to get preliminary insight on the intra-tumor heterogeneity in colitis-associated cancer (CAC) and to reveal a potential evolutionary trajectory from ulcerative colitis (UC) to CAC at the single-cell level.",
			"category": 2,
			"name": "Wang Quan,2022"
		},
		{
			"PMID": 34149820,
			"title": "GRMT: Generative Reconstruction of Mutation Tree From Scratch Using Single-Cell Sequencing Data.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Yu Zhenhua",
				"Liu Huidong",
				"Du Fang",
				"Tang Xiaofen"
			],
			"DOI": "10.3389/fgene.2021.692964",
			"date": "2021-06-22",
			"PMC": "",
			"citation": "",
			"abstract": "Single-cell sequencing (SCS) now promises the landscape of genetic diversity at single cell level, and is particularly useful to reconstruct the evolutionary history of tumor. There are multiple types of noise that make the SCS data notoriously error-prone, and significantly complicate tumor tree reconstruction. Existing methods for tumor phylogeny estimation suffer from either high computational intensity or low-resolution indication of clonal architecture, giving a necessity of developing new methods for efficient and accurate reconstruction of tumor trees. We introduce GRMT (Generative Reconstruction of Mutation Tree from scratch), a method for inferring tumor mutation tree from SCS data. GRMT exploits the ",
			"category": 2,
			"name": "Yu Zhenhua,2021"
		},
		{
			"PMID": 34148893,
			"title": "Genome instability and lymphoma.",
			"journal": "Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences",
			"authorList": [
				"Cao Pengfei",
				"Li Guiyuan",
				"Xiang Juanjuan"
			],
			"DOI": "10.11817/j.issn.1672-7347.2021.190427",
			"date": "2021-06-22",
			"PMC": "",
			"citation": "",
			"abstract": "Lymphoma is one of the most common malignant tumor of the hematologic system. The genome instability is not only an important molecular basis for the development of lymphoma, but also has important value in the diagnosis and prognosis of lymphoma. There are 2 types of genome instability: Microsatellite instability (MSI/MIN) at gene level and chromosomal instability at chromosome level. Through the study on genes associated with lymphoma, the unstable genes associated with lymphoma could be found, meanwhile the mechanism of its occurrence and development of lymphoma could be explored, and the important basis of molecular biology could also be provided in the field of current hot lymphoma precision medical research.",
			"category": 2,
			"name": "Cao Pengfei,2021"
		},
		{
			"PMID": 34123863,
			"title": "Immunotherapy in the Treatment of Urothelial Bladder Cancer: Insights From Single-Cell Analysis.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Zang Jingyu",
				"Ye Kaiyan",
				"Fei Yang",
				"Zhang Ruiyun",
				"Chen Haige",
				"Zhuang Guanglei"
			],
			"DOI": "10.3389/fonc.2021.696716",
			"date": "2024-04-02",
			"PMC": "",
			"citation": "",
			"abstract": "Urothelial bladder cancer (UBC) is a global challenge of public health with limited therapeutic options. Although the emergence of cancer immunotherapy, most notably immune checkpoint inhibitors, represents a major breakthrough in the past decade, many patients still suffer from unsatisfactory clinical outcome. A thorough understanding of the fundamental cellular and molecular mechanisms responsible for antitumor immunity may lead to optimized treatment guidelines and new immunotherapeutic strategies. With technological developments and protocol refinements, single-cell approaches have become powerful tools that provide unprecedented insights into the kaleidoscopic tumor microenvironment and intricate cell-cell communications. In this review, we summarize recent applications of single-cell analysis in characterizing the UBC multicellular ecosystem, and discuss how to leverage the high-resolution information for more effective immune-based therapies.",
			"category": 2,
			"name": "Zang Jingyu,2024"
		},
		{
			"PMID": 34113354,
			"title": "Improvement of Neoantigen Identification Through Convolution Neural Network.",
			"journal": "Frontiers in immunology",
			"authorList": [
				"Hao Qing",
				"Wei Ping",
				"Shu Yang",
				"Zhang Yi-Guan",
				"Xu Heng",
				"Zhao Jun-Ning"
			],
			"DOI": "10.3389/fimmu.2021.682103",
			"date": "2021-10-27",
			"PMC": "",
			"citation": "",
			"abstract": "Accurate prediction of neoantigens and the subsequent elicited protective anti-tumor response are particularly important for the development of cancer vaccine and adoptive T-cell therapy. However, current algorithms for predicting neoantigens are limited by ",
			"category": 2,
			"name": "Hao Qing,2021"
		},
		{
			"PMID": 34102905,
			"title": "Systematic analysis of molecular characterization and clinical relevance of m6A regulators in digestive system pan-cancers.",
			"journal": "Experimental biology and medicine (Maywood, N.J.)",
			"authorList": [
				"Kou Tiankuo",
				"Chai Ruizhi",
				"Jin Lan",
				"Bai Zhigang",
				"Yang Yun",
				"Zhao Yongtian",
				"Wu Dongfang",
				"Zhang Zhongtao",
				"Yang Yingchi"
			],
			"DOI": "10.1177/15353702211019681",
			"date": "2021-12-03",
			"PMC": "",
			"citation": "",
			"abstract": "Digestive system tumors, which mainly include esophagus, stomach, colorectum, liver, pancreas, bile duct, and some other tumors, often have a poor prognosis. N6-methyladenosine (m6A) has critical functions in development and tumorigenesis and may help improve the molecular mechanisms of digestive system tumors. However, current understanding of the reconstitution of m6A in digestive system tumors is far from comprehensive. Herein, this study systematically analyzed multi-layered genomic characteristics and clinical relevance of m6A regulators in 1906 patients involving seven digestive system tumor types. We discovered that m6A regulators showed extensive genetic changes and highly consistent expression regulation. The m6A expression was closely related to the activity of cancer pathways. At the same time, we also identified m6A regulators significantly related to the common cancer pathways of digestive system tumors and specific cancer pathways of digestive tract and digestive glands. These cancer pathways may explain the prognostic differences of patients with digestive tract tumors. In addition, m6A regulators demonstrated strong potential in prognostic stratification and drug development, especially in multiple research cohorts on pancreatic cancer, pointing to a strong prognostic stratification capability of m6A regulators. Finally, a m6A scoring model significantly related to highly active ubiquitin-mediated proteolysis, mismatch repair, cell cycle, ebasal transcription factors was constructed and had a strong prognostic stratification ability in digestive gland tumors. The score showed a significant negative correlation with the tumor immune microenvironment. This study demonstrated that the similarities and difference of the action mechanism m6A regulators in the digestive tract and digestive gland tumor progression could guide potential drug development.",
			"category": 2,
			"name": "Kou Tiankuo,2021"
		},
		{
			"PMID": 34094193,
			"title": "Structure-tuned membrane active Ir-complexed oligoarginine overcomes cancer cell drug resistance and triggers immune responses in mice.",
			"journal": "Chemical science",
			"authorList": [
				"Ji Shuangshuang",
				"Yang Xiuzhu",
				"Chen Xiaolong",
				"Li Ang",
				"Yan Doudou",
				"Xu Haiyan",
				"Fei Hao"
			],
			"DOI": "10.1039/d0sc03975f",
			"date": "2024-04-02",
			"PMC": "",
			"citation": "",
			"abstract": "The development of chemotherapy, an important cancer treatment modality, is hindered by the frequently found drug-resistance phenomenon. Meanwhile, researchers have been enthused lately by the synergistic use of chemotherapy with emerging immunotherapeutic treatments. In an effort to address both of the two unmet needs, reported herein is a study on a series of membrane active iridium(iii) complexed oligoarginine peptides with a new cell death mechanism capable of overcoming drug resistance as well as stimulating immunological responses. A systematic structure-activity relationship study elucidated the interdependent effects of three structural factors, ",
			"category": 2,
			"name": "Ji Shuangshuang,2024"
		},
		{
			"PMID": 34093666,
			"title": "DNA Methylation, Deamination, and Translesion Synthesis Combine to Generate Footprint Mutations in Cancer Driver Genes in B-Cell Derived Lymphomas and Other Cancers.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Rogozin Igor B",
				"Roche-Lima Abiel",
				"Tyryshkin Kathrin",
				"Carrasquillo-Carri\u00f3n Kelvin",
				"Lada Artem G",
				"Poliakov Lennard Y",
				"Schwartz Elena",
				"Saura Andreu",
				"Yurchenko Vyacheslav",
				"Cooper David N",
				"Panchenko Anna R",
				"Pavlov Youri I"
			],
			"DOI": "10.3389/fgene.2021.671866",
			"date": "2021-06-08",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer genomes harbor numerous genomic alterations and many cancers accumulate thousands of nucleotide sequence variations. A prominent fraction of these mutations arises as a consequence of the off-target activity of DNA/RNA editing cytosine deaminases followed by the replication/repair of edited sites by DNA polymerases (pol), as deduced from the analysis of the DNA sequence context of mutations in different tumor tissues. We have used the weight matrix (sequence profile) approach to analyze mutagenesis due to Activation Induced Deaminase (AID) and two error-prone DNA polymerases. Control experiments using shuffled weight matrices and somatic mutations in immunoglobulin genes confirmed the power of this method. Analysis of somatic mutations in various cancers suggested that AID and DNA polymerases \u03b7 and \u03b8 contribute to mutagenesis in contexts that almost universally correlate with the context of mutations in A:T and G:C sites during the affinity maturation of immunoglobulin genes. Previously, we demonstrated that AID contributes to mutagenesis in (de)methylated genomic DNA in various cancers. Our current analysis of methylation data from malignant lymphomas suggests that driver genes are subject to different (de)methylation processes than non-driver genes and, in addition to AID, the activity of pols \u03b7 and \u03b8 contributes to the establishment of methylation-dependent mutation profiles. This may reflect the functional importance of interplay between mutagenesis in cancer and (de)methylation processes in different groups of genes. The resulting changes in CpG methylation levels and chromatin modifications are likely to cause changes in the expression levels of driver genes that may affect cancer initiation and/or progression.",
			"category": 2,
			"name": "Rogozin Igor B,2021"
		},
		{
			"PMID": 34090480,
			"title": "Translational precision medicine: an industry perspective.",
			"journal": "Journal of translational medicine",
			"authorList": [
				"Hartl Dominik",
				"de Luca Valeria",
				"Kostikova Anna",
				"Laramie Jason",
				"Kennedy Scott",
				"Ferrero Enrico",
				"Siegel Richard",
				"Fink Martin",
				"Ahmed Sohail",
				"Millholland John",
				"Schuhmacher Alexander",
				"Hinder Markus",
				"Piali Luca",
				"Roth Adrian"
			],
			"DOI": "10.1186/s12967-021-02910-6",
			"date": "2021-06-30",
			"PMC": "",
			"citation": "",
			"abstract": "In the era of precision medicine, digital technologies and artificial intelligence, drug discovery and development face unprecedented opportunities for product and business model innovation, fundamentally changing the traditional approach of how drugs are discovered, developed and marketed. Critical to this transformation is the adoption of new technologies in the drug development process, catalyzing the transition from serendipity-driven to data-driven medicine. This paradigm shift comes with a need for both translation and precision, leading to a modern Translational Precision Medicine approach to drug discovery and development. Key components of Translational Precision Medicine are multi-omics profiling, digital biomarkers, model-based data integration, artificial intelligence, biomarker-guided trial designs and patient-centric companion diagnostics. In this review, we summarize and critically discuss the potential and challenges of Translational Precision Medicine from a cross-industry perspective.",
			"category": 2,
			"name": "Hartl Dominik,2021"
		},
		{
			"PMID": 34076361,
			"title": "Transcriptomic heterogeneity of driver gene mutations reveals novel mutual exclusivity and improves exploration of functional associations.",
			"journal": "Cancer medicine",
			"authorList": [
				"Lan Yujia",
				"Liu Wei",
				"Zhang Wanmei",
				"Hu Jing",
				"Zhu Xiaojing",
				"Wan Linyun",
				"A Suru",
				"Ping Yanyan",
				"Xiao Yun"
			],
			"DOI": "10.1002/cam4.4039",
			"date": "2021-12-31",
			"PMC": "",
			"citation": "",
			"abstract": "Lung adenocarcinoma (LUAD), as the most common subtype of lung cancer, is the leading cause of cancer deaths in the world. The accumulation of driver gene mutations enables cancer cells to gradually acquire growth advantage. Therefore, it is important to understand the functions and interactions of driver gene mutations in cancer progression.",
			"category": 2,
			"name": "Lan Yujia,2021"
		},
		{
			"PMID": 34070173,
			"title": "Untangling Dual-Targeting Therapeutic Mechanism of Epidermal Growth Factor Receptor (EGFR) Based on Reversed Allosteric Communication.",
			"journal": "Pharmaceutics",
			"authorList": [
				"Qiu Yuran",
				"Yin Xiaolan",
				"Li Xinyi",
				"Wang Yuanhao",
				"Fu Qiang",
				"Huang Renhua",
				"Lu Shaoyong"
			],
			"DOI": "10.3390/pharmaceutics13050747",
			"date": "2024-04-02",
			"PMC": "",
			"citation": "",
			"abstract": "Dual-targeting therapeutics by coadministration of allosteric and orthosteric drugs is drawing increased attention as a revolutionary strategy for overcoming the drug-resistance problems. It was further observed that the occupation of orthosteric sites by therapeutics agents has the potential to enhance allosteric ligand binding, which leads to improved potency of allosteric drugs. Epidermal growth factor receptor (EGFR), as one of the most critical anti-cancer targets belonging to the receptor tyrosine kinase family, represents a quintessential example. It was revealed that osimertinib, an ATP-competitive covalent EGFR inhibitor, remarkably enhanced the affinity of a recently developed allosteric inhibitor JBJ-04-125-02 for EGFR",
			"category": 2,
			"name": "Qiu Yuran,2024"
		},
		{
			"PMID": 34068918,
			"title": "Sequence Neighborhoods Enable Reliable Prediction of Pathogenic Mutations in Cancer Genomes.",
			"journal": "Cancers",
			"authorList": [
				"Banerjee Shayantan",
				"Raman Karthik",
				"Ravindran Balaraman"
			],
			"DOI": "10.3390/cancers13102366",
			"date": "2021-06-05",
			"PMC": "",
			"citation": "",
			"abstract": "Identifying cancer-causing mutations from sequenced cancer genomes hold much promise for targeted therapy and precision medicine. \"Driver\" mutations are primarily responsible for cancer progression, while \"passengers\" are functionally neutral. Although several computational approaches have been developed for distinguishing between driver and passenger mutations, very few have concentrated on using the raw nucleotide sequences surrounding a particular mutation as potential features for building predictive models. Using experimentally validated cancer mutation data in this study, we explored various string-based feature representation techniques to incorporate information on the neighborhood bases immediately 5' and 3' from each mutated position. Density estimation methods showed significant distributional differences between the neighborhood bases surrounding driver and passenger mutations. Binary classification models derived using repeated cross-validation experiments provided comparable performances across all window sizes. Integrating sequence features derived from raw nucleotide sequences with other genomic, structural, and evolutionary features resulted in the development of a pan-cancer mutation effect prediction tool, NBDriver, which was highly efficient in identifying pathogenic variants from five independent validation datasets. An ensemble predictor obtained by combining the predictions from NBDriver with three other commonly used driver prediction tools (FATHMM (cancer), CONDEL, and MutationTaster) significantly outperformed existing pan-cancer models in prioritizing a literature-curated list of driver and passenger mutations. Using the list of true positive mutation predictions derived from NBDriver, we identified a list of 138 known driver genes with functional evidence from various sources. Overall, our study underscores the efficacy of using raw nucleotide sequences as features to distinguish between driver and passenger mutations from sequenced cancer genomes.",
			"category": 2,
			"name": "Banerjee Shayantan,2021"
		},
		{
			"PMID": 34065872,
			"title": "Making Sense of Genetic Information: The Promising Evolution of Clinical Stratification and Precision Oncology Using Machine Learning.",
			"journal": "Genes",
			"authorList": [
				"Baptiste Mahaly",
				"Moinuddeen Sarah Shireen",
				"Soliz Courtney Lace",
				"Ehsan Hashimul",
				"Kaneko Gen"
			],
			"DOI": "10.3390/genes12050722",
			"date": "2021-08-30",
			"PMC": "",
			"citation": "",
			"abstract": "Precision medicine is a medical approach to administer patients with a tailored dose of treatment by taking into consideration a person's variability in genes, environment, and lifestyles. The accumulation of omics big sequence data led to the development of various genetic databases on which clinical stratification of high-risk populations may be conducted. In addition, because cancers are generally caused by tumor-specific mutations, large-scale systematic identification of single nucleotide polymorphisms (SNPs) in various tumors has propelled significant progress of tailored treatments of tumors (i.e., precision oncology). Machine learning (ML), a subfield of artificial intelligence in which computers learn through experience, has a great potential to be used in precision oncology chiefly to help physicians make diagnostic decisions based on tumor images. A promising venue of ML in precision oncology is the integration of all available data from images to multi-omics big data for the holistic care of patients and high-risk healthy subjects. In this review, we provide a focused overview of precision oncology and ML with attention to breast cancer and glioma as well as the Bayesian networks that have the flexibility and the ability to work with incomplete information. We also introduce some state-of-the-art attempts to use and incorporate ML and genetic information in precision oncology.",
			"category": 2,
			"name": "Baptiste Mahaly,2021"
		},
		{
			"PMID": 34057285,
			"title": "Genetic alterations associated with multiple primary malignancies.",
			"journal": "Cancer medicine",
			"authorList": [
				"Nyqvist Jenny",
				"Kov\u00e1cs Anik\u00f3",
				"Einbeigi Zakaria",
				"Karlsson Per",
				"Forssell-Aronsson Eva",
				"Helou Khalil",
				"Parris Toshima Z"
			],
			"DOI": "10.1002/cam4.3975",
			"date": "2021-12-31",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer (BC) patients are frequently at risk of developing other malignancies following treatment. Although studies have been conducted to elucidate the etiology of multiple primary malignancies (MPM) after a BC diagnosis, few studies have investigated other previously diagnosed primary malignancies (OPPM) before BC. Here, genome-wide profiling was used to identify potential driver DNA copy number alterations and somatic mutations that promote the development of MPMs. To compare the genomic profiles for two primary tumors (BC and OPPM) from the same patient, tumor pairs from 26 young women (\u226450\u00a0years) diagnosed with one or more primary malignancies before breast cancer were analyzed. Malignant melanoma was the most frequent OPPM, followed by gynecologic- and hematologic malignancies. However, significantly more genetic alterations were detected in BC compared to the OPPM. BC also showed more genetic similarity as a group than the tumor pairs. Clonality testing showed that genetic alterations on chromosomes 1, 3, 16, and 19 were concordant in both tumors in 13 patients. TP53 mutations were also found to be prevalent in BC, MM, and HM. Although all samples were classified as genetically unstable, chromothripsis-like patterns were primarily observed in BC. Taken together, few recurrent genetic alterations were identified in both tumor pairs that can explain the development of MPMs in the same patient. However, larger studies are warranted to further investigate key driver mutations associated with MPMs.",
			"category": 2,
			"name": "Nyqvist Jenny,2021"
		},
		{
			"PMID": 34031811,
			"title": "Is cancer a disease set up by cellular stress responses?",
			"journal": "Cell stress & chaperones",
			"authorList": [
				"Aranda-Anzaldo Armando",
				"Dent Myrna A R"
			],
			"DOI": "10.1007/s12192-021-01214-4",
			"date": "2022-01-25",
			"PMC": "",
			"citation": "",
			"abstract": "For several decades, the somatic mutation theory (SMT) has been the dominant paradigm on cancer research, leading to the textbook notion that cancer is fundamentally a genetic disease. However, recent discoveries indicate that mutations, including \"oncogenic\" ones, are widespread in normal somatic cells, suggesting that mutations may be necessary but not sufficient for cancer to develop. Indeed, a fundamental but as yet unanswered question is whether or not the first step in oncogenesis corresponds to a mutational event. On the other hand, for some time, it has been acknowledged the important role in cancer progression of molecular processes that participate in buffering cellular stress. However, their role is considered secondary or complementary to that of putative oncogenic mutations. Here we present and discuss evidence that cancer may have its origin in epigenetic processes associated with cellular adaptation to stressful conditions, and so it could be a direct consequence of stress-buffering mechanisms that allow cells with aberrant phenotypes (not necessarily associated with genetic mutations) to survive and propagate within the organism. We put forward the hypothesis that there would be an inverse correlation between the activation threshold of the cellular stress responses (CSRs) and the risk of cancer, so that species or individuals with low-threshold CSRs will display a higher incidence or risk of cancer.",
			"category": 2,
			"name": "Aranda-Anzaldo Armando,2022"
		},
		{
			"PMID": 34030627,
			"title": "driveR: a novel method for prioritizing cancer driver genes using somatic genomics data.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"\u00dclgen Ege",
				"Sezerman O U\u011fur"
			],
			"DOI": "10.1186/s12859-021-04203-7",
			"date": "2021-05-27",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer develops due to \"driver\" alterations. Numerous approaches exist for predicting cancer drivers from cohort-scale genomics data. However, methods for personalized analysis of driver genes are underdeveloped. In this study, we developed a novel personalized/batch analysis approach for driver gene prioritization utilizing somatic genomics data, called driveR.",
			"category": 2,
			"name": "\u00dclgen Ege,2021"
		},
		{
			"PMID": 33981601,
			"title": "Role of Chromodomain-Helicase-DNA-Binding Protein 4 (CHD4) in Breast Cancer.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Novillo Apolonia",
				"Fern\u00e1ndez-Santander Ana",
				"Gaibar Maria",
				"Gal\u00e1n Miguel",
				"Romero-Lorca Alicia",
				"El Abdellaoui-Soussi Fadoua",
				"G\u00f3mez-Del Arco Pablo"
			],
			"DOI": "10.3389/fonc.2021.633233",
			"date": "2021-05-14",
			"PMC": "",
			"citation": "",
			"abstract": "Chromodomain-helicase-DNA-binding protein 4 (CHD4) is an epigenetic regulator identified as an oncogenic element that may provide a novel therapeutic target for the treatment of breast cancer (BC). CHD4-the core component of the nucleosome remodeling and deacetylase (NuRD) complex-may be mutated in patients with this disease. However, information on ",
			"category": 2,
			"name": "Novillo Apolonia,2021"
		},
		{
			"PMID": 33979534,
			"title": "Brain Somatic Mutation in Aging and Alzheimer's Disease.",
			"journal": "Annual review of genomics and human genetics",
			"authorList": [
				"Miller Michael B",
				"Reed Hannah C",
				"Walsh Christopher A"
			],
			"DOI": "10.1146/annurev-genom-121520-081242",
			"date": "2021-10-25",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic mutations arise postzygotically, producing genetic differences between cells in an organism. Well established as a driver of cancer, somatic mutations also exist in nonneoplastic cells, including in the brain. Technological advances in nucleic acid sequencing have enabled recent breakthroughs that illuminate the roles of somatic mutations in aging and degenerative diseases of the brain. Somatic mutations accumulate during aging in human neurons, a process termed genosenium. A number of recent studies have examined somatic mutations in Alzheimer's disease (AD), primarily from the perspective of genes causing familial AD. We have also gained new information on genome-wide mutations, providing insights into the cellular events driving somatic mutation and cellular dysfunction. This review highlights recent concepts, methods, and findings in the progress to understand the role of brain somatic mutation in aging and AD.",
			"category": 2,
			"name": "Miller Michael B,2021"
		},
		{
			"PMID": 33977021,
			"title": "Advances in development and application of human organoids.",
			"journal": "3 Biotech",
			"authorList": [
				"Shankaran Abhijith",
				"Prasad Keshava",
				"Chaudhari Sima",
				"Brand Angela",
				"Satyamoorthy Kapaettu"
			],
			"DOI": "10.1007/s13205-021-02815-7",
			"date": "2023-11-01",
			"PMC": "",
			"citation": "",
			"abstract": "Innumerable studies associated with cellular differentiation, tissue response and disease modeling have been conducted in two-dimensional (2D) culture systems or animal models. This has been invaluable in deciphering the normal and disease states in cell biology; the key shortcomings of it being suitability for translational or clinical correlations. The past decade has seen several major advances in organoid culture technologies and this has enhanced our understanding of mimicking organ reconstruction. The term organoid has generally been used to describe cellular aggregates derived from primary tissues or stem cells that can self-organize into organotypic structures. Organoids mimic the cellular microenvironment of tissues better than 2D cell culture systems and represent the tissue physiology. Human organoids of brain, thyroid, gastrointestinal, lung, cardiac, liver, pancreatic and kidney have been established from various diseases, healthy tissues and from pluripotent stem cells (PSCs). Advances in patient-derived organoid culture further provides a unique perspective from which treatment modalities can be personalized. In this review article, we have discussed the current strategies for establishing various types of organoids of ectodermal, endodermal and mesodermal origin. We have also discussed their applications in modeling human health and diseases (such as cancer, genetic, neurodegenerative and infectious diseases), applications in regenerative medicine and evolutionary studies.",
			"category": 2,
			"name": "Shankaran Abhijith,2023"
		},
		{
			"PMID": 33968062,
			"title": "Discovering Panel of Autoantibodies for Early Detection of Lung Cancer Based on Focused Protein Array.",
			"journal": "Frontiers in immunology",
			"authorList": [
				"Jiang Di",
				"Zhang Xue",
				"Liu Man",
				"Wang Yulin",
				"Wang Tingting",
				"Pei Lu",
				"Wang Peng",
				"Ye Hua",
				"Shi Jianxiang",
				"Song Chunhua",
				"Wang Kaijuan",
				"Wang Xiao",
				"Dai Liping",
				"Zhang Jianying"
			],
			"DOI": "10.3389/fimmu.2021.658922",
			"date": "2021-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "Substantial studies indicate that autoantibodies to tumor-associated antigens (TAAbs) arise in early stage of lung cancer (LC). However, since single TAAbs as non-invasive biomarkers reveal low diagnostic performances, a panel approach is needed to provide more clues for early detection of LC. In the present research, potential TAAbs were screened in 150 serum samples by focused protein array based on 154 proteins encoded by cancer driver genes. Indirect enzyme-linked immunosorbent assay (ELISA) was used to verify and validate TAAbs in two independent datasets with 1,054 participants (310 in verification cohort, 744 in validation cohort). In both verification and validation cohorts, eight TAAbs were higher in serum of LC patients compared with normal controls. Moreover, diagnostic models were built and evaluated in the training set and the test set of validation cohort by six data mining methods. In contrast to the other five models, the decision tree (DT) model containing seven TAAbs (TP53, NPM1, FGFR2, PIK3CA, GNA11, HIST1H3B, and TSC1), built in the training set, yielded the highest diagnostic value with the area under the receiver operating characteristic curve (AUC) of 0.897, the sensitivity of 94.4% and the specificity of 84.9%. The model was further assessed in the test set and exhibited an AUC of 0.838 with the sensitivity of 89.4% and the specificity of 78.2%. Interestingly, the accuracies of this model in both early and advanced stage were close to 90%, much more effective than that of single TAAbs. Protein array based on cancer driver genes is effective in screening and discovering potential TAAbs of LC. The TAAbs panel with TP53, NPM1, FGFR2, PIK3CA, GNA11, HIST1H3B, and TSC1 is excellent in early detection of LC, and they might be new target in LC immunotherapy.",
			"category": 2,
			"name": "Jiang Di,2021"
		},
		{
			"PMID": 33964209,
			"title": "Neutrophil elastase selectively kills cancer cells and attenuates tumorigenesis.",
			"journal": "Cell",
			"authorList": [
				"Cui Chang",
				"Chakraborty Kasturi",
				"Tang Xu Anna",
				"Zhou Guolin",
				"Schoenfelt Kelly Q",
				"Becker Kristen M",
				"Hoffman Alexandria",
				"Chang Ya-Fang",
				"Blank Ariane",
				"Reardon Catherine A",
				"Kenny Hilary A",
				"Vaisar Tomas",
				"Lengyel Ernst",
				"Greene Geoffrey",
				"Becker Lev"
			],
			"DOI": "10.1016/j.cell.2021.04.016",
			"date": "2022-01-05",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer cell genetic variability and similarity to host cells have stymied development of broad anti-cancer therapeutics. Our innate immune system evolved to clear genetically diverse pathogens and limit host toxicity; however, whether/how innate immunity can produce similar effects in cancer is unknown. Here, we show that human, but not murine, neutrophils release catalytically active neutrophil elastase (ELANE) to kill many cancer cell types while sparing non-cancer cells. ELANE proteolytically liberates the CD95 death domain, which interacts with histone H1 isoforms to selectively eradicate cancer cells. ELANE attenuates primary tumor growth and produces a CD8",
			"category": 2,
			"name": "Cui Chang,2022"
		},
		{
			"PMID": 33945523,
			"title": "CBFB cooperates with p53 to maintain TAp73 expression and suppress breast cancer.",
			"journal": "PLoS genetics",
			"authorList": [
				"Malik Navdeep",
				"Yan Hualong",
				"Yang Howard H",
				"Ayaz Gamze",
				"DuBois Wendy",
				"Tseng Yu-Chou",
				"Kim Young-Im",
				"Jiang Shunlin",
				"Liu Chengyu",
				"Lee Maxwell",
				"Huang Jing"
			],
			"DOI": "10.1371/journal.pgen.1009553",
			"date": "2021-09-22",
			"PMC": "",
			"citation": "",
			"abstract": "The CBFB gene is frequently mutated in several types of solid tumors. Emerging evidence suggests that CBFB is a tumor suppressor in breast cancer. However, our understanding of the tumor suppressive function of CBFB remains incomplete. Here, we analyze genetic interactions between mutations of CBFB and other highly mutated genes in human breast cancer datasets and find that CBFB and TP53 mutations are mutually exclusive, suggesting a functional association between CBFB and p53. Integrated genomic studies reveal that TAp73 is a common transcriptional target of CBFB and p53. CBFB cooperates with p53 to maintain TAp73 expression, as either CBFB or p53 loss leads to TAp73 depletion. TAp73 re-expression abrogates the tumorigenic effect of CBFB deletion. Although TAp73 loss alone is insufficient for tumorigenesis, it enhances the tumorigenic effect of NOTCH3 overexpression, a downstream event of CBFB loss. Immunohistochemistry shows that p73 loss is coupled with higher proliferation in xenografts. Moreover, TAp73 loss-of-expression is a frequent event in human breast cancer tumors and cell lines. Together, our results significantly advance our understanding of the tumor suppressive functions of CBFB and reveal a mechanism underlying the communication between the two tumor suppressors CBFB and p53.",
			"category": 2,
			"name": "Malik Navdeep,2021"
		},
		{
			"PMID": 33945019,
			"title": "Gain and loss of function mutations in biological chemical reaction networks: a mathematical model with application to colorectal cancer cells.",
			"journal": "Journal of mathematical biology",
			"authorList": [
				"Sommariva Sara",
				"Caviglia Giacomo",
				"Piana Michele"
			],
			"DOI": "10.1007/s00285-021-01607-0",
			"date": "2021-07-30",
			"PMC": "",
			"citation": "",
			"abstract": "This paper studies a system of Ordinary Differential Equations modeling a chemical reaction network and derives from it a simulation tool mimicking Loss of Function and Gain of Function mutations found in cancer cells. More specifically, from a theoretical perspective, our approach focuses on the determination of moiety conservation laws for the system and their relation with the corresponding stoichiometric surfaces. Then we show that Loss of Function mutations can be implemented in the model via modification of the initial conditions in the system, while Gain of Function mutations can be implemented by eliminating specific reactions. Finally, the model is utilized to examine in detail the G1-S phase of a colorectal cancer cell.",
			"category": 2,
			"name": "Sommariva Sara,2021"
		},
		{
			"PMID": 33931593,
			"title": "MIR99AHG is a noncoding tumor suppressor gene in lung adenocarcinoma.",
			"journal": "Cell death & disease",
			"authorList": [
				"Han Chencheng",
				"Li Hong",
				"Ma Zhifei",
				"Dong Guozhang",
				"Wang Qianyun",
				"Wang Siwei",
				"Fang Panqi",
				"Li Xiang",
				"Chen Hao",
				"Liu Tongyan",
				"Xu Lin",
				"Wang Jie",
				"Wang Jun",
				"Yin Rong"
			],
			"DOI": "10.1038/s41419-021-03715-7",
			"date": "2021-10-05",
			"PMC": "",
			"citation": "",
			"abstract": "Little is known about noncoding tumor suppressor genes. An effective way to identify these genes is by analyzing somatic copy number variation (CNV)-related noncoding genes. By integrated bioinformatics analyses of differentially expressed long noncoding RNAs (lncRNAs) and arm-level CNVs in lung adenocarcinoma (LUAD), we identified a potential antitumor gene, MIR99AHG, encoding lncRNA MIR99AHG as well as a miR-99a/let-7c/miR-125b2 cluster on chromosome 21q. All four of these transcripts were downregulated in LUAD tissues partly due to the copy number deletion of the MIR99AHG gene. Both MIR99AHG and miR-99a expression was positively correlated with the survival of LUAD patients. MIR99AHG suppressed proliferation and metastasis and promoted autophagy both in vitro and in vivo. Mechanistically, the interaction between MIR99AHG and ANXA2 could accelerate the ANXA2-induced ATG16L",
			"category": 2,
			"name": "Han Chencheng,2021"
		},
		{
			"PMID": 33926541,
			"title": "Evaluating the transcriptional fidelity of cancer models.",
			"journal": "Genome medicine",
			"authorList": [
				"Peng Da",
				"Gleyzer Rachel",
				"Tai Wen-Hsin",
				"Kumar Pavithra",
				"Bian Qin",
				"Isaacs Bradley",
				"da Rocha Edroaldo Lummertz",
				"Cai Stephanie",
				"DiNapoli Kathleen",
				"Huang Franklin W",
				"Cahan Patrick"
			],
			"DOI": "10.1186/s13073-021-00888-w",
			"date": "2022-01-18",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer researchers use cell lines, patient-derived xenografts, engineered mice, and tumoroids as models to investigate tumor biology and to identify therapies. The generalizability and power of a model derive from the fidelity with which it represents the tumor type under investigation; however, the extent to which this is true is often unclear. The preponderance of models and the ability to readily generate new ones has created a demand for tools that can measure the extent and ways in which cancer models resemble or diverge from native tumors.",
			"category": 2,
			"name": "Peng Da,2022"
		},
		{
			"PMID": 33916923,
			"title": "Next Generation Sequencing Technology in the Clinic and Its Challenges.",
			"journal": "Cancers",
			"authorList": [
				"Vestergaard Lau K",
				"Oliveira Douglas N P",
				"H\u00f8gdall Claus K",
				"H\u00f8gdall Estrid V"
			],
			"DOI": "10.3390/cancers13081751",
			"date": "2021-05-02",
			"PMC": "",
			"citation": "",
			"abstract": "Data analysis has become a crucial aspect in clinical oncology to interpret output from next-generation sequencing-based testing. NGS being able to resolve billions of sequencing reactions in a few days has consequently increased the demand for tools to handle and analyze such large data sets. Many tools have been developed since the advent of NGS, featuring their own peculiarities. Increased awareness when interpreting alterations in the genome is therefore of utmost importance, as the same data using different tools can provide diverse outcomes. Hence, it is crucial to evaluate and validate bioinformatic pipelines in clinical settings. Moreover, personalized medicine implies treatment targeting efficacy of biological drugs for specific genomic alterations. Here, we focused on different sequencing technologies, features underlying the genome complexity, and bioinformatic tools that can impact the final annotation. Additionally, we discuss the clinical demand and design for implementing NGS.",
			"category": 2,
			"name": "Vestergaard Lau K,2021"
		},
		{
			"PMID": 33916417,
			"title": "Integrative RNA-Seq and H3 Trimethylation ChIP-Seq Analysis of Human Lung Cancer Cells Isolated by Laser-Microdissection.",
			"journal": "Cancers",
			"authorList": [
				"Ong Quang",
				"Sakashita Shingo",
				"Hanawa Emi",
				"Kaneko Naomi",
				"Noguchi Masayuki",
				"Muratani Masafumi"
			],
			"DOI": "10.3390/cancers13071719",
			"date": "2021-05-02",
			"PMC": "",
			"citation": "",
			"abstract": "Our previous integrative study in gastric cancer discovered cryptic promoter activation events that drive the expression of important developmental genes. However, it was unclear if such cancer-associated epigenetic changes occurred in cancer cells or other cell types in bulk tissue samples. An integrative analysis consisting of RNA-Seq and H3K4me3 ChIP-Seq was used. This workflow was applied to a set of matched normal lung tissues and non-small cell lung cancer (NSCLC) tissues, for which the stroma and tumor cell parts could be isolated by laser-microdissection microscopy (LMD). RNA-Seq analysis showed subtype-specific differential expressed genes and enriched pathways in NSCLC. ChIP-Seq analysis results suggested that the proximal altered H3K4me3 regions were located at differentially expressed genes involved in cancer-related pathways, while altered distal H3K4me3 regions were annotated with enhancer activity of cancer regulatory genes. Interestingly, integration with ENCODE data revealed that proximal tumor-gained promoters were associated with EZH2 and SUZ12 occupancies, which are the core components of polycomb repressive complex 2 (PRC2). This study used LMD on clinical samples for an integrative analysis to overcome the tissue heterogeneity problem in cancer research. The results also contribute to the overall understanding of genetic and epigenetic dysregulation of lung malignancy.",
			"category": 2,
			"name": "Ong Quang,2021"
		},
		{
			"PMID": 33902785,
			"title": "Increased risk of leukaemia in children with Down syndrome: a somatic evolutionary view.",
			"journal": "Expert reviews in molecular medicine",
			"authorList": [
				"Hasaart K A L",
				"Bertrums E J M",
				"Manders F",
				"Goemans B F",
				"van Boxtel R"
			],
			"DOI": "10.1017/erm.2021.6",
			"date": "2021-10-25",
			"PMC": "",
			"citation": "",
			"abstract": "Children show a higher incidence of leukaemia compared with young adolescents, yet their cells are less damaged because of their young age. Children with Down syndrome (DS) have an even higher risk of developing leukaemia during the first years of life. The presence of a constitutive trisomy of chromosome 21 (T21) in DS acts as a genetic driver for leukaemia development, however, additional oncogenic mutations are required. Therefore, T21 provides the opportunity to better understand leukaemogenesis in children. Here, we describe the increased risk of leukaemia in DS during childhood from a somatic evolutionary view. According to this idea, cancer is caused by a variation in inheritable phenotypes within cell populations that are subjected to selective forces within the tissue context. We propose a model in which the increased risk of leukaemia in DS children derives from higher rates of mutation accumulation, already present during fetal development, which is further enhanced by changes in selection dynamics within the fetal liver niche. This model could possibly be used to understand the rate-limiting steps of leukaemogenesis early in life.",
			"category": 2,
			"name": "Hasaart K A L,2021"
		},
		{
			"PMID": 33877535,
			"title": "Double-endpoint Genotoxicity Quantification and PAHs Characterization of Drinking Water Source alongside Polluted Yinghe River with High Tumor Mortality.",
			"journal": "Current medical science",
			"authorList": [
				"Zhang Wei",
				"Guo Chen",
				"Wang Xiao-Li",
				"Lv Zhan-Lu",
				"Fan Lin",
				"Yang Yu-Yan",
				"Li Xu",
				"Qi Jing",
				"Zhao Shu-Li",
				"Wang Xian-Liang"
			],
			"DOI": "10.1007/s11596-021-2336-z",
			"date": "2021-11-11",
			"PMC": "",
			"citation": "",
			"abstract": "The etiology for the high tumor mortality in heavy polluted Yinghe river basin is still unclear and polycyclic aromatic hydrocarbons (PAHs) belong to the priority pollutants in water based on the former surveillance data. In order to explore the potential genotoxicants contributing to the double-endpoint genotoxicity of polluted drinking water source, 12 groundwater and 3 surface water samples were collected from 3 villages and the nearby rivers alongside Yinghe river basin, respectively and their comprehensive genotoxicity was estimated with a bioassay group of SOS/umu test and micronucleus (MN) test (MNT). Some groundwater samples showed positive genotoxicity and all surface water samples were highly genotoxic. Eight groundwater samples showed DNA genotoxic effect with the average 4-NQO equivalent concentration (TEQ",
			"category": 2,
			"name": "Zhang Wei,2021"
		},
		{
			"PMID": 33854067,
			"title": "Comprehensive omic characterization of breast cancer in Mexican-Hispanic women.",
			"journal": "Nature communications",
			"authorList": [
				"Romero-Cordoba Sandra L",
				"Salido-Guadarrama Ivan",
				"Rebollar-Vega Rosa",
				"Bautista-Pi\u00f1a Veronica",
				"Dominguez-Reyes Carlos",
				"Tenorio-Torres Alberto",
				"Villegas-Carlos Felipe",
				"Fern\u00e1ndez-L\u00f3pez Juan C",
				"Uribe-Figueroa Laura",
				"Alfaro-Ruiz Luis",
				"Hidalgo-Miranda Alfredo"
			],
			"DOI": "10.1038/s41467-021-22478-5",
			"date": "2021-05-11",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer is a heterogeneous pathology, but the genomic basis of its variability remains poorly understood in populations other than Caucasians. Here, through DNA and RNA portraits we explored the molecular features of breast cancers in a set of Hispanic-Mexican (HM) women and compared them to public multi-ancestry datasets. HM patients present an earlier onset of the disease, particularly in aggressive clinical subtypes, compared to non-Hispanic women. The age-related COSMIC signature 1 was more frequent in HM women than in those from other ancestries. We found the AKT1",
			"category": 2,
			"name": "Romero-Cordoba Sandra L,2021"
		},
		{
			"PMID": 33777727,
			"title": "Characteristics of T-Cell Receptor Repertoire and Correlation With ",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Yang Huaxia",
				"Wang Yadong",
				"Jia Ziqi",
				"Wang Yanyu",
				"Yang Xiaoying",
				"Wu Pancheng",
				"Song Yang",
				"Xu Huihui",
				"Gu Dejian",
				"Chen Rongrong",
				"Xia Xuefeng",
				"Bing Zhongxing",
				"Gao Chao",
				"Cao Lei",
				"Li Shanqing",
				"Cao Zhili",
				"Liang Naixin"
			],
			"DOI": "10.3389/fonc.2021.537735",
			"date": "2021-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer is the leading cause of cancer-related deaths worldwide, and its occurrence is related to the accumulation of gene mutations and immune escape of the tumor. Sequencing of the T-cell receptor (TCR) repertoire can reveal the immunosurveillance status of the tumor microenvironment, which is related to tumor escape and immunotherapy. This study aimed to determine the characteristics and clinical significance of the TCR repertoire in lung cancer. To comprehensively profile the TCR repertoire, results from high-throughput sequencing of samples from 93 Chinese patients with lung cancer were analyzed. We found that the TCR clonality of tissues was related to smoking, with higher clonality in patients who had quit smoking for less than 1 year. As expected, TCR clonality was correlated with stages: patients with stage IV disease showed higher clonality than others. The correlation between TCR repertoire and epidermal growth factor receptor (EGFR) status was also investigated. Patients with ",
			"category": 2,
			"name": "Yang Huaxia,2021"
		},
		{
			"PMID": 33747899,
			"title": "Metastatic Spread in Prostate Cancer Patients Influencing Radiotherapy Response.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Klusa Daria",
				"Lohaus Fabian",
				"Furesi Giulia",
				"Rauner Martina",
				"Bene\u0161ov\u00e1 Martina",
				"Krause Mechthild",
				"Kurth Ina",
				"Peitzsch Claudia"
			],
			"DOI": "10.3389/fonc.2020.627379",
			"date": "2023-11-11",
			"PMC": "",
			"citation": "",
			"abstract": "Radiotherapy and surgery are curative treatment options for localized prostate cancer (PCa) with a 5-year survival rate of nearly 100%. Once PCa cells spread into distant organs, such as bone, the overall survival rate of patients drops dramatically. The metastatic cascade and organotropism of PCa cells are regulated by different cellular subtypes, organ microenvironment, and their interactions. This cross-talk leads to pre-metastatic niche formation that releases chemo-attractive factors enforcing the formation of distant metastasis. Biological characteristics of PCa metastasis impacting on metastatic sites, burden, and latency is of clinical relevance. Therefore, the implementation of modern hybrid imaging technologies into clinical routine increased the sensitivity to detect metastases at earlier stages. This enlarged the number of PCa patients diagnosed with a limited number of metastases, summarized as oligometastatic disease. These patients can be treated with androgen deprivation in combination with local-ablative radiotherapy or radiopharmaceuticals directed to metastatic sites. Unfortunately, the number of patients with disease recurrence is high due to the enormous heterogeneity within the oligometastatic patient population and the lack of available biomarkers with predictive potential for metastasis-directed radiotherapy. Another, so far unmet clinical need is the diagnosis of minimal residual disease before onset of clinical manifestation and/or early relapse after initial therapy. Here, monitoring of circulating and disseminating tumor cells in PCa patients during the course of radiotherapy may give us novel insight into how metastatic spread is influenced by radiotherapy and vice versa. In summary, this review critically compares current clinical concepts for metastatic PCa patients and discuss the implementation of recent preclinical findings improving our understanding of metastatic dissemination and radiotherapy resistance into standard of care.",
			"category": 2,
			"name": "Klusa Daria,2023"
		},
		{
			"PMID": 33742146,
			"title": "Kinome-wide analysis of the effect of statins in colorectal cancer.",
			"journal": "British journal of cancer",
			"authorList": [
				"Ouahoud Sarah",
				"Jacobs Rutger J",
				"Peppelenbosch Maikel P",
				"F\u00fchler G M",
				"Heijmans Jarom",
				"Diks Sander",
				"Wildenberg Manon E",
				"Hawinkels Lukas J A C",
				"Kodach Liudmila L",
				"Voorneveld Philip W",
				"Hardwick James C H"
			],
			"DOI": "10.1038/s41416-021-01318-9",
			"date": "2021-12-10",
			"PMC": "",
			"citation": "",
			"abstract": "Epidemiological studies and meta-analyses show an association between statin use and a reduced incidence of colorectal cancer (CRC). We have shown that statins act on CRC through bone morphogenetic protein (BMP) signalling, but the exact cellular targets and underlying mechanism of statin action remain elusive. In this study, we set out to assess the influence of statins on global cancer cell signalling by performing an array-based kinase assay using immobilised kinase substrates spanning the entire human kinome.",
			"category": 2,
			"name": "Ouahoud Sarah,2021"
		},
		{
			"PMID": 33732568,
			"title": "Genome-editing approaches and applications: a brief review on CRISPR technology and its role in cancer.",
			"journal": "3 Biotech",
			"authorList": [
				"Siva Narmadhaa",
				"Gupta Sonal",
				"Gupta Ayam",
				"Shukla Jayendra Nath",
				"Malik Babita",
				"Shukla Nidhi"
			],
			"DOI": "10.1007/s13205-021-02680-4",
			"date": "2023-11-10",
			"PMC": "",
			"citation": "",
			"abstract": "The development of genome-editing technologies in 1970s has discerned a new beginning in the field of science. Out of different genome-editing approaches such as Zing-finger nucleases, TALENs, and meganucleases, clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 (CRISPR/Cas9) is a recent and versatile technology that has the ability of making changes to the genome of different organisms with high specificity. Cancer is a complex process that is characterized by multiple genetic and epigenetic changes resulting in abnormal cell growth and proliferation. As cancer is one of the leading causes of deaths worldwide, a large number of studies are done to understand the molecular mechanisms underlying the development of cancer. Because of its high efficiency and specificity, CRISPR/Cas9 has emerged as a novel and powerful tool in the field of cancer research. CRISPR/Cas9 has the potential to accelerate cancer research by dissecting tumorigenesis process, generating animal and cellular models, and identify drug targets for chemotherapeutic approaches. However, despite having tremendous potential, there are certain challenges associated with CRISPR/Cas9 such as safe delivery to the target, potential off-target effects and its efficacy which needs to be addressed prior to its clinical application. In this review, we give a gist of different genome-editing technologies with a special focus on CRISPR/Cas9 development, its mechanism of action and its applications, especially in different type of cancers. We also highlight the importance of CRISPR/Cas9 in generating animal models of different cancers. Finally, we present an overview of the clinical trials and discuss the challenges associated with translating CRISPR/Cas9 in clinical use.",
			"category": 2,
			"name": "Siva Narmadhaa,2023"
		},
		{
			"PMID": 33718380,
			"title": null,
			"journal": "Frontiers in cell and developmental biology",
			"authorList": [
				"Custers Lars",
				"Paassen Irene",
				"Drost Jarno"
			],
			"DOI": "10.3389/fcell.2021.640633",
			"date": "2024-03-31",
			"PMC": "",
			"citation": "",
			"abstract": "A subset of pediatric tumors affects very young children and are thought to arise during fetal life. A common theme is that these embryonal tumors hijack developmental programs, causing a block in differentiation and, as a consequence, unrestricted proliferation. Embryonal tumors, therefore typically maintain an embryonic gene signature not found in their differentiated progeny. Still, the processes underpinning malignant transformation remain largely unknown, which is hampering therapeutic innovation. To gain more insight into these processes, ",
			"category": 2,
			"name": "Custers Lars,2024"
		},
		{
			"PMID": 33679394,
			"title": "The Widely Used Antihelmintic Drug Albendazole is a Potent Inducer of Loss of Heterozygosity.",
			"journal": "Frontiers in pharmacology",
			"authorList": [
				"Will Castro Luiza S E P",
				"Pieters Wietske",
				"Alemdehy Mir Farshid",
				"Aslam Muhammad A",
				"Buoninfante Olimpia Alessandra",
				"Raaijmakers Jonne A",
				"Pilzecker Bas",
				"van den Berk Paul C M",
				"Te Riele Hein",
				"Medema Ren\u00e9 H",
				"Pedrosa Rozangela C",
				"Jacobs Heinz"
			],
			"DOI": "10.3389/fphar.2021.596535",
			"date": "2021-03-10",
			"PMC": "",
			"citation": "",
			"abstract": "The antihelmintic drug ABZ and its metabolites belong to the chemical family of benzimidazoles (BZM) that act as potent tubulin polymerization inhibitors, suggesting a potential re-direction of BZMs for cancer therapy. Applying UV-Vis spectrometry we here demonstrate ABZ as a DNA intercalator. This insight led us to determine the primary mode of ABZ action in mammalian cells. As revealed by RNA sequencing, ABZ did neither grossly affect replication as analyzed by survival and replication stress signaling, nor the transcriptome. Actually, unbiased transcriptome analysis revealed a marked cell cycle signature in ABZ exposed cells. Indeed, short-term exposure to ABZ arrested mammalian cells in G2/M cell cycle stages associated with frequent gains and losses of chromatin. Cellular analyses revealed ABZ as a potent mammalian spindle poison for normal and malignant cells, explaining the serious chromosome segregation defects. Since chromosomal aberrations promote both cancer development and cell death, we determined if besides its general cytotoxicity, ABZ could predispose to tumor development. As measured by loss of heterozygosity (LOH) ",
			"category": 2,
			"name": "Will Castro Luiza S E P,2021"
		},
		{
			"PMID": 33667368,
			"title": "An expanded universe of cancer targets.",
			"journal": "Cell",
			"authorList": [
				"Hahn William C",
				"Bader Joel S",
				"Braun Theodore P",
				"Califano Andrea",
				"Clemons Paul A",
				"Druker Brian J",
				"Ewald Andrew J",
				"Fu Haian",
				"Jagu Subhashini",
				"Kemp Christopher J",
				"Kim William",
				"Kuo Calvin J",
				"McManus Michael",
				"B Mills Gordon",
				"Mo Xiulei",
				"Sahni Nidhi",
				"Schreiber Stuart L",
				"Talamas Jessica A",
				"Tamayo Pablo",
				"Tyner Jeffrey W",
				"Wagner Bridget K",
				"Weiss William A",
				"Gerhard Daniela S",
				"Cancer Target Discovery and Development Network"
			],
			"DOI": "10.1016/j.cell.2021.02.020",
			"date": "2021-09-14",
			"PMC": "",
			"citation": "",
			"abstract": "The characterization of cancer genomes has provided insight into somatically altered genes across tumors, transformed our understanding of cancer biology, and enabled tailoring of therapeutic strategies. However, the function of most cancer alleles remains mysterious, and many cancer features transcend their genomes. Consequently, tumor genomic characterization does not influence therapy for most patients. Approaches to understand the function and circuitry of cancer genes provide complementary approaches to elucidate both oncogene and non-oncogene dependencies. Emerging work indicates that the diversity of therapeutic targets engendered by non-oncogene dependencies is much larger than the list of recurrently mutated genes. Here we describe a framework for this expanded list of cancer targets, providing novel opportunities for clinical translation.",
			"category": 2,
			"name": "Hahn William C,2021"
		},
		{
			"PMID": 33639676,
			"title": "Underexpression of miR-126-3p in Patients with Cholangiocarcinoma.",
			"journal": "Asian Pacific journal of cancer prevention : APJCP",
			"authorList": [
				"Poleto Spinola Lucas",
				"F Vieira Gabriel",
				"Fernandes Ferreira Rafael",
				"Calastri Maria C J",
				"D Tenani Graciele",
				"Aguiar Franciana L",
				"Santana Ferreira Boin Ilka F",
				"B E Da Costa Larissa",
				"Chaim Correia Maria Fernanda",
				"Zanovelo Eliane M",
				"B De Souza Daniele C",
				"Martins Alves Da Silva Rita C",
				"Ferreira Da Silva Renato",
				"Coelho Abrantes Ana Margarida",
				"R R Botelho Maria Filomena",
				"L R Tralh\u00e3o Jose Guilherme",
				"R S Souza Doroteia"
			],
			"DOI": "10.31557/APJCP.2021.22.2.573",
			"date": "2021-11-08",
			"PMC": "",
			"citation": "",
			"abstract": "To evaluate the expression of miR-126-3p and its potential as a biomarker for cholangiocarcinoma (CCA) and to better understand the prognosis, comorbidities, and lifestyle habits associated with the disease.",
			"category": 2,
			"name": "Poleto Spinola Lucas,2021"
		},
		{
			"PMID": 33638948,
			"title": "Integrative analysis of genomic, epigenomic and transcriptomic data identified molecular subtypes of esophageal carcinoma.",
			"journal": "Aging",
			"authorList": [
				"Ma Mingyang",
				"Chen Yang",
				"Chong Xiaoyi",
				"Jiang Fangli",
				"Gao Jing",
				"Shen Lin",
				"Zhang Cheng"
			],
			"DOI": "10.18632/aging.202556",
			"date": "2021-07-20",
			"PMC": "",
			"citation": "",
			"abstract": "Esophageal cancer (EC) involves many genomic, epigenetic and transcriptomic disorders, which play key roles in the heterogeneous progression of cancer. However, the study of EC with multi-omics has not been conducted. This study identified a high consistency between DNA copy number variations and abnormal methylations in EC by analyzing genomics, epigenetics and transcriptomics data and investigating mutual correlations of DNA copy number variation, methylation and gene expressions, and stratified copy number variation genes (CNV-Gs) and methylation genes (MET-Gs). The methylation, CNVs and expression profiles of CNV-Gs and MET-Gs were analyzed by consistent clustering using iCluster integration, here, we determined three subtypes (iC1, iC2, iC3) with different molecular traits, prognostic characteristics and tumor immune microenvironment features. We also identified 4 prognostic genes (CLDN3, FAM221A, GDF15 and YBX2) differentially expressed in the three subtypes, and could therefore be used as representative biomarkers for the three subtypes of EC. In conclusion, by performing comprehensive analysis on genomic, epigenetic and transcriptomic regulations, the current study provided new insights into the multilayer molecular and pathological traits of EC, and contributed to the precision medication for EC patients.",
			"category": 2,
			"name": "Ma Mingyang,2021"
		},
		{
			"PMID": 33637962,
			"title": "Considering the potential for gene-based therapy in prostate cancer.",
			"journal": "Nature reviews. Urology",
			"authorList": [
				"Gregg Justin R",
				"Thompson Timothy C"
			],
			"DOI": "10.1038/s41585-021-00431-x",
			"date": "2021-08-26",
			"PMC": "",
			"citation": "",
			"abstract": "Therapeutic gene manipulation has been at the forefront of popular scientific discussion and basic and clinical research for decades. Basic and clinical research applications of CRISPR-Cas9-based technologies and ongoing clinical trials in this area have demonstrated the potential of genome editing to cure human disease. Evaluation of research and clinical trials in gene therapy reveals a concentration of activity in prostate cancer research and practice. Multiple aspects of prostate cancer care - including anatomical considerations that enable direct tumour injections and sampling, the availability of preclinical immune-competent models and the delineation of tumour-related antigens that might provide targets for an induced immune system - make gene therapy an appealing treatment option for this common malignancy. Vaccine-based therapies that induce an immune response and new technologies exploiting CRISPR-Cas9-assisted approaches, including chimeric antigen receptor (CAR) T cell therapies, are very promising and are currently under investigation both in the laboratory and in the clinic. Although laboratory and preclinical advances have, thus far, not led to oncologically relevant outcomes in the clinic, future studies offer great promise for gene therapy to become established in prostate cancer care.",
			"category": 2,
			"name": "Gregg Justin R,2021"
		},
		{
			"PMID": 33637765,
			"title": "Distinct genetic pathways define pre-malignant versus compensatory clonal hematopoiesis in Shwachman-Diamond syndrome.",
			"journal": "Nature communications",
			"authorList": [
				"Kennedy Alyssa L",
				"Myers Kasiani C",
				"Bowman James",
				"Gibson Christopher J",
				"Camarda Nicholas D",
				"Furutani Elissa",
				"Muscato Gwen M",
				"Klein Robert H",
				"Ballotti Kaitlyn",
				"Liu Shanshan",
				"Harris Chad E",
				"Galvin Ashley",
				"Malsch Maggie",
				"Dale David",
				"Gansner John M",
				"Nakano Taizo A",
				"Bertuch Alison",
				"Vlachos Adrianna",
				"Lipton Jeffrey M",
				"Castillo Paul",
				"Connelly James",
				"Churpek Jane",
				"Edwards John R",
				"Hijiya Nobuko",
				"Ho Richard H",
				"Hofmann Inga",
				"Huang James N",
				"Keel Siob\u00e1n",
				"Lamble Adam",
				"Lau Bonnie W",
				"Norkin Maxim",
				"Stieglitz Elliot",
				"Stock Wendy",
				"Walkovich Kelly",
				"Boettcher Steffen",
				"Brendel Christian",
				"Fleming Mark D",
				"Davies Stella M",
				"Weller Edie A",
				"Bahl Christopher",
				"Carter Scott L",
				"Shimamura Akiko",
				"Lindsley R Coleman"
			],
			"DOI": "10.1038/s41467-021-21588-4",
			"date": "2021-03-15",
			"PMC": "",
			"citation": "",
			"abstract": "To understand the mechanisms that mediate germline genetic leukemia predisposition, we studied the inherited ribosomopathy Shwachman-Diamond syndrome (SDS), a bone marrow failure disorder with high risk of myeloid malignancies at an early age. To define the mechanistic basis of clonal hematopoiesis in SDS, we investigate somatic mutations acquired by patients with SDS followed longitudinally. Here we report that multiple independent somatic hematopoietic clones arise early in life, most commonly harboring heterozygous mutations in EIF6 or TP53. We show that germline SBDS deficiency establishes a fitness constraint that drives selection of somatic clones via two distinct mechanisms with different clinical consequences. EIF6 inactivation mediates a compensatory pathway with limited leukemic potential by ameliorating the underlying SDS ribosome defect and enhancing clone fitness. TP53 mutations define a maladaptive pathway with enhanced leukemic potential by inactivating tumor suppressor checkpoints without correcting the ribosome defect. Subsequent development of leukemia was associated with acquisition of biallelic TP53 alterations. These results mechanistically link leukemia predisposition to germline genetic constraints on cellular fitness, and provide a rational framework for clinical surveillance strategies.",
			"category": 2,
			"name": "Kennedy Alyssa L,2021"
		},
		{
			"PMID": 33617468,
			"title": "Molecular analysis of cyclin D1 modulators PRKN and FBX4 as candidate tumor suppressors in sporadic parathyroid adenomas.",
			"journal": "Endocrine connections",
			"authorList": [
				"Brewer Kelly",
				"Nip Isabel",
				"Bellizzi Justin",
				"Costa-Guda Jessica",
				"Arnold Andrew"
			],
			"DOI": "10.1530/EC-21-0055",
			"date": "2022-04-21",
			"PMC": "",
			"citation": "",
			"abstract": "Primary hyperparathyroidism is most often caused by a sporadic single-gland parathyroid adenoma (PTA), a tumor type for which cyclin D1 is the only known and experimentally validated oncoprotein. However, the molecular origins of its frequent overexpression have remained mostly elusive. In this study, we explored a potential tumorigenic mechanism that could increase cyclin D1 stability through a defect in molecules responsible for its degradation.",
			"category": 2,
			"name": "Brewer Kelly,2022"
		},
		{
			"PMID": 33608386,
			"title": "A Functional Taxonomy of Tumor Suppression in Oncogenic KRAS-Driven Lung Cancer.",
			"journal": "Cancer discovery",
			"authorList": [
				"Cai Hongchen",
				"Chew Su Kit",
				"Li Chuan",
				"Tsai Min K",
				"Andrejka Laura",
				"Murray Christopher W",
				"Hughes Nicholas W",
				"Shuldiner Emily G",
				"Ashkin Emily L",
				"Tang Rui",
				"Hung King L",
				"Chen Leo C",
				"Lee Shi Ya C",
				"Yousefi Maryam",
				"Lin Wen-Yang",
				"Kunder Christian A",
				"Cong Le",
				"McFarland Christopher D",
				"Petrov Dmitri A",
				"Swanton Charles",
				"Winslow Monte M"
			],
			"DOI": "10.1158/2159-8290.CD-20-1325",
			"date": "2022-02-28",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer genotyping has identified a large number of putative tumor suppressor genes. Carcinogenesis is a multistep process, but the importance and specific roles of many of these genes during tumor initiation, growth, and progression remain unknown. Here we use a multiplexed mouse model of oncogenic KRAS-driven lung cancer to quantify the impact of 48 known and putative tumor suppressor genes on diverse aspects of carcinogenesis at an unprecedented scale and resolution. We uncover many previously understudied functional tumor suppressors that constrain cancer ",
			"category": 2,
			"name": "Cai Hongchen,2022"
		},
		{
			"PMID": 33570999,
			"title": "FrenchFISH: Poisson Models for Quantifying DNA Copy Number From Fluorescence In Situ Hybridization of Tissue Sections.",
			"journal": "JCO clinical cancer informatics",
			"authorList": [
				"Macintyre Geoff",
				"Piskorz Anna M",
				"Berman Adam",
				"Ross Edith",
				"Morse David B",
				"Yuan Ke",
				"Ennis Darren",
				"Pike Jeremy A",
				"Goranova Teodora",
				"McNeish Iain A",
				"Brenton James D",
				"Markowetz Florian"
			],
			"DOI": "10.1200/CCI.20.00075",
			"date": "2021-08-31",
			"PMC": "",
			"citation": "",
			"abstract": "Chromosomal aberration and DNA copy number change are robust hallmarks of cancer. The gold standard for detecting copy number changes in tumor cells is fluorescence in situ hybridization (FISH) using locus-specific probes that are imaged as fluorescent spots. However, spot counting often does not perform well on solid tumor tissue sections due to partially represented or overlapping nuclei.",
			"category": 2,
			"name": "Macintyre Geoff,2021"
		},
		{
			"PMID": 33532180,
			"title": "Recent advances in drug delivery systems for targeting cancer stem cells.",
			"journal": "Acta pharmaceutica Sinica. B",
			"authorList": [
				"Duan Hongxia",
				"Liu Yanhong",
				"Gao Zhonggao",
				"Huang Wei"
			],
			"DOI": "10.1016/j.apsb.2020.09.016",
			"date": "2023-11-10",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer stem cells (CSCs) are a subpopulation of cancer cells with functions similar to those of normal stem cells. Although few in number, they are capable of self-renewal, unlimited proliferation, and multi-directional differentiation potential. In addition, CSCs have the ability to escape immune surveillance. Thus, they play an important role in the occurrence and development of tumors, and they are closely related to tumor invasion, metastasis, drug resistance, and recurrence after treatment. Therefore, specific targeting of CSCs may improve the efficiency of cancer therapy. A series of corresponding promising therapeutic strategies based on CSC targeting, such as the targeting of CSC niche, CSC signaling pathways, and CSC mitochondria, are currently under development. Given the rapid progression in this field and nanotechnology, drug delivery systems (DDSs) for CSC targeting are increasingly being developed. In this review, we summarize the advances in CSC-targeted DDSs. Furthermore, we highlight the latest developmental trends through the main line of CSC occurrence and development process; some considerations about the rationale, advantages, and limitations of different DDSs for CSC-targeted therapies were discussed.",
			"category": 2,
			"name": "Duan Hongxia,2023"
		},
		{
			"PMID": 33513945,
			"title": "Mutational Signatures Driven by Epigenetic Determinants Enable the Stratification of Patients with Gastric Cancer for Therapeutic Intervention.",
			"journal": "Cancers",
			"authorList": [
				"Buttura Jaqueline Ramalho",
				"Provisor Santos Monize Nakamoto",
				"Valieris Renan",
				"Drummond Rodrigo Duarte",
				"Defelicibus Alexandre",
				"Lima Jo\u00e3o Paulo",
				"Calsavara Vinicius Fernando",
				"Freitas Helano Carioca",
				"Cordeiro de Lima Vladmir C",
				"Fernanda Bartelli Thais",
				"Wiedner Marc",
				"Rosales Rafael",
				"Gollob Kenneth John",
				"Loizou Joanna",
				"Dias-Neto Emmanuel",
				"Nunes Diana Noronha",
				"da Silva Israel Tojal"
			],
			"DOI": "10.3390/cancers13030490",
			"date": "2023-09-19",
			"PMC": "",
			"citation": "",
			"abstract": "DNA mismatch repair deficiency (dMMR) is associated with the microsatellite instability (MSI) phenotype and leads to increased mutation load, which in turn may impact anti-tumor immune responses and treatment effectiveness. Various mutational signatures directly linked to dMMR have been described for primary cancers. To investigate which mutational signatures are associated with prognosis in gastric cancer, we performed a ",
			"category": 2,
			"name": "Buttura Jaqueline Ramalho,2023"
		},
		{
			"PMID": 33513276,
			"title": "Single-cell transcriptomics reveal the intratumoral landscape of infiltrated T-cell subpopulations in oral squamous cell carcinoma.",
			"journal": "Molecular oncology",
			"authorList": [
				"Chen Jingtao",
				"Yang Jiefeng",
				"Li Huan",
				"Yang Zhongyuan",
				"Zhang Xing",
				"Li Xiyuan",
				"Wang Jia",
				"Zhang Ying",
				"Chen Shuwei",
				"Song Ming"
			],
			"DOI": "10.1002/1878-0261.12910",
			"date": "2022-01-14",
			"PMC": "",
			"citation": "",
			"abstract": "Systematic analysis of tumor-infiltrating lymphocytes is essential for the development of new cancer treatments and the prediction of clinical responses to immunotherapy. Immunomodulatory drugs are used for the treatment of oral squamous cell carcinoma (OSCC), depending on immune infiltration profiles of the tumor microenvironment. In this study, we isolated 11,866 single T cells from tumors and paired adjacent normal tissues of three patients with OSCC. Using single-cell RNA sequencing, we identified 14 distinct T-cell subpopulations within the tumors and 5 T-cell subpopulations in the adjacent normal tissues and delineated their developmental trajectories. Exhausted CD8",
			"category": 2,
			"name": "Chen Jingtao,2022"
		},
		{
			"PMID": 33509178,
			"title": "Development and validation of prognostic markers in sarcomas base on a multi-omics analysis.",
			"journal": "BMC medical genomics",
			"authorList": [
				"Song Yongchun",
				"Yang Kui",
				"Sun Tuanhe",
				"Tang Ruixiang"
			],
			"DOI": "10.1186/s12920-021-00876-4",
			"date": "2021-11-25",
			"PMC": "",
			"citation": "",
			"abstract": "In sarcomas, the DNA copy number and DNA methylation exhibit genomic aberrations. Transcriptome imbalances play a driving role in the heterogeneous progression of sarcomas. However, it is still unclear whether abnormalities of DNA copy numbers are systematically related to epigenetic DNA methylation, thus, a comprehensive analysis of sarcoma occurrence and development from the perspective of epigenetic and genomics is required.",
			"category": 2,
			"name": "Song Yongchun,2021"
		},
		{
			"PMID": 33498235,
			"title": "Targeting Non-Oncogene Addiction for Cancer Therapy.",
			"journal": "Biomolecules",
			"authorList": [
				"Chang Hae Ryung",
				"Jung Eunyoung",
				"Cho Soobin",
				"Jeon Young-Jun",
				"Kim Yonghwan"
			],
			"DOI": "10.3390/biom11020129",
			"date": "2021-07-22",
			"PMC": "",
			"citation": "",
			"abstract": "While Next-Generation Sequencing (NGS) and technological advances have been useful in identifying genetic profiles of tumorigenesis, novel target proteins and various clinical biomarkers, cancer continues to be a major global health threat. DNA replication, DNA damage response (DDR) and repair, and cell cycle regulation continue to be essential systems in targeted cancer therapies. Although many genes involved in DDR are known to be tumor suppressor genes, cancer cells are often dependent and addicted to these genes, making them excellent therapeutic targets. In this review, genes implicated in DNA replication, DDR, DNA repair, cell cycle regulation are discussed with reference to peptide or small molecule inhibitors which may prove therapeutic in cancer patients. Additionally, the potential of utilizing novel synthetic lethal genes in these pathways is examined, providing possible new targets for future therapeutics. Specifically, we evaluate the potential of ",
			"category": 2,
			"name": "Chang Hae Ryung,2021"
		},
		{
			"PMID": 33494239,
			"title": "Recent Advances and Implication of Bioengineered Nanomaterials in Cancer Theranostics.",
			"journal": "Medicina (Kaunas, Lithuania)",
			"authorList": [
				"Rai Ayushi",
				"Noor Saba",
				"Ahmad Syed Ishraque",
				"Alajmi Mohamed F",
				"Hussain Afzal",
				"Abbas Hashim",
				"Hasan Gulam Mustafa"
			],
			"DOI": "10.3390/medicina57020091",
			"date": "2021-05-07",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is one of the most common causes of death and affects millions of lives every year. In addition to non-infectious carcinogens, infectious agents contribute significantly to increased incidence of several cancers. Several therapeutic techniques have been used for the treatment of such cancers. Recently, nanotechnology has emerged to advance the diagnosis, imaging, and therapeutics of various cancer types. Nanomaterials have multiple advantages over other materials due to their small size and high surface area, which allow retention and controlled drug release to improve the anti-cancer property. Most cancer therapies have been known to damage healthy cells due to poor specificity, which can be avoided by using nanosized particles. Nanomaterials can be combined with various types of biomaterials to make it less toxic and improve its biocompatibility. Based on these properties, several nanomaterials have been developed which possess excellent anti-cancer efficacy potential and improved diagnosis. This review presents the latest update on novel nanomaterials used to improve the diagnostic and therapeutic of pathogen-associated and non-pathogenic cancers. We further highlighted mechanistic insights into their mode of action, improved features, and limitations.",
			"category": 2,
			"name": "Rai Ayushi,2021"
		},
		{
			"PMID": 33492339,
			"title": "Mechanistic insights into KDM4A driven genomic instability.",
			"journal": "Biochemical Society transactions",
			"authorList": [
				"Young Nicolas L",
				"Dere Ruhee"
			],
			"DOI": "10.1042/BST20191219",
			"date": "2022-01-25",
			"PMC": "",
			"citation": "",
			"abstract": "Alterations in global epigenetic signatures on chromatin are well established to contribute to tumor initiation and progression. Chromatin methylation status modulates several key cellular processes that maintain the integrity of the genome. KDM4A, a demethylase that belongs to the Fe-II dependent dioxygenase family that uses \u03b1-ketoglutarate and molecular oxygen as cofactors, is overexpressed in several cancers and is associated with an overall poor prognosis. KDM4A demethylates lysine 9 (H3K9me2/3) and lysine 36 (H3K36me3) methyl marks on histone H3. Given the complexity that exists with these marks on chromatin and their effects on transcription and proliferation, it naturally follows that demethylation serves an equally important role in these cellular processes. In this review, we highlight the role of KDM4A in transcriptional modulation, either dependent or independent of its enzymatic activity, arising from the amplification of this demethylase in cancer. KDM4A modulates re-replication of distinct genomic loci, activates cell cycle inducers, and represses proteins involved in checkpoint control giving rise to proliferative damage, mitotic disturbances and chromosomal breaks, ultimately resulting in genomic instability. In parallel, emerging evidence of non-nuclear substrates of epigenetic modulators emphasize the need to investigate the role of KDM4A in regulating non-nuclear substrates and evaluate their contribution to genomic instability in this context. The existence of promising KDM-specific inhibitors makes these demethylases an attractive target for therapeutic intervention in cancers.",
			"category": 2,
			"name": "Young Nicolas L,2022"
		},
		{
			"PMID": 33479121,
			"title": "Single-cell lineages reveal the rates, routes, and drivers of metastasis in cancer xenografts.",
			"journal": "Science (New York, N.Y.)",
			"authorList": [
				"Quinn Jeffrey J",
				"Jones Matthew G",
				"Okimoto Ross A",
				"Nanjo Shigeki",
				"Chan Michelle M",
				"Yosef Nir",
				"Bivona Trever G",
				"Weissman Jonathan S"
			],
			"DOI": "10.1126/science.abc1944",
			"date": "2021-03-09",
			"PMC": "",
			"citation": "",
			"abstract": "Detailed phylogenies of tumor populations can recount the history and chronology of critical events during cancer progression, such as metastatic dissemination. We applied a Cas9-based, single-cell lineage tracer to study the rates, routes, and drivers of metastasis in a lung cancer xenograft mouse model. We report deeply resolved phylogenies for tens of thousands of cancer cells traced over months of growth and dissemination. This revealed stark heterogeneity in metastatic capacity, arising from preexisting and heritable differences in gene expression. We demonstrate that these identified genes can drive invasiveness and uncovered an unanticipated suppressive role for ",
			"category": 2,
			"name": "Quinn Jeffrey J,2021"
		},
		{
			"PMID": 33448107,
			"title": "Circulating tumor cell profiling for precision oncology.",
			"journal": "Molecular oncology",
			"authorList": [
				"Labib Mahmoud",
				"Kelley Shana O"
			],
			"DOI": "10.1002/1878-0261.12901",
			"date": "2022-03-21",
			"PMC": "",
			"citation": "",
			"abstract": "Analysis of circulating tumor cells (CTCs) collected from patient's blood offers a broad range of opportunities in the field of precision oncology. With new advances in profiling technology, it is now possible to demonstrate an association between the molecular profiles of CTCs and tumor response to therapy. In this Review, we discuss mechanisms of tumor resistance to therapy and their link to phenotypic and genotypic properties of CTCs. We summarize key technologies used to isolate and analyze CTCs and discuss recent clinical studies that examined CTCs for genomic and proteomic predictors of responsiveness to therapy. We also point out current limitations that still hamper the implementation of CTCs into clinical practice. We finally reflect on how these shortcomings can be addressed with the likely contribution of multiparametric approaches and advanced data analytics.",
			"category": 2,
			"name": "Labib Mahmoud,2022"
		},
		{
			"PMID": 33435206,
			"title": "The Functions and Unique Features of LncRNAs in Cancer Development and Tumorigenesis.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Taniue Kenzui",
				"Akimitsu Nobuyoshi"
			],
			"DOI": "10.3390/ijms22020632",
			"date": "2021-04-07",
			"PMC": "",
			"citation": "",
			"abstract": "Over the past decades, research on cancer biology has focused on the involvement of protein-coding genes in cancer development. Long noncoding RNAs (lncRNAs), which are transcripts longer than 200 nucleotides that lack protein-coding potential, are an important class of RNA molecules that are involved in a variety of biological functions. Although the functions of a majority of lncRNAs have yet to be clarified, some lncRNAs have been shown to be associated with human diseases such as cancer. LncRNAs have been shown to contribute to many important cancer phenotypes through their interactions with other cellular macromolecules including DNA, protein and RNA. Here we describe the literature regarding the biogenesis and features of lncRNAs. We also present an overview of the current knowledge regarding the roles of lncRNAs in cancer from the view of various aspects of cellular homeostasis, including proliferation, survival, migration and genomic stability. Furthermore, we discuss the methodologies used to identify the function of lncRNAs in cancer development and tumorigenesis. Better understanding of the molecular mechanisms involving lncRNA functions in cancer is critical for the development of diagnostic and therapeutic strategies against tumorigenesis.",
			"category": 2,
			"name": "Taniue Kenzui,2021"
		},
		{
			"PMID": 33425983,
			"title": "Biased Influences of Low Tumor Purity on Mutation Detection in Cancer.",
			"journal": "Frontiers in molecular biosciences",
			"authorList": [
				"Cheng Jun",
				"He Jun",
				"Wang Shanshan",
				"Zhao Zhangxiang",
				"Yan Haidan",
				"Guan Qingzhou",
				"Li Jing",
				"Guo Zheng",
				"Ao Lu"
			],
			"DOI": "10.3389/fmolb.2020.533196",
			"date": "2021-01-12",
			"PMC": "",
			"citation": "",
			"abstract": "The non-cancerous components in tumor tissues, e.g., infiltrating stromal cells and immune cells, dilute tumor purity and might confound genomic mutation profile analyses and the identification of pathological biomarkers. It is necessary to systematically evaluate the influence of tumor purity. Here, using public gastric cancer samples from The Cancer Genome Atlas (TCGA), we firstly showed that numbers of mutation, separately called by four algorithms, were significant positively correlated with tumor purities (all ",
			"category": 2,
			"name": "Cheng Jun,2021"
		},
		{
			"PMID": 33424554,
			"title": "Sevoflurane Exposure Induces Neuronal Cell Parthanatos Initiated by DNA Damage in the Developing Brain via an Increase of Intracellular Reactive Oxygen Species.",
			"journal": "Frontiers in cellular neuroscience",
			"authorList": [
				"Piao Meihua",
				"Wang Yingying",
				"Liu Nan",
				"Wang Xuedong",
				"Chen Rui",
				"Qin Jing",
				"Ge Pengfei",
				"Feng Chunsheng"
			],
			"DOI": "10.3389/fncel.2020.583782",
			"date": "2021-01-12",
			"PMC": "",
			"citation": "",
			"abstract": "The safety of volatile anesthetics in infants and young children has been drawing increasing concern due to its potential neurotoxicity in the developing brain. Neuronal death is considered a major factor associated with developmental neurotoxicity after exposure to volatile anesthetics sevoflurane, but its mechanism remains elusive. Parthanatos, a new type of programmed cell death, resulting from poly (ADP-ribose) polymerase 1 (PARP-1) hyperactivation in response to DNA damage, was found to account for the pathogenesis of multiple neurological disorders. However, the role of Parthanatos in sevoflurane-induced neonatal neuronal cell death has not been investigated. To test it, neuronal cells treated with 2, 4, and 8% sevoflurane for 6, 12, and 24 h and postnatal day 7 rats exposed to 2.5% sevoflurane for 6 h were used in the present study. Our results found sevoflurane exposure induced neuronal cell death, which was accompanied by PARP-1 hyperactivation, cytoplasmic polymerized ADP-ribose (PAR) accumulation, mitochondrial depolarization, and apoptosis-inducing factor (AIF) nuclear translocation in the neuronal cells and hippocampi of rats. Pharmacological or genetic inhibition of PAPR-1 significantly alleviated sevoflurane-induced neuronal cell death and accumulation of PAR polymer and AIF nuclear translocation, which were consistent with the features of Parthanatos. We observed ",
			"category": 2,
			"name": "Piao Meihua,2021"
		},
		{
			"PMID": 33423960,
			"title": "Untangling a complex web: Computational analyses of tumor molecular profiles to decode driver mechanisms.",
			"journal": "Journal of genetics and genomics = Yi chuan xue bao",
			"authorList": [
				"Khalighi Sirvan",
				"Singh Salendra",
				"Varadan Vinay"
			],
			"DOI": "10.1016/j.jgg.2020.11.001",
			"date": "2021-08-13",
			"PMC": "",
			"citation": "",
			"abstract": "Genome-scale studies focusing on molecular profiling of cancers across tissue types have revealed a plethora of aberrations across the genomic, transcriptomic, and epigenomic scales. The significant molecular heterogeneity across individual tumors even within the same tissue context complicates decoding the key etiologic mechanisms of this disease. Furthermore, it is increasingly likely that biologic mechanisms underlying the pathobiology of cancer involve multiple molecular entities interacting across functional scales. This has motivated the development of computational approaches that integrate molecular measurements with prior biological knowledge in increasingly intricate ways to enable the discovery of driver genomic aberrations across cancers. Here, we review diverse methodological approaches that have powered significant advances in our understanding of the genomic underpinnings of cancer at the cohort and at the individual tumor scales. We outline the key advances and challenges in the computational discovery of cancer mechanisms while motivating the development of systems biology approaches to comprehensively decode the biologic drivers of this complex disease.",
			"category": 2,
			"name": "Khalighi Sirvan,2021"
		},
		{
			"PMID": 33419895,
			"title": "Noncoding RNAs Serve as the Deadliest Universal Regulators of all Cancers.",
			"journal": "Cancer genomics & proteomics",
			"authorList": [
				"Wang Anyou",
				"Hai Rong"
			],
			"DOI": "10.21873/cgp.20240",
			"date": "2021-08-20",
			"PMC": "",
			"citation": "",
			"abstract": "Numerous cancer drivers have been identified, but they are specific to a given cancer type and condition; universal cancer drivers and universal cancer mechanisms still remain largely unclear. Here, we identified the deadliest universal drivers for all cancers via developing algorithms to analyze massive RNAseqs and clinical data from The Cancer Genome Atlas (TCGA). In general, noncoding RNAs primarily serve as the most important inducers and suppressors for all types of cancers. In particular, pseudogenes are primary inducers, and specifically the antisense RNA RP11-335K5.2 serves as the most universal cancerous driver, independently of the cancer type and condition. Therefore, noncoding RNAs, instead of proteins as conventionally thought, primarily drive cancer, which establishes a novel field for future cancer research and therapy.",
			"category": 2,
			"name": "Wang Anyou,2021"
		},
		{
			"PMID": 33408844,
			"title": "The molecular pathogenesis of multiple myeloma.",
			"journal": "Hematology reports",
			"authorList": [
				"Bolli Niccol\u00f2",
				"Martinelli Giovanni",
				"Cerchione Claudio"
			],
			"DOI": "10.4081/hr.2020.9054",
			"date": "2023-11-10",
			"PMC": "",
			"citation": "",
			"abstract": "Multiple Myeloma (MM) is characterized by uncontrolled proliferation and accumulation of clonal plasma cells within the bone marrow. However, the cell of origin is a B-lymphocyte acquiring aberrant genomic events in the germinal center of a lymph node as off-target events during somatichypermutation and class-switch recombination driven by activation-induced-deaminase. Whether pre-germinal center events are also required for transformation, and which additional events are required for disease progression is still matter of debate. As early treatment in asymptomatic phases is gaining traction in the clinic, a better understanding of the molecular pathogenesis of myeloma progression would allow stratification of patients based on their risk of progression, thus rationalizing efficacy and cost of clinical interventions. In this review, we will discuss the development of MM, from the cell of origin through asymptomatic stages such as monoclonal gammopathy of undetermined significance and smoldering MM, to the development of symptomatic disease. We will explain the genetic heterogeneity of MM, one of the major drivers of disease recurrence. In this context, moreover, we will propose how this knowledge may influence future diagnostic and therapeutic interventions.",
			"category": 2,
			"name": "Bolli Niccol\u00f2,2023"
		},
		{
			"PMID": 33402975,
			"title": "Determination of expression profile of p53 gene in different grades of breast cancer tissues by real time PCR.",
			"journal": "African health sciences",
			"authorList": [
				"Sadia Haleema",
				"Bhinder Munir Ahmad",
				"Irshad Asma",
				"Zahid Beenish",
				"Ahmed Rais",
				"Ashiq Sana",
				"Malik Kausar",
				"Riaz Muhammad",
				"Nadeem Tariq",
				"Ashiq Kanwal",
				"Akbar Ali"
			],
			"DOI": "10.4314/ahs.v20i3.32",
			"date": "2021-06-30",
			"PMC": "",
			"citation": "",
			"abstract": "Pakistan has a high incidence of breast cancer in Asia, where annually 16,232 deaths are reported. There are many exogenous and endogenous risk factors that affect the tumor suppressor genes and oncogenes. The p53 gene is a tumor suppressor gene and it has a role to protect the whole genome from external and internal stresses, which causes damages to the genome.",
			"category": 2,
			"name": "Sadia Haleema,2021"
		},
		{
			"PMID": 33381450,
			"title": "Identification of Somatic Mutations in Papanicolaou Smear DNA and Plasma Circulating Cell-Free DNA for Detection of Endometrial and Epithelial Ovarian Cancers: A Pilot Study.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Jiang Xuan",
				"Li Weihua",
				"Yang Jiaxin",
				"Wang Shuzhen",
				"Cao Dongyan",
				"Yu Mei",
				"Shen Keng",
				"Bai Jian",
				"Gao Yang"
			],
			"DOI": "10.3389/fonc.2020.582546",
			"date": "2022-04-19",
			"PMC": "",
			"citation": "",
			"abstract": "The aim of this study was to identify tumor-derived DNA from Papanicolaou (Pap) smear and plasma specimens collected from patients with endometrial cancer or atypical hyperplasia (EC/AH) or epithelial ovarian cancer (OC).",
			"category": 2,
			"name": "Jiang Xuan,2022"
		},
		{
			"PMID": 33314633,
			"title": "Predictive Biomarkers for Immune Checkpoint Inhibitors in Metastatic Breast Cancer.",
			"journal": "Cancer medicine",
			"authorList": [
				"Sivapiragasam Abirami",
				"Ashok Kumar Prashanth",
				"Sokol Ethan S",
				"Albacker Lee A",
				"Killian Jonathan K",
				"Ramkissoon Shakti H",
				"Huang Richard S P",
				"Severson Eric A",
				"Brown Charlotte A",
				"Danziger Natalie",
				"McGregor Kimberly",
				"Ross Jeffrey S"
			],
			"DOI": "10.1002/cam4.3550",
			"date": "2021-07-20",
			"PMC": "",
			"citation": "",
			"abstract": "We examined a large dataset of female metastatic breast cancers (MBCs) profiled with comprehensive genomic profiling (CGP) to identify the prevalence and distribution of immunotherapy responsiveness-associated biomarkers. DNA was extracted from 3831 consecutive MBCs: 1237 (ER",
			"category": 2,
			"name": "Sivapiragasam Abirami,2021"
		},
		{
			"PMID": 33307203,
			"title": "The effect of age on the acquisition and selection of cancer driver mutations in sun-exposed normal skin.",
			"journal": "Annals of oncology : official journal of the European Society for Medical Oncology",
			"authorList": [
				"Hernando B",
				"Dietzen M",
				"Parra G",
				"Gil-Barrachina M",
				"Pitarch G",
				"Mahiques L",
				"Valcuende-Cavero F",
				"McGranahan N",
				"Martinez-Cadenas C"
			],
			"DOI": "10.1016/j.annonc.2020.11.023",
			"date": "2021-03-05",
			"PMC": "",
			"citation": "",
			"abstract": "The accumulation of somatic mutations contributes to ageing and cancer. Sunlight is the principal aetiological factor associated with skin cancer development. However, genetic and phenotypic factors also contribute to skin cancer risk. This study aimed at exploring the role of photoaging, as well as other well-known epidemiological risk factors, in the accumulation of somatic mutations in cancer-free human epidermis.",
			"category": 2,
			"name": "Hernando B,2021"
		},
		{
			"PMID": 33283171,
			"title": "A Journey Through Myeloma Evolution: From the Normal Plasma Cell to Disease Complexity.",
			"journal": "HemaSphere",
			"authorList": [
				"Da Vi\u00e0 Matteo C",
				"Ziccheddu Bachisio",
				"Maeda Akihiro",
				"Bagnoli Filippo",
				"Perrone Giulia",
				"Bolli Niccol\u00f2"
			],
			"DOI": "10.1097/HS9.0000000000000502",
			"date": "2024-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "The knowledge of cancer origin and the subsequent tracking of disease evolution represent unmet needs that will soon be within clinical reach. This will provide the opportunity to improve patient's stratification and to personalize treatments based on cancer biology along its life history. In this review, we focus on the molecular pathogenesis of multiple myeloma (MM), a hematologic malignancy with a well-known multi-stage disease course, where such approach can sooner translate into a clinical benefit. We describe novel insights into modes and timing of disease initiation. We dissect the biology of the preclinical and pre-malignant phases, elucidating how knowledge of the genomics of the disease and the composition of the microenvironment allow stratification of patients based on risk of disease progression. Then, we explore cell-intrinsic and cell-extrinsic drivers of MM evolution to symptomatic disease. Finally, we discuss how this may relate to the development of refractory disease after treatment. By integrating an evolutionary view of myeloma biology with the recent acquisitions on its clonal heterogeneity, we envision a way to drive the clinical management of the disease based on its detailed biological features more than surrogates of disease burden.",
			"category": 2,
			"name": "Da Vi\u00e0 Matteo C,2024"
		},
		{
			"PMID": 33235715,
			"title": "Potential anticancer activity of Mn (II) complexes containing arginine dithiocarbamate ligand on MCF-7 breast cancer cell lines.",
			"journal": "Annals of medicine and surgery (2012)",
			"authorList": [
				"Irfandi Rizal",
				"Raya Indah"
			],
			"DOI": "10.1016/j.amsu.2020.11.018",
			"date": "2022-04-18",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer refer to genetic changes in the DNA structure accompanied by abnormal growth of normal cells, and resulting in the death of these structures, and is a disease currently recognized as a major cause of mortality globally. Chemotherapy plays important role in breast cancer management. Non-toxic metals have been developed to replace the highly toxic cisplatin, an example being Manganese. Furthermore, Ligands have displayed great capabilities in the determination of anticancer properties, and an essential agent exploited in drug development is arginine dithiocarbamate. Therefore, this study was conducted to examine the anticancer potentials of Mn (II) arginine dithiocarbamate.",
			"category": 2,
			"name": "Irfandi Rizal,2022"
		},
		{
			"PMID": 33212364,
			"title": "Patient-derived xenograft (PDX) models of colorectal carcinoma (CRC) as a platform for chemosensitivity and biomarker analysis in personalized medicine.",
			"journal": "Neoplasia (New York, N.Y.)",
			"authorList": [
				"Rivera Maria",
				"Fichtner Iduna",
				"Wulf-Goldenberg Annika",
				"Sers Christine",
				"Merk Johannes",
				"Patone Giannino",
				"Alp Keziban M",
				"Kanashova Tamara",
				"Mertins Philipp",
				"Hoffmann Jens",
				"Stein Ulrike",
				"Walther Wolfgang"
			],
			"DOI": "10.1016/j.neo.2020.11.005",
			"date": "2021-10-04",
			"PMC": "",
			"citation": "",
			"abstract": "Patient-derived xenograft (PDX) tumor models represent a valuable platform for identifying new biomarkers and novel targets, to evaluate therapy response and resistance mechanisms. This study aimed at establishment, characterization and therapy testing of colorectal carcinoma-derived PDX. We generated 49 PDX and validated identity between patient tumor and corresponding PDX. Sensitivity of PDX toward conventional and targeted drugs revealed that 92% of PDX responded toward irinotecan, 45% toward 5-FU, 65% toward bevacizumab, and 61% toward cetuximab. Expression of epidermal growth factor receptor (EGFR) ligands correlated to the sensitivity toward cetuximab. Proto-oncogene B-RAF, EGFR, Kirsten rat sarcoma virus oncogene homolog gene copy number correlated positively with cetuximab and erlotinib sensitivity. The mutational analyses revealed an individual mutational profile of PDX and mainly identical profiles of PDX from primary tumor vs corresponding metastasis. Mutation in PIK3CA was a determinant of accelerated tumor doubling time. PDX with wildtype Kirsten rat sarcoma virus oncogene homolog, proto-oncogene B-RAF, and phosphatidylinositol-4,5-bisphosphate 3-kinaseM catalytic subunit alfa showed higher sensitivity toward cetuximab and erlotinib. To study the molecular mechanism of cetuximab resistance, cetuximab resistant PDX models were generated, and changes in HER2, HER3, betacellulin, transforming growth factor alfa were observed. Global proteome and phosphoproteome profiling showed a reduction in canonical EGFR-mediated signaling via PTPN11 (SHP2) and AKT1S1 (PRAS40) and an increase in anti-apoptotic signaling as a consequence of acquired cetuximab resistance. This demonstrates that PDX models provide a multitude of possibilities to identify and validate biomarkers, signaling pathways and resistance mechanisms for clinically relevant improvement in cancer therapy.",
			"category": 2,
			"name": "Rivera Maria,2021"
		},
		{
			"PMID": 33199048,
			"title": "Hotspots of Human Mutation.",
			"journal": "Trends in genetics : TIG",
			"authorList": [
				"Nesta Alex V",
				"Tafur Denisse",
				"Beck Christine R"
			],
			"DOI": "10.1016/j.tig.2020.10.003",
			"date": "2021-09-07",
			"PMC": "",
			"citation": "",
			"abstract": "Mutation of the human genome results in three classes of genomic variation: single nucleotide variants; short insertions or deletions; and large structural variants (SVs). Some mutations occur during normal processes, such as meiotic recombination or B cell development, and others result from DNA replication or aberrant repair of breaks in sequence-specific contexts. Regardless of mechanism, mutations are subject to selection, and some hotspots can manifest in disease. Here, we discuss genomic regions prone to mutation, mechanisms contributing to mutation susceptibility, and the processes leading to their accumulation in normal and somatic genomes. With further, more accurate human genome sequencing, additional mutation hotspots, mechanistic details of their formation, and the relevance of hotspots to evolution and disease are likely to be discovered.",
			"category": 2,
			"name": "Nesta Alex V,2021"
		},
		{
			"PMID": 33168834,
			"title": "CaMuS: simultaneous fitting and de novo imputation of cancer mutational signature.",
			"journal": "Scientific reports",
			"authorList": [
				"Cartolano Maria",
				"Abedpour Nima",
				"Achter Viktor",
				"Yang Tsun-Po",
				"Ackermann Sandra",
				"Fischer Matthias",
				"Peifer Martin"
			],
			"DOI": "10.1038/s41598-020-75753-8",
			"date": "2021-04-30",
			"PMC": "",
			"citation": "",
			"abstract": "The identification of the mutational processes operating in tumour cells has implications for cancer diagnosis and therapy. These processes leave mutational patterns on the cancer genomes, which are referred to as mutational signatures. Recently, 81 mutational signatures have been inferred using computational algorithms on sequencing data of 23,879 samples. However, these published signatures may not always offer a comprehensive view on the biological processes underlying tumour types that are not included or underrepresented in the reference studies. To circumvent this problem, we designed CaMuS (Cancer Mutational Signatures) to construct de novo signatures while simultaneously fitting publicly available mutational signatures. Furthermore, we propose to estimate signature similarity by comparing probability distributions using the Hellinger distance. We applied CaMuS to infer signatures of mutational processes in poorly studied cancer types. We used whole genome sequencing data of 56 neuroblastoma, thus providing evidence for the versatility of CaMuS. Using simulated data, we compared the performance of CaMuS to sigfit, a recently developed algorithm with comparable inference functionalities. CaMuS and sigfit reconstructed the simulated datasets with similar accuracy; however two main features may argue for CaMuS over sigfit: (i) superior computational performance and (ii) a reliable parameter selection method to avoid spurious signatures.",
			"category": 2,
			"name": "Cartolano Maria,2021"
		},
		{
			"PMID": 33144218,
			"title": "Defining the clinical genomic landscape for real-world precision oncology.",
			"journal": "Genomics",
			"authorList": [
				"Beer Philip A",
				"Cooke Susanna L",
				"Chang David K",
				"Biankin Andrew V"
			],
			"DOI": "10.1016/j.ygeno.2020.10.032",
			"date": "2021-08-19",
			"PMC": "",
			"citation": "",
			"abstract": "Through the delivery of large international projects including ICGC and TCGA, knowledge of cancer genomics is reaching saturation point. Enabling this to improve patient outcomes now requires embedding comprehensive genomic profiling into routine oncology practice. Towards this goal, this study defined the biologically and clinically relevant genomic features of adult cancer through detailed curation and analysis of large genomic datasets, accumulated literature and biomarker-driven therapeutics in clinic and development. The characteristics and prevalence of these features were then interrogated in 2348 whole genome sequences, covering 21 solid tumour types, generated by the PCAWG project. This analysis highlights the predominant contribution of copy number alterations and identifies a critical role for disruptive structural variants in the inactivation of clinically important tumour suppressor genes, including PTEN and RB1, which are not currently captured by diagnostic assays. This study defines a set of essential genomic features for the characterisation of common adult cancers.",
			"category": 2,
			"name": "Beer Philip A,2021"
		},
		{
			"PMID": 33141183,
			"title": "Splicing machinery dysregulation drives glioblastoma development/aggressiveness: oncogenic role of SRSF3.",
			"journal": "Brain : a journal of neurology",
			"authorList": [
				"Fuentes-Fayos Antonio C",
				"V\u00e1zquez-Borrego Mari C",
				"Jim\u00e9nez-Vacas Juan M",
				"Bejarano Leire",
				"Pedraza-Ar\u00e9valo Sergio",
				"L-L\u00f3pez Fernando",
				"Blanco-Acevedo Crist\u00f3bal",
				"S\u00e1nchez-S\u00e1nchez Rafael",
				"Reyes Oscar",
				"Ventura Sebasti\u00e1n",
				"Solivera Juan",
				"Breunig Joshua J",
				"Blasco Mar\u00eda A",
				"Gahete Manuel D",
				"Casta\u00f1o Justo P",
				"Luque Ra\u00fal M"
			],
			"DOI": "10.1093/brain/awaa273",
			"date": "2021-03-01",
			"PMC": "",
			"citation": "",
			"abstract": "Glioblastomas remain the deadliest brain tumour, with a dismal \u223c12-16-month survival from diagnosis. Therefore, identification of new diagnostic, prognostic and therapeutic tools to tackle glioblastomas is urgently needed. Emerging evidence indicates that the cellular machinery controlling the splicing process (spliceosome) is altered in tumours, leading to oncogenic splicing events associated with tumour progression and aggressiveness. Here, we identify for the first time a profound dysregulation in the expression of relevant spliceosome components and splicing factors (at mRNA and protein levels) in well characterized cohorts of human high-grade astrocytomas, mostly glioblastomas, compared to healthy brain control samples, being SRSF3, RBM22, PTBP1 and RBM3 able to perfectly discriminate between tumours and control samples, and between proneural-like or mesenchymal-like tumours versus control samples from different mouse models with gliomas. Results were confirmed in four additional and independent human cohorts. Silencing of SRSF3, RBM22, PTBP1 and RBM3 decreased aggressiveness parameters in vitro (e.g. proliferation, migration, tumorsphere-formation, etc.) and induced apoptosis, especially SRSF3. Remarkably, SRSF3 was correlated with patient survival and relevant tumour markers, and its silencing in vivo drastically decreased tumour development and progression, likely through a molecular/cellular mechanism involving PDGFRB and associated oncogenic signalling pathways (PI3K-AKT/ERK), which may also involve the distinct alteration of alternative splicing events of specific transcription factors controlling PDGFRB (i.e. TP73). Altogether, our results demonstrate a drastic splicing machinery-associated molecular dysregulation in glioblastomas, which could potentially be considered as a source of novel diagnostic and prognostic biomarkers as well as therapeutic targets for glioblastomas. Remarkably, SRSF3 is directly associated with glioblastoma development, progression, aggressiveness and patient survival and represents a novel potential therapeutic target to tackle this devastating pathology.",
			"category": 2,
			"name": "Fuentes-Fayos Antonio C,2021"
		},
		{
			"PMID": 33126384,
			"title": "The single nucleotide polymorphisms of interleukin-10 are associated with the risk of leukaemia: Evidence from 18 case-control studies.",
			"journal": "Medicine",
			"authorList": [
				"Gao Shupei",
				"Tang Kun",
				"Chen Jinqing",
				"Wang Jianmiao"
			],
			"DOI": "10.1097/MD.0000000000023006",
			"date": "2020-11-11",
			"PMC": "",
			"citation": "",
			"abstract": "Interleukin-10(IL-10) is an immunosuppressive cytokine and plays an important role in inflammation and cancers. Numerous studies have explored the association between single nucleotide polymorphisms of IL-10 and leukemia, but their results were conflicting, so we performed this meta-analysis to elucidate the association between 3 common single nucleotide polymorphisms of IL-10 (rs1800896, rs1800871 and rs1800872) and risk of leukemia.We conducted a comprehensive research in Pubmed, Chinese Biomedical Literature Database disc and Embase using related terms. After strict selection, 18 studies with 2264 cases and 3846 controls were included into this meta-analysis. Odds ratio and 95% confidence interval were used to evaluate the strength of the association.We found that polymorphism of IL-10\u200a-1082A/G was associated with decreased risk of leukemia both in overall analysis and in stratified analysis according to ethnicity and cancer type. A strong relationship was also uncovered between polymorphism of IL-10\u200a-592C/A and increased risk of leukemia in non-Chinese.GG genotype of IL-10\u200a-1082A/G is associated with decreased risk of leukemia, especially chronic lymphocytic leukemia. CC genotype of -592C/A is associated with decreased risk of leukemia in non-Chinese.",
			"category": 2,
			"name": "Gao Shupei,2020"
		},
		{
			"PMID": 33116814,
			"title": "Breast Cancer and Tamoxifen: A Nigerian Perspective to Effective Personalised Therapy.",
			"journal": "Breast cancer (Dove Medical Press)",
			"authorList": [
				"Adehin Ayorinde",
				"Kennedy Martin Alexander",
				"Soyinka Julius Olugbenga",
				"Alatise Olusegun Isaac",
				"Olasehinde Olalekan",
				"Bolaji Oluseye Oladotun"
			],
			"DOI": "10.2147/BCTT.S266314",
			"date": "2020-10-30",
			"PMC": "",
			"citation": "",
			"abstract": "Estrogen-receptor positivity in tumour, often requiring long-term tamoxifen therapy, is thought to characterise between 43% and 65% of breast cancer cases in Nigeria. The patient population is further marked by late-stage diagnosis which significantly heightens the tendency for tumour relapse in the course of tamoxifen therapy. Despite tamoxifen being considered a reliable chemopreventive in high-risk individuals and an effective adjuvant therapy for hormone-sensitive tumours, mortality has remained high among breast cancer patients in the West African region where Nigeria belongs. The Nigerian breast cancer population, like other similar patient-populations in the West African region, provides a mix of intrinsic genome-diversity and perhaps unique tumour biology and evolution. These peculiarities suggest the need for a rational approach to tumour management and a personalised delivery of therapy in Nigeria's dominant estrogen-receptor-positive patient population. Herein, critical indices of tamoxifen-therapy success are discussed in the context of the Nigerian breast cancer population with emphasis on salient aspects of tamoxifen-biotransformation, host- and tumour-genomics, and epigenetics.",
			"category": 2,
			"name": "Adehin Ayorinde,2020"
		},
		{
			"PMID": 33106540,
			"title": "MutSignatures: an R package for extraction and analysis of cancer mutational signatures.",
			"journal": "Scientific reports",
			"authorList": [
				"Fantini Damiano",
				"Vidimar Vania",
				"Yu Yanni",
				"Condello Salvatore",
				"Meeks Joshua J"
			],
			"DOI": "10.1038/s41598-020-75062-0",
			"date": "2021-03-12",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer cells accumulate somatic mutations as result of DNA damage, inaccurate repair and other mechanisms. Different genetic instability processes result in characteristic non-random patterns of DNA mutations, also known as mutational signatures. We developed mutSignatures, an integrated R-based computational framework aimed at deciphering DNA mutational signatures. Our software provides advanced functions for importing DNA variants, computing mutation types, and extracting mutational signatures via non-negative matrix factorization. Specifically, mutSignatures accepts multiple types of input data, is compatible with non-human genomes, and supports the analysis of non-standard mutation types, such as tetra-nucleotide mutation types. We applied mutSignatures to analyze somatic mutations found in smoking-related cancer datasets. We characterized mutational signatures that were consistent with those reported before in independent investigations. Our work demonstrates that selected mutational signatures correlated with specific clinical and molecular features across different cancer types, and revealed complementarity of specific mutational patterns that has not previously been identified. In conclusion, we propose mutSignatures as a powerful open-source tool for detecting the molecular determinants of cancer and gathering insights into cancer biology and treatment.",
			"category": 2,
			"name": "Fantini Damiano,2021"
		},
		{
			"PMID": 33099473,
			"title": "The KDR (VEGFR-2) Genetic Polymorphism Q472H and c-KIT Polymorphism M541L Are Associated With More Aggressive Behaviour in Astrocytic Gliomas.",
			"journal": "Cancer genomics & proteomics",
			"authorList": [
				"Zaman Niyaz",
				"Dass Serena Santhana",
				"DU Parcq Persephone",
				"Macmahon Suzanne",
				"Gallagher Lewis",
				"Thompson Lisa",
				"Khorashad Jamshid S",
				"Limb\u00c4ck-Stanic Clara"
			],
			"DOI": "10.21873/cgp.20226",
			"date": "2021-06-21",
			"PMC": "",
			"citation": "",
			"abstract": "Better diagnostic and prognostic markers are required for a more accurate diagnosis and an earlier detection of glioma progression and for suggesting better treatment strategies. This retrospective study aimed to identify actionable gene variants to define potential markers of clinical significance.",
			"category": 2,
			"name": "Zaman Niyaz,2021"
		},
		{
			"PMID": 33099186,
			"title": "Landscape of clinically actionable mutations in breast cancer 'A cohort study'.",
			"journal": "Translational oncology",
			"authorList": [
				"Ghosh Mithua",
				"Naik Radheshyam",
				"Lingaraju Sheela Mysore",
				"Susheela Sridhar Papaiah",
				"Patil Shekar",
				"Srinivasachar Gopinath Kodaganur",
				"Thungappa Satheesh Chiradoni",
				"Murugan Krithika",
				"Jayappa Srinivas Belagutty",
				"Bhattacharjee Somorat",
				"Rao Nalini",
				"Bandimegal Mahesh",
				"Krishnappa Roopesh",
				"Poppareddy Shashidhara Haragadde",
				"Raghavendrachar Krishna Chennagiri",
				"Shivakumar Yogesh",
				"Nagesh Sunitha",
				"Kodandapani Ramya",
				"Rajan Ashwini",
				"Bahadur Urvashi",
				"Agrawal Pooja",
				"Ramaswamy Veena",
				"Nanjaiah Tejaswini Bangalore",
				"Kunigal Sateesh",
				"Katragadda Shanmukh",
				"Manjunath Ashwini",
				"Ram Amritanshu",
				"Ajaikumar Basavalinga S"
			],
			"DOI": "10.1016/j.tranon.2020.100877",
			"date": "2024-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer (BC) is a heterogeneous disease. Numerous chemotherapeutic agents are available for early stage or advanced/metastatic breast cancer to provide maximum benefit with minimum side effects. However, the clinical outcome of patients with the same clinical and pathological characteristics and treated with similar treatments may show major differences and a vast majority of patients still develop treatment resistance and eventually succumb to disease. It remains an unmet need to identify specific molecular defects, new biomarkers to enable clinicians to adopt individualized treatment for every patient in terms of endocrine, chemotherapy or targeted therapy which will improve clinical outcomes in BC. Our study aimed to identify frequent hotspot mutation profile in BC by targeted deep sequencing in cancer-related genes using Illumina Truseq amplicon/Swift Accel-Amplicon panel and MiSeq technology in an IRB-approved prospective study in a CLIA compliant laboratory. All the cases had pathology review for stage, histological type, hormonal status and Ki-67. Data was processed using Strand NGS\u2122. Mutations identified in the tumor were assessed for 'actionability' i.e. response to therapy and impact on prognosis.",
			"category": 2,
			"name": "Ghosh Mithua,2024"
		},
		{
			"PMID": 33083472,
			"title": "Application of BERT to Enable Gene Classification Based on Clinical Evidence.",
			"journal": "BioMed research international",
			"authorList": [
				"Su Yuhan",
				"Xiang Hongxin",
				"Xie Haotian",
				"Yu Yong",
				"Dong Shiyan",
				"Yang Zhaogang",
				"Zhao Na"
			],
			"DOI": "10.1155/2020/5491963",
			"date": "2021-05-03",
			"PMC": "",
			"citation": "",
			"abstract": "The identification of profiled cancer-related genes plays an essential role in cancer diagnosis and treatment. Based on literature research, the classification of genetic mutations continues to be done manually nowadays. Manual classification of genetic mutations is pathologist-dependent, subjective, and time-consuming. To improve the accuracy of clinical interpretation, scientists have proposed computational-based approaches for automatic analysis of mutations with the advent of next-generation sequencing technologies. Nevertheless, some challenges, such as multiple classifications, the complexity of texts, redundant descriptions, and inconsistent interpretation, have limited the development of algorithms. To overcome these difficulties, we have adapted a deep learning method named Bidirectional Encoder Representations from Transformers (BERT) to classify genetic mutations based on text evidence from an annotated database. During the training, three challenging features such as the extreme length of texts, biased data presentation, and high repeatability were addressed. Finally, the BERT+abstract demonstrates satisfactory results with 0.80 logarithmic loss, 0.6837 recall, and 0.705 ",
			"category": 2,
			"name": "Su Yuhan,2021"
		},
		{
			"PMID": 33057820,
			"title": "Cancer research using organoid technology.",
			"journal": "Journal of molecular medicine (Berlin, Germany)",
			"authorList": [
				"Kretzschmar Kai"
			],
			"DOI": "10.1007/s00109-020-01990-z",
			"date": "2021-11-29",
			"PMC": "",
			"citation": "",
			"abstract": "Organoid technology has rapidly transformed basic biomedical research and contributed to significant discoveries in the last decade. With the application of protocols to generate organoids from cancer tissue, organoid technology has opened up new opportunities for cancer research and therapy. Using organoid cultures derived from healthy tissues, different aspects of tumour initiation and progression are widely studied including the role of pathogens or specific cancer genes. Cancer organoid cultures, on the other hand, are applied to generate biobanks, perform drug screens, and study mutational signatures. With the incorporation of cellular components of the tumour microenvironment such as immune cells into the organoid cultures, the technology is now also exploited in the rapidly advancing field of immuno-oncology. In this review, I discuss how organoid technology is currently being utilised in cancer research and what obstacles are still to be overcome for its broader use in anti-cancer therapy.",
			"category": 2,
			"name": "Kretzschmar Kai,2021"
		},
		{
			"PMID": 33042282,
			"title": "Comprehensive characterization of functional eRNAs in lung adenocarcinoma reveals novel regulators and a prognosis-related molecular subtype.",
			"journal": "Theranostics",
			"authorList": [
				"Qin Na",
				"Ma Zijian",
				"Wang Cheng",
				"Zhang Erbao",
				"Li Yuancheng",
				"Huang Mingtao",
				"Chen Congcong",
				"Zhang Chang",
				"Fan Jingyi",
				"Gu Yayun",
				"Xu Xianfeng",
				"Yang Liu",
				"Wei Xiaoxia",
				"Yin Rong",
				"Jiang Yue",
				"Dai Juncheng",
				"Jin Guangfu",
				"Xu Lin",
				"Hu Zhibin",
				"Shen Hongbing",
				"Ma Hongxia"
			],
			"DOI": "10.7150/thno.47039",
			"date": "2021-06-07",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "Qin Na,2021"
		},
		{
			"PMID": 33015626,
			"title": "Characteristics of mutational signatures of unknown etiology.",
			"journal": "NAR cancer",
			"authorList": [
				"Hu Xiaoju",
				"Xu Zhuxuan",
				"De Subhajyoti"
			],
			"DOI": "10.1093/narcan/zcaa026",
			"date": "2023-07-01",
			"PMC": "",
			"citation": "",
			"abstract": "Although not all somatic mutations are cancer drivers, their mutational signatures, i.e. the patterns of genomic alterations at a genome-wide scale, provide insights into past exposure to mutagens, DNA damage and repair processes. Computational deconvolution of somatic mutation patterns and expert curation pan-cancer studies have identified a number of mutational signatures associated with point mutations, dinucleotide substitutions, insertions and deletions, and rearrangements,\u00a0and have established etiologies for a subset of these signatures. However, the mechanisms underlying nearly one-third of all mutational signatures are not yet understood. The signatures with established etiology and those with hitherto unknown origin appear to have some differences in strand bias, GC content and nucleotide context diversity. It is possible that some of the hitherto 'unknown' signatures predominantly occur outside gene regions. While nucleotide contexts might be adequate to establish etiologies of some mutational signatures, in other cases additional features, such as broader (epi)genomic contexts, including chromatin, replication timing, processivity and local mutational patterns, may help fully understand the underlying DNA damage and repair processes.\u00a0Nonetheless, remarkable progress in characterization of mutational signatures has provided fundamental insights into the biology of cancer, informed disease etiology and opened up new opportunities for cancer prevention, risk management, and therapeutic decision making.",
			"category": 2,
			"name": "Hu Xiaoju,2023"
		},
		{
			"PMID": 33009502,
			"title": "Deep phylogeny of cancer drivers and compensatory mutations.",
			"journal": "Communications biology",
			"authorList": [
				"Rochman Nash D",
				"Wolf Yuri I",
				"Koonin Eugene V"
			],
			"DOI": "10.1038/s42003-020-01276-7",
			"date": "2021-06-21",
			"PMC": "",
			"citation": "",
			"abstract": "Driver mutations (DM) are the genetic impetus for most cancers. The DM are assumed to be deleterious in species evolution, being eliminated by purifying selection unless compensated by other mutations. We present deep phylogenies for 84 cancer driver genes and investigate the prevalence of 434 DM across gene-species trees. The DM are rare in species evolution, and 181 are completely absent, validating their negative fitness effect. The DM are more common in unicellular than in multicellular eukaryotes, suggesting a link between these mutations and cell proliferation control. 18 DM appear as the ancestral state in one or more major clades, including 3 among mammals. We identify within-gene, compensatory mutations for 98 DM and infer likely interactions between the DM and compensatory sites in protein structures. These findings elucidate the evolutionary status of DM and are expected to advance the understanding of the functions and evolution of oncogenes and tumor suppressors.",
			"category": 2,
			"name": "Rochman Nash D,2021"
		},
		{
			"PMID": 33008377,
			"title": "Highly multiplexed quantifications of 299 somatic mutations in colorectal cancer patients by automated MALDI-TOF mass spectrometry.",
			"journal": "BMC medical genomics",
			"authorList": [
				"Xu Chang",
				"Peng Danli",
				"Li Jialu",
				"Chen Meihua",
				"Hu Yujie",
				"Hou Mingliang",
				"Shang Qingjuan",
				"Liang Qi",
				"Li Jie",
				"Li Wenfeng",
				"Wu Xiaoli",
				"Liu Changbao",
				"Hu Wanle",
				"Cai Mao",
				"Zhang Huxiang",
				"Chen Guorong",
				"Yu Lingling",
				"Zheng Xiaoqun",
				"Jiang Feizhao",
				"Luan Ju",
				"Jin Shengnan",
				"Ding Chunming"
			],
			"DOI": "10.1186/s12920-020-00804-y",
			"date": "2021-05-10",
			"PMC": "",
			"citation": "",
			"abstract": "Detection of somatic mutations in tumor tissues helps to understand tumor biology and guide treatment selection. Methods such as quantitative PCR can analyze a few mutations with high efficiency, while next generation sequencing (NGS) based methods can analyze hundreds to thousands of mutations. However, there is a lack of cost-effective method for quantitatively analyzing tens to a few hundred mutations of potential biological and clinical significance.",
			"category": 2,
			"name": "Xu Chang,2021"
		},
		{
			"PMID": 32999836,
			"title": "Charge and Size Dual Switchable Nanocage for Novel Triple-Interlocked Combination Therapy Pattern.",
			"journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)",
			"authorList": [
				"Yang Rui",
				"Zhang Zipeng",
				"Fu Shunli",
				"Hou Teng",
				"Mu Weiwei",
				"Liang Shuang",
				"Gao Tong",
				"Guan Li",
				"Fang Yuxiao",
				"Liu Yongjun",
				"Zhang Na"
			],
			"DOI": "10.1002/advs.202000906",
			"date": "2023-11-12",
			"PMC": "",
			"citation": "",
			"abstract": "Combination therapy is a current hot topic in cancer treatment. Multiple synergistic effects elicited by combined drugs are essential in improving antitumor activity. Herein, a pH-triggered charge and size dual switchable nanocage co-loaded with abemaciclib and IMD-0354 (PA/PI-ND) is reported, exhibiting a novel triple-interlocked combination of chemotherapy, immunotherapy, and chemoimmunotherapy. The charge reversal polymer NGR-poly(ethylene glycol)-poly(l-lysine)-dimethylmaleic anhydride (NGR-PEG-PLL-DMA, ND) in PA/PI-ND promotes the pH-triggered charge reversal from negative to positive and size reduction from about 180 to 10\u00a0nm in an acidic tumor microenvironment, which greatly enhances cellular uptake and tumor tissue deep penetration. With the PA/PI-ND triple-interlocked combination therapy, the chemotherapeutic effect is enhanced by the action of abemaciclib to induce cell cycle arrest in the G1 phase, together with the reduction in cyclin D levels caused by IMD-0354. The dual anti-tumor promoting immunotherapy is achieved by abemaciclib selectively inhibiting the proliferation of regulatory T cells (Tregs) and by IMD-0354 promoting tumor-associated macrophage (TAM) repolarization from an M2 to M1 phenotype. Furthermore, PA/PI-ND has improved anti-tumor efficiency resulting from the third synergistic effect provided by chemoimmunotherapy. Taken together, PA/PI-ND is a promising strategy to guide the design of future drug delivery carriers and cancer combination therapy.",
			"category": 2,
			"name": "Yang Rui,2023"
		},
		{
			"PMID": 32992754,
			"title": "Parallelized Latent Dirichlet Allocation Provides a Novel Interpretability of Mutation Signatures in Cancer Genomes.",
			"journal": "Genes",
			"authorList": [
				"Matsutani Taro",
				"Hamada Michiaki"
			],
			"DOI": "10.3390/genes11101127",
			"date": "2021-07-15",
			"PMC": "",
			"citation": "",
			"abstract": "Mutation signatures are defined as the distribution of specific mutations such as activity of AID/APOBEC family proteins. Previous studies have reported numerous signatures, using matrix factorization methods for mutation catalogs. Different mutation signatures are active in different tumor types; hence, signature activity varies greatly among tumor types and becomes sparse. Because of this, many previous methods require dividing mutation catalogs for each tumor type. Here, we propose parallelized latent Dirichlet allocation (PLDA), a novel Bayesian model to simultaneously predict mutation signatures with all mutation catalogs. PLDA is an extended model of latent Dirichlet allocation (LDA), which is one of the methods used for signature prediction. It has parallelized hyperparameters of Dirichlet distributions for LDA, and they represent the sparsity of signature activities for each tumor type, thus facilitating simultaneous analyses. First, we conducted a simulation experiment to compare PLDA with previous methods (including SigProfiler and SignatureAnalyzer) using artificial data and confirmed that PLDA could predict signature structures as accurately as previous methods without searching for the optimal hyperparameters. Next, we applied PLDA to PCAWG (Pan-Cancer Analysis of Whole Genomes) mutation catalogs and obtained a signature set different from the one predicted by SigProfiler. Further, we have shown that the mutation spectrum represented by the predicted signature with PLDA provides a novel interpretability through post-analyses.",
			"category": 2,
			"name": "Matsutani Taro,2021"
		},
		{
			"PMID": 32982438,
			"title": "The Clinical Characteristics and Prognosis of Different Age Patients with Lung Cancer.",
			"journal": "Cancer management and research",
			"authorList": [
				"Chen Xiaorao",
				"Han Xiaoling",
				"Zhou Honglian",
				"Liang Yahai",
				"Huang Zhong",
				"Li Shujun",
				"Lin Yanming",
				"Huang Xiaobi",
				"Wu Jiancong",
				"Su Wenmei",
				"Lai Zhennan",
				"Yang Zhixiong"
			],
			"DOI": "10.2147/CMAR.S240318",
			"date": "2022-04-17",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is closely related to age, and the incidence of cancer increases with age. However, there are few studies on the relationship between age and clinical characteristics of lung cancer.",
			"category": 2,
			"name": "Chen Xiaorao,2022"
		},
		{
			"PMID": 32968016,
			"title": "Trajectory and uniqueness of mutational signatures in yeast mutators.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Loeillet Sophie",
				"Herzog Mareike",
				"Puddu Fabio",
				"Legoix Patricia",
				"Baulande Sylvain",
				"Jackson Stephen P",
				"Nicolas Alain G"
			],
			"DOI": "10.1073/pnas.2011332117",
			"date": "2020-11-24",
			"PMC": "",
			"citation": "",
			"abstract": "The acquisition of mutations plays critical roles in adaptation, evolution, senescence, and tumorigenesis. Massive genome sequencing has allowed extraction of specific features of many mutational landscapes but it remains difficult to retrospectively determine the mechanistic origin(s), selective forces, and trajectories of transient or persistent mutations and genome rearrangements. Here, we conducted a prospective reciprocal approach to inactivate 13 single or multiple evolutionary conserved genes involved in distinct genome maintenance processes and characterize de novo mutations in 274 diploid ",
			"category": 2,
			"name": "Loeillet Sophie,2020"
		},
		{
			"PMID": 32966158,
			"title": "Wound Healing Driver Gene and Therapeutic Development: Political and Scientific Hurdles.",
			"journal": "Advances in wound care",
			"authorList": [
				"Tang Xin",
				"Hao Michelle",
				"Chang Cheng",
				"Bhatia Ayesha",
				"O'Brien Kathrine",
				"Chen Mei",
				"Armstrong David G",
				"Li Wei"
			],
			"DOI": "10.1089/wound.2019.1143",
			"date": "2021-12-23",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "Tang Xin,2021"
		},
		{
			"PMID": 32940377,
			"title": "Quantification of cancer driver mutations in human breast and lung DNA using targeted, error-corrected CarcSeq.",
			"journal": "Environmental and molecular mutagenesis",
			"authorList": [
				"Harris Kelly L",
				"Walia Vijay",
				"Gong Binsheng",
				"McKim Karen L",
				"Myers Meagan B",
				"Xu Joshua",
				"Parsons Barbara L"
			],
			"DOI": "10.1002/em.22409",
			"date": "2021-02-08",
			"PMC": "",
			"citation": "",
			"abstract": "There is a need for scientifically-sound, practical approaches to improve carcinogenicity testing. Advances in DNA sequencing technology and knowledge of events underlying cancer development have created an opportunity for progress in this area. The long-term goal of this work is to develop variation in cancer driver mutation (CDM) levels as a metric of clonal expansion of cells carrying CDMs because these important early events could inform carcinogenicity testing. The first step toward this goal was to develop and validate an error-corrected next-generation sequencing method to analyze panels of hotspot cancer driver mutations (hCDMs). The \"CarcSeq\" method that was developed uses unique molecular identifier sequences to construct single-strand consensus sequences for error correction. CarcSeq was used for mutational analysis of 13 amplicons encompassing >20 hotspot CDMs in normal breast, normal lung, ductal carcinomas, and lung adenocarcinomas. The approach was validated by detecting expected differences related to tissue type (normal vs. tumor and breast vs. lung) and mutation spectra. CarcSeq mutant fractions (MFs) correlated strongly with previously obtained ACB-PCR mutant fraction (MF) measurements from the same samples. A reconstruction experiment, in conjunction with other analyses, showed CarcSeq accurately quantifies MFs \u226510",
			"category": 2,
			"name": "Harris Kelly L,2021"
		},
		{
			"PMID": 32925942,
			"title": "Genetic buffering and potentiation in metabolism.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Poyatos Juan F"
			],
			"DOI": "10.1371/journal.pcbi.1008185",
			"date": "2020-10-13",
			"PMC": "",
			"citation": "",
			"abstract": "Cells adjust their metabolism in response to mutations, but how this reprogramming depends on the genetic context is not well known. Specifically, the absence of individual enzymes can affect reprogramming, and thus the impact of mutations in cell growth. Here, we examine this issue with an in silico model of Saccharomyces cerevisiae's metabolism. By quantifying the variability in the growth rate of 10000 different mutant metabolisms that accumulated changes in their reaction fluxes, in the presence, or absence, of a specific enzyme, we distinguish a subset of modifier genes serving as buffers or potentiators of variability. We notice that the most potent modifiers refer to the glycolysis pathway and that, more broadly, they show strong pleiotropy and epistasis. Moreover, the evidence that this subset depends on the specific growing condition strengthens its systemic underpinning, a feature only observed before in a toy model of a gene-regulatory network. Some of these enzymes also modulate the effect that biochemical noise and environmental fluctuations produce in growth. Thus, the reorganization of metabolism induced by mutations has not only direct physiological implications but also transforms the influence that other mutations have on growth. This is a general result with implications in the development of cancer therapies based on metabolic inhibitors.",
			"category": 2,
			"name": "Poyatos Juan F,2020"
		},
		{
			"PMID": 32883331,
			"title": "Modeling tumor development and metastasis using paired organoids derived from patients with colorectal cancer liver metastases.",
			"journal": "Journal of hematology & oncology",
			"authorList": [
				"Li He",
				"Dai Weixing",
				"Xia Xi",
				"Wang Renjie",
				"Zhao Jing",
				"Han Lingyu",
				"Mo Shaobo",
				"Xiang Wenqiang",
				"Du Lin",
				"Zhu Guangya",
				"Xie Jingjing",
				"Yu Jun",
				"Liu Nan",
				"Huang Mingzhu",
				"Zhu Jidong",
				"Cai Guoxiang"
			],
			"DOI": "10.1186/s13045-020-00957-4",
			"date": "2021-04-05",
			"PMC": "",
			"citation": "",
			"abstract": "Tumor metastasis accounts for the majority of cancer-related deaths; it is therefore important to develop preclinical models that faithfully recapitulate disease progression. Here, we generated paired organoids derived from primary tumors and matched liver metastases in the same colorectal cancer (CRC) patients. Despite the fact that paired organoids exhibit comparable gene expression and cell morphology, organoids from metastatic lesions demonstrate more aggressive phenotypes, tumorigenesis, and metastatic capacity than those from primary lesions. Transcriptional analyses of the paired organoids reveal signature genes and pathways altered during the progression of CRC, including SOX2. Further study shows that inducible knockdown of SOX2\u00a0attenuated invasion, proliferation, and liver metastasis outgrowth. Taken together, we use patient-derived paired primary and metastatic cancer organoids to model CRC metastasis and illustrate that SOX2 is associated with CRC progression and may serve as a potential prognostic biomarker and therapeutic target of CRC.",
			"category": 2,
			"name": "Li He,2021"
		},
		{
			"PMID": 32850843,
			"title": "Progress in Neoantigen Targeted Cancer Immunotherapies.",
			"journal": "Frontiers in cell and developmental biology",
			"authorList": [
				"Han Xue-Jiao",
				"Ma Xue-Lei",
				"Yang Li",
				"Wei Yu-Quan",
				"Peng Yong",
				"Wei Xia-Wei"
			],
			"DOI": "10.3389/fcell.2020.00728",
			"date": "2023-01-06",
			"PMC": "",
			"citation": "",
			"abstract": "Immunotherapies that harness the immune system to kill cancer cells have showed significant therapeutic efficacy in many human malignancies. A growing number of studies have highlighted the relevance of neoantigens in recognizing cancer cells by intrinsic T cells. Cancer neoantigens are a direct consequence of somatic mutations presenting on the surface of individual cancer cells. Neoantigens are fully cancer-specific and exempt from central tolerance. In addition, neoantigens are important targets for checkpoint blockade therapy. Recently, technological innovations have made neoantigen discovery possible in a variety of malignancies, thus providing an impetus to develop novel immunotherapies that selectively enhance T cell reactivity for the destruction of cancer cells while leaving normal tissues unharmed. In this review, we aim to introduce the methods of the identification of neoantigens, the mutational patterns of human cancers, related clinical trials, neoantigen burden and sensitivity to immune checkpoint blockade. Moreover, we focus on relevant challenges of targeting neoantigens for cancer treatment.",
			"category": 2,
			"name": "Han Xue-Jiao,2023"
		},
		{
			"PMID": 32832349,
			"title": "Can Environmental Manipulation Help Suppress Cancer? Non-Linear Competition Among Tumor Cells in Periodically Changing Conditions.",
			"journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)",
			"authorList": [
				"Babajanyan S G",
				"Koonin Eugene V",
				"Cheong Kang Hao"
			],
			"DOI": "10.1002/advs.202000340",
			"date": "2024-03-29",
			"PMC": "",
			"citation": "",
			"abstract": "It has been shown that the tumor population growth dynamics in a periodically varying environment can drastically differ from the one in a fixed environment. Thus, the environment of a tumor can potentially be manipulated to suppress cancer progression. Diverse evolutionary processes play vital roles in cancer progression and accordingly, understanding the interplay between these processes is essential in optimizing the treatment strategy. Somatic evolution and genetic instability result in intra-tumor cell heterogeneity. Various models have been developed to analyze the interactions between different types of tumor cells. Here, models of density-dependent interaction between different types of tumor cells under fast periodical environmental changes are examined. It is illustrated that tumor population densities, which vary on a slow time scale, are affected by fast environmental variations. Finally, the intriguing density-dependent interactions in metastatic castration-resistant prostate cancer (mCRPC) in which the different types of tumor cells are defined with respect to the production of and dependence on testosterone are\u00a0discussed.",
			"category": 2,
			"name": "Babajanyan S G,2024"
		},
		{
			"PMID": 32820006,
			"title": "Chromatin activation as a unifying principle underlying pathogenic mechanisms in multiple myeloma.",
			"journal": "Genome research",
			"authorList": [
				"Ordo\u00f1ez Raquel",
				"Kulis Marta",
				"Russi\u00f1ol Nuria",
				"Chapaprieta Vicente",
				"Carrasco-Leon Arantxa",
				"Garc\u00eda-Torre Beatriz",
				"Charalampopoulou Stella",
				"Clot Guillem",
				"Beekman Ren\u00e9e",
				"Meydan Cem",
				"Duran-Ferrer Mart\u00ed",
				"Verdaguer-Dot N\u00faria",
				"Vilarrasa-Blasi Roser",
				"Soler-Vila Paula",
				"Garate Leire",
				"Miranda Est\u00edbaliz",
				"San Jos\u00e9-En\u00e9riz Edurne",
				"Rodriguez-Madoz Juan R",
				"Ezponda Teresa",
				"Mart\u00ednez-Turrilas Rebeca",
				"Vilas-Zornoza Amaia",
				"Lara-Astiaso David",
				"Dup\u00e9r\u00e9-Richer Daphn\u00e9",
				"Martens Joost H A",
				"El-Omri Halima",
				"Taha Ruba Y",
				"Calasanz Maria J",
				"Paiva Bruno",
				"San Miguel Jesus",
				"Flicek Paul",
				"Gut Ivo",
				"Melnick Ari",
				"Mitsiades Constantine S",
				"Licht Jonathan D",
				"Campo Elias",
				"Stunnenberg Hendrik G",
				"Agirre Xabier",
				"Prosper Felipe",
				"Martin-Subero Jose I"
			],
			"DOI": "10.1101/gr.265520.120",
			"date": "2021-10-29",
			"PMC": "",
			"citation": "",
			"abstract": "Multiple myeloma (MM) is a plasma cell neoplasm associated with a broad variety of genetic lesions. In spite of this genetic heterogeneity, MMs share a characteristic malignant phenotype whose underlying molecular basis remains poorly characterized. In the present study, we examined plasma cells from MM using a multi-epigenomics approach and demonstrated that, when compared to normal B cells, malignant plasma cells showed an extensive activation of regulatory elements, in part affecting coregulated adjacent genes. Among target genes up-regulated by this process, we found members of the NOTCH, NF-kB, MTOR signaling, and TP53 signaling pathways. Other activated genes included sets involved in osteoblast differentiation and response to oxidative stress, all of which have been shown to be associated with the MM phenotype and clinical behavior. We functionally characterized MM-specific active distant enhancers controlling the expression of thioredoxin (",
			"category": 2,
			"name": "Ordo\u00f1ez Raquel,2021"
		},
		{
			"PMID": 32812000,
			"title": "Understanding genomics and the immune environment of penile cancer to improve therapy.",
			"journal": "Nature reviews. Urology",
			"authorList": [
				"Aydin Ahmet Murat",
				"Chahoud Jad",
				"Adashek Jacob J",
				"Azizi Mounsif",
				"Magliocco Anthony",
				"Ross Jeffrey S",
				"Necchi Andrea",
				"Spiess Philippe E"
			],
			"DOI": "10.1038/s41585-020-0359-z",
			"date": "2022-01-21",
			"PMC": "",
			"citation": "",
			"abstract": "The incidence of penile squamous cell carcinoma (PSCC) has increased in developed countries over the past decades owing to increased human papilloma virus (HPV) exposure. Despite successful surgical treatment of locoregional PSCC, effective treatment options for advanced disease are limited. The prognosis of patients with bulky nodal and metastatic PSCC is dismal and new management approaches are urgently needed. Genomic analyses have provided transformative knowledge on the genomic and molecular landscape and tumour microenvironment of PSCC. Around one-quarter of patients with metastatic PSCC have clinically actionable genomic alterations in mechanistic target of rapamycin, DNA repair and receptor tyrosine kinase pathways. These patients might benefit from combined and sequential targeted therapies. HPV vaccination might be another therapeutic option as PSCC is genetically similar to\u00a0other HPV-driven cancers. In addition, 40-60% of PSCC tumours show strong PDL1 expression, and the frequency of mutational signatures suggestive of immunotherapy resistance is low, pointing to potential utility of immunotherapy for PSCC. Finally, identification of the composition of the penile microbiota and its biological role might lead to new cancer prevention and treatment strategies.",
			"category": 2,
			"name": "Aydin Ahmet Murat,2022"
		},
		{
			"PMID": 32791233,
			"title": "The Underlying Tumor Genomics of Predominant Histologic Subtypes in Lung Adenocarcinoma.",
			"journal": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer",
			"authorList": [
				"Caso Raul",
				"Sanchez-Vega Francisco",
				"Tan Kay See",
				"Mastrogiacomo Brooke",
				"Zhou Jian",
				"Jones Gregory D",
				"Nguyen Bastien",
				"Schultz Nikolaus",
				"Connolly James G",
				"Brandt Whitney S",
				"Bott Matthew J",
				"Rocco Gaetano",
				"Molena Daniela",
				"Isbell James M",
				"Liu Yuan",
				"Mayo Marty W",
				"Adusumilli Prasad S",
				"Travis William D",
				"Jones David R"
			],
			"DOI": "10.1016/j.jtho.2020.08.005",
			"date": "2021-02-01",
			"PMC": "",
			"citation": "",
			"abstract": "The purpose of the study is to genomically characterize the biology and related therapeutic opportunities of prognostically important predominant histologic subtypes in lung adenocarcinoma (LUAD).",
			"category": 2,
			"name": "Caso Raul,2021"
		},
		{
			"PMID": 32778778,
			"title": "A compendium of mutational cancer driver genes.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Mart\u00ednez-Jim\u00e9nez Francisco",
				"Mui\u00f1os Ferran",
				"Sent\u00eds In\u00e9s",
				"Deu-Pons Jordi",
				"Reyes-Salazar Iker",
				"Arnedo-Pac Claudia",
				"Mularoni Loris",
				"Pich Oriol",
				"Bonet Jose",
				"Kranas Hanna",
				"Gonzalez-Perez Abel",
				"Lopez-Bigas Nuria"
			],
			"DOI": "10.1038/s41568-020-0290-x",
			"date": "2020-12-21",
			"PMC": "",
			"citation": "",
			"abstract": "A fundamental goal in cancer research is to understand the mechanisms of cell transformation. This is key to developing more efficient cancer detection methods and therapeutic approaches. One milestone towards this objective is the identification of all the genes with mutations capable of driving tumours. Since the 1970s, the list of cancer genes has been growing steadily. Because cancer driver genes are under positive selection in tumorigenesis, their observed patterns of somatic mutations across tumours in a cohort deviate from those expected from neutral mutagenesis. These deviations, which constitute signals of positive selection, may be detected by carefully designed bioinformatics methods, which have become the state of the art in the identification of driver genes. A systematic approach combining several of these signals could lead to a compendium of mutational cancer genes. In this Review, we present the Integrative OncoGenomics (IntOGen) pipeline, an implementation of such an approach to obtain the compendium of mutational cancer drivers. Its application to somatic mutations of more than 28,000 tumours of 66 cancer types reveals 568 cancer genes and points towards their mechanisms of tumorigenesis. The application of this approach to the ever-growing datasets of somatic tumour mutations will support the continuous refinement of our knowledge of the genetic basis of cancer.",
			"category": 2,
			"name": "Mart\u00ednez-Jim\u00e9nez Francisco,2020"
		},
		{
			"PMID": 32748835,
			"title": "Translating Evidence from Clonal Hematopoiesis to Cardiovascular Disease: A Systematic Review.",
			"journal": "Journal of clinical medicine",
			"authorList": [
				"Papa Veronica",
				"Marracino Luisa",
				"Fortini Francesca",
				"Rizzo Paola",
				"Campo Gianluca",
				"Vaccarezza Mauro",
				"Vieceli Dalla Sega Francesco"
			],
			"DOI": "10.3390/jcm9082480",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Some random mutations can confer a selective advantage to a hematopoietic stem cell. As a result, mutated hematopoietic stem cells can give rise to a significant proportion of mutated clones of blood cells. This event is known as \"clonal hematopoiesis.\" Clonal hematopoiesis is closely associated with age, and carriers show an increased risk of developing blood cancers. Clonal hematopoiesis of indeterminate potential is defined by the presence of clones carrying a mutation associated with a blood neoplasm without obvious hematological malignancies. Unexpectedly, in recent years, it has emerged that clonal hematopoiesis of indeterminate potential carriers also have an increased risk of developing cardiovascular disease. Mechanisms linking clonal hematopoiesis of indeterminate potential to cardiovascular disease are only partially known. Findings in animal models indicate that clonal hematopoiesis of indeterminate potential-related mutations amplify inflammatory responses. Consistently, clinical studies have revealed that clonal hematopoiesis of indeterminate potential carriers display increased levels of inflammatory markers. In this review, we describe progress in our understanding of clonal hematopoiesis in the context of cancer, and we discuss the most recent findings linking clonal hematopoiesis of indeterminate potential and cardiovascular diseases.",
			"category": 2,
			"name": "Papa Veronica,2020"
		},
		{
			"PMID": 32747711,
			"title": "Mutational signature SBS8 predominantly arises due to late replication errors in cancer.",
			"journal": "Communications biology",
			"authorList": [
				"Singh Vinod Kumar",
				"Rastogi Arnav",
				"Hu Xiaoju",
				"Wang Yaqun",
				"De Subhajyoti"
			],
			"DOI": "10.1038/s42003-020-01119-5",
			"date": "2021-06-21",
			"PMC": "",
			"citation": "",
			"abstract": "Although a majority of somatic mutations in cancer are passengers, their mutational signatures provide mechanistic insights into mutagenesis and DNA repair processes. Mutational signature SBS8 is common in most cancers, but its etiology is debated. Incorporating genomic, epigenomic, and cellular process features for multiple cell-types we develop genome-wide composite epigenomic context-maps relevant for mutagenesis and DNA repair. Analyzing somatic mutation data from multiple cancer types in their epigenomic contexts, we show that SBS8 preferentially occurs in gene-poor, lamina-proximal, late replicating heterochromatin domains. While SBS8 is uncommon among mutations in non-malignant tissues, in tumor genomes its proportions increase with replication timing and speed, and checkpoint defects further promote this signature - suggesting that SBS8 probably arises due to uncorrected late replication errors during cancer progression. Our observations offer a potential reconciliation among different perspectives in the debate about the etiology of SBS8 and its relationship with other mutational signatures.",
			"category": 2,
			"name": "Singh Vinod Kumar,2021"
		},
		{
			"PMID": 32747659,
			"title": "A deep learning model to predict RNA-Seq expression of tumours from whole slide images.",
			"journal": "Nature communications",
			"authorList": [
				"Schmauch Beno\u00eet",
				"Romagnoni Alberto",
				"Pronier Elodie",
				"Saillard Charlie",
				"Maill\u00e9 Pascale",
				"Calderaro Julien",
				"Kamoun Aur\u00e9lie",
				"Sefta Meriem",
				"Toldo Sylvain",
				"Zaslavskiy Mikhail",
				"Clozel Thomas",
				"Moarii Matahi",
				"Courtiol Pierre",
				"Wainrib Gilles"
			],
			"DOI": "10.1038/s41467-020-17678-4",
			"date": "2020-09-08",
			"PMC": "",
			"citation": "",
			"abstract": "Deep learning methods for digital pathology analysis are an effective way to address multiple clinical questions, from diagnosis to prediction of treatment outcomes. These methods have also been used to predict gene mutations from pathology images, but no comprehensive evaluation of their potential for extracting molecular features from histology slides has yet been performed. We show that HE2RNA, a model based on the integration of multiple data modes, can be trained to systematically predict RNA-Seq profiles from whole-slide images alone, without expert annotation. Through its interpretable design, HE2RNA provides virtual spatialization of gene expression, as validated by CD3- and CD20-staining on an independent dataset. The transcriptomic representation learned by HE2RNA can also be transferred on other datasets, even of small size, to increase prediction performance for specific molecular phenotypes. We illustrate the use of this approach in clinical diagnosis purposes such as the identification of tumors with microsatellite instability.",
			"category": 2,
			"name": "Schmauch Beno\u00eet,2020"
		},
		{
			"PMID": 32743344,
			"title": "Exploiting the circuit breaker cancer evolution model in human clear cell renal cell carcinoma.",
			"journal": "Cell stress",
			"authorList": [
				"Hsieh James J",
				"Cheng Emily H"
			],
			"DOI": "10.15698/cst2020.08.227",
			"date": "2023-11-11",
			"PMC": "",
			"citation": "",
			"abstract": "The incessant interactions between susceptible humans and their respective macro/microenvironments registered throughout their lifetime result in the ultimate manifestation of individual cancers. With the average lifespan exceeding 50 years of age in humans since the beginning of 20",
			"category": 2,
			"name": "Hsieh James J,2023"
		},
		{
			"PMID": 32737409,
			"title": "Mutation accumulation and developmental lineages in normal and Down syndrome human fetal haematopoiesis.",
			"journal": "Scientific reports",
			"authorList": [
				"Hasaart Karlijn A L",
				"Manders Freek",
				"van der Hoorn Marie-Louise",
				"Verheul Mark",
				"Poplonski Tomasz",
				"Kuijk Ewart",
				"de Sousa Lopes Susana M Chuva",
				"van Boxtel Ruben"
			],
			"DOI": "10.1038/s41598-020-69822-1",
			"date": "2020-12-10",
			"PMC": "",
			"citation": "",
			"abstract": "Children show a higher incidence of leukemia compared to young adolescents, yet their cells have less age-related (oncogenic) somatic mutations. Newborns with Down syndrome have an even higher risk of developing leukemia, which is thought to be driven by mutations that accumulate during fetal development. To characterize mutation accumulation in individual stem and progenitor cells of Down syndrome and karyotypically normal fetuses, we clonally expanded single cells and performed whole-genome sequencing. We found a higher mutation rate in haematopoietic stem and progenitor cells during fetal development compared to the post-infant rate. In fetal trisomy 21 cells the number of somatic mutations is even further increased, which was already apparent during the first cell divisions of embryogenesis before gastrulation. The number and types of mutations in fetal trisomy 21 haematopoietic stem and progenitor cells were similar to those in Down syndrome-associated myeloid preleukemia and could be attributed to mutational processes that were active during normal fetal haematopoiesis. Finally, we found that the contribution of early embryonic cells to human fetal tissues can vary considerably between individuals. The increased mutation rates found in this study, may contribute to the increased risk of leukemia early during life and the higher incidence of leukemia in Down syndrome.",
			"category": 2,
			"name": "Hasaart Karlijn A L,2020"
		},
		{
			"PMID": 32719513,
			"title": "Tracking the expression of therapeutic protein targets in rare cells by antibody-mediated nanoparticle labelling and magnetic sorting.",
			"journal": "Nature biomedical engineering",
			"authorList": [
				"Labib Mahmoud",
				"Wang Zongjie",
				"Ahmed Sharif U",
				"Mohamadi Reza M",
				"Duong Bill",
				"Green Brenda",
				"Sargent Edward H",
				"Kelley Shana O"
			],
			"DOI": "10.1038/s41551-020-0590-1",
			"date": "2021-02-19",
			"PMC": "",
			"citation": "",
			"abstract": "Molecular-level features of tumours can be tracked using single-cell analyses of circulating tumour cells (CTCs). However, single-cell measurements of protein expression for rare CTCs are hampered by the presence of a large number of non-target cells. Here, we show that antibody-mediated labelling of intracellular proteins in the nucleus, mitochondria and cytoplasm of human cells with magnetic nanoparticles enables analysis of target proteins at the single-cell level by sorting the cells according to their nanoparticle content in a microfluidic device with cell-capture zones sandwiched between arrays of magnets. We used the magnetic labelling and cell-sorting approach to track the expression of therapeutic protein targets in CTCs isolated from blood samples of mice with orthotopic prostate xenografts and from patients with metastatic castration-resistant prostate cancer. We also show that mutated proteins that are drug targets or markers of therapeutic response can be directly identified in CTCs, analysed at the single-cell level and used to predict how mice with drug-susceptible and drug-resistant pancreatic tumour xenografts respond to therapy.",
			"category": 2,
			"name": "Labib Mahmoud,2021"
		},
		{
			"PMID": 32714860,
			"title": "Network-Based Approach to Identify the Antiproliferative Mechanisms of Bruceine D in Breast Cancer From the Cancer Genome Atlas.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Tian Saisai",
				"Jing Rui",
				"Zhang Weidong"
			],
			"DOI": "10.3389/fonc.2020.01001",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Bruceine D (BD) is a natural compound extracted from a Chinese herb ",
			"category": 2,
			"name": "Tian Saisai,2020"
		},
		{
			"PMID": 32708098,
			"title": "Impact of Chromosome 9 Numerical Imbalances in Oral Squamous Cell Carcinoma: A Pilot Grid-Based Centromere Analysis.",
			"journal": "Diagnostics (Basel, Switzerland)",
			"authorList": [
				"Kyrodimos Efthymios",
				"Chrysovergis Aristeidis",
				"Mastronikolis Nicholas",
				"Tsiambas Evangelos",
				"Riziotis Christos",
				"Roukas Dimitrios",
				"Fotiades Panagiotis",
				"Stavraka Chara",
				"Ragos Vasileios",
				"Paschopoulos Minas",
				"Papanikolaou Vasileios"
			],
			"DOI": "10.3390/diagnostics10070501",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Oral squamous cell carcinoma (OSCC) is considered an aggressive malignancy, mainly due to its increased propensity to provide local and distant lymph node metastases. Gross chromosome instability (CI; polysomy/aneuploidy/monosomy), combined or not with specific gene alterations, is implicated in the development and progression of solid malignancies, including OSCC. In order to further study the relationship between these genetic alterations and the aggressive biological behavior of OSCCs, we investigated the frequency and impact of chromosome 9 numerical imbalances in these tumors. Fifty (",
			"category": 2,
			"name": "Kyrodimos Efthymios,2020"
		},
		{
			"PMID": 32677979,
			"title": "Modeling neoplastic disease with spheroids and organoids.",
			"journal": "Journal of hematology & oncology",
			"authorList": [
				"Zanoni Michele",
				"Cortesi Michela",
				"Zamagni Alice",
				"Arienti Chiara",
				"Pignatta Sara",
				"Tesei Anna"
			],
			"DOI": "10.1186/s13045-020-00931-0",
			"date": "2021-04-05",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a complex disease in which both genetic defects and microenvironmental components contribute to the development, progression, and metastasization of disease, representing major hurdles in the identification of more effective and safer treatment regimens for patients. Three-dimensional (3D) models are changing the paradigm of preclinical cancer research as they more closely resemble the complex tissue environment and architecture found in clinical tumors than in bidimensional (2D) cell cultures. Among 3D models, spheroids and organoids represent the most versatile and promising models in that they are capable of recapitulating the heterogeneity and pathophysiology of human cancers and of filling the gap between conventional 2D in vitro testing and animal models. Such 3D systems represent a powerful tool for studying cancer biology, enabling us to model the dynamic evolution of neoplastic disease from the early stages to metastatic dissemination and the interactions with the microenvironment. Spheroids and organoids have recently been used in the field of drug discovery and personalized medicine. The combined use of 3D models could potentially improve the robustness and reliability of preclinical research data, reducing the need for animal testing and favoring their transition to clinical practice. In this review, we summarize the recent advances in the use of these 3D systems for cancer modeling, focusing on their innovative translational applications, looking at future challenges, and comparing them with most widely used animal models.",
			"category": 2,
			"name": "Zanoni Michele,2021"
		},
		{
			"PMID": 32657757,
			"title": "Cancer systems immunology.",
			"journal": "eLife",
			"authorList": [
				"Reticker-Flynn Nathan E",
				"Engleman Edgar G"
			],
			"DOI": "10.7554/eLife.53839",
			"date": "2021-02-22",
			"PMC": "",
			"citation": "",
			"abstract": "Tumor immunology is undergoing a renaissance due to the recent profound clinical successes of tumor immunotherapy. These advances have coincided with an exponential growth in the development of -omics technologies. Armed with these technologies and their associated computational and modeling toolsets, systems biologists have turned their attention to tumor immunology in an effort to understand the precise nature and consequences of interactions between tumors and the immune system. Such interactions are inherently multivariate, spanning multiple time and size scales, cell types, and organ systems, rendering systems biology approaches particularly amenable to their interrogation. While in its infancy, the field of 'Cancer Systems Immunology' has already influenced our understanding of tumor immunology and immunotherapy. As the field matures, studies will move beyond descriptive characterizations toward functional investigations of the emergent behavior that govern tumor-immune responses. Thus, Cancer Systems Immunology holds incredible promise to advance our ability to fight this disease.",
			"category": 2,
			"name": "Reticker-Flynn Nathan E,2021"
		},
		{
			"PMID": 32640634,
			"title": "Identification of GSN and LAMC2 as Key Prognostic Genes of Bladder Cancer by Integrated Bioinformatics Analysis.",
			"journal": "Cancers",
			"authorList": [
				"Yang Jia-Lian",
				"Wang Charles C N",
				"Cai Jia-Hua",
				"Chou Che-Yi",
				"Lin Yu-Chao",
				"Hung Chin-Chuan"
			],
			"DOI": "10.3390/cancers12071809",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Bladder cancer is a common malignancy with mechanisms of pathogenesis and progression. This study aimed to identify the prognostic hub genes, which are the central modulators to regulate the progression and proliferation in the specific subtype of bladder cancer. The identification of the candidate hub gene was performed by weighted gene co-expression network analysis to construct a free-scale gene co-expression network. The gene expression profile of GSE97768 from the Gene Expression Omnibus database was used. The association between prognosis and hub gene was evaluated by The Cancer Genome Atlas database. Four gene-expression modules were significantly related to bladder cancer disease: the red module (human adenocarcinoma lymph node metastasis), the darkturquioise module (grade 2 carcinoma), the lightgreen module (grade 3 carcinoma), and the royalblue module (transitional cell carcinoma lymphatic metastasis). Based on betweenness centrality and survival analysis, we identified laminin subunit gamma-2 (LAMC2) in the grade 2 carcinoma, gelsolin (GSN) in the grade 3 carcinoma, and homeodomain-interacting protein kinase 2 (HIPK2) in the transitional cell carcinoma lymphatic metastasis. Subsequently, the protein levels of LAMC2 and GSN were respectively down-regulated and up-regulated in tumor tissue with the Human Protein Atlas (HPA) database. Our results suggested that LAMC2 and GSN are the central modulators to transfer information in the specific subtype of the disease.",
			"category": 2,
			"name": "Yang Jia-Lian,2020"
		},
		{
			"PMID": 32637104,
			"title": "A review of big data and medical research.",
			"journal": "SAGE open medicine",
			"authorList": [
				"Mallappallil Mary",
				"Sabu Jacob",
				"Gruessner Angelika",
				"Salifu Moro"
			],
			"DOI": "10.1177/2050312120934839",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Universally, the volume of data has increased, with the collection rate doubling every 40 months, since the 1980s. \"Big data\" is a term that was introduced in the 1990s to include data sets too large to be used with common software. Medicine is a major field predicted to increase the use of big data in 2025. Big data in medicine may be used by commercial, academic, government, and public sectors. It includes biologic, biometric, and electronic health data. Examples of biologic data include biobanks; biometric data may have individual wellness data from devices; electronic health data include the medical record; and other data demographics and images. Big data has also contributed to the changes in the research methodology. Changes in the clinical research paradigm has been fueled by large-scale biological data harvesting (biobanks), which is developed, analyzed, and managed by cheaper computing technology (big data), supported by greater flexibility in study design (real-world data) and the relationships between industry, government regulators, and academics. Cultural changes along with easy access to information via the Internet facilitate ease of participation by more people. Current needs demand quick answers which may be supplied by big data, biobanks, and changes in flexibility in study design. Big data can reveal health patterns, and promises to provide solutions that have previously been out of society's grasp; however, the murkiness of international laws, questions of data ownership, public ignorance, and privacy and security concerns are slowing down the progress that could otherwise be achieved by the use of big data. The goal of this descriptive review is to create awareness of the ramifications for big data and to encourage readers that this trend is positive and will likely lead to better clinical solutions, but, caution must be exercised to reduce harm.",
			"category": 2,
			"name": "Mallappallil Mary,2020"
		},
		{
			"PMID": 32612154,
			"title": "The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications.",
			"journal": "Cellular & molecular immunology",
			"authorList": [
				"Zhang Yuanyuan",
				"Zhang Zemin"
			],
			"DOI": "10.1038/s41423-020-0488-6",
			"date": "2021-07-28",
			"PMC": "",
			"citation": "",
			"abstract": "Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology. Several types of immunotherapy, including adoptive cell transfer (ACT) and immune checkpoint inhibitors (ICIs), have obtained durable clinical responses, but their efficacies vary, and only subsets of cancer patients can benefit from them. Immune infiltrates in the tumor microenvironment (TME) have been shown to play a key role in tumor development and will affect the clinical outcomes of cancer patients. Comprehensive profiling of tumor-infiltrating immune cells would shed light on the mechanisms of cancer-immune evasion, thus providing opportunities for the development of novel therapeutic strategies. However, the highly heterogeneous and dynamic nature of the TME impedes the precise dissection of intratumoral immune cells. With recent advances in single-cell technologies such as single-cell RNA sequencing (scRNA-seq) and mass cytometry, systematic interrogation of the TME is feasible and will provide insights into the functional diversities of tumor-infiltrating immune cells. In this review, we outline the recent progress in cancer immunotherapy, particularly by focusing on landmark studies and the recent single-cell characterization of tumor-associated immune cells, and we summarize the phenotypic diversities of intratumoral immune cells and their connections with cancer immunotherapy. We believe such a review could strengthen our understanding of the progress in cancer immunotherapy, facilitate the elucidation of immune cell modulation in tumor progression, and thus guide the development of novel immunotherapies for cancer treatment.",
			"category": 2,
			"name": "Zhang Yuanyuan,2021"
		},
		{
			"PMID": 32604993,
			"title": "Genetic Markers in Lung Cancer Diagnosis: A Review.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Wadowska Katarzyna",
				"Bil-Lula Iwona",
				"Trembecki \u0141ukasz",
				"\u015aliwi\u0144ska-Mosso\u0144 Mariola"
			],
			"DOI": "10.3390/ijms21134569",
			"date": "2021-02-15",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer is the most often diagnosed cancer in the world and the most frequent cause of cancer death. The prognosis for lung cancer is relatively poor and 75% of patients are diagnosed at its advanced stage. The currently used diagnostic tools are not sensitive enough and do not enable diagnosis at the early stage of the disease. Therefore, searching for new methods of early and accurate diagnosis of lung cancer is crucial for its effective treatment. Lung cancer is the result of multistage carcinogenesis with gradually increasing genetic and epigenetic changes. Screening for the characteristic genetic markers could enable the diagnosis of lung cancer at its early stage. The aim of this review was the summarization of both the preclinical and clinical approaches in the genetic diagnostics of lung cancer. The advancement of molecular strategies and analytic platforms makes it possible to analyze the genome changes leading to cancer development-i.e., the potential biomarkers of lung cancer. In the reviewed studies, the diagnostic values of microsatellite changes, DNA hypermethylation, and ",
			"category": 2,
			"name": "Wadowska Katarzyna,2021"
		},
		{
			"PMID": 32579168,
			"title": "Druggable binding sites in the multicomponent assemblies that characterise DNA double-strand-break repair through non-homologous end joining.",
			"journal": "Essays in biochemistry",
			"authorList": [
				"Kefala Stavridi Antonia",
				"Appleby Robert",
				"Liang Shikang",
				"Blundell Tom L",
				"Chaplin Amanda K"
			],
			"DOI": "10.1042/EBC20190092",
			"date": "2021-06-07",
			"PMC": "",
			"citation": "",
			"abstract": "Non-homologous end joining (NHEJ) is one of the two principal damage repair pathways for DNA double-strand breaks in cells. In this review, we give a brief overview of the system including a discussion of the effects of deregulation of NHEJ components in carcinogenesis and resistance to cancer therapy. We then discuss the relevance of targeting NHEJ components pharmacologically as a potential cancer therapy and review previous approaches to orthosteric regulation of NHEJ factors. Given the limited success of previous investigations to develop inhibitors against individual components, we give a brief discussion of the recent advances in computational and structural biology that allow us to explore different targets, with a particular focus on modulating protein-protein interaction interfaces. We illustrate this discussion with three examples showcasing some current approaches to developing protein-protein interaction inhibitors to modulate the assembly of NHEJ multiprotein complexes in space and time.",
			"category": 2,
			"name": "Kefala Stavridi Antonia,2021"
		},
		{
			"PMID": 32566745,
			"title": "Somatic genetic aberrations in benign breast disease and the risk of subsequent breast cancer.",
			"journal": "NPJ breast cancer",
			"authorList": [
				"Zeng Zexian",
				"Vo Andy",
				"Li Xiaoyu",
				"Shidfar Ali",
				"Saldana Paulette",
				"Blanco Luis",
				"Xuei Xiaoling",
				"Luo Yuan",
				"Khan Seema A",
				"Clare Susan E"
			],
			"DOI": "10.1038/s41523-020-0165-z",
			"date": "2024-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "It is largely unknown how the development of breast cancer (BC) is transduced by somatic genetic alterations in the benign breast. Since benign breast disease is an established risk factor for BC, we established a case-control study of women with a history of benign breast biopsy (BBB). Cases developed BC at least one year after BBB and controls did not develop BC over an average of 17 years following BBB. 135 cases were matched to 69 controls by age and type of benign change: non-proliferative or proliferation without atypia (PDWA). Whole-exome sequencing (WES) was performed for the BBB. Germline DNA (available from ",
			"category": 2,
			"name": "Zeng Zexian,2024"
		},
		{
			"PMID": 32548785,
			"title": "Organotypic Models in Drug Development \"Tumor Models and Cancer Systems Biology for the Investigation of Anticancer Drugs and Resistance Development\".",
			"journal": "Handbook of experimental pharmacology",
			"authorList": [
				"de Oliveira \u00c9rica Aparecida",
				"Goding Colin R",
				"Maria-Engler Silvya Stuchi"
			],
			"DOI": "10.1007/164_2020_369",
			"date": "2021-03-11",
			"PMC": "",
			"citation": "",
			"abstract": "The landscape of cancer treatment has improved over the past decades, aiming to reduce systemic toxicity and enhance compatibility with the quality of life of the patient. However, at the therapeutic level, metastatic cancer remains hugely challenging, based on the almost inevitable emergence of therapy resistance. A small subpopulation of cells able to survive drug treatment termed the minimal residual disease may either harbor resistance-associated mutations or be phenotypically resistant, allowing them to regrow and become the dominant population in the therapy-resistant tumor. Characterization of the profile of minimal residual disease represents the key to the identification of resistance drivers that underpin cancer evolution. Therapeutic regimens must, therefore, be dynamic and tailored to take into account the emergence of resistance as tumors evolve within a complex microenvironment in vivo. This requires the adoption of new technologies based on the culture of cancer cells in ways that more accurately reflect the intratumor microenvironment, and their analysis using omics and system-based technologies to enable a new era in the diagnostics, classification, and treatment of many cancer types by applying the concept \"from the cell plate to the patient.\" In this chapter, we will present and discuss 3D model building and use, and provide comprehensive information on new genomic techniques that are increasing our understanding of drug action and the emergence of resistance.",
			"category": 2,
			"name": "de Oliveira \u00c9rica Aparecida,2021"
		},
		{
			"PMID": 32497093,
			"title": "Exploration of the effects of the CYCLOPS gene RBM17 in hepatocellular carcinoma.",
			"journal": "PloS one",
			"authorList": [
				"Li Can",
				"Ge Shanghua",
				"Zhou Jialu",
				"Peng Jie",
				"Chen Jiayu",
				"Dong Shuhui",
				"Feng Xiaofang",
				"Su Ning",
				"Zhang Lunli",
				"Zhong Yuanbin",
				"Deng Libin",
				"Tang Xiaoli"
			],
			"DOI": "10.1371/journal.pone.0234062",
			"date": "2020-08-26",
			"PMC": "",
			"citation": "",
			"abstract": "Hepatocellular carcinoma (HCC) is one of the most lethal and malignant tumours worldwide. New therapeutic targets for HCC are urgently needed. CYCLOPS (copy number alterations yielding cancer liabilities owing to partial loss) genes have been noted to be associated with cancer-targeted therapies. Therefore, we intended to explore the effects of the CYCLOPS gene RBM17 on HCC oncogenesis to determine if it could be further used for targeted therapy.",
			"category": 2,
			"name": "Li Can,2020"
		},
		{
			"PMID": 32492969,
			"title": "PD-1: Its Discovery, Involvement in Cancer Immunotherapy, and Beyond.",
			"journal": "Cells",
			"authorList": [
				"Ishida Yasumasa"
			],
			"DOI": "10.3390/cells9061376",
			"date": "2021-03-02",
			"PMC": "",
			"citation": "",
			"abstract": "On December 10, 2018, I was sitting among the big crowd of audience, as one of the invited guests to the ceremony, in the Stockholm Concert Hall. When King of Sweden Carl XVI Gustaf bestowed the diploma and medal of Nobel Prize of Physiology or Medicine 2018 on Dr. Tasuku Honjo and shook his hand for a while, surrounded by the thunderous applause and energetically blessing orchestral music, I thought that it had been a long journey for the molecule that we had first isolated in the early 1990s. Although it was truly a commemorable moment in the history of the programmed death-1 (PD-1) research, I believe we still have a long way to go. In this review article, I will explain why I think so, particularly by focusing on the potential role(s) that PD-1 appears to play in self-nonself discrimination by the immune system.",
			"category": 2,
			"name": "Ishida Yasumasa,2021"
		},
		{
			"PMID": 32487021,
			"title": "Identification and characterization of male reproduction-related genes in pig (Sus scrofa) using transcriptome analysis.",
			"journal": "BMC genomics",
			"authorList": [
				"Yang Wenjing",
				"Zhao Feiyang",
				"Chen Mingyue",
				"Li Ye",
				"Lan Xianyong",
				"Yang Ruolin",
				"Pan Chuanying"
			],
			"DOI": "10.1186/s12864-020-06790-w",
			"date": "2021-01-11",
			"PMC": "",
			"citation": "",
			"abstract": "The systematic interrogation of reproduction-related genes was key to gain a comprehensive understanding of the molecular mechanisms underlying male reproductive traits in mammals. Here, based on the\u00a0data collected from the NCBI SRA database, this study first revealed the genes involved in porcine male reproduction as well their uncharacterized transcriptional characteristics.",
			"category": 2,
			"name": "Yang Wenjing,2021"
		},
		{
			"PMID": 32483453,
			"title": "Multifunctional magnetic iron oxide nanoparticles: an advanced platform for cancer theranostics.",
			"journal": "Theranostics",
			"authorList": [
				"Zhao Shengzhe",
				"Yu Xujiang",
				"Qian Yuna",
				"Chen Wei",
				"Shen Jianliang"
			],
			"DOI": "10.7150/thno.42564",
			"date": "2021-05-18",
			"PMC": "",
			"citation": "",
			"abstract": "Multifunctional magnetic nanoparticles and derivative nanocomposites have aroused great concern for multimode imaging and cancer synergistic therapies in recent years. Among the rest, functional magnetic iron oxide nanoparticles (Fe",
			"category": 2,
			"name": "Zhao Shengzhe,2021"
		},
		{
			"PMID": 32470133,
			"title": "Fcirc: A comprehensive pipeline for the exploration of fusion linear and circular RNAs.",
			"journal": "GigaScience",
			"authorList": [
				"Cai Zhaoqing",
				"Xue Hongzhang",
				"Xu Yue",
				"K\u00f6hler Jens",
				"Cheng Xiaojie",
				"Dai Yao",
				"Zheng Jie",
				"Wang Haiyun"
			],
			"DOI": "10.1093/gigascience/giaa054",
			"date": "2021-10-04",
			"PMC": "",
			"citation": "",
			"abstract": "In cancer cells, fusion genes can produce linear and chimeric fusion-circular RNAs (f-circRNAs), which are functional in gene expression regulation and implicated in malignant transformation, cancer progression, and therapeutic resistance. For specific cancers, proteins encoded by fusion transcripts have been identified as innovative therapeutic targets (e.g., EML4-ALK). Even though RNA sequencing (RNA-Seq) technologies combined with existing bioinformatics approaches have enabled researchers to systematically identify fusion transcripts, specifically detecting f-circRNAs in cells remains challenging owing to their general sparsity and low abundance in cancer cells but also owing to imperfect computational methods.",
			"category": 2,
			"name": "Cai Zhaoqing,2021"
		},
		{
			"PMID": 32421773,
			"title": "The Evolution of Human Cancer Gene Duplications across\u00a0Mammals.",
			"journal": "Molecular biology and evolution",
			"authorList": [
				"Tollis Marc",
				"Schneider-Utaka Aika K",
				"Maley Carlo C"
			],
			"DOI": "10.1093/molbev/msaa125",
			"date": "2021-04-15",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is caused by genetic alterations that affect cellular fitness, and multicellular organisms have evolved mechanisms to suppress cancer such as cell cycle checkpoints and apoptosis. These pathways may be enhanced by the addition of tumor suppressor gene paralogs or deletion of oncogenes. To provide insights to the evolution of cancer suppression across the mammalian radiation, we estimated copy numbers for 548 human tumor suppressor gene and oncogene homologs in 63 mammalian genome assemblies. The naked mole rat contained the most cancer gene copies, consistent with the extremely low rates of cancer found in this species. We found a positive correlation between a species' cancer gene copy number and its longevity, but not body size, contrary to predictions from Peto's Paradox. Extremely long-lived mammals also contained more copies of caretaker genes in their genomes, suggesting that the maintenance of genome integrity is an essential form of cancer prevention in long-lived species. We found the strongest association between longevity and copy numbers of genes that are both germline and somatic tumor suppressor genes, suggesting that selection has acted to suppress both hereditary and sporadic cancers. We also found a strong relationship between the number of tumor suppressor genes and the number of oncogenes in mammalian genomes, suggesting that complex regulatory networks mediate the balance between cell proliferation and checks on tumor progression. This study is the first to investigate cancer gene expansions across the mammalian radiation and provides a springboard for potential human therapies based on evolutionary medicine.",
			"category": 2,
			"name": "Tollis Marc,2021"
		},
		{
			"PMID": 32411180,
			"title": "Prioritizing Cancer Genes Based on an Improved Random Walk Method.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Wei Pi-Jing",
				"Wu Fang-Xiang",
				"Xia Junfeng",
				"Su Yansen",
				"Wang Jing",
				"Zheng Chun-Hou"
			],
			"DOI": "10.3389/fgene.2020.00377",
			"date": "2024-03-28",
			"PMC": "",
			"citation": "",
			"abstract": "Identifying driver genes that contribute to cancer progression from numerous passenger genes, although a central goal, is a major challenge. The protein-protein interaction network provides convenient and reasonable assistance for driver gene discovery. Random walk-based methods have been widely used to prioritize nodes in social or biological networks. However, most studies select the next arriving node uniformly from the random walker's neighbors. Few consider transiting preference according to the degree of random walker's neighbors. In this study, based on the random walk method, we propose a novel approach named Driver_IRW (Driver genes discovery with Improved Random Walk method), to prioritize cancer genes in cancer-related network. The key idea of Driver_IRW is to assign different transition probabilities for different edges of a constructed cancer-related network in accordance with the degree of the nodes' neighbors. Furthermore, the global centrality (here is betweenness centrality) and Katz feedback centrality are incorporated into the framework to evaluate the probability to walk to the seed nodes. Experimental results on four cancer types indicate that Driver_IRW performs more efficiently than some previously published methods for uncovering known cancer-related genes. In conclusion, our method can aid in prioritizing cancer-related genes and complement traditional frequency and network-based methods.",
			"category": 2,
			"name": "Wei Pi-Jing,2024"
		},
		{
			"PMID": 32399610,
			"title": "Adverse outcome pathways for ionizing radiation and breast cancer involve direct and indirect DNA damage, oxidative stress, inflammation, genomic instability, and interaction with hormonal regulation of the breast.",
			"journal": "Archives of toxicology",
			"authorList": [
				"Helm Jessica S",
				"Rudel Ruthann A"
			],
			"DOI": "10.1007/s00204-020-02752-z",
			"date": "2021-04-22",
			"PMC": "",
			"citation": "",
			"abstract": "Knowledge about established breast carcinogens can support improved and modernized toxicological testing methods by identifying key mechanistic events. Ionizing radiation (IR) increases the risk of breast cancer, especially for women and for exposure at younger ages, and evidence overall supports a linear dose-response relationship. We used the Adverse Outcome Pathway (AOP)\u00a0framework to outline and evaluate the evidence linking ionizing radiation with breast cancer from molecular initiating events to the adverse outcome through intermediate key events, creating a qualitative AOP. We identified key events based on review articles, searched PubMed for recent literature on key events and IR, and identified additional papers using references. We manually curated publications and evaluated data quality. Ionizing radiation directly and indirectly causes DNA damage and increases production of reactive oxygen and nitrogen species (RONS). RONS lead to DNA damage and epigenetic changes leading to mutations and genomic instability (GI). Proliferation amplifies the effects of DNA damage and mutations leading to the AO of breast cancer. Separately, RONS and DNA damage also increase inflammation. Inflammation contributes to direct and indirect effects (effects in cells not directly reached by IR) via positive feedback to RONS and DNA damage, and separately increases proliferation and breast cancer through pro-carcinogenic effects on cells and tissue. For example, gene expression changes alter inflammatory mediators, resulting in improved survival and growth of cancer cells and a more hospitable tissue environment. All of these events overlap at multiple points with events characteristic of \"background\" induction of breast carcinogenesis, including hormone-responsive proliferation, oxidative activity, and DNA damage. These overlaps make the breast particularly susceptible to ionizing radiation and reinforce that these biological activities are important characteristics of carcinogens. Agents that increase these biological processes should be considered potential breast carcinogens, and predictive methods are needed to identify chemicals that increase these processes. Techniques are available to measure RONS, DNA damage and mutation, cell proliferation, and some inflammatory proteins or processes. Improved assays are needed to measure GI and chronic inflammation, as well as the interaction with hormonally driven development and proliferation. Several methods measure diverse epigenetic changes, but it is not clear which changes are relevant to breast cancer. In addition, most toxicological assays are not conducted in mammary tissue, and so it is a priority to evaluate if results from other tissues are generalizable to breast, or to conduct assays in breast tissue. Developing and applying these assays to identify exposures of concern will facilitate efforts to reduce subsequent breast cancer risk.",
			"category": 2,
			"name": "Helm Jessica S,2021"
		},
		{
			"PMID": 32397295,
			"title": "Oncogene-Addicted Non-Small-Cell Lung Cancer: Treatment Opportunities and Future Perspectives.",
			"journal": "Cancers",
			"authorList": [
				"Ferrara Miriam Grazia",
				"Di Noia Vincenzo",
				"D'Argento Ettore",
				"Vita Emanuele",
				"Damiano Paola",
				"Cannella Antonella",
				"Ribelli Marta",
				"Pilotto Sara",
				"Milella Michele",
				"Tortora Giampaolo",
				"Bria Emilio"
			],
			"DOI": "10.3390/cancers12051196",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Before the introduction of tyrosine kinase inhibitors (TKIs) for a particular subgroup of patients, despite platinum-based combination chemotherapy, the majority of patients affected by non-small-cell lung cancer (NSCLC) did not live longer than one year. With deeper understanding of tumor molecular biology, treatment of NSCLC has progressively entered the era of treatment customization according to tumor molecular characteristics, as well as histology. All this information allowed the development of personalized molecular targeted therapies. A series of studies have shown that, in some cases, cancer cells can grow and survive as result of the presence of a single driver genomic abnormality. This phenomenon, called oncogene-addiction, more often occurs in adenocarcinoma histology, in non-smokers (except BRAF mutations, also frequent in smoking patients), young, and female patients. Several different driver mutations have been identified and many studies have clearly shown that upfront TKI monotherapy may improve the overall outcome of these patients. The greater efficacy of these drugs is also associated with a better tolerability and safety than chemotherapy, with fewer side effects and an extremely good compliance to treatment. The most frequent oncogene-addicted disease is represented by those tumors carrying a mutation of the epidermal growth factor receptor (EGFR). The development of first, second and third generation TKIs against EGFR mutations have dramatically changed the prognosis of these patients. Currently, osimertinib (which demonstrated to improve efficacy with a better tolerability in comparison with first-generation TKIs) is considered the best treatment option for patients affected by NSCLC harboring a common EGFR mutation. EML4-ALK-driven disease (which gene re-arrangement occurs in 3-7% of NSCLC), has demonstrated to be significantly targeted by specific TKIs, which have improved outcome in comparison with chemotherapy. To date, alectinib is considered the best treatment option for these patients, with other newer agents upcoming. Other additional driver abnormalities, such as ROS1, BRAF, MET, RET and NTRK, have been identified as a target mirroring peculiar vulnerability to specific agents. Oncogene-addicted disease typically has a low early resistance rate, but late acquired resistance always develops and therefore therapy needs to be changed when progression occurs. In this narrative review, the state of art of scientific literature about targeted therapy options in oncogene-addicted disease is summarized and critically discussed. We also aim to analyze future perspectives to maximize benefits for this subgroup of patients.",
			"category": 2,
			"name": "Ferrara Miriam Grazia,2020"
		},
		{
			"PMID": 32395722,
			"title": "Targeting the PI3K/AKT/mTOR/NF\u03baB Axis in Ovarian Cancer.",
			"journal": "Journal of cellular immunology",
			"authorList": [
				"Ghoneum Alia",
				"Abdulfattah Ammar Yasser",
				"Said Neveen"
			],
			"DOI": "10.33696/immunology.1.022",
			"date": "2024-03-28",
			"PMC": "",
			"citation": "",
			"abstract": "Ovarian cancer stands as the most lethal gynecologic malignancy and remains the fifth most common gynecologic cancer. Poor prognosis and low five-year survival rate are attributed to nonspecific symptoms at early phases along with a lack of effective treatment at advanced stages. It is thus paramount, that ovarian carcinoma be viewed through several lenses in order to gain a thorough comprehension of its molecular pathogenesis, epidemiology, histological subtypes, hereditary factors, diagnostic approaches, and methods of treatment. Above all, it is crucial to dissect the role that the unique peritoneal tumor microenvironment plays in ovarian cancer progression and metastasis. This short communication seeks to underscore several important aspects of the PI3K/AKT/mTOR/NF\u03baB pathway in the context of ovarian cancer and discuss recent advances in targeting this pathway.",
			"category": 2,
			"name": "Ghoneum Alia,2024"
		},
		{
			"PMID": 32395543,
			"title": "Molecular subtypes and precision treatment of triple-negative breast cancer.",
			"journal": "Annals of translational medicine",
			"authorList": [
				"Zhao Shen",
				"Zuo Wen-Jia",
				"Shao Zhi-Ming",
				"Jiang Yi-Zhou"
			],
			"DOI": "10.21037/atm.2020.03.194",
			"date": "2022-08-30",
			"PMC": "",
			"citation": "",
			"abstract": "Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Despite the progress made in precision treatment of cancer patients, targeted treatment is still at its early stage in TNBC, and chemotherapy remains the standard treatment. With the advances in next generation sequencing technology, genomic and transcriptomic analyses have provided deeper insight into the inter-tumoral heterogeneity of TNBC. Much effort has been made to classify TNBCs into different molecular subtypes according to genetic aberrations and expression signatures and to uncover novel treatment targets. In this review, we summarized the current knowledge regarding the molecular classification of TNBC and explore the future paradigm for using molecular classification to guide the development of precision treatment and clinical practice.",
			"category": 2,
			"name": "Zhao Shen,2022"
		},
		{
			"PMID": 32341410,
			"title": "TMB: a promising immune-response biomarker, and potential spearhead in advancing targeted therapy trials.",
			"journal": "Cancer gene therapy",
			"authorList": [
				"Choucair Khalil",
				"Morand Susan",
				"Stanbery Laura",
				"Edelman Gerald",
				"Dworkin Lance",
				"Nemunaitis John"
			],
			"DOI": "10.1038/s41417-020-0174-y",
			"date": "2021-12-21",
			"PMC": "",
			"citation": "",
			"abstract": "Immune checkpoint inhibition (ICI) has revolutionized cancer treatment, and produced durable responses in many cancer types. However, there remains a subset of patients that do not respond despite their tumors exhibiting PD-L1 expression, which highlights the need for additional biomarkers relevant to response. Here, we review checkpoint inhibitor signal pathways, resistance and sensitivity mechanisms, as well as response rates. We also investigate the correlation and response to ICI with BRCA1/2 mutation status and homologous recombination deficient tumors. Collectively we show that the use of tumor mutational burden may be effective as an emerging biomarker.",
			"category": 2,
			"name": "Choucair Khalil,2021"
		},
		{
			"PMID": 32318338,
			"title": "Computational Oncology in the Multi-Omics Era: State of the Art.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"de Anda-J\u00e1uregui Guillermo",
				"Hern\u00e1ndez-Lemus Enrique"
			],
			"DOI": "10.3389/fonc.2020.00423",
			"date": "2023-11-03",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is the quintessential complex disease. As technologies evolve faster each day, we are able to quantify the different layers of biological elements that contribute to the emergence and development of malignancies. In this multi-omics context, the use of integrative approaches is mandatory in order to gain further insights on oncological phenomena, and to move forward toward the precision medicine paradigm. In this review, we will focus on computational oncology as an integrative discipline that incorporates knowledge from the mathematical, physical, and computational fields to further the biomedical understanding of cancer. We will discuss the current roles of computation in oncology in the context of multi-omic technologies, which include: data acquisition and processing; data management in the clinical and research settings; classification, diagnosis, and prognosis; and the development of models in the research setting, including their use for therapeutic target identification. We will discuss the machine learning and network approaches as two of the most promising emerging paradigms, in computational oncology. These approaches provide a foundation on how to integrate different layers of biological description into coherent frameworks that allow advances both in the basic and clinical settings.",
			"category": 2,
			"name": "de Anda-J\u00e1uregui Guillermo,2023"
		},
		{
			"PMID": 32291971,
			"title": "Mutational landscape and characteristics of ERBB2 in non-small cell lung cancer.",
			"journal": "Thoracic cancer",
			"authorList": [
				"Wei Xue-Wu",
				"Gao Xin",
				"Zhang Xu-Chao",
				"Yang Jin-Ji",
				"Chen Zhi-Hong",
				"Wu Yi-Long",
				"Zhou Qing"
			],
			"DOI": "10.1111/1759-7714.13419",
			"date": "2021-03-11",
			"PMC": "",
			"citation": "",
			"abstract": "Tyrosine kinase domain (TKD) mutation and particularly exon 20 insertion mutations of ERBB2 have been extensively reported in non-small cell lung cancer (NSCLC). Due to the increased accessibility of next-generation sequencing, more ERBB2 mutations within the non-TKD can be detected in clinical practice. Nevertheless, the clinical significance of non-TKD mutations remains unknown. Hence, this study was designed to comprehensively outline the landscape and characteristics of ERBB2 mutations in NSCLC.",
			"category": 2,
			"name": "Wei Xue-Wu,2021"
		},
		{
			"PMID": 32282938,
			"title": "Molecular subtype, biological sex and age shape melanoma tumour evolution.",
			"journal": "The British journal of dermatology",
			"authorList": [
				"Lotz M",
				"Budden T",
				"Furney S J",
				"Vir\u00f3s A"
			],
			"DOI": "10.1111/bjd.19128",
			"date": "2021-05-14",
			"PMC": "",
			"citation": "",
			"abstract": "Many cancer types display sex and age disparity in incidence and outcome. The mutational load of tumours, including melanoma, varies according to sex and age. However, there are no tools to explore systematically whether clinical variables such as age and sex determine the genomic landscape of cancer.",
			"category": 2,
			"name": "Lotz M,2021"
		},
		{
			"PMID": 32282885,
			"title": "CScape-somatic: distinguishing driver and passenger point mutations in the cancer genome.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Rogers Mark F",
				"Gaunt Tom R",
				"Campbell Colin"
			],
			"DOI": "10.1093/bioinformatics/btaa242",
			"date": "2020-12-23",
			"PMC": "",
			"citation": "",
			"abstract": "Next-generation sequencing technologies have accelerated the discovery of single nucleotide variants in the human genome, stimulating the development of predictors for classifying which of these variants are likely functional in disease, and which neutral. Recently, we proposed CScape, a method for discriminating between cancer driver mutations and presumed benign variants. For the neutral class, this method relied on benign germline variants found in the 1000 Genomes Project database. Discrimination could, therefore, be influenced by the distinction of germline versus somatic, rather than neutral versus disease driver. This motivates this article in which we consider predictive discrimination between recurrent and rare somatic single point mutations based solely on using cancer data, and the distinction between these two somatic classes and germline single point mutations.",
			"category": 2,
			"name": "Rogers Mark F,2020"
		},
		{
			"PMID": 32257951,
			"title": "Intratumor Heterogeneity in Early Lung Adenocarcinoma.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Senosain Maria-Fernanda",
				"Massion Pierre P"
			],
			"DOI": "10.3389/fonc.2020.00349",
			"date": "2023-11-03",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer is one of the deadliest diseases in the world and is the leading cause of cancer-related deaths. Among the histological types, adenocarcinoma is the most common, and it is characterized by a high degree of heterogeneity at many levels including clinical, behavioral, cellular and molecular. While most lung cancers are known for their aggressive behavior, up to 18.5% of lung cancers detected by CT screening are indolent and put patients at risk for overdiagnosis and overtreatment. The cellular and molecular underpinnings of tumor behavior remain largely unknown. In the recent years, the study of intratumor heterogeneity has become an attractive strategy to understand tumor progression. This review will summarize some of the current known determinants of lung adenocarcinoma behavior and discuss recent efforts to dissect its intratumor heterogeneity.",
			"category": 2,
			"name": "Senosain Maria-Fernanda,2023"
		},
		{
			"PMID": 32226775,
			"title": "The Landscape of Somatic Copy Number Alterations in Head and Neck Squamous Cell Carcinoma.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Yang Jian",
				"Chen Yi",
				"Luo Hong",
				"Cai Haoyang"
			],
			"DOI": "10.3389/fonc.2020.00321",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Somatic copy number alterations (CNAs) play a significant role in the development of this lethal cancer. In this study, we present a meta-analysis of CNAs for a total of 1,395 HNSCC samples. Publicly available R packages and in-house scripts were used for genomic array data processing, including normalization, segmentation and CNA calling. We detected 125 regions of significant gains or losses using GISTIC algorithm and found several potential driver genes in these regions. The incidence of chromothripsis in HNSCC was estimated to be 6%, and the chromosome pulverization hotspot regions were detected. We determined 323 genomic locations significantly enriched for breakpoints, which indicate HNSCC-specific genomic instability regions. Unsupervised clustering of genome-wide CNA data revealed a sub-cluster predominantly composed of nasopharynx tumors and presented a large proportion of HPV-positive samples. These results will facilitate the discovery of therapeutic candidates and extend our molecular understanding of HNSCC.",
			"category": 2,
			"name": "Yang Jian,2020"
		},
		{
			"PMID": 32218271,
			"title": "Development of Prostate Cancer Organoid Culture Models in Basic Medicine and Translational Research.",
			"journal": "Cancers",
			"authorList": [
				"Elbadawy Mohamed",
				"Abugomaa Amira",
				"Yamawaki Hideyuki",
				"Usui Tatsuya",
				"Sasaki Kazuaki"
			],
			"DOI": "10.3390/cancers12040777",
			"date": "2023-11-03",
			"PMC": "",
			"citation": "",
			"abstract": "Prostate cancer (PC) is the most prevalent cancer in men and the second main cause of cancer-related death in Western society. The lack of proper PC models that recapitulate the molecular and genomic landscape of clinical disease has hampered progress toward translational research to understand the disease initiation, progression, and therapeutic responses in each patient. Although several models have been developed, they hardly emulated the complicated PC microenvironment. Precision medicine is an emerging approach predicting appropriate therapies for individual cancer patients by means of various analyses of individual genomic profiling and targeting specific cancer pathways. In PC, precision medicine also has the potential to impose changes in clinical practices. Here, we describe the various PC models with special focus on PC organoids and their values in basic medicine, personalized therapy, and translational researches in vitro and in vivo, which could help to achieve the full transformative power of cancer precision medicine.",
			"category": 2,
			"name": "Elbadawy Mohamed,2023"
		},
		{
			"PMID": 32211327,
			"title": "Germline and Somatic ",
			"journal": "Frontiers in oncology",
			"authorList": [
				"You Yan",
				"Li Lei",
				"Lu Junliang",
				"Wu Huanwen",
				"Wang Jing",
				"Gao Jie",
				"Wu Ming",
				"Liang Zhiyong"
			],
			"DOI": "10.3389/fonc.2020.00295",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "You Yan,2020"
		},
		{
			"PMID": 32165590,
			"title": "The prognostic value of tumor mutational burden and immune cell infiltration in esophageal cancer patients with or without radiotherapy.",
			"journal": "Aging",
			"authorList": [
				"Yuan Cheng",
				"Xiang Liyang",
				"Cao Kuo",
				"Zhang Jianguo",
				"Luo Yuan",
				"Sun Wenjie",
				"Zhang Nannan",
				"Ren Jiangbo",
				"Zhang Junhong",
				"Gong Yan",
				"Xie Conghua"
			],
			"DOI": "10.18632/aging.102917",
			"date": "2021-02-18",
			"PMC": "",
			"citation": "",
			"abstract": "Growing evidence highlighted the tumor mutational burden (TMB) as an important feature of carcinogenesis and therapeutic efficacy in esophageal cancer (EC). Our study aimed to explore the genomic landscape and the correlation between TMB and immune cell infiltration in EC patients with or without radiotherapy. The EC patients were categorized into high TMB (TMB-H) and low TMB (TMB-L) groups by the ESTIMATE algorithm, and subgroup analysis was performed based on receiving radiotherapy or not. Univariate regression analysis indicated TMB and TNM stages as high-risk prognostic factors (Hazard ratio > 1 and P < 0.05). Multivariate regression analysis suggested TMB as an independent prognostic factor (Hazard ratio = 1.051, P = 0.003). Kaplan-Meier analysis showed no significant difference of the overall survival (OS) between TMB-H and TMB-L groups (P = 0.082). However, EC patients without radiotherapy in the TMB-H group had significantly decreased OS (P = 0.038) and increased Tregs cell infiltration (P = 0.033). These results suggested TMB as a prognostic marker for EC patients. Especially for patients who did not receive radiotherapy, the prognosis of TMB-H patients was significantly poorer than that of TMB-L patients, which might result from the different regulatory T cell infiltration.",
			"category": 2,
			"name": "Yuan Cheng,2021"
		},
		{
			"PMID": 32152280,
			"title": "The X-linked trichothiodystrophy-causing gene RNF113A links the spliceosome to cell survival upon DNA damage.",
			"journal": "Nature communications",
			"authorList": [
				"Shostak Kateryna",
				"Jiang Zheshen",
				"Charloteaux Benoit",
				"Mayer Alice",
				"Habraken Yvette",
				"Tharun Lars",
				"Klein Sebastian",
				"Xu Xinyi",
				"Duong Hong Quan",
				"Vislovukh Andrii",
				"Close Pierre",
				"Florin Alexandra",
				"Rambow Florian",
				"Marine Jean-Christophe",
				"B\u00fcttner Reinhard",
				"Chariot Alain"
			],
			"DOI": "10.1038/s41467-020-15003-7",
			"date": "2020-07-01",
			"PMC": "",
			"citation": "",
			"abstract": "Prolonged cell survival occurs through the expression of specific protein isoforms generated by alternate splicing of mRNA precursors in cancer cells. How alternate splicing regulates tumor development and resistance to targeted therapies in cancer remain poorly understood. Here we show that RNF113A, whose loss-of-function causes the X-linked trichothiodystrophy, is overexpressed in lung cancer and protects from Cisplatin-dependent cell death. RNF113A is a RNA-binding protein which regulates the splicing of multiple candidates involved in cell survival. RNF113A deficiency triggers cell death upon DNA damage through multiple mechanisms, including apoptosis via the destabilization of the prosurvival protein MCL-1, ferroptosis due to enhanced SAT1 expression, and increased production of ROS due to altered Noxa1 expression. RNF113A deficiency circumvents the resistance to Cisplatin and to BCL-2 inhibitors through the destabilization of MCL-1, which thus defines spliceosome inhibitors as a therapeutic approach to treat tumors showing acquired resistance to specific drugs due to MCL-1 stabilization.",
			"category": 2,
			"name": "Shostak Kateryna,2020"
		},
		{
			"PMID": 32139011,
			"title": "Reconstructing the evolutionary history of multiple myeloma.",
			"journal": "Best practice & research. Clinical haematology",
			"authorList": [
				"Maura Francesco",
				"Rustad Even H",
				"Boyle Eileen M",
				"Morgan Gareth J"
			],
			"DOI": "10.1016/j.beha.2020.101145",
			"date": "2020-12-17",
			"PMC": "",
			"citation": "",
			"abstract": "Multiple myeloma is the second most common lymphoproliferative disorder, characterized by aberrant expansion of monoclonal plasma cells. In the last years, thanks to novel next generation sequencing technologies, multiple myeloma has emerged as one of the most complex hematological cancers, shaped over time by the activity of multiple mutational processes and by the acquisition of key driver events. In this review, we describe how whole genome sequencing is emerging as a key technology to decipher this complexity at every stage of myeloma development: precursors, diagnosis and relapsed/refractory. Defining the time windows when driver events are acquired improves our understanding of cancer etiology and paves the way for early diagnosis and ultimately prevention.",
			"category": 2,
			"name": "Maura Francesco,2020"
		},
		{
			"PMID": 32127924,
			"title": "Biomarker testing for personalized, first-line therapy in advanced nonsquamous non-small cell lung cancer patients in the real world setting in Japan: a retrospective, multicenter, observational study (the BRAVE study).",
			"journal": "Therapeutic advances in medical oncology",
			"authorList": [
				"Shimizu Junichi",
				"Masago Katsuhiro",
				"Saito Haruhiro",
				"Nishino Kazumi",
				"Kurata Takayasu",
				"Itoh Yohji",
				"Yoshimura Yoko",
				"Yabuki Yutaka",
				"Dosaka-Akita Hirotoshi"
			],
			"DOI": "10.1177/1758835920904522",
			"date": "2022-04-13",
			"PMC": "",
			"citation": "",
			"abstract": "Molecular diagnostic testing is necessary to guide optimal first-line treatment. The number of patients who receive first-line treatment based on biomarker analysis in Japan is unknown. We aimed to determine the proportion of nonsquamous non-small cell lung cancer (NSCLC) patients for whom first-line treatment was selected based on biomarker testing.",
			"category": 2,
			"name": "Shimizu Junichi,2022"
		},
		{
			"PMID": 32058723,
			"title": "Comprehensive Detection of Single Amino Acid Variants and Evaluation of Their Deleterious Potential in a PANC-1 Cell Line.",
			"journal": "Journal of proteome research",
			"authorList": [
				"Tan Zhijing",
				"Zhu Jianhui",
				"Stemmer Paul M",
				"Sun Liangliang",
				"Yang Zhichang",
				"Schultz Kendall",
				"Gaffrey Matthew J",
				"Cesnik Anthony J",
				"Yi Xinpei",
				"Hao Xiaohu",
				"Shortreed Michael R",
				"Shi Tujin",
				"Lubman David M"
			],
			"DOI": "10.1021/acs.jproteome.9b00840",
			"date": "2021-06-17",
			"PMC": "",
			"citation": "",
			"abstract": "Identifying single amino acid variants (SAAVs) in cancer is critical for precision oncology. Several advanced algorithms are now available to identify SAAVs, but attempts to combine different algorithms and optimize them on large data sets to achieve a more comprehensive coverage of SAAVs have not been implemented. Herein, we report an expanded detection of SAAVs in the PANC-1 cell line using three different strategies, which results in the identification of 540 SAAVs in the mass spectrometry data. Among the set of 540 SAAVs, 79 are evaluated as deleterious SAAVs based on analysis using the novel AssVar software in which one of the driver mutations found in each protein of KRAS, TP53, and SLC37A4 is further validated using independent selected reaction monitoring (SRM) analysis. Our study represents the most comprehensive discovery of SAAVs to date and the first large-scale detection of deleterious SAAVs in the PANC-1 cell line. This work may serve as the basis for future research in pancreatic cancer and personal immunotherapy and treatment.",
			"category": 2,
			"name": "Tan Zhijing,2021"
		},
		{
			"PMID": 32024818,
			"title": "Combined burden and functional impact tests for cancer driver discovery using DriverPower.",
			"journal": "Nature communications",
			"authorList": [
				"Shuai Shimin",
				"PCAWG Drivers and Functional Interpretation Working Group",
				"Gallinger Steven",
				"Stein Lincoln D",
				"PCAWG Consortium"
			],
			"DOI": "10.1038/s41467-019-13929-1",
			"date": "2020-05-12",
			"PMC": "",
			"citation": "",
			"abstract": "The discovery of driver mutations is one of the key motivations for cancer genome sequencing. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic features derived from public sources, DriverPower's background mutation model explains up to 93% of the regional variance in the mutation rate across multiple tumour types. By incorporating functional impact scores, we are able to further increase the accuracy of driver discovery. Testing across a collection of 2583 cancer genomes from the PCAWG project, DriverPower identifies 217 coding and 95 non-coding driver candidates. Comparing to six published methods used by the PCAWG Drivers and Functional Interpretation Working Group, DriverPower has the highest F1 score for both coding and non-coding driver discovery. This demonstrates that DriverPower is an effective framework for computational driver discovery.",
			"category": 2,
			"name": "Shuai Shimin,2020"
		},
		{
			"PMID": 32017470,
			"title": "Integrative analysis of highly mutated genes in hepatitis B virus-related hepatic carcinoma.",
			"journal": "Cancer medicine",
			"authorList": [
				"Kong Fanyun",
				"Kong Delong",
				"Yang Xiaoying",
				"Yuan Dongchen",
				"Zhang Ning",
				"Hua Xuan",
				"You Hongjuan",
				"Zheng Kuiyang",
				"Tang Renxian"
			],
			"DOI": "10.1002/cam4.2903",
			"date": "2021-05-14",
			"PMC": "",
			"citation": "",
			"abstract": "Gene mutation is responsible for the development of hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) infection; however, the characteristics and associated biological functions of highly mutated genes, in which the mutation frequencies are at least 5% in HCC patients with HBV infection, are not clearly evaluated. In the study, we analyzed the information regarding somatic mutation obtained by whole-exome sequencing in 280 HBV-related HCC tissues from public databases and published studies. Via integrative analysis, 78 genes, including TP53, TTN, MUC16, CTNNB1, and PCLO were summarized as highly mutated genes, and some of these mutated genes were further identified as cancer driver genes. Besides, we discovered that the highly mutated genes were enriched with various biological functions and pathways. The expression of many of highly mutated genes was found to be significantly altered in HBV-related HCC, and several highly mutated genes were related to a variety of clinical factors and associated with the poor survival of the disease. Taken together, these results could enrich our understanding of highly mutated genes and their relationships with HBV-related HCC. Some of the identified highly mutated genes might be used as novel biomarkers of disease prognosis, or as molecular targets for the treatment of HCC with HBV infection.",
			"category": 2,
			"name": "Kong Fanyun,2021"
		},
		{
			"PMID": 32014773,
			"title": "Mutagenicity assessment downstream of oil and gas produced water discharges intended for agricultural beneficial reuse.",
			"journal": "The Science of the total environment",
			"authorList": [
				"McLaughlin Molly C",
				"Blotevogel Jens",
				"Watson Ruth A",
				"Schell Baylee",
				"Blewett Tamzin A",
				"Folkerts Erik J",
				"Goss Greg G",
				"Truong Lisa",
				"Tanguay Robyn L",
				"Argueso Juan Lucas",
				"Borch Thomas"
			],
			"DOI": "10.1016/j.scitotenv.2020.136944",
			"date": "2020-04-06",
			"PMC": "",
			"citation": "",
			"abstract": "Produced water is the largest waste stream associated with oil and gas operations. This complex fluid contains petroleum hydrocarbons, heavy metals, salts, naturally occurring radioactive materials and any remaining chemical additives. In the United States, west of the 98th meridian, the federal National Pollutant Discharge Elimination System (NPDES) exemption allows release of produced water for agricultural beneficial reuse. The goal of this study was to quantify mutagenicity of a produced water NPDES release and discharge stream. We used four mutation assays in budding yeast cells that provide rate estimates for copy number variation (CNV) duplications and deletions, as well as forward and reversion point mutations. Higher mutation rates were observed at the discharge and decreased with distance downstream, which correlated with the concentrations of known carcinogens detected in the stream (e.g., benzene, radium), described in a companion study. Mutation rate increases were most prominent for CNV duplications and were higher than mutations observed in mixtures of known toxic compounds. Additionally, the samples were evaluated for acute toxicity in Daphnia magna and developmental toxicity in zebrafish. Acute toxicity was minimal, and no developmental toxicity was observed. This study illustrates that chemical analysis alone (McLaughlin et al., 2020) is insufficient for characterizing the risk of produced water NPDES releases and that a thorough evaluation of chronic toxicity is necessary to fully assess produced water for beneficial reuse.",
			"category": 2,
			"name": "McLaughlin Molly C,2020"
		},
		{
			"PMID": 32013076,
			"title": "Rapid, Paralog-Sensitive CNV Analysis of 2457 Human Genomes Using QuicK-mer2.",
			"journal": "Genes",
			"authorList": [
				"Shen Feichen",
				"Kidd Jeffrey M"
			],
			"DOI": "10.3390/genes11020141",
			"date": "2020-12-04",
			"PMC": "",
			"citation": "",
			"abstract": "Gene duplication is a major mechanism for the evolution of gene novelty, and copy-number variation makes a major contribution to inter-individual genetic diversity. However, most approaches for studying copy-number variation rely upon uniquely mapping reads to a genome reference and are unable to distinguish among duplicated sequences. Specialized approaches to interrogate specific paralogs are comparatively slow and have a high degree of computational complexity, limiting their effective application to emerging population-scale data sets. We present QuicK-mer2, a self-contained, mapping-free approach that enables the rapid construction of paralog-specific copy-number maps from short-read sequence data. This approach is based on the tabulation of unique k-mer sequences from short-read data sets, and is able to analyze a 20X coverage human genome in approximately 20 min. We applied our approach to newly released sequence data from the 1000 Genomes Project, constructed paralog-specific copy-number maps from 2457 unrelated individuals, and uncovered copy-number variation of paralogous genes. We identify nine genes where none of the analyzed samples have a copy number of two, 92 genes where the majority of samples have a copy number other than two, and describe rare copy number variation effecting multiple genes at the APOBEC3 locus.",
			"category": 2,
			"name": "Shen Feichen,2020"
		},
		{
			"PMID": 32010778,
			"title": "Single-cell morphology encodes metastatic potential.",
			"journal": "Science advances",
			"authorList": [
				"Wu Pei-Hsun",
				"Gilkes Daniele M",
				"Phillip Jude M",
				"Narkar Akshay",
				"Cheng Thomas Wen-Tao",
				"Marchand Jorge",
				"Lee Meng-Horng",
				"Li Rong",
				"Wirtz Denis"
			],
			"DOI": "10.1126/sciadv.aaw6938",
			"date": "2020-09-23",
			"PMC": "",
			"citation": "",
			"abstract": "A central goal of precision medicine is to predict disease outcomes and design treatments based on multidimensional information from afflicted cells and tissues. Cell morphology is an emergent readout of the molecular underpinnings of a cell's functions and, thus, can be used as a method to define the functional state of an individual cell. We measured 216 features derived from cell and nucleus morphology for more than 30,000 breast cancer cells. We find that single cell-derived clones (SCCs) established from the same parental cells exhibit distinct and heritable morphological traits associated with genomic (ploidy) and transcriptomic phenotypes. Using unsupervised clustering analysis, we find that the morphological classes of SCCs predict distinct tumorigenic and metastatic potentials in vivo using multiple mouse models of breast cancer. These findings lay the groundwork for using quantitative morpho-profiling in vitro as a potentially convenient and economical method for phenotyping function in cancer in vivo.",
			"category": 2,
			"name": "Wu Pei-Hsun,2020"
		},
		{
			"PMID": 32001676,
			"title": "Comprehensive T cell repertoire characterization of non-small cell lung cancer.",
			"journal": "Nature communications",
			"authorList": [
				"Reuben Alexandre",
				"Zhang Jiexin",
				"Chiou Shin-Heng",
				"Gittelman Rachel M",
				"Li Jun",
				"Lee Won-Chul",
				"Fujimoto Junya",
				"Behrens Carmen",
				"Liu Xiaoke",
				"Wang Feng",
				"Quek Kelly",
				"Wang Chunlin",
				"Kheradmand Farrah",
				"Chen Runzhe",
				"Chow Chi-Wan",
				"Lin Heather",
				"Bernatchez Chantale",
				"Jalali Ali",
				"Hu Xin",
				"Wu Chang-Jiun",
				"Eterovic Agda Karina",
				"Parra Edwin Roger",
				"Yusko Erik",
				"Emerson Ryan",
				"Benzeno Sharon",
				"Vignali Marissa",
				"Wu Xifeng",
				"Ye Yuanqing",
				"Little Latasha D",
				"Gumbs Curtis",
				"Mao Xizeng",
				"Song Xingzhi",
				"Tippen Samantha",
				"Thornton Rebecca L",
				"Cascone Tina",
				"Snyder Alexandra",
				"Wargo Jennifer A",
				"Herbst Roy",
				"Swisher Stephen",
				"Kadara Humam",
				"Moran Cesar",
				"Kalhor Neda",
				"Zhang Jianhua",
				"Scheet Paul",
				"Vaporciyan Ara A",
				"Sepesi Boris",
				"Gibbons Don L",
				"Robins Harlan",
				"Hwu Patrick",
				"Heymach John V",
				"Sharma Padmanee",
				"Allison James P",
				"Baladandayuthapani Veera",
				"Lee Jack J",
				"Davis Mark M",
				"Wistuba Ignacio I",
				"Futreal P Andrew",
				"Zhang Jianjun"
			],
			"DOI": "10.1038/s41467-019-14273-0",
			"date": "2020-04-13",
			"PMC": "",
			"citation": "",
			"abstract": "Immunotherapy targeting T cells is increasingly utilized to treat solid tumors including non-small cell lung cancer (NSCLC). This requires a better understanding of the T cells in the lungs of patients with NSCLC. Here, we report T cell repertoire analysis in a cohort of 236 early-stage NSCLC patients. T cell repertoire attributes are associated with clinicopathologic features, mutational and immune landscape. A considerable proportion of the most prevalent T cells in tumors are also prevalent in the uninvolved tumor-adjacent lungs and appear specific to shared background mutations or viral infections. Patients with higher T cell repertoire homology between the tumor and uninvolved tumor-adjacent lung, suggesting a less tumor-focused T cell response, exhibit inferior survival. These findings indicate that a concise understanding of antigens and T cells in NSCLC is needed to improve therapeutic efficacy and reduce toxicity with immunotherapy, particularly adoptive T cell therapy.",
			"category": 2,
			"name": "Reuben Alexandre,2020"
		},
		{
			"PMID": 31986218,
			"title": "Holistic cancer genome profiling for every patient.",
			"journal": "Swiss medical weekly",
			"authorList": [
				"Nik-Zainal Serena",
				"Memari Yasin",
				"Davies Helen R"
			],
			"DOI": "10.4414/smw.2020.20158",
			"date": "2021-02-19",
			"PMC": "",
			"citation": "",
			"abstract": "Technological advances in the ability to read the human genome have accelerated the speed of sequencing, such that today we can perform whole genome sequencing (WGS) in one day. Until recently, genomic studies have largely been limited to seeking novel scientific discoveries. The application of new insights gained through cancer WGS into the clinical domain, have been relatively limited. Looking ahead, a vast amount of data can be generated by genomic studies. Of note, excellent organisation of genomic and clinical data permits the application of machine-learning methods which can lead to the development of clinical algorithms that could assist future clinicians and genomicists in the analysis and interpretation of individual cancer genomes. Here, we describe what can be gleaned from holistic whole cancer genome profiling and argue that we must build the infrastructure and educational frameworks to support the modern clinical genomicist to prepare for a future where WGS will be the norm.",
			"category": 2,
			"name": "Nik-Zainal Serena,2021"
		},
		{
			"PMID": 31968594,
			"title": "Germline Variants in Driver Genes of Breast Cancer and Their Association with Familial and Early-Onset Breast Cancer Risk in a Chilean Population.",
			"journal": "Cancers",
			"authorList": [
				"Fernandez-Moya Alejandro",
				"Morales Sebastian",
				"Arancibia Trinidad",
				"Gonzalez-Hormazabal Patricio",
				"Tapia Julio C",
				"Godoy-Herrera Raul",
				"Reyes Jose Miguel",
				"Gomez Fernando",
				"Waugh Enrique",
				"Jara Lilian"
			],
			"DOI": "10.3390/cancers12010249",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "The genetic variations responsible for tumorigenesis are called driver mutations. In breast cancer (BC), two studies have demonstrated that germline mutations in driver genes linked to sporadic tumors may also influence BC risk. The present study evaluates the association between SNPs and SNP-SNP interaction in driver genes ",
			"category": 2,
			"name": "Fernandez-Moya Alejandro,2020"
		},
		{
			"PMID": 31963488,
			"title": "Assessment of Tumor Mutational Burden in Pediatric Tumors by Real-Life Whole-Exome Sequencing and In Silico Simulation of Targeted Gene Panels: How the Choice of Method Could Affect the Clinical Decision?",
			"journal": "Cancers",
			"authorList": [
				"Noskova Hana",
				"Kyr Michal",
				"Pal Karol",
				"Merta Tomas",
				"Mudry Peter",
				"Polaskova Kristyna",
				"Ivkovic Tina Catela",
				"Adamcova Sona",
				"Hornakova Tekla",
				"Jezova Marta",
				"Kren Leos",
				"Sterba Jaroslav",
				"Slaby Ondrej"
			],
			"DOI": "10.3390/cancers12010230",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Tumor mutational burden (TMB) is an emerging genomic biomarker in cancer that has been associated with improved response to immune checkpoint inhibitors (ICIs) in adult cancers. It was described that variability in TMB assessment is introduced by different laboratory techniques and various settings of bioinformatic pipelines. In pediatric oncology, no study has been published describing this variability so far.",
			"category": 2,
			"name": "Noskova Hana,2020"
		},
		{
			"PMID": 31948514,
			"title": "Correlating Transcriptional Networks to Papillary Renal Cell Carcinoma Survival: A Large-Scale Coexpression Analysis and Clinical Validation.",
			"journal": "Oncology research",
			"authorList": [
				"Feng Xingliang",
				"Zhang Meng",
				"Meng Jialin",
				"Wang Yongqiang",
				"Liu Yi",
				"Liang Chaozhao",
				"Fan Song"
			],
			"DOI": "10.3727/096504020X15791676105394",
			"date": "2020-11-19",
			"PMC": "",
			"citation": "",
			"abstract": "We aimed to investigate the potential mechanisms of progression and identify novel prognosis-related biomarkers for papillary renal cell carcinoma (PRCC) patients. The related data were derived from The Cancer Genome Atlas (TCGA) and then analyzed by weighted gene coexpression network analysis (WGCNA). The correlation between each module and the clinical traits were analyzed by Pearson's correlation analysis. Pathway analysis was conducted to reveal potential mechanisms. Hub genes within each module were screened by intramodule analysis, and visualized by Cytoscape software. Furthermore, important hub genes were validated in an external dataset and clinical samples. A total of 5,839 differentially expressed genes were identified. By using WGCNA, we identified 21 coregulatory gene clusters based on 289 PRCC samples. We found many modules were significantly associated with clinicopathological characteristics. The gray, pink, light yellow, and salmon modules served as prognosis indicators for PRCC patients. Pathway enrichment analyses found that the hub genes were significantly enriched in the cancer-related pathways. With the external Gene Expression Omnibus (GEO) validation dataset, we found that PCDH12, GPR4, and KIF18A in the pink and yellow modules were continually associated with the survival status of PRCC, and their expressions were positively correlated with pathological grade. Notably, we randomly chose PCDH12 for validation, and the results suggested that the PRCC patients with higher pathological grades (II\u2009+\u2009III) mostly had higher PCDH12 protein expression levels compared with those patients in grade I. These validated hub genes play critical roles in the prognosis prediction of PRCC and serve as potential biomarkers for future personalized treatment.",
			"category": 2,
			"name": "Feng Xingliang,2020"
		},
		{
			"PMID": 31937561,
			"title": null,
			"journal": "Journal of medical genetics",
			"authorList": [
				"Shen Erica",
				"Xiu Joanne",
				"Lopez Giselle Y",
				"Bentley Rex",
				"Jalali Ali",
				"Heimberger Amy B",
				"Bainbridge Matthew N",
				"Bondy Melissa L",
				"Walsh Kyle M"
			],
			"DOI": "10.1136/jmedgenet-2019-106657",
			"date": "2021-07-08",
			"PMC": "",
			"citation": "",
			"abstract": "The shelterin complex is composed of six proteins that protect and regulate telomere length, including protection of telomeres 1 (POT1). Germline ",
			"category": 2,
			"name": "Shen Erica,2021"
		},
		{
			"PMID": 31933881,
			"title": "A detrimental mutation on USP40 unlocks the tumorigenesis in a rare case of lung cancer.",
			"journal": "International journal of clinical and experimental pathology",
			"authorList": [
				"Xu Zhi-Hong",
				"Wang Hui",
				"Ji Xiao-Yang",
				"Zhang Fei-Xu",
				"Gao Bei-Li",
				"Hu Jia-An",
				"Zheng Jing"
			],
			"DOI": "",
			"date": "2020-03-25",
			"PMC": "",
			"citation": "",
			"abstract": "Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer. Previous research has shown heterogeneity in lung cancer, with the parallel existence of multiple subclones characterized by their own specific mutational landscape. The aim of our study was to gain insight into the evolutionary pattern of lung cancer by investigating the genomic heterogeneity between a nodule and its distant tumor. Luckily, we obtained nodule and tumor samples derived from surgery and a blood sample from a single patient. The samples are very unique, for tissues with the same genetic background from nodules to malignant tumors are rarely available and require precise micro-cutting. In this study, we performed whole-genome sequencing of these two samples, to identify novel candidate driver genes associated with LUAD. The nodule and tumor were found to have common significant ubiquitin-specific protease 40 (USP40) mutations, indicating an important driver role for the gene. Moreover, we also observed the two novel candidate driver genes ASCL5 and CAPNS1 in the LUAD sample. In summary, we pinpoint the predominant mutations in LUAD by WES, highlighting the substantial genetic alterations contributing to LUAD tumorigenesis. This may provide a better understanding of the clonal evolution during tumor development.",
			"category": 2,
			"name": "Xu Zhi-Hong,2020"
		},
		{
			"PMID": 31919445,
			"title": "A community effort to create standards for evaluating tumor subclonal reconstruction.",
			"journal": "Nature biotechnology",
			"authorList": [
				"Salcedo Adriana",
				"Tarabichi Maxime",
				"Espiritu Shadrielle Melijah G",
				"Deshwar Amit G",
				"David Matei",
				"Wilson Nathan M",
				"Dentro Stefan",
				"Wintersinger Jeff A",
				"Liu Lydia Y",
				"Ko Minjeong",
				"Sivanandan Srinivasan",
				"Zhang Hongjiu",
				"Zhu Kaiyi",
				"Ou Yang Tai-Hsien",
				"Chilton John M",
				"Buchanan Alex",
				"Lalansingh Christopher M",
				"P'ng Christine",
				"Anghel Catalina V",
				"Umar Imaad",
				"Lo Bryan",
				"Zou William",
				"DREAM SMC-Het Participants",
				"Simpson Jared T",
				"Stuart Joshua M",
				"Anastassiou Dimitris",
				"Guan Yuanfang",
				"Ewing Adam D",
				"Ellrott Kyle",
				"Wedge David C",
				"Morris Quaid",
				"Van Loo Peter",
				"Boutros Paul C"
			],
			"DOI": "10.1038/s41587-019-0364-z",
			"date": "2020-04-08",
			"PMC": "",
			"citation": "",
			"abstract": "Tumor DNA sequencing data can be interpreted by computational methods that analyze genomic heterogeneity to infer evolutionary dynamics. A growing number of studies have used these approaches to link cancer evolution with clinical progression and response to therapy. Although the inference of tumor phylogenies is rapidly becoming standard practice in cancer genome analyses, standards for evaluating them are lacking. To address this need, we systematically assess methods for reconstructing tumor subclonality. First, we elucidate the main algorithmic problems in subclonal reconstruction and develop quantitative metrics for evaluating them. Then we simulate realistic tumor genomes that harbor all known clonal and subclonal mutation types and processes. Finally, we benchmark 580 tumor reconstructions, varying tumor read depth, tumor type and somatic variant detection. Our analysis provides a baseline for the establishment of gold-standard methods to analyze tumor heterogeneity.",
			"category": 2,
			"name": "Salcedo Adriana,2020"
		},
		{
			"PMID": 31894314,
			"title": "Comprehensive identification and characterization of somatic copy number alterations in triple\u2011negative breast cancer.",
			"journal": "International journal of oncology",
			"authorList": [
				"Li Zaibing",
				"Zhang Xiao",
				"Hou Chenxin",
				"Zhou Yuqing",
				"Chen Junli",
				"Cai Haoyang",
				"Ye Yifeng",
				"Liu Jinping",
				"Huang Ning"
			],
			"DOI": "10.3892/ijo.2019.4950",
			"date": "2020-10-15",
			"PMC": "",
			"citation": "",
			"abstract": "Triple\u2011negative breast cancer (TNBC) accounts for ~15% of all breast cancer diagnoses each year. Patients with TNBC tend to have a higher risk for early relapse and a worse prognosis. TNBC is characterized by extensive somatic copy number alterations (CNAs). However, the DNA CNA profile of TNBC remains to be extensively investigated. The present study assessed the genomic profile of CNAs in 201\u00a0TNBC samples, aiming to identify recurrent CNAs that may drive the pathogenesis of TNBC. In total, 123\u00a0regions of significant amplification and deletion were detected using the Genomic Identification of Significant Targets in Cancer algorithm, and potential driver genes for TNBC were identified. A total of 31\u00a0samples exhibited signs of chromothripsis and revealed chromosome pulverization hotspot regions. The present study further determined 199\u00a0genomic locations that were significantly enriched for breakpoints, which indicated TNBC\u2011specific genomic instability regions. Unsupervised hierarchical clustering of tumors resulted in three main subgroups that exhibited distinct CNA profiles, which may reveal the heterogeneity of molecular mechanisms in TNBC subgroups. These results will extend the molecular understanding of TNBC and will facilitate the discovery of therapeutic and diagnostic target candidates.",
			"category": 2,
			"name": "Li Zaibing,2020"
		},
		{
			"PMID": 31882448,
			"title": "Revisiting the tumorigenesis timeline with a data-driven generative model.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Lahouel Kamel",
				"Younes Laurent",
				"Danilova Ludmila",
				"Giardiello Francis M",
				"Hruban Ralph H",
				"Groopman John",
				"Kinzler Kenneth W",
				"Vogelstein Bert",
				"Geman Donald",
				"Tomasetti Cristian"
			],
			"DOI": "10.1073/pnas.1914589117",
			"date": "2020-04-16",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is driven by the sequential accumulation of genetic and epigenetic changes in oncogenes and tumor suppressor genes. The timing of these events is not well understood. Moreover, it is currently unknown why the same driver gene change appears as an early event in some cancer types and as a later event, or not at all, in others. These questions have become even more topical with the recent progress brought by genome-wide sequencing studies of cancer. Focusing on mutational events, we provide a mathematical model of the full process of tumor evolution that includes different types of fitness advantages for driver genes and carrying-capacity considerations. The model is able to recapitulate a substantial proportion of the observed cancer incidence in several cancer types (colorectal, pancreatic, and leukemia) and inherited conditions (Lynch and familial adenomatous polyposis), by changing only 2 tissue-specific parameters: the number of stem cells in a tissue and its cell division frequency. The model sheds light on the evolutionary dynamics of cancer by suggesting a generalized early onset of tumorigenesis followed by slow mutational waves, in contrast to previous conclusions. Formulas and estimates are provided for the fitness increases induced by driver mutations, often much larger than previously described, and highly tissue dependent. Our results suggest a mechanistic explanation for why the selective fitness advantage introduced by specific driver genes is tissue dependent.",
			"category": 2,
			"name": "Lahouel Kamel,2020"
		},
		{
			"PMID": 31874647,
			"title": "Comparison of somatic variant detection algorithms using Ion Torrent targeted deep sequencing data.",
			"journal": "BMC medical genomics",
			"authorList": [
				"Wang Qing",
				"Kotoula Vassiliki",
				"Hsu Pei-Chen",
				"Papadopoulou Kyriaki",
				"Ho Joshua W K",
				"Fountzilas George",
				"Giannoulatou Eleni"
			],
			"DOI": "10.1186/s12920-019-0636-y",
			"date": "2020-06-29",
			"PMC": "",
			"citation": "",
			"abstract": "The application of next-generation sequencing in cancer has revealed the genomic landscape of many tumour types and is nowadays routinely used in research and clinical settings. Multiple algorithms have been developed to detect somatic variation from sequencing data using either paired tumour-blood or tumour-only samples. Most of these methods have been developed and evaluated for the identification of somatic variation using Illumina sequencing datasets of moderate coverage. However, a comprehensive evaluation of somatic variant detection algorithms on Ion Torrent targeted deep sequencing data has not been performed.",
			"category": 2,
			"name": "Wang Qing,2020"
		},
		{
			"PMID": 31845427,
			"title": "Spatial and temporal expansion of intrahepatic metastasis by molecularly-defined clonality in multiple liver cancers.",
			"journal": "Cancer science",
			"authorList": [
				"Yamamoto Shogo",
				"Midorikawa Yutaka",
				"Nagae Genta",
				"Tatsuno Kenji",
				"Ueda Hiroki",
				"Moriyama Mitsuhiko",
				"Takayama Tadatoshi",
				"Aburatani Hiroyuki"
			],
			"DOI": "10.1111/cas.14282",
			"date": "2020-02-19",
			"PMC": "",
			"citation": "",
			"abstract": "Multiple hepatocellular carcinoma (HCC) is divided into two categories: intrahepatic metastasis (IM), which is a true relapse of HCC, and multicentric origin (MO), which is a second primary tumor. Clinical diagnosis of multiple HCC is usually made based on tumor location and/or time to recurrence; however, it is often difficult to distinguish the two types of multiple HCC. Using 41 matched pairs of multiple HCC specimens, we confirmed the accuracy of clinical diagnoses using exome sequence data and investigated the importance of discriminating the type of multiple HCC. Genomic analysis revealed that 18 (43.9%) patients diagnosed as having genomic IM had common mutations in a pair of HCC tumors with the main tumor of these patients being more progressive compared to those with genomic MO. The accuracy of clinical diagnosis based on lobe (Definition 1) and segment (Definition 2) were 68.3% and 78.0%, respectively. Intriguingly, recurrence \u22652\u00a0years after initial surgery for 3 patients was IM. The survival of patients with clinical IM was significantly shorter than for those with clinical MO based on both Definition 1 (P\u00a0=\u00a00.045) and Definition 2 (P\u00a0=\u00a00.043). However, mean survival was not different between the patients with genomic IM and those with MO (P\u00a0=\u00a00.364). Taken together, genomic analysis elucidated that liver cancer may spread more extensively and more slowly than previously thought. In addition, distinguishing multiple HCC as IM or MC may have provided biological information but was not of clinical importance with respect to patient prognosis.",
			"category": 2,
			"name": "Yamamoto Shogo,2020"
		},
		{
			"PMID": 31842489,
			"title": "Somatic Mutation of ",
			"journal": "Cancers",
			"authorList": [
				"Lee Kang-Hoon",
				"Hwang Hyeon-Ji",
				"Noh Hyun Ji",
				"Shin Tae-Jin",
				"Cho Je-Yoel"
			],
			"DOI": "10.3390/cancers11122006",
			"date": "2024-03-28",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer is one of the most frequently diagnosed cancers in both women and female dogs. Genome-wide association studies in human breast cancer (HBC) have identified hundreds of genetic variations and somatic driver mutations. However, only a handful of variants have been studied for rare HBC and their associations remain inconclusive. Spontaneous canine mammary tumor (CMT) is a great model for HBC, with clinical similarity. We thus performed whole-exome sequencing in 20 pairs of CMT and normal tissues in dogs. We newly found that ",
			"category": 2,
			"name": "Lee Kang-Hoon,2024"
		},
		{
			"PMID": 31830214,
			"title": "Moving From Cancer Burden to Cancer Genomics for Smoldering Myeloma: A Review.",
			"journal": "JAMA oncology",
			"authorList": [
				"Maura Francesco",
				"Bolli Niccol\u00f2",
				"Rustad Even H",
				"Hultcrantz Malin",
				"Munshi Nikhil",
				"Landgren Ola"
			],
			"DOI": "10.1001/jamaoncol.2019.4659",
			"date": "2020-12-18",
			"PMC": "",
			"citation": "",
			"abstract": "All patients who develop multiple myeloma have a preceding asymptomatic expansion of clonal plasma cells, clinically recognized as monoclonal gammopathy of undetermined significance or smoldering multiple myeloma (SMM). During the past decade, significant progress has been made in the classification and risk stratification of SMM.",
			"category": 2,
			"name": "Maura Francesco,2020"
		},
		{
			"PMID": 31818027,
			"title": "Noncoding RNAs and Liquid Biopsy in Lung Cancer: A Literature Review.",
			"journal": "Diagnostics (Basel, Switzerland)",
			"authorList": [
				"Harangu\u0219 Antonia",
				"Berindan-Neagoe Ioana",
				"Todea Doina Adina",
				"\u0218imon Ioan",
				"\u0218imon M\u0103rioara"
			],
			"DOI": "10.3390/diagnostics9040216",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer represents a genetically heterogeneous disease with low survival rates. Recent data have evidenced key roles of noncoding RNAs in lung cancer initiation and progression. These functional RNA molecules that can act as both oncogenes and tumor suppressors may become future biomarkers and more efficient therapeutic targets. In the precision medicine era, circulating nucleic acids have the potential to reshape the management and prognosis of cancer patients. Detecting genomic alterations and level variations of circulating nucleic acids in liquid biopsy samples represents a noninvasive method for portraying tumor burden. Research is currently trying to validate the potential role of liquid biopsy in lung cancer screening, prognosis, monitoring of disease progression, and treatment response. However, this method requires complex detection assays, and implementation of plasma genotyping in clinical practice continues to be hindered by discrepancies that arise when compared to tissue genotyping. Understanding the genomic landscape of lung cancer is essential in order to provide useful and innovative research in the age of patient-tailored therapy. In this landscape, the noncoding RNAs play a crucial role due to their target genes that dramatically influence the tumor microenvironment and the response to therapy. This article addresses present and future possible roles of liquid biopsy in lung cancer. It also discusses how the complex role of noncoding RNAs in lung tumorigenesis could influence the management of this pathology.",
			"category": 2,
			"name": "Harangu\u0219 Antonia,2020"
		},
		{
			"PMID": 31817150,
			"title": "Assessing the Concordance of Genomic Alterations between Circulating-Free DNA and Tumour Tissue in Cancer Patients.",
			"journal": "Cancers",
			"authorList": [
				"Jahangiri Leila",
				"Hurst Tara"
			],
			"DOI": "10.3390/cancers11121938",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic alterations to the genomes of solid tumours, which in some cases represent actionable drivers, provide diagnostic and prognostic insight into these complex diseases. Spatial and longitudinal tracking of somatic genomic alterations (SGAs) in patient tumours has emerged as a new avenue of investigation, not only as a disease monitoring strategy, but also to improve our understanding of heterogeneity and clonal evolution from diagnosis through disease progression. Furthermore, analysis of circulating-free DNA (cfDNA) in the so-called \"liquid biopsy\" has emerged as a non-invasive method to identify genomic information to inform targeted therapy and may also capture the heterogeneity of the primary and metastatic tumours. Considering the potential of cfDNA analysis as a translational laboratory tool in clinical practice, establishing the extent to which cfDNA represents the SGAs of tumours, particularly actionable driver alterations, becomes a matter of importance, warranting standardisation of methods and practices. Here, we assess the utilisation of cfDNA for molecular profiling of SGAs in tumour tissue across a broad range of solid tumours. Moreover, we examine the underlying factors contributing to discordance of detected SGAs between cfDNA and tumour tissue.",
			"category": 2,
			"name": "Jahangiri Leila,2020"
		},
		{
			"PMID": 31782731,
			"title": "Characterizing causality in cancer.",
			"journal": "eLife",
			"authorList": [
				"Rondeau Elena",
				"Larmonier Nicolas",
				"Pradeu Thomas",
				"Bikfalvi Andreas"
			],
			"DOI": "10.7554/eLife.53755",
			"date": "2020-05-07",
			"PMC": "",
			"citation": "",
			"abstract": "Philosophers have explored the concept of causality for centuries. Here we argue that ideas about causality from philosophy can help scientists to better understand how cancerous tumors grow and spread in the body. After outlining six characteristics of causality that are relevant to cancer, we emphasize the importance of feedback loops and interactions between tumor-cell-intrinsic and tumor-cell-extrinsic factors for explaining the formation and dissemination of tumors.",
			"category": 2,
			"name": "Rondeau Elena,2020"
		},
		{
			"PMID": 31774481,
			"title": "A comparative study of multi-omics integration tools for cancer driver gene identification and tumour subtyping.",
			"journal": "Briefings in bioinformatics",
			"authorList": [
				"Sathyanarayanan Anita",
				"Gupta Rohit",
				"Thompson Erik W",
				"Nyholt Dale R",
				"Bauer Denis C",
				"Nagaraj Shivashankar H"
			],
			"DOI": "10.1093/bib/bbz121",
			"date": "2021-10-28",
			"PMC": "",
			"citation": "",
			"abstract": "Oncogenesis and cancer can arise as a consequence of a wide range of genomic aberrations including mutations, copy number alterations, expression changes and epigenetic modifications encompassing multiple omics layers. Integrating genomic, transcriptomic, proteomic and epigenomic datasets via multi-omics analysis provides the opportunity to derive a deeper and holistic understanding of the development and progression of cancer. There are two primary approaches to integrating multi-omics data: multi-staged (focused on identifying genes driving cancer) and meta-dimensional (focused on establishing clinically relevant tumour or sample classifications). A number of ready-to-use bioinformatics tools are available to perform both multi-staged and meta-dimensional integration of multi-omics data. In this study, we compared nine different integration tools using real and simulated cancer datasets. The performance of the multi-staged integration tools were assessed at the gene, function and pathway levels, while meta-dimensional integration tools were assessed based on the sample classification performance. Additionally, we discuss the influence of factors such as data representation, sample size, signal and noise on multi-omics data integration. Our results provide current and much needed guidance regarding selection and use of the most appropriate and best performing multi-omics integration tools.",
			"category": 2,
			"name": "Sathyanarayanan Anita,2021"
		},
		{
			"PMID": 31766602,
			"title": "pMHC Structural Comparisons as a Pivotal Element to Detect and Validate T-Cell Targets for Vaccine Development and Immunotherapy-A New Methodological Proposal.",
			"journal": "Cells",
			"authorList": [
				"Vianna Priscila",
				"Mendes Marcus F A",
				"Bragatte Marcelo A",
				"Ferreira Priscila S",
				"Salzano Francisco M",
				"Bonamino Martin H",
				"Vieira Gustavo F"
			],
			"DOI": "10.3390/cells8121488",
			"date": "2020-09-21",
			"PMC": "",
			"citation": "",
			"abstract": "The search for epitopes that will effectively trigger an immune response remains the \"El Dorado\" for immunologists. The development of promising immunotherapeutic approaches requires the appropriate targets to elicit a proper immune response. Considering the high degree of HLA/TCR diversity, as well as the heterogeneity of viral and tumor proteins, this number will invariably be higher than ideal to test. It is known that the recognition of a peptide-MHC (pMHC) by the T-cell receptor is performed entirely in a structural fashion, where the atomic interactions of both structures, pMHC and TCR, dictate the fate of the process. However, epitopes with a similar composition of amino acids can produce dissimilar surfaces. Conversely, sequences with no conspicuous similarities can exhibit similar TCR interaction surfaces. In the last decade, our group developed a database and in silico structural methods to extract molecular fingerprints that trigger T-cell immune responses, mainly referring to physicochemical similarities, which could explain the immunogenic differences presented by different pMHC-I complexes. Here, we propose an immunoinformatic approach that considers a structural level of information, combined with an experimental technology that simulates the presentation of epitopes for a T cell, to improve vaccine production and immunotherapy efficacy.",
			"category": 2,
			"name": "Vianna Priscila,2020"
		},
		{
			"PMID": 31757986,
			"title": "Ontology-based prediction of cancer driver genes.",
			"journal": "Scientific reports",
			"authorList": [
				"Althubaiti Sara",
				"Karwath Andreas",
				"Dallol Ashraf",
				"Noor Adeeb",
				"Alkhayyat Shadi Salem",
				"Alwassia Rolina",
				"Mineta Katsuhiko",
				"Gojobori Takashi",
				"Beggs Andrew D",
				"Schofield Paul N",
				"Gkoutos Georgios V",
				"Hoehndorf Robert"
			],
			"DOI": "10.1038/s41598-019-53454-1",
			"date": "2020-11-05",
			"PMC": "",
			"citation": "",
			"abstract": "Identifying and distinguishing cancer driver genes among thousands of candidate mutations remains a major challenge. Accurate identification of driver genes and driver mutations is critical for advancing cancer research and personalizing treatment based on accurate stratification of patients. Due to inter-tumor genetic heterogeneity many driver mutations within a gene occur at low frequencies, which make it challenging to distinguish them from non-driver mutations. We have developed a novel method for identifying cancer driver genes. Our approach utilizes multiple complementary types of information, specifically cellular phenotypes, cellular locations, functions, and whole body physiological phenotypes as features. We demonstrate that our method can accurately identify known cancer driver genes and distinguish between their role in different types of cancer. In addition to confirming known driver genes, we identify several novel candidate driver genes. We demonstrate the utility of our method by validating its predictions in nasopharyngeal cancer and colorectal cancer using whole exome and whole genome sequencing.",
			"category": 2,
			"name": "Althubaiti Sara,2020"
		},
		{
			"PMID": 31754995,
			"title": "Mutation Yield of a Custom 212-Gene Next-Generation Sequencing Panel for Solid Tumors: Clinical Experience of the First 260 Cases Tested Using the JAX ActionSeq\u2122 Assay.",
			"journal": "Molecular diagnosis & therapy",
			"authorList": [
				"Selvam Pavalan",
				"Hsiao Meng-Chang",
				"Omerza Gregory",
				"Bergeron Daniel",
				"Rowe Shannon",
				"Uvalic Jasmina",
				"Soucy Melissa",
				"Peracchio Michael",
				"Burns Shelbi",
				"Meyers Bridgette",
				"Prego Matthew",
				"Nie Qian",
				"Ananda Guruprasad",
				"Chandok Harshpreet",
				"Kelly Kevin",
				"Hesse Andrew",
				"Reddi Honey V"
			],
			"DOI": "10.1007/s40291-019-00435-9",
			"date": "2021-01-28",
			"PMC": "",
			"citation": "",
			"abstract": "The study aimed to retrospectively evaluate the positive yield rate of a custom 212-gene next-generation sequencing (NGS) panel, the JAX ActionSeq\u2122 assay, used in molecular profiling of solid tumors for precision medicine.",
			"category": 2,
			"name": "Selvam Pavalan,2021"
		},
		{
			"PMID": 31737046,
			"title": "The Role of Tumor Microenvironment in Genomic Instability of Malignant Tumors.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Sonug\u00fcr F Gizem",
				"Akbulut Hakan"
			],
			"DOI": "10.3389/fgene.2019.01063",
			"date": "2020-09-29",
			"PMC": "",
			"citation": "",
			"abstract": "Genomic instability is an essential feature of cancer cells. The somatic mutation theory suggests that along with inherited ones, the changes in DNA caused by environmental factors may cause cancer. Although approximately 50-60 mutations per tumor are observed in established cancer tissue, it is known that not all of these mutations occur at the beginning of carcinogenesis but also occur later in the disease progression. The high frequency of somatic mutations referring to genomic instability contributes to the intratumoral genetic heterogeneity and treatment resistance. The contribution of the tumor microenvironment to the mutations observed following the acquirement of essential malignant characteristics of a cancer cell is one of the topics that have been extensively investigated in recent years. The frequency of mutations in hematologic tumors is generally less than solid tumors. Although it is a hematologic tumor, multiple myeloma is more similar to solid tumors in terms of the high number of chromosomal abnormalities and genetic heterogeneity. In multiple myeloma, bone marrow microenvironment also plays a role in genomic instability that occurs in the very early stages of the disease. In this review, we will briefly summarize the role of the tumor microenvironment and bone marrow microenvironment in the genomic instability seen in solid tumors and multiple myeloma.",
			"category": 2,
			"name": "Sonug\u00fcr F Gizem,2020"
		},
		{
			"PMID": 31731769,
			"title": "Enriching Human Interactome with Functional Mutations to Detect High-Impact Network Modules Underlying Complex Diseases.",
			"journal": "Genes",
			"authorList": [
				"Cui Hongzhu",
				"Srinivasan Suhas",
				"Korkin Dmitry"
			],
			"DOI": "10.3390/genes10110933",
			"date": "2020-05-05",
			"PMC": "",
			"citation": "",
			"abstract": "Rapid progress in high-throughput -omics technologies moves us one step closer to the datacalypse in life sciences. In spite of the already generated volumes of data, our knowledge of the molecular mechanisms underlying complex genetic diseases remains limited. Increasing evidence shows that biological networks are essential, albeit not sufficient, for the better understanding of these mechanisms. The identification of disease-specific functional modules in the human interactome can provide a more focused insight into the mechanistic nature of the disease. However, carving a disease network module from the whole interactome is a difficult task. In this paper, we propose a computational framework, Discovering most IMpacted SUbnetworks in interactoMe (DIMSUM), which enables the integration of genome-wide association studies (GWAS) and functional effects of mutations into the protein-protein interaction (PPI) network to improve disease module detection. Specifically, our approach incorporates and propagates the functional impact of non-synonymous single nucleotide polymorphisms (nsSNPs) on PPIs to implicate the genes that are most likely influenced by the disruptive mutations, and to identify the module with the greatest functional impact. Comparison against state-of-the-art seed-based module detection methods shows that our approach could yield modules that are biologically more relevant and have stronger association with the studied disease. We expect for our method to become a part of the common toolbox for the disease module analysis, facilitating the discovery of new disease markers.",
			"category": 2,
			"name": "Cui Hongzhu,2020"
		},
		{
			"PMID": 31689861,
			"title": "Identification of modules and hub genes associated with platinum-based chemotherapy resistance and treatment response in ovarian cancer by weighted gene co-expression network analysis.",
			"journal": "Medicine",
			"authorList": [
				"Zhang Luoyan",
				"Zhang Xuejie",
				"Fan Shoujin",
				"Zhang Zhen"
			],
			"DOI": "10.1097/MD.0000000000017803",
			"date": "2019-11-13",
			"PMC": "",
			"citation": "",
			"abstract": "High-grade serous ovarian carcinoma (HGSOC) is the most prevalent and malignant ovarian tumor.To identify co-expression modules and hub genes correlated with platinum-based chemotherapy resistant and sensitive HGSOC, we performed weighted gene co-expression network analysis (WGCNA) on microarray data of HGSOC with 12 resistant samples and 16 sensitive samples of GSE51373 dataset.A total of 5122 genes were included in WGCNA, and 16 modules were identified. Module-trait analysis identified that the module salmon (cor\u200a=\u200a0.50), magenta (cor\u200a=\u200a0.49), and black (cor\u200a=\u200a0.45) were discovered associated with chemotherapy resistant, and the significance for these platinum-resistant modules were validated in the GSE63885 dataset. Given that the black module was validated to be the most related one, hub genes of this module, alcohol dehydrogenase 1B, cadherin 11, and vestigial like family member 3were revealed to be expressional related with platinum resistance, and could serve as prognostic markers for ovarian cancer.Our analysis might provide insight for molecular mechanisms of platinum-based chemotherapy resistance and treatment response in ovarian cancer.",
			"category": 2,
			"name": "Zhang Luoyan,2019"
		},
		{
			"PMID": 31681944,
			"title": "PRODIGY: personalized prioritization of driver genes.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Dinstag Gal",
				"Shamir Ron"
			],
			"DOI": "10.1093/bioinformatics/btz815",
			"date": "2020-09-16",
			"PMC": "",
			"citation": "",
			"abstract": "Evolution of cancer is driven by few somatic mutations that disrupt cellular processes, causing abnormal proliferation and tumor development, whereas most somatic mutations have no impact on progression. Distinguishing those mutated genes that drive tumorigenesis in a patient is a primary goal in cancer therapy: Knowledge of these genes and the pathways on which they operate can illuminate disease mechanisms and indicate potential therapies and drug targets. Current research focuses mainly on cohort-level driver gene identification but patient-specific driver gene identification remains a challenge.",
			"category": 2,
			"name": "Dinstag Gal,2020"
		},
		{
			"PMID": 31671657,
			"title": "The Many Faces of Gene Regulation in Cancer: A Computational Oncogenomics Outlook.",
			"journal": "Genes",
			"authorList": [
				"Hern\u00e1ndez-Lemus Enrique",
				"Reyes-Gopar Helena",
				"Espinal-Enr\u00edquez Jes\u00fas",
				"Ochoa Soledad"
			],
			"DOI": "10.3390/genes10110865",
			"date": "2020-04-13",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a complex disease at many different levels. The molecular phenomenology of cancer is also quite rich. The mutational and genomic origins of cancer and their downstream effects on processes such as the reprogramming of the gene regulatory control and the molecular pathways depending on such control have been recognized as central to the characterization of the disease. More important though is the understanding of their causes, prognosis, and therapeutics. There is a multitude of factors associated with anomalous control of gene expression in cancer. Many of these factors are now amenable to be studied comprehensively by means of experiments based on diverse omic technologies. However, characterizing each dimension of the phenomenon individually has proven to fall short in presenting a clear picture of expression regulation as a whole. In this review article, we discuss some of the more relevant factors affecting gene expression control both, under normal conditions and in tumor settings. We describe the different omic approaches that we can use as well as the computational genomic analysis needed to track down these factors. Then we present theoretical and computational frameworks developed to integrate the amount of diverse information provided by such single-omic analyses. We contextualize this within a systems biology-based multi-omic regulation setting, aimed at better understanding the complex interplay of gene expression deregulation in cancer.",
			"category": 2,
			"name": "Hern\u00e1ndez-Lemus Enrique,2020"
		},
		{
			"PMID": 31668701,
			"title": "Evolution and Impact of Subclonal Mutations in Papillary Thyroid Cancer.",
			"journal": "American journal of human genetics",
			"authorList": [
				"Masoodi Tariq",
				"Siraj Abdul K",
				"Siraj Sarah",
				"Azam Saud",
				"Qadri Zeeshan",
				"Parvathareddy Sandeep K",
				"Al-Sobhi Saif S",
				"AlDawish Mohammed",
				"Alkuraya Fowzan S",
				"Al-Kuraya Khawla S"
			],
			"DOI": "10.1016/j.ajhg.2019.09.026",
			"date": "2020-03-31",
			"PMC": "",
			"citation": "",
			"abstract": "Unlike many cancers, the pattern of tumor evolution in papillary thyroid cancer (PTC) and its potential role in relapse have not been elucidated. In this study, multi-region whole-exome sequencing (WES) was performed on early-stage PTC tumors (n = 257 tumor regions) from 79 individuals, including 17 who had developed relapse, to understand the temporal and spatial framework within which subclonal mutations catalyze tumor evolution and its potential clinical relevance. Paired primary-relapse tumor tissues were also available for a subset of individuals. The resulting catalog of variants was analyzed to explore evolutionary histories, define clonal and subclonal events, and assess the relationship between intra-tumor heterogeneity and relapse-free survival. The multi-region WES approach was key in correctly classifying subclonal mutations, 40% of which would have otherwise been erroneously considered clonal. We observed both linear and branching evolution patterns in our PTC cohort. A higher burden of subclonal mutations was significantly associated with increased risk of relapse. We conclude that relapse in PTC, while generally rare, does not follow a predictable evolutionary path and that subclonal mutation burden may serve as a prognostic factor. Larger studies utilizing multi-region sequencing in relapsed PTC case subjects with matching primary tissues are needed to confirm these observations.",
			"category": 2,
			"name": "Masoodi Tariq,2020"
		},
		{
			"PMID": 31660856,
			"title": "A hierarchical integration deep flexible neural forest framework for cancer subtype classification by integrating multi-omics data.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"Xu Jing",
				"Wu Peng",
				"Chen Yuehui",
				"Meng Qingfang",
				"Dawood Hussain",
				"Dawood Hassan"
			],
			"DOI": "10.1186/s12859-019-3116-7",
			"date": "2019-12-13",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer subtype classification attains the great importance for accurate diagnosis and personalized treatment of cancer. Latest developments in high-throughput sequencing technologies have rapidly produced multi-omics data of the same cancer sample. Many computational methods have been proposed to classify cancer subtypes, however most of them generate the model by only employing gene expression data. It has been shown that integration of multi-omics data contributes to cancer subtype classification.",
			"category": 2,
			"name": "Xu Jing,2019"
		},
		{
			"PMID": 31612045,
			"title": "Identification of RAD54 homolog B as a promising therapeutic target for breast cancer.",
			"journal": "Oncology letters",
			"authorList": [
				"Feng Jing",
				"Hu Juanjuan",
				"Xia Ying"
			],
			"DOI": "10.3892/ol.2019.10854",
			"date": "2023-10-14",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer is a recognized threat to the health of women globally. Due to the lack of the knowledge about the molecular pathogenesis of breast cancer, therapeutic strategies remain inadequate, especially for aggressive breast cancer. In the present study, sequential bioinformatics analysis was performed using data from the GSE20711 dataset, and the results demonstrated that three genes may impact the survival of patients with breast cancer. One of these genes, RAD54 homolog B (RAD54B), may be a potential prognostic factor for breast cancer. A signature was established that could evaluate the overall survival for patients with breast cancer based on the risk score calculated from RAD54B expression and the Tumor-Node-Metastasis (TNM) stage [risk score=expRAD54B \u00d7 0.236 + TNM stage (I/II=0 or III/IV=1) \u00d71.025]. In addition, based on the GSE85871 dataset and inhibitory assay, the study identified a natural compound, Japonicone A, which may reduce the proliferation of breast cancer cells by inhibiting the expression of RAD54B. Overall, the present study identified a novel candidate gene and a candidate compound as promising therapeutic targets for the treatment of breast cancer.",
			"category": 2,
			"name": "Feng Jing,2023"
		},
		{
			"PMID": 31602383,
			"title": "Genetic Screening and Personalized Prevention in Colorectal Cancer.",
			"journal": "Visceral medicine",
			"authorList": [
				"Steinke-Lange Verena",
				"Holinski-Feder Elke"
			],
			"DOI": "10.1159/000501941",
			"date": "2024-07-20",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer per se is a genetic disease, either originating in germline mutations in cancer genes or in somatic mutations only present in the cancer cells. Therefore, personalized risk prediction, prevention, and treatment for cancer can be based on the results of genetic testing either in the germline or in the tumor. Surveillance regimens need to be based on appropriate risk assessment, which includes germline monogenic genetic testing - where appropriate - and in the future polygenic risk - possibly - for the general population. Treatment regimens should also include germline testing at least for cases suspicious of hereditary tumor diseases, followed by the analysis of somatic mutations within the tumor cell genome, raising a possible target for personalized therapy. Appropriate risk assessment is the key for suitable and, most importantly, individualized surveillance strategies especially in hereditary tumor syndromes. This concerns not only the patient but also the family members at risk. An overview about the different fields and aspects of genetic testing in colorectal cancer and its impact on personalized prevention will be given below.",
			"category": 2,
			"name": "Steinke-Lange Verena,2024"
		},
		{
			"PMID": 31572297,
			"title": "Analytical and Clinical Validation of Expressed Variants and Fusions From the Whole Transcriptome of Thyroid FNA Samples.",
			"journal": "Frontiers in endocrinology",
			"authorList": [
				"Angell Trevor E",
				"Wirth Lori J",
				"Cabanillas Maria E",
				"Shindo Maisie L",
				"Cibas Edmund S",
				"Babiarz Joshua E",
				"Hao Yangyang",
				"Kim Su Yeon",
				"Walsh P Sean",
				"Huang Jing",
				"Kloos Richard T",
				"Kennedy Giulia C",
				"Waguespack Steven G"
			],
			"DOI": "10.3389/fendo.2019.00612",
			"date": "2019-10-23",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "Angell Trevor E,2019"
		},
		{
			"PMID": 31570621,
			"title": "On the feasibility of saltational evolution.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Katsnelson Mikhail I",
				"Wolf Yuri I",
				"Koonin Eugene V"
			],
			"DOI": "10.1073/pnas.1909031116",
			"date": "2020-03-27",
			"PMC": "",
			"citation": "",
			"abstract": "Is evolution always gradual or can it make leaps? We examine a mathematical model of an evolutionary process on a fitness landscape and obtain analytic solutions for the probability of multimutation leaps, that is, several mutations occurring simultaneously, within a single generation in 1 genome, and being fixed all together in the evolving population. The results indicate that, for typical, empirically observed combinations of the parameters of the evolutionary process, namely, effective population size, mutation rate, and distribution of selection coefficients of mutations, the probability of a multimutation leap is low, and accordingly the contribution of such leaps is minor at best. However, we show that, taking sign epistasis into account, leaps could become an important factor of evolution in cases of substantially elevated mutation rates, such as stress-induced mutagenesis in microbes. We hypothesize that stress-induced mutagenesis is an evolvable adaptive strategy.",
			"category": 2,
			"name": "Katsnelson Mikhail I,2020"
		},
		{
			"PMID": 31565199,
			"title": "Diversity in tumor territory of meningioma: Protein expression in vascular endothelial growth factor and epidermal growth factor.",
			"journal": "Iranian journal of neurology",
			"authorList": [
				"Mehdipour Parvin",
				"Javan Firoozeh",
				"Faghih-Jouibari Morteza",
				"Khaleghi Mehdi"
			],
			"DOI": "",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": null,
			"category": 2,
			"name": "Mehdipour Parvin,2020"
		},
		{
			"PMID": 31547595,
			"title": "Cytogenetics and Cytogenomics Evaluation in Cancer.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Ribeiro Ilda Patr\u00edcia",
				"Melo Joana Barbosa",
				"Carreira Isabel Marques"
			],
			"DOI": "10.3390/ijms20194711",
			"date": "2020-02-04",
			"PMC": "",
			"citation": "",
			"abstract": "The availability of cytogenetics and cytogenomics technologies improved the detection and identification of tumor molecular signatures as well as the understanding of cancer initiation and progression. The use of large-scale and high-throughput cytogenomics technologies has led to a fast identification of several cancer candidate biomarkers associated with diagnosis, prognosis, and therapeutics. The advent of array comparative genomic hybridization and next-generation sequencing technologies has significantly improved the knowledge about cancer biology, underlining driver genes to guide targeted therapy development, drug-resistance prediction, and pharmacogenetics. However, few of these candidate biomarkers have made the transition to the clinic with a clear benefit for the patients. Technological progress helped to demonstrate that cellular heterogeneity plays a significant role in tumor progression and resistance/sensitivity to cancer therapies, representing the major challenge of precision cancer therapy. A paradigm shift has been introduced in cancer genomics with the recent advent of single-cell sequencing, since it presents a lot of applications with a clear benefit to oncological patients, namely, detection of intra-tumoral heterogeneity, mapping clonal evolution, monitoring the development of therapy resistance, and detection of rare tumor cell populations. It seems now evident that no single biomarker could provide the whole information necessary to early detect and predict the behavior and prognosis of tumors. The promise of precision medicine is based on the molecular profiling of tumors being vital the continuous progress of high-throughput technologies and the multidisciplinary efforts to catalogue chromosomal rearrangements and genomic alterations of human cancers and to do a good interpretation of the relation genotype-phenotype.",
			"category": 2,
			"name": "Ribeiro Ilda Patr\u00edcia,2020"
		},
		{
			"PMID": 31526759,
			"title": "Passenger Hotspot Mutations in Cancer.",
			"journal": "Cancer cell",
			"authorList": [
				"Hess Julian M",
				"Bernards Andre",
				"Kim Jaegil",
				"Miller Mendy",
				"Taylor-Weiner Amaro",
				"Haradhvala Nicholas J",
				"Lawrence Michael S",
				"Getz Gad"
			],
			"DOI": "10.1016/j.ccell.2019.08.002",
			"date": "2020-05-18",
			"PMC": "",
			"citation": "",
			"abstract": "Current statistical models for assessing hotspot significance do not properly account for variation in site-specific mutability, thereby yielding many false-positives. We thus (i) detail a Log-normal-Poisson (LNP) background model that accounts for this variability in a manner consistent with models of mutagenesis; (ii) use it to show that passenger hotspots arise from all common mutational processes; and (iii) apply it to a \u223c10,000-patient cohort to nominate driver hotspots with far fewer false-positives compared with conventional methods. Overall, we show that many cancer hotspot mutations recurring at the same genomic site across multiple tumors are actually passenger events, recurring at inherently mutable genomic sites under no positive selection.",
			"category": 2,
			"name": "Hess Julian M,2020"
		},
		{
			"PMID": 31521180,
			"title": "TCR-like antibodies in cancer immunotherapy.",
			"journal": "Journal of hematology & oncology",
			"authorList": [
				"He Qinghua",
				"Liu Zhaoyu",
				"Liu Zhihua",
				"Lai Yuxiong",
				"Zhou Xinke",
				"Weng Jinsheng"
			],
			"DOI": "10.1186/s13045-019-0788-4",
			"date": "2020-06-23",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer immunotherapy has been regarded as the most significant scientific breakthrough of 2013, and antibody therapy is at the core of this breakthrough. Despite significant success achieved in recent years, it is still difficult to target intracellular antigens of tumor cells with traditional antibodies, and novel therapeutic strategies are needed. T cell receptor (TCR)-like antibodies comprise a novel family of antibodies that can recognize peptide/MHC complexes on tumor cell surfaces. TCR-like antibodies can execute specific and significant anti-tumor immunity through several distinct molecular mechanisms, and the success of this type of antibody therapy in melanoma, leukemia, and breast, colon, and prostate tumor models has excited researchers in the immunotherapy field. Here, we summarize the generation strategy, function, and molecular mechanisms of TCR-like antibodies described in publications, focusing on the most significant discoveries.",
			"category": 2,
			"name": "He Qinghua,2020"
		},
		{
			"PMID": 31513583,
			"title": "Computational tools to detect signatures of mutational processes in DNA from tumours: A review and empirical comparison of performance.",
			"journal": "PloS one",
			"authorList": [
				"Omichessan Hanane",
				"Severi Gianluca",
				"Perduca Vittorio"
			],
			"DOI": "10.1371/journal.pone.0221235",
			"date": "2020-03-16",
			"PMC": "",
			"citation": "",
			"abstract": "Mutational signatures refer to patterns in the occurrence of somatic mutations that might be uniquely ascribed to particular mutational process. Tumour mutation catalogues can reveal mutational signatures but are often consistent with the mutation spectra produced by a variety of mutagens. To date, after the analysis of tens of thousands of exomes and genomes from about 40 different cancer types, tens of mutational signatures characterized by a unique probability profile across the 96 trinucleotide-based mutation types have been identified, validated and catalogued. At the same time, several concurrent methods have been developed for either the quantification of the contribution of catalogued signatures in a given cancer sequence or the identification of new signatures from a sample of cancer sequences. A review of existing computational tools has been recently published to guide researchers and practitioners through their mutational signature analyses, but other tools have been introduced since its publication and, a systematic evaluation and comparison of the performance of such tools is still lacking. In order to fill this gap, we have carried out an empirical evaluation of the main packages available to date, using both real and simulated data. Among other results, our empirical study shows that the identification of signatures is more difficult for cancers characterized by multiple signatures each having a small contribution. This work suggests that detection methods based on probabilistic models, especially EMu and bayesNMF, have in general better performance than NMF-based methods.",
			"category": 2,
			"name": "Omichessan Hanane,2020"
		},
		{
			"PMID": 31504231,
			"title": "Friend or foe-IDH1 mutations in glioma 10 years on.",
			"journal": "Carcinogenesis",
			"authorList": [
				"Huang L Eric"
			],
			"DOI": "10.1093/carcin/bgz134",
			"date": "2020-05-27",
			"PMC": "",
			"citation": "",
			"abstract": "The identification of recurrent point mutations in the isocitrate dehydrogenase 1 (IDH1) gene, albeit in only a small percentage of glioblastomas a decade ago, has transformed our understanding of glioma biology, genomics and metabolism. More than 1000 scientific papers have been published since, propelling bench-to-bedside investigations that have led to drug development and clinical trials. The rapid biomedical advancement has been driven primarily by the realization of a neomorphic activity of IDH1 mutation that produces high levels of (d)-2-hydroxyglutarate, a metabolite believed to promote glioma initiation and progression through epigenetic and metabolic reprogramming. Thus, novel inhibitors of mutant IDH1 have been developed for therapeutic targeting. However, numerous clinical and experimental findings are at odds with this simple concept. By taking into consideration a large body of findings in the literature, this article analyzes how different approaches have led to opposing conclusions and proffers a counterintuitive hypothesis that IDH1 mutation is intrinsically tumor suppressive in glioma but functionally undermined by the glutamate-rich cerebral environment, inactivation of tumor-suppressor genes and IDH1 copy-number alterations. This theory also provides an explanation for some of the most perplexing observations, including the scarcity of proper model systems and the prevalence of IDH1 mutation in glioma.",
			"category": 2,
			"name": "Huang L Eric,2020"
		},
		{
			"PMID": 31489109,
			"title": "Mouse models to decipher anti-tumor immunity.",
			"journal": "Oncotarget",
			"authorList": [
				"Parigger Thomas",
				"Greil Richard",
				"Zaborsky Nadja"
			],
			"DOI": "10.18632/oncotarget.27111",
			"date": "2020-02-25",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Parigger Thomas,2020"
		},
		{
			"PMID": 31484939,
			"title": "Interrogating Mutant Allele Expression via Customized Reference Genomes to Define Influential Cancer Mutations.",
			"journal": "Scientific reports",
			"authorList": [
				"Grant Adam D",
				"Vail Paris",
				"Padi Megha",
				"Witkiewicz Agnieszka K",
				"Knudsen Erik S"
			],
			"DOI": "10.1038/s41598-019-48967-8",
			"date": "2020-10-20",
			"PMC": "",
			"citation": "",
			"abstract": "Genetic alterations are essential for cancer initiation and progression. However, differentiating mutations that drive the tumor phenotype from mutations that do not affect tumor fitness remains a fundamental challenge in cancer biology. To better understand the impact of a given mutation within cancer, RNA-sequencing data was used to categorize mutations based on their allelic expression. For this purpose, we developed the MAXX (Mutation Allelic Expression Extractor) software, which is highly effective at delineating the allelic expression of both single nucleotide variants and small insertions and deletions. Results from MAXX demonstrated that mutations can be separated into three groups based on their expression of the mutant allele, lack of expression from both alleles, or expression of only the wild-type allele. By taking into consideration the allelic expression patterns of genes that are mutated in PDAC, it was possible to increase the sensitivity of widely used driver mutation detection methods, as well as identify subtypes that have prognostic significance and are associated with sensitivity to select classes of therapeutic agents in cell culture. Thus, differentiating mutations based on their mutant allele expression via MAXX represents a means to parse somatic variants in tumor genomes, helping to elucidate a gene's respective role in cancer.",
			"category": 2,
			"name": "Grant Adam D,2020"
		},
		{
			"PMID": 31480292,
			"title": "Molecular Subtyping and Prognostic Assessment Based on Tumor Mutation Burden in Patients with Lung Adenocarcinomas.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Wang Changzheng",
				"Liang Han",
				"Lin Cong",
				"Li Fuqiang",
				"Xie Guoyun",
				"Qiao Sitan",
				"Shi Xulian",
				"Deng Jianlian",
				"Zhao Xin",
				"Wu Kui",
				"Zhang Xiuqing"
			],
			"DOI": "10.3390/ijms20174251",
			"date": "2020-01-21",
			"PMC": "",
			"citation": "",
			"abstract": "The distinct molecular subtypes of lung cancer are defined by monogenic biomarkers, such as ",
			"category": 2,
			"name": "Wang Changzheng,2020"
		},
		{
			"PMID": 31480259,
			"title": "Etiology-Specific Analysis of Hepatocellular Carcinoma Transcriptome Reveals Genetic Dysregulation in Pathways Implicated in Immunotherapy Efficacy.",
			"journal": "Cancers",
			"authorList": [
				"Li Wei Tse",
				"Zou Angela E",
				"Honda Christine O",
				"Zheng Hao",
				"Wang Xiao Qi",
				"Kisseleva Tatiana",
				"Chang Eric Y",
				"Ongkeko Weg M"
			],
			"DOI": "10.3390/cancers11091273",
			"date": "2023-11-04",
			"PMC": "",
			"citation": "",
			"abstract": "Immunotherapy has emerged in recent years as arguably the most effective treatment for advanced hepatocellular carcinoma (HCC), but the failure of a large percentage of patients to respond to immunotherapy remains as the ultimate obstacle to successful treatment. Etiology-associated dysregulation of immune-associated (IA) genes may be central to the development of this differential clinical response. We identified immune-associated genes potentially dysregulated by alcohol or viral hepatitis B in HCC and validated alcohol-induced dysregulations in vitro while using large-scale RNA-sequencing data from The Cancer Genome Atlas (TCGA). Thirty-four clinically relevant dysregulated IA genes were identified. We profiled the correlation of all genomic alterations in HCC patients to IA gene expression while using the information theory-based algorithm REVEALER to investigate the molecular mechanism for their dysregulation and explore the possibility of genome-based patient stratification. We also studied gene expression regulators and identified multiple microRNAs that were implicated in HCC pathogenesis that can potentially regulate these IA genes' expression. Our study identified potential key pathways, including the IL-7 signaling pathway and TNFRSF4 (OX40)- NF-\u03baB pathway, to target in immunotherapy treatments and presents microRNAs as promising therapeutic targets for dysregulated IA genes because of their extensive regulatory roles in the cancer immune landscape.",
			"category": 2,
			"name": "Li Wei Tse,2023"
		},
		{
			"PMID": 31472684,
			"title": "Germline and somatic mutations of multi-gene panel in Chinese patients with epithelial ovarian cancer: a prospective cohort study.",
			"journal": "Journal of ovarian research",
			"authorList": [
				"Li Wenhui",
				"Shao Di",
				"Li Lei",
				"Wu Ming",
				"Ma Shuiqing",
				"Tan Xianjie",
				"Zhong Sen",
				"Guo Fengming",
				"Wang Zhe",
				"Ye Mingzhi"
			],
			"DOI": "10.1186/s13048-019-0560-y",
			"date": "2020-02-06",
			"PMC": "",
			"citation": "",
			"abstract": "Multiple targeted gene sequencing is seldom performed in both germline and somatic testing for ovarian cancer. This study is to evaluate the specific genetic alterations, including both somatic and germline mutations, in Chinese patients with epithelial ovarian cancer (EOC) in a prospective cohort study.",
			"category": 2,
			"name": "Li Wenhui,2020"
		},
		{
			"PMID": 31469467,
			"title": "Rationale and Roadmap for Developing Panels of Hotspot Cancer Driver Gene Mutations as Biomarkers of Cancer Risk.",
			"journal": "Environmental and molecular mutagenesis",
			"authorList": [
				"Harris Kelly L",
				"Myers Meagan B",
				"McKim Karen L",
				"Elespuru Rosalie K",
				"Parsons Barbara L"
			],
			"DOI": "10.1002/em.22326",
			"date": "2020-07-17",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer driver mutations (CDMs) are necessary and causal for carcinogenesis and have advantages as reporters of carcinogenic risk. However, little progress has been made toward developing measurements of CDMs as biomarkers for use in cancer risk assessment. Impediments for using a CDM-based metric to inform cancer risk include the complexity and stochastic nature of carcinogenesis, technical difficulty in quantifying low-frequency CDMs, and lack of established relationships between cancer driver mutant fractions and tumor incidence. Through literature review and database analyses, this review identifies the most promising targets to investigate as biomarkers of cancer risk. Mutational hotspots were discerned within the 20 most mutated genes across the 10 deadliest cancers. Forty genes were identified that encompass 108 mutational hotspot codons overrepresented in the COSMIC database; 424 different mutations within these hotspot codons account for approximately 63,000 tumors and their prevalence across tumor types is described. The review summarizes literature on the prevalence of CDMs in normal tissues and suggests such mutations are direct and indirect substrates for chemical carcinogenesis, which occurs in a spatially stochastic manner. Evidence that hotspot CDMs (hCDMs) frequently occur as tumor subpopulations is presented, indicating COSMIC data may underestimate mutation prevalence. Analyses of online databases show that genes containing hCDMs are enriched in functions related to intercellular communication. In its totality, the review provides a roadmap for the development of tissue-specific, CDM-based biomarkers of carcinogenic potential, comprised of batteries of hCDMs and can be measured by error-correct next-generation sequencing. Environ. Mol. Mutagen. 61:152-175, 2020. Published 2019. This article is a U.S. Government work and is in the public domain in the USA. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.",
			"category": 2,
			"name": "Harris Kelly L,2020"
		},
		{
			"PMID": 31468363,
			"title": "DNA repair in cancer initiation, progression, and therapy-a double-edged sword.",
			"journal": "Journal of applied genetics",
			"authorList": [
				"Kiwerska Katarzyna",
				"Szyfter Krzysztof"
			],
			"DOI": "10.1007/s13353-019-00516-9",
			"date": "2020-02-10",
			"PMC": "",
			"citation": "",
			"abstract": "Genomic and mitochondrial DNA molecules are exposed continuously for a damaging activity of chemical, physical, and internal genotoxicants. When DNA repair machinery is not working efficiently, the generation of DNA lesions and mutations leads to carcinogenic transformation. The high number of mutation going up to 10",
			"category": 2,
			"name": "Kiwerska Katarzyna,2020"
		},
		{
			"PMID": 31447604,
			"title": "Dietary Carbohydrate Promotes Cell Survival in Cancer Via the Up-Regulation of Fat Mass and Obesity-Associated Gene Expression Level.",
			"journal": "The Malaysian journal of medical sciences : MJMS",
			"authorList": [
				"Doaei Saeid",
				"Gholamalizadeh Maryam",
				"Akbari Mohammad Esmaeil",
				"Akbari Shayan",
				"Feradova Hyuliya",
				"Rahimzadeh Ghazaleh",
				"Mosavi Jarrahi Alireza"
			],
			"DOI": "10.21315/mjms2019.26.2.2",
			"date": "2020-09-29",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer cells are mainly dependent on glycolysis for their growth and survival. Dietary carbohydrates play a critical role in the growth and proliferation of cancer and a low-carbohydrate diet may help slow down the growth of tumours. However, the exact mechanisms behind this effect are unclear. This review study aimed to investigate the effect of fat mass and obesity-associated (FTO) gene in the association between dietary carbohydrates and cancer. This study was carried out using keywords such as polymorphism and/or cancer and/or dietary carbohydrate and/or FTO gene. PubMed and Science Direct databases were used to collect all related articles published from 1990 to 2018. Recent studies showed that the level of FTO gene expression in cancer cells is dramatically increased and may play a role in the growth of these cells through the regulation of the cellular metabolic pathways, including the phosphoinositide 3-kinases/protein kinaseB (PI3K/AKT) signaling pathway. Dietary carbohydrate may influence the FTO gene expression by eliminating the inhibitory effect of adenosine monophosphate-activated protein kinase (AMPK) on the FTO gene expression. This review summarised what has been recently discovered about the effects of dietary carbohydrate on cancer cells and tried to determine the mediating role of the FTO gene in these effects.",
			"category": 2,
			"name": "Doaei Saeid,2020"
		},
		{
			"PMID": 31404287,
			"title": "Meta-analysis of gene expression alterations and clinical significance of the HECT domain-containing ubiquitin ligase HUWE1 in cancer.",
			"journal": "Oncology letters",
			"authorList": [
				"Su Chen",
				"Wang Tao",
				"Zhao Jiabao",
				"Cheng Jia",
				"Hou Jingjing"
			],
			"DOI": "10.3892/ol.2019.10579",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "E3 ubiquitin-protein ligase (HUWE1) has previously been identified as a HECT domain-containing ubiquitin ligase (E3) that is involved in several signaling pathways, transcriptional regulation, neural differentiation, DNA damage responses and apoptosis. However, the function of HUWE1 in the various types of cancer remains unclear. A previous study indicated that HUWE1 exhibited different roles depending on the cancer type due to the ubiquitination of various substrates. The objective of the present study was to determine whether HUWE1 can be employed as a prognostic indicator in human cancer. The expression of HUWE1 was examined using the Oncomine database, and gene alterations during carcinogenesis, copy number alterations and mutations of HUWE1 were then analyzed using cBioPortal, which is the International Cancer Genome Consortium and the Tumorscape database. Furthermore, the association between HUWE1 expression and patient survival was evaluated using Kaplan-Meier plotter and the PrognoScan databases. In addition, the present study attempted to establish the functional association between HUWE1 expression and cancer phenotypes, and the results revealed that HUWE1 may serve as a diagnostic marker or therapeutic target for certain types of cancer. HUWE1 may serve an oncogenic role in breast, brain and prostate cancer, while it may serve an anti-oncogenic role in colorectal cancer and certain lung cancers. The function of HUWE1 and its mechanisms require more in-depth and extensive investigation in future studies.",
			"category": 2,
			"name": "Su Chen,2020"
		},
		{
			"PMID": 31402092,
			"title": "Identifying Putative Susceptibility Genes and Evaluating Their Associations with Somatic Mutations in Human Cancers.",
			"journal": "American journal of human genetics",
			"authorList": [
				"Chen Zhishan",
				"Wen Wanqing",
				"Beeghly-Fadiel Alicia",
				"Shu Xiao-Ou",
				"D\u00edez-Obrero Virginia",
				"Long Jirong",
				"Bao Jiandong",
				"Wang Jing",
				"Liu Qi",
				"Cai Qiuyin",
				"Moreno Victor",
				"Zheng Wei",
				"Guo Xingyi"
			],
			"DOI": "10.1016/j.ajhg.2019.07.006",
			"date": "2020-04-02",
			"PMC": "",
			"citation": "",
			"abstract": "Genome-wide association studies (GWASs) have identified hundreds of genetic risk variants for human cancers. However, target genes for the majority of risk loci remain largely unexplored. It is also unclear whether GWAS risk-loci-associated genes contribute to mutational signatures and tumor mutational burden (TMB) in cancer tissues. We systematically conducted cis-expression quantitative trait loci (cis-eQTL) analyses for 294 GWAS-identified variants for six major types of cancer-colorectal, lung, ovary, prostate, pancreas, and melanoma-by using transcriptome data from the Genotype-Tissue Expression (GTEx) Project, the Cancer Genome Atlas (TCGA), and other public data sources. By using integrative analysis strategies, we identified 270 candidate target genes, including 99 with previously unreported associations, for six cancer types. By analyzing functional genomic data, our results indicate that 180 genes (66.7% of 270) had evidence of cis-regulation by putative functional variants via proximal promoter or distal enhancer-promoter interactions. Together with our previously reported associations for breast cancer risk, our results show that 24 genes are shared by at least two cancer types, including four genes for both breast and ovarian cancer. By integrating mutation data from TCGA, we found that expression levels of 33 and 66 putative susceptibility genes were associated with specific mutational signatures and TMB of cancer-driver genes, respectively, at a Bonferroni-corrected p < 0.05. Together, these findings provide further insight into our understanding of how genetic risk variants might contribute to carcinogenesis through the regulation of susceptibility genes that are related to the biogenesis of somatic mutations.",
			"category": 2,
			"name": "Chen Zhishan,2020"
		},
		{
			"PMID": 31392032,
			"title": "DISSEQT-DIStribution-based modeling of SEQuence space Time dynamics.",
			"journal": "Virus evolution",
			"authorList": [
				"Henningsson R",
				"Moratorio G",
				"Border\u00eda A V",
				"Vignuzzi M",
				"Fontes M"
			],
			"DOI": "10.1093/ve/vez028",
			"date": "2024-07-20",
			"PMC": "",
			"citation": "",
			"abstract": "Rapidly evolving microbes are a challenge to model because of the volatile, complex, and dynamic nature of their populations. We developed the DISSEQT pipeline (DIStribution-based SEQuence space Time dynamics) for analyzing, visualizing, and predicting the evolution of heterogeneous biological populations in multidimensional genetic space, suited for population-based modeling of deep sequencing and high-throughput data. The pipeline is openly available on GitHub (https://github.com/rasmushenningsson/DISSEQT.jl, accessed 23 June 2019) and Synapse (https://www.synapse.org/#!Synapse: syn11425758, accessed 23 June 2019), covering the entire workflow from read alignment to visualization of results. Our pipeline is centered around robust dimension and model reduction algorithms for analysis of genotypic data with additional capabilities for including phenotypic features to explore dynamic genotype-phenotype maps. We illustrate its utility and capacity with examples from evolving RNA virus populations, which present one of the highest degrees of genetic heterogeneity within a given population found in nature. Using our pipeline, we empirically reconstruct the evolutionary trajectories of evolving populations in sequence space and genotype-phenotype fitness landscapes. We show that while sequence space is vastly multidimensional, the relevant genetic space of evolving microbial populations is of intrinsically low dimension. In addition, evolutionary trajectories of these populations can be faithfully monitored to identify the key minority genotypes contributing most to evolution. Finally, we show that empirical fitness landscapes, when reconstructed to include minority variants, can predict phenotype from genotype with high accuracy.",
			"category": 2,
			"name": "Henningsson R,2024"
		},
		{
			"PMID": 31387777,
			"title": "Inflammation-induced DNA damage, mutations and cancer.",
			"journal": "DNA repair",
			"authorList": [
				"Kay Jennifer",
				"Thadhani Elina",
				"Samson Leona",
				"Engelward Bevin"
			],
			"DOI": "10.1016/j.dnarep.2019.102673",
			"date": "2020-05-18",
			"PMC": "",
			"citation": "",
			"abstract": "The relationships between inflammation and cancer are varied and complex. An important connection linking inflammation to cancer development is DNA damage. During inflammation reactive oxygen and nitrogen species (RONS) are created to combat pathogens and to stimulate tissue repair and regeneration, but these chemicals can also damage DNA, which in turn can promote mutations that initiate and promote cancer. DNA repair pathways are essential for preventing DNA damage from causing mutations and cytotoxicity, but RONS can interfere with repair mechanisms, reducing their efficacy. Further, cellular responses to DNA damage, such as damage signaling and cytotoxicity, can promote inflammation, creating a positive feedback loop. Despite coordination of DNA repair and oxidative stress responses, there are nevertheless examples whereby inflammation has been shown to promote mutagenesis, tissue damage, and ultimately carcinogenesis. Here, we discuss the DNA damage-mediated associations between inflammation, mutagenesis and cancer.",
			"category": 2,
			"name": "Kay Jennifer,2020"
		},
		{
			"PMID": 31383000,
			"title": "Characterisation of DNA methylation changes in EBF3 and TBC1D16 associated with tumour progression and metastasis in multiple cancer types.",
			"journal": "Clinical epigenetics",
			"authorList": [
				"Rodger Euan J",
				"Chatterjee Aniruddha",
				"Stockwell Peter A",
				"Eccles Michael R"
			],
			"DOI": "10.1186/s13148-019-0710-5",
			"date": "2020-06-26",
			"PMC": "",
			"citation": "",
			"abstract": "Characteristic DNA methylation differences have been identified between primary and metastatic melanomas at EBF3 and/or TBC1D16 gene loci. To further evaluate whether these epigenetic changes may act more generally as drivers of tumour onset and metastasis, we have investigated DNA methylation changes involving EBF3 and TBC1D16 in additional publicly available data of multiple different tumour types.",
			"category": 2,
			"name": "Rodger Euan J,2020"
		},
		{
			"PMID": 31382519,
			"title": "Identification of Prognostic Candidate Genes in Breast Cancer by Integrated Bioinformatic Analysis.",
			"journal": "Journal of clinical medicine",
			"authorList": [
				"Wang Charles C N",
				"Li Chia Ying",
				"Cai Jia-Hua",
				"Sheu Phillip C-Y",
				"Tsai Jeffrey J P",
				"Wu Meng-Yu",
				"Li Chia-Jung",
				"Hou Ming-Feng"
			],
			"DOI": "10.3390/jcm8081160",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer is one of the most common malignancies. However, the molecular mechanisms underlying its pathogenesis remain to be elucidated. The present study aimed to identify the potential prognostic marker genes associated with the progression of breast cancer. Weighted gene coexpression network analysis was used to construct free-scale gene coexpression networks, evaluate the associations between the gene sets and clinical features, and identify candidate biomarkers. The gene expression profiles of GSE48213 were selected from the Gene Expression Omnibus database. RNA-seq data and clinical information on breast cancer from The Cancer Genome Atlas were used for validation. Four modules were identified from the gene coexpression network, one of which was found to be significantly associated with patient survival time. The expression status of 28 genes formed the black module (basal); 18 genes, dark red module (claudin-low); nine genes, brown module (luminal), and seven genes, midnight blue module (nonmalignant). These modules were clustered into two groups according to significant difference in survival time between the groups. Therefore, based on betweenness centrality, we identified ",
			"category": 2,
			"name": "Wang Charles C N,2020"
		},
		{
			"PMID": 31371581,
			"title": "Somatic evolution and global expansion of an ancient transmissible cancer lineage.",
			"journal": "Science (New York, N.Y.)",
			"authorList": [
				"Baez-Ortega Adrian",
				"Gori Kevin",
				"Strakova Andrea",
				"Allen Janice L",
				"Allum Karen M",
				"Bansse-Issa Leontine",
				"Bhutia Thinlay N",
				"Bisson Jocelyn L",
				"Brice\u00f1o Crist\u00f3bal",
				"Castillo Domracheva Artemio",
				"Corrigan Anne M",
				"Cran Hugh R",
				"Crawford Jane T",
				"Davis Eric",
				"de Castro Karina F",
				"B de Nardi Andrigo",
				"de Vos Anna P",
				"Delgadillo Keenan Laura",
				"Donelan Edward M",
				"Espinoza Huerta Adela R",
				"Faramade Ibikunle A",
				"Fazil Mohammed",
				"Fotopoulou Eleni",
				"Fruean Skye N",
				"Gallardo-Arrieta Fanny",
				"Glebova Olga",
				"Gouletsou Pagona G",
				"H\u00e4felin Manrique Rodrigo F",
				"Henriques Joaquim J G P",
				"Horta Rodrigo S",
				"Ignatenko Natalia",
				"Kane Yaghouba",
				"King Cathy",
				"Koenig Debbie",
				"Krupa Ada",
				"Kruzeniski Steven J",
				"Kwon Young-Mi",
				"Lanza-Perea Marta",
				"Lazyan Mihran",
				"Lopez Quintana Adriana M",
				"Losfelt Thibault",
				"Marino Gabriele",
				"Mart\u00ednez Casta\u00f1eda Sim\u00f3n",
				"Mart\u00ednez-L\u00f3pez Mayra F",
				"Meyer Michael",
				"Migneco Edward J",
				"Nakanwagi Berna",
				"Neal Karter B",
				"Neunzig Winifred",
				"N\u00ed Leathlobhair M\u00e1ire",
				"Nixon Sally J",
				"Ortega-Pacheco Antonio",
				"Pedraza-Ordo\u00f1ez Francisco",
				"Peleteiro Maria C",
				"Polak Katherine",
				"Pye Ruth J",
				"Reece John F",
				"Rojas Gutierrez Jose",
				"Sadia Haleema",
				"Schmeling Sheila K",
				"Shamanova Olga",
				"Sherlock Alan G",
				"Stammnitz Maximilian",
				"Steenland-Smit Audrey E",
				"Svitich Alla",
				"Tapia Mart\u00ednez Lester J",
				"Thoya Ngoka Ismail",
				"Torres Cristian G",
				"Tudor Elizabeth M",
				"van der Wel Mirjam G",
				"Vi\u0163\u0103laru Bogdan A",
				"Vural Sevil A",
				"Walkinton Oliver",
				"Wang Jinhong",
				"Wehrle-Martinez Alvaro S",
				"Widdowson Sophie A E",
				"Stratton Michael R",
				"Alexandrov Ludmil B",
				"Martincorena I\u00f1igo",
				"Murchison Elizabeth P"
			],
			"DOI": "10.1126/science.aau9923",
			"date": "2020-02-20",
			"PMC": "",
			"citation": "",
			"abstract": "The canine transmissible venereal tumor (CTVT) is a cancer lineage that arose several millennia ago and survives by \"metastasizing\" between hosts through cell transfer. The somatic mutations in this cancer record its phylogeography and evolutionary history. We constructed a time-resolved phylogeny from 546 CTVT exomes and describe the lineage's worldwide expansion. Examining variation in mutational exposure, we identify a highly context-specific mutational process that operated early in the cancer's evolution but subsequently vanished, correlate ultraviolet-light mutagenesis with tumor latitude, and describe tumors with heritable hyperactivity of an endogenous mutational process. CTVT displays little evidence of ongoing positive selection, and negative selection is detectable only in essential genes. We illustrate how long-lived clonal organisms capture changing mutagenic environments, and reveal that neutral genetic drift is the dominant feature of long-term cancer evolution.",
			"category": 2,
			"name": "Baez-Ortega Adrian,2020"
		},
		{
			"PMID": 31349673,
			"title": "New Monoclonal Antibodies for a Selective Detection of Membrane-Associated and Soluble Forms of Carbonic Anhydrase IX in Human Cell Lines and Biological Samples.",
			"journal": "Biomolecules",
			"authorList": [
				"Stravinskiene Dovile",
				"Imbrasaite Aiste",
				"Petrikaite Vilma",
				"Matulis Daumantas",
				"Matuliene Jurgita",
				"Zvirbliene Aurelija"
			],
			"DOI": "10.3390/biom9080304",
			"date": "2020-05-08",
			"PMC": "",
			"citation": "",
			"abstract": "Monoclonal antibodies (MAbs) selectively targeting tumor-associated antigens such as carbonic anhydrase IX (CA IX) can significantly contribute to research, diagnostics, and treatment of CA IX-related cancers. CA IX is overexpressed in numerous hypoxic cancers where it promotes tumor progression. Therefore, it is considered as a promising tumor biomarker. A novel collection of MAbs against recombinant CA IX was developed and evaluated in different immunoassays for studying CA IX expression. The reactivity of MAbs with native cell surface protein was confirmed by flow cytometry and the presence of hypoxia-inducible CA IX was investigated in several human cancer cell lines. In addition, the applicability of MAbs for visualization of CA IX-positive tumor cells by immunofluorescence microscopy was demonstrated. MAb H7 was identified as the most promising MAb for different immunoassays. It recognized a linear epitope covering CA IX sequence of 12 amino acid residues 55-GEDDPLGEEDLP-66 within the proteoglycan domain. The MAb H7 was the only one of the collection to immunoprecipitate CA IX protein from cell lysates and detect the denatured CA IX with near-infrared fluorescence Western blot. It was also employed in sandwich enzyme-linked immunosorbent assay to detect a soluble form of CA IX in growth medium of tumor cells and blood plasma samples. The diagnostic potential of the MAb H7 was confirmed on formalin-fixed and paraffin-embedded tissue specimen of cervical carcinoma in situ by immunohistochemistry. The generated MAbs, in particularly clone H7, have great potential in diagnostics and research of CA IX-related cancers.",
			"category": 2,
			"name": "Stravinskiene Dovile,2020"
		},
		{
			"PMID": 31336886,
			"title": "Genetic Aberration Analysis in Thai Colorectal Adenoma and Early-Stage Adenocarcinoma Patients by Whole-Exome Sequencing.",
			"journal": "Cancers",
			"authorList": [
				"Intarajak Thoranin",
				"Udomchaiprasertkul Wandee",
				"Bunyoo Chakrit",
				"Yimnoon Jutamas",
				"Soonklang Kamonwan",
				"Wiriyaukaradecha Kriangpol",
				"Lamlertthon Wisut",
				"Sricharunrat Thaniya",
				"Chaiwiriyawong Worawit",
				"Siriphongpreeda Bunchorn",
				"Sutheeworapong Sawannee",
				"Kusonmano Kanthida",
				"Kittichotirat Weerayuth",
				"Thammarongtham Chinae",
				"Jenjaroenpun Piroon",
				"Wongsurawat Thidathip",
				"Nookaew Intawat",
				"Auewarakul Chirayu",
				"Cheevadhanarak Supapon"
			],
			"DOI": "10.3390/cancers11070977",
			"date": "2023-11-04",
			"PMC": "",
			"citation": "",
			"abstract": "Colorectal adenomas are precursor lesions of colorectal adenocarcinoma. The transition from adenoma to carcinoma in patients with colorectal cancer (CRC) has been associated with an accumulation of genetic aberrations. However, criteria that can screen adenoma progression to adenocarcinoma are still lacking. This present study is the first attempt to identify genetic aberrations, such as the somatic mutations, copy number variations (CNVs), and high-frequency mutated genes, found in Thai patients. In this study, we identified the genomic abnormality of two sample groups. In the first group, five cases matched normal-colorectal adenoma-colorectal adenocarcinoma. In the second group, six cases matched normal-colorectal adenomas. For both groups, whole-exome sequencing was performed. We compared the genetic aberration of the two sample groups. In both normal tissues compared with colorectal adenoma and colorectal adenocarcinoma analyses, somatic mutations were observed in the tumor suppressor gene ",
			"category": 2,
			"name": "Intarajak Thoranin,2023"
		},
		{
			"PMID": 31334812,
			"title": "Quantifying gene selection in cancer through protein functional alteration bias.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Brandes Nadav",
				"Linial Nathan",
				"Linial Michal"
			],
			"DOI": "10.1093/nar/gkz546",
			"date": "2020-01-06",
			"PMC": "",
			"citation": "",
			"abstract": "Compiling the catalogue of genes actively involved in cancer is an ongoing endeavor, with profound implications to the understanding and treatment of the disease. An abundance of computational methods have been developed to screening the genome for candidate driver genes based on genomic data of somatic mutations in tumors. Existing methods make many implicit and explicit assumptions about the distribution of random mutations. We present FABRIC, a new framework for quantifying the selection of genes in cancer by assessing the effects of de-novo somatic mutations on protein-coding genes. Using a machine-learning model, we quantified the functional effects of \u223c3M somatic mutations extracted from over 10\u00a0000 human cancerous samples, and compared them against the effects of all possible single-nucleotide mutations in the coding human genome. We detected 593 protein-coding genes showing statistically significant bias towards harmful mutations. These genes, discovered without any prior knowledge, show an overwhelming overlap with known cancer genes, but also include many overlooked genes. FABRIC is designed to avoid false discoveries by comparing each gene to its own background model using rigorous statistics, making minimal assumptions about the distribution of random somatic mutations. The framework is an open-source project with a simple command-line interface.",
			"category": 2,
			"name": "Brandes Nadav,2020"
		},
		{
			"PMID": 31321735,
			"title": "(Cyto)genomic and epigenetic characterization of BICR 10 cell line and three new established primary human head and neck squamous cell carcinoma cultures.",
			"journal": "Genes & genomics",
			"authorList": [
				"Ribeiro Ilda P",
				"Rodrigues Joana M",
				"Mascarenhas Alexandra",
				"Marques Vanessa",
				"Caramelo Francisco",
				"Juli\u00e3o Maria J",
				"Liehr Thomas",
				"Melo Joana B",
				"Carreira Isabel M"
			],
			"DOI": "10.1007/s13258-019-00850-6",
			"date": "2020-03-16",
			"PMC": "",
			"citation": "",
			"abstract": "Head and neck squamous cell carcinoma cell lines are useful preclinical models to understand the molecular processes underlying the development of such tumors, and to establish targeted therapies.",
			"category": 2,
			"name": "Ribeiro Ilda P,2020"
		},
		{
			"PMID": 31285446,
			"title": "mTOR Signaling Upregulates CDC6 via Suppressing miR-3178 and Promotes the Loading of DNA Replication Helicase.",
			"journal": "Scientific reports",
			"authorList": [
				"Wu Xianjin",
				"Li Shenghua",
				"Hu Xing",
				"Xiang Xiaoliang",
				"Halloran Megan",
				"Yang Linlin",
				"Williams Terence M",
				"Houghton Peter J",
				"Shen Changxian",
				"He Zhengfu"
			],
			"DOI": "10.1038/s41598-019-46052-8",
			"date": "2020-10-21",
			"PMC": "",
			"citation": "",
			"abstract": "mTOR signaling pathway is deregulated in most cancers and uncontrolled cell cycle progression is a hallmark of cancer cell. However, the precise molecular mechanisms of the regulation of DNA replication and chromatin metabolism by mTOR signaling are largely unknown. We herein report that mTOR signaling promotes the loading of MCM2-7 helicase onto chromatin and upregulates DNA replication licensing factor CDC6. Pharmacological inhibition of mTOR kinase resulted in CHK1 checkpoint activation and decreased MCM2-7 replication helicase and PCNA associated with chromatins. Further pharmacological and genetic studies demonstrated CDC6 is positively controlled by mTORC1-S6K1 and mTORC2 signaling. miRNA screening revealed mTOR signaling suppresses miR-3178 thereby upregulating CDC6. Analysis of TCGA data found that CDC6 is overexpressed in most cancers and associates with the poor survival of cancer patients. Our findings suggest that mTOR signaling may control DNA replication origin licensing and replisome stability thereby cell cycle progression through CDC6 regulation.",
			"category": 2,
			"name": "Wu Xianjin,2020"
		},
		{
			"PMID": 31285391,
			"title": "Co-expression of key gene modules and pathways of human breast cancer cell lines.",
			"journal": "Bioscience reports",
			"authorList": [
				"Wu Yadong",
				"Liu Feng",
				"Luo Siyang",
				"Yin Xinhai",
				"He Dengqi",
				"Liu Jianguo",
				"Yue Zhaohui",
				"Song Jukun"
			],
			"DOI": "10.1042/BSR20181925",
			"date": "2020-09-07",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer (BC) is the most common leading cause of cancer-related death in women worldwide. Gene expression profiling analysis for human BCs has been studied previously. However, co-expression analysis for BC cell lines is still devoid to date. The aim of the study was to identify key pathways and hub genes that may serve as a biomarker for BC and uncover potential molecular mechanism using weighted correlation network analysis. We analyzed microarray data of BC cell lines (GSE 48213) listed in the Gene Expression Omnibus database. Gene co-expression networks were used to construct and explore the biological function in hub modules using the weighted correlation network analysis algorithm method. Meanwhile, Gene ontology and KEGG pathway analysis were performed using Cytoscape plug-in ClueGo. The network of the key module was also constructed using Cytoscape. A total of 5000 genes were selected, 28 modules of co-expressed genes were identified from the gene co-expression network, one of which was found to be significantly associated with a subtype of BC lines. Functional enrichment analysis revealed that the brown module was mainly involved in the pathway of the autophagy, spliceosome, and mitophagy, the black module was mainly enriched in the pathway of colorectal cancer and pancreatic cancer, and genes in midnightblue module played critical roles in ribosome and regulation of lipolysis in adipocytes pathway. Three hub genes CBR3, SF3B6, and RHPN1 may play an important role in the development and malignancy of the disease. The findings of the present study could improve our understanding of the molecular pathogenesis of breast cancer.",
			"category": 2,
			"name": "Wu Yadong,2020"
		},
		{
			"PMID": 31285282,
			"title": "Correlation Analysis of Histopathology and Proteogenomics Data for Breast Cancer.",
			"journal": "Molecular & cellular proteomics : MCP",
			"authorList": [
				"Zhan Xiaohui",
				"Cheng Jun",
				"Huang Zhi",
				"Han Zhi",
				"Helm Bryan",
				"Liu Xiaowen",
				"Zhang Jie",
				"Wang Tian-Fu",
				"Ni Dong",
				"Huang Kun"
			],
			"DOI": "10.1074/mcp.RA118.001232",
			"date": "2020-06-15",
			"PMC": "",
			"citation": "",
			"abstract": "Tumors are heterogeneous tissues with different types of cells such as cancer cells, fibroblasts, and lymphocytes. Although the morphological features of tumors are critical for cancer diagnosis and prognosis, the underlying molecular events and genes for tumor morphology are far from being clear. With the advancement in computational pathology and accumulation of large amount of cancer samples with matched molecular and histopathology data, researchers can carry out integrative analysis to investigate this issue. In this study, we systematically examine the relationships between morphological features and various molecular data in breast cancers. Specifically, we identified 73 breast cancer patients from the TCGA and CPTAC projects matched whole slide images, RNA-seq, and proteomic data. By calculating 100 different morphological features and correlating them with the transcriptomic and proteomic data, we inferred four major biological processes associated with various interpretable morphological features. These processes include metabolism, cell cycle, immune response, and extracellular matrix development, which are all hallmarks of cancers and the associated morphological features are related to area, density, and shapes of epithelial cells, fibroblasts, and lymphocytes. In addition, protein specific biological processes were inferred solely from proteomic data, suggesting the importance of proteomic data in obtaining a holistic understanding of the molecular basis for tumor tissue morphology. Furthermore, survival analysis yielded specific morphological features related to patient prognosis, which have a strong association with important molecular events based on our analysis. Overall, our study demonstrated the power for integrating multiple types of biological data for cancer samples in generating new hypothesis as well as identifying potential biomarkers predicting patient outcome. Future work includes causal analysis to identify key regulators for cancer tissue development and validating the findings using more independent data sets.",
			"category": 2,
			"name": "Zhan Xiaohui,2020"
		},
		{
			"PMID": 31284467,
			"title": "PI3K-AKT-mTOR and NF\u03baB Pathways in Ovarian Cancer: Implications for Targeted Therapeutics.",
			"journal": "Cancers",
			"authorList": [
				"Ghoneum Alia",
				"Said Neveen"
			],
			"DOI": "10.3390/cancers11070949",
			"date": "2023-06-02",
			"PMC": "",
			"citation": "",
			"abstract": "Ovarian cancer is the most lethal gynecologic malignancy in the United States, with an estimated 22,530 new cases and 13,980 deaths in 2019. Recent studies have indicated that the phosphoinositol 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), as well as the nuclear factor-\u03ba light chain enhancer of activated B cells (NF\u03baB) pathways are highly mutated and/or hyper-activated in a majority of ovarian cancer patients, and are associated with advanced grade and stage disease and poor prognosis. In this review, we will investigate PI3K/AKT/mTOR and their interconnection with NF\u03baB pathway in ovarian cancer cells.",
			"category": 2,
			"name": "Ghoneum Alia,2023"
		},
		{
			"PMID": 31278357,
			"title": "A practical guide for mutational signature analysis in hematological malignancies.",
			"journal": "Nature communications",
			"authorList": [
				"Maura Francesco",
				"Degasperi Andrea",
				"Nadeu Ferran",
				"Leongamornlert Daniel",
				"Davies Helen",
				"Moore Luiza",
				"Royo Romina",
				"Ziccheddu Bachisio",
				"Puente Xose S",
				"Avet-Loiseau Herve",
				"Campbell Peter J",
				"Nik-Zainal Serena",
				"Campo Elias",
				"Munshi Nikhil",
				"Bolli Niccol\u00f2"
			],
			"DOI": "10.1038/s41467-019-11037-8",
			"date": "2019-10-21",
			"PMC": "",
			"citation": "",
			"abstract": "Analysis of mutational signatures is becoming routine in cancer genomics, with implications for pathogenesis, classification, prognosis, and even treatment decisions. However, the field lacks a consensus on analysis and result interpretation. Using whole-genome sequencing of multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and acute myeloid leukemia, we compare the performance of public signature analysis tools. We describe caveats and pitfalls of de novo signature extraction and fitting approaches, reporting on common inaccuracies: erroneous signature assignment, identification of localized hyper-mutational processes, overcalling of signatures. We provide reproducible solutions to solve these issues and use orthogonal approaches to validate our results. We show how a comprehensive mutational signature analysis may provide relevant biological insights, reporting evidence of c-AID activity among unmutated CLL cases or the absence of BRCA1/BRCA2-mediated homologous recombination deficiency in a MM cohort. Finally, we propose a general analysis framework to ensure production of accurate and reproducible mutational signature data.",
			"category": 2,
			"name": "Maura Francesco,2019"
		},
		{
			"PMID": 31272500,
			"title": "A novel knowledge-derived data potentizing method revealed unique liver cancer-associated genetic variants.",
			"journal": "Human genomics",
			"authorList": [
				"Sultana Naznin",
				"Rahman Mijanur",
				"Myti Sanat",
				"Islam Jikrul",
				"Mustafa Md G",
				"Nag Kakon"
			],
			"DOI": "10.1186/s40246-019-0213-7",
			"date": "2020-03-17",
			"PMC": "",
			"citation": "",
			"abstract": "Next-generation sequencing (NGS) has been advancing the progress of detection of disease-associated genetic variants and genome-wide profiling of expressed sequences over the past decade. NGS enables the analyses of multiple regions of a genome in a single reaction format and has been shown to be a cost-effective and efficient tool for root-cause analysis of disease and optimization of treatment. NGS has been leading global efforts to device personalized and precision medicine (PM) in clinical practice. The effectiveness of NGS for the aforementioned applications has been proven unequivocal for multifactorial diseases like cancer. However, definitive prediction of cancer markers for all types of diseases and for global populations still remains highly rewarding because of the diversity of cancer types and genetic variants in human.",
			"category": 2,
			"name": "Sultana Naznin,2020"
		},
		{
			"PMID": 31271844,
			"title": "Cancer classification and pathway discovery using non-negative matrix factorization.",
			"journal": "Journal of biomedical informatics",
			"authorList": [
				"Zeng Zexian",
				"Vo Andy H",
				"Mao Chengsheng",
				"Clare Susan E",
				"Khan Seema A",
				"Luo Yuan"
			],
			"DOI": "10.1016/j.jbi.2019.103247",
			"date": "2020-09-29",
			"PMC": "",
			"citation": "",
			"abstract": "Extracting genetic information from a full range of sequencing data is important for understanding disease. We propose a novel method to effectively explore the landscape of genetic mutations and aggregate them to predict cancer type.",
			"category": 2,
			"name": "Zeng Zexian,2020"
		},
		{
			"PMID": 31253940,
			"title": "The role of telomeres and telomerase in cirrhosis and liver cancer.",
			"journal": "Nature reviews. Gastroenterology & hepatology",
			"authorList": [
				"Nault Jean-Charles",
				"Ningarhari Massih",
				"Rebouissou Sandra",
				"Zucman-Rossi Jessica"
			],
			"DOI": "10.1038/s41575-019-0165-3",
			"date": "2019-12-02",
			"PMC": "",
			"citation": "",
			"abstract": "Telomerase is a key enzyme for cell survival that prevents telomere shortening and the subsequent cellular senescence that is observed after many rounds of cell division. In contrast, inactivation of telomerase is observed in most cells of the adult liver. Absence of telomerase activity and shortening of telomeres has been implicated in hepatocyte senescence and the development of cirrhosis, a chronic liver disease that can lead to hepatocellular carcinoma (HCC) development. During hepatocarcinogenesis, telomerase reactivation is required to enable the uncontrolled cell proliferation that leads to malignant transformation and HCC development. Part of the telomerase complex, telomerase reverse transcriptase, is encoded by TERT, and several mechanisms of telomerase reactivation have been described in HCC that include somatic TERT promoter mutations, TERT amplification, TERT translocation and viral insertion into the TERT gene. An understanding of the role of telomeres and telomerase in HCC development is important to develop future targeted therapies and improve survival of this disease. In this Review, the roles of telomeres and telomerase in liver carcinogenesis are discussed, in addition to their potential translation to clinical practice as biomarkers and therapeutic targets.",
			"category": 2,
			"name": "Nault Jean-Charles,2019"
		},
		{
			"PMID": 31250328,
			"title": "Bioinformatic Methods and Bridging of Assay Results for Reliable Tumor Mutational Burden Assessment in Non-Small-Cell Lung Cancer.",
			"journal": "Molecular diagnosis & therapy",
			"authorList": [
				"Chang Han",
				"Sasson Ariella",
				"Srinivasan Sujaya",
				"Golhar Ryan",
				"Greenawalt Danielle M",
				"Geese William J",
				"Green George",
				"Zerba Kim",
				"Kirov Stefan",
				"Szustakowski Joseph"
			],
			"DOI": "10.1007/s40291-019-00408-y",
			"date": "2020-05-04",
			"PMC": "",
			"citation": "",
			"abstract": "Tumor mutational burden (TMB) has emerged as a clinically relevant biomarker that may be associated with immune checkpoint inhibitor efficacy. Standardization of TMB measurement is essential for implementing diagnostic tools to guide treatment.",
			"category": 2,
			"name": "Chang Han,2020"
		},
		{
			"PMID": 31243108,
			"title": "Comparative Proteome Profiling and Mutant Protein Identification in Metastatic Prostate Cancer Cells by Quantitative Mass Spectrometry-based Proteogenomics.",
			"journal": "Cancer genomics & proteomics",
			"authorList": [
				"Kwon Oh Kwang",
				"Ha Yun-Sok",
				"Lee Jun Nyung",
				"Kim Sunjoo",
				"Lee Hyesuk",
				"Chun So Young",
				"Kwon Tae Gyun",
				"Lee Sangkyu"
			],
			"DOI": "10.21873/cgp.20132",
			"date": "2019-12-11",
			"PMC": "",
			"citation": "",
			"abstract": "Prostate cancer (PCa) is the most frequent cancer found in males worldwide. The aim of this study was to identify new biomarkers using mutated peptides for the prognosis and prediction of advanced PCa, based on proteogenomics.",
			"category": 2,
			"name": "Kwon Oh Kwang,2019"
		},
		{
			"PMID": 31181609,
			"title": "AXL Is a Novel Predictive Factor and Therapeutic Target for Radioactive Iodine Refractory Thyroid Cancer.",
			"journal": "Cancers",
			"authorList": [
				"Collina Francesca",
				"La Sala Lucia",
				"Liotti Federica",
				"Prevete Nella",
				"La Mantia Elvira",
				"Chiofalo Maria Grazia",
				"Aquino Gabriella",
				"Arenare Laura",
				"Cantile Monica",
				"Liguori Giuseppina",
				"Di Gennaro Francesca",
				"Pezzullo Luciano",
				"Losito Nunzia Simona",
				"Vecchio Giancarlo",
				"Botti Gerardo",
				"Melillo Rosa Marina",
				"Franco Renato"
			],
			"DOI": "10.3390/cancers11060785",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "Papillary thyroid carcinomas (PTCs) have an excellent prognosis, but a fraction of them show aggressive behavior, becoming radioiodine (RAI)-resistant and/or metastatic. AXL (Anexelekto) is a tyrosine kinase receptor regulating viability, invasiveness and chemoresistance in various human cancers, including PTCs. Here, we analyze the role of AXL in PTC prognosis and as a marker of RAI refractoriness. Immunohistochemistry was used to assess AXL positivity in a cohort of human PTC samples. Normal and cancerous thyroid cell lines were used in vitro for signaling, survival and RAI uptake evaluations. 38.2% of human PTCs displayed high expression of AXL that positively correlated with RAI-refractoriness and disease persistence or recurrence, especially when combined with v-raf murine sarcoma viral oncogene homolog B(BRAF) V600E mutation. In human PTC samples, AXL expression correlated with V-akt murine thymoma viral oncogene homolog 1 (AKT1) and p65 nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation levels. Consistently, AXL stimulation with its ligand growth arrest-specific gene 6 (GAS6) increased AKT1- and p65 NF-kB-phosphorylation and promoted survival of thyroid cancer cell lines in culture. Enforced expression or activation of AXL in normal rat thyroid cells significantly reduced the expression of the sodium/iodide symporter (NIS) and the radioiodine uptake. These data indicate that AXL expression levels could be used as predictor of RAI refractoriness and as a possible novel therapeutic target of RAI resistant PTCs.",
			"category": 2,
			"name": "Collina Francesca,2020"
		},
		{
			"PMID": 31174340,
			"title": "Shortcomings of Phylogenetic Studies on Recent Radiated Insular Groups: A Meta-Analysis Using Cabo Verde Biodiversity.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Romeiras Maria M",
				"Pena Ana Rita",
				"Menezes Tiago",
				"Vasconcelos Raquel",
				"Monteiro Filipa",
				"Paulo Oct\u00e1vio S",
				"Moura M\u00f3nica"
			],
			"DOI": "10.3390/ijms20112782",
			"date": "2019-11-19",
			"PMC": "",
			"citation": "",
			"abstract": "Over the previous decades, numerous studies focused on how oceanic islands have contributed to determine the phylogenetic relationships and times of origin and diversification of different endemic lineages. The Macaronesian Islands (i.e., Azores, Madeira, Selvagens, Canaries, and Cabo Verde), harbour biotas with exceptionally high levels of endemism. Within the region, the vascular plants and reptiles constitute two of the most important radiations. In this study we compare relevant published phylogenetic data and diversification rates retrieved within Cabo Verde endemic lineages and discuss the importance of choosing appropriate phylogeny-based methods to investigate diversification dynamics on islands. From this selective literature-based review, we summarize the software packages used in Macaronesian studies and discuss their adequacy considering the published data to obtain well-supported phylogenies in the target groups. We further debate the importance of Next Generation Sequencing (NGS), to investigate the evolutionary processes of diversification in the Macaronesian Islands. Analysis of genomic data provides phylogenetic resolution for rapidly evolving species radiations, suggesting a great potential to improve the phylogenetic signal and divergence time estimates in insular lineages. The most important Macaronesian reptile radiations provide good case-studies to compare classical phylogenetic methods with new tools, such as phylogenomics, revealing a high value for research on this hotspot area.",
			"category": 2,
			"name": "Romeiras Maria M,2019"
		},
		{
			"PMID": 31164905,
			"title": "Gene Expression Noise Produces Cell-to-Cell Heterogeneity in Eukaryotic Homologous Recombination Rate.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Liu Jian",
				"Fran\u00e7ois Jean-Marie",
				"Capp Jean-Pascal"
			],
			"DOI": "10.3389/fgene.2019.00475",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "Variation in gene expression among genetically identical individual cells (called gene expression noise) directly contributes to phenotypic diversity. Whether such variation can impact genome stability and lead to variation in genotype remains poorly explored. We addressed this question by investigating whether noise in the expression of genes affecting homologous recombination (HR) activity either directly (",
			"category": 2,
			"name": "Liu Jian,2020"
		},
		{
			"PMID": 31092228,
			"title": "Portrait of a cancer: mutational signature analyses for cancer diagnostics.",
			"journal": "BMC cancer",
			"authorList": [
				"Van Hoeck Arne",
				"Tjoonk Niels H",
				"van Boxtel Ruben",
				"Cuppen Edwin"
			],
			"DOI": "10.1186/s12885-019-5677-2",
			"date": "2019-09-02",
			"PMC": "",
			"citation": "",
			"abstract": "In the past decade, systematic and comprehensive analyses of cancer genomes have identified cancer driver genes and revealed unprecedented insight into the molecular mechanisms underlying the initiation and progression of cancer. These studies illustrate that although every cancer has a unique genetic make-up, there are only a limited number of mechanisms that shape the mutational landscapes of cancer genomes, as reflected by characteristic computationally-derived mutational signatures. Importantly, the molecular mechanisms underlying specific signatures can now be dissected and coupled to treatment strategies. Systematic characterization of mutational signatures in a cancer patient's genome may thus be a promising new tool for molecular tumor diagnosis and classification.",
			"category": 2,
			"name": "Van Hoeck Arne,2019"
		},
		{
			"PMID": 31076843,
			"title": "An evolving view of copy number variants.",
			"journal": "Current genetics",
			"authorList": [
				"Lauer Stephanie",
				"Gresham David"
			],
			"DOI": "10.1007/s00294-019-00980-0",
			"date": "2020-04-13",
			"PMC": "",
			"citation": "",
			"abstract": "Copy number variants (CNVs) are regions of the genome that vary in integer copy number. CNVs, which comprise both amplifications and deletions of DNA sequence, have been identified across all domains of life, from bacteria and archaea to plants and animals. CNVs are an important source of genetic diversity, and can drive rapid adaptive evolution and progression of heritable and somatic human diseases, such as cancer. However, despite their evolutionary importance and clinical relevance, CNVs remain understudied compared to single-nucleotide variants (SNVs). This is a consequence of the inherent difficulties in detecting CNVs at low-to-intermediate frequencies in heterogeneous populations of cells. Here, we discuss molecular methods used to detect CNVs, the limitations associated with using these techniques, and the application of new and emerging technologies that present solutions to these challenges. The goal of this short review and perspective is to highlight aspects of CNV biology that are understudied and define avenues for further research that address specific gaps in our knowledge of these complex alleles. We describe our recently developed method for CNV detection in which a fluorescent gene functions as a single-cell CNV reporter and present key findings from our evolution experiments in Saccharomyces cerevisiae. Using a CNV reporter, we found that CNVs are generated at a high rate and undergo selection with predictable dynamics across independently evolving replicate populations. Many CNVs appear to be generated through DNA replication-based processes that are mediated by the presence of short, interrupted, inverted-repeat sequences. Our results have important implications for the role of CNVs in evolutionary processes and the molecular mechanisms that underlie CNV formation. We discuss the possible extension of our method to other applications, including tracking the dynamics of CNVs in models of human tumors.",
			"category": 2,
			"name": "Lauer Stephanie,2020"
		},
		{
			"PMID": 31015295,
			"title": "In silico learning of tumor evolution through mutational time series.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Auslander Noam",
				"Wolf Yuri I",
				"Koonin Eugene V"
			],
			"DOI": "10.1073/pnas.1901695116",
			"date": "2020-03-16",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer arises through the accumulation of somatic mutations over time. Understanding the sequence of mutation occurrence during cancer progression can assist early and accurate diagnosis and improve clinical decision-making. Here we employ long short-term memory (LSTM) networks, a class of recurrent neural network, to learn the evolution of a tumor through an ordered sequence of mutations. We demonstrate the capacity of LSTMs to learn complex dynamics of the mutational time series governing tumor progression, allowing accurate prediction of the mutational burden and the occurrence of mutations in the sequence. Using the probabilities learned by the LSTM, we simulate mutational data and show that the simulation results are statistically indistinguishable from the empirical data. We identify passenger mutations that are significantly associated with established cancer drivers in the sequence and demonstrate that the genes carrying these mutations are substantially enriched in interactions with the corresponding driver genes. Breaking the network into modules consisting of driver genes and their interactors, we show that these interactions are associated with poor patient prognosis, thus likely conferring growth advantage for tumor progression. Thus, application of LSTM provides for prediction of numerous additional conditional drivers and reveals hitherto unknown aspects of cancer evolution.",
			"category": 2,
			"name": "Auslander Noam,2020"
		},
		{
			"PMID": 30999636,
			"title": "EGFR and KRAS Mutations in the Non-Tumoral Lung. Prognosis in Patients with Adenocarcinoma.",
			"journal": "Journal of clinical medicine",
			"authorList": [
				"Chalela Roberto",
				"Bellosillo Beatriz",
				"Curull V\u00edctor",
				"Longar\u00f3n Raquel",
				"Pascual-Guardia Sergi",
				"Badenes-Bonet Diana",
				"Arriola Edurne",
				"S\u00e1nchez-Font Albert",
				"Pijuan Lara",
				"Gea Joaquim"
			],
			"DOI": "10.3390/jcm8040529",
			"date": "2023-11-04",
			"PMC": "",
			"citation": "",
			"abstract": "Tumor recurrence is frequent and survival rates remain extremely low in lung adenocarcinoma (ADC). We hypothesize that carcinogenic factors will promote loco-regional modifications not only in the future tumor, but throughout the exposed lung.",
			"category": 2,
			"name": "Chalela Roberto,2023"
		},
		{
			"PMID": 30993319,
			"title": "Discovering novel mutation signatures by latent Dirichlet allocation with variational Bayes inference.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Matsutani Taro",
				"Ueno Yuki",
				"Fukunaga Tsukasa",
				"Hamada Michiaki"
			],
			"DOI": "10.1093/bioinformatics/btz266",
			"date": "2020-07-01",
			"PMC": "",
			"citation": "",
			"abstract": "A cancer genome includes many mutations derived from various mutagens and mutational processes, leading to specific mutation patterns. It is known that each mutational process leads to characteristic mutations, and when a mutational process has preferences for mutations, this situation is called a 'mutation signature.' Identification of mutation signatures is an important task for elucidation of carcinogenic mechanisms. In previous studies, analyses with statistical approaches (e.g. non-negative matrix factorization and latent Dirichlet allocation) revealed a number of mutation signatures. Nonetheless, strictly speaking, these existing approaches employ an ad hoc method or incorrect approximation to estimate the number of mutation signatures, and the whole picture of mutation signatures is unclear.",
			"category": 2,
			"name": "Matsutani Taro,2020"
		},
		{
			"PMID": 30967648,
			"title": "Family history of cancer and risk of paediatric and young adult's testicular cancer: A Norwegian cohort study.",
			"journal": "British journal of cancer",
			"authorList": [
				"Del Risco Kollerud Ruby",
				"Ruud Ellen",
				"Haugnes Hege S",
				"Cannon-Albright Lisa A",
				"Thoresen Magne",
				"Nafstad Per",
				"Vlatkovic Ljiljana",
				"Blaasaas Karl Gerhard",
				"N\u00e6ss \u00d8yvind",
				"Claussen Bj\u00f8rgulf"
			],
			"DOI": "10.1038/s41416-019-0445-2",
			"date": "2020-03-02",
			"PMC": "",
			"citation": "",
			"abstract": "The aim of this study was to examine the association of a family history of cancer with the risk of testicular cancer in young adults.",
			"category": 2,
			"name": "Del Risco Kollerud Ruby,2020"
		},
		{
			"PMID": 30953124,
			"title": "Splicing, genome stability and disease: splice like your genome depends on it!",
			"journal": "Current genetics",
			"authorList": [
				"Tam Annie S",
				"Stirling Peter C"
			],
			"DOI": "10.1007/s00294-019-00964-0",
			"date": "2019-12-03",
			"PMC": "",
			"citation": "",
			"abstract": "The spliceosome has been implicated in genome maintenance for decades. Recently, a surge in discoveries in cancer has suggested that the oncogenic mechanism of spliceosomal defects may involve defective genome stability. The action of the core spliceosome prevents R-loop accumulation, and regulates the expression of genome stability factors. At the same time, specific spliceosomal components have non-canonical functions in genome maintenance. Here we review these different models, highlighting their discovery in different model systems, and describing their potential impact on human disease states.",
			"category": 2,
			"name": "Tam Annie S,2019"
		},
		{
			"PMID": 30898264,
			"title": "Polytherapy and Targeted Cancer Drug Resistance.",
			"journal": "Trends in cancer",
			"authorList": [
				"Chatterjee Nilanjana",
				"Bivona Trever G"
			],
			"DOI": "10.1016/j.trecan.2019.02.003",
			"date": "2020-07-01",
			"PMC": "",
			"citation": "",
			"abstract": "A current challenge in cancer treatment is drug resistance. Even the most effective therapies often fail to produce a complete and durable tumor response and ultimately give rise to therapy resistance and tumor relapse. However, how resistance arises in cancer remains incompletely understood. While drug resistance in cancer is thought to be driven by irreversible genetic mutations, emerging evidence also implicates reversible proteomic and epigenetic mechanisms in the development of drug resistance. Tumor microenvironment-mediated mechanisms and tumor heterogeneity can significantly contribute to cancer treatment resistance. Here, we discuss the diverse and dynamic strategies that cancers use to evade drug response, the promise of upfront combination and intermittent therapies and therapy switching in forestalling resistance, and epigenetic reprogramming to combat resistance.",
			"category": 2,
			"name": "Chatterjee Nilanjana,2020"
		},
		{
			"PMID": 30890735,
			"title": "Burden of unique and low prevalence somatic mutations correlates with cancer survival.",
			"journal": "Scientific reports",
			"authorList": [
				"Klebanov Nikolai",
				"Artomov Mykyta",
				"Goggins William B",
				"Daly Emma",
				"Daly Mark J",
				"Tsao Hensin"
			],
			"DOI": "10.1038/s41598-019-41015-5",
			"date": "2020-09-24",
			"PMC": "",
			"citation": "",
			"abstract": "Tumor mutational burden correlates with improved survival and immunotherapy response in some malignancies, and with tumor aggressiveness in others. To study the link between mutational burden and survival, we analyzed survival effects of tumor exonic missense mutation burden (TEMMB) across 6947 specimens spanning 31 cancers which have undergone whole exome sequencing as part of TCGA. We adjusted TEMMB for age, sex, stage, and recruitment center, and computed Cox-proportional models of TEMMB survival effects. We assigned a recurrence score (RS) to each cohort, defining RS as the burden of recurrent mutations exceeding 1% population prevalence. High TEMMB was associated with improved survival in cutaneous melanoma: hazard ratio (HR)\u2009=\u20090.71 [0.60-0.85], p\u2009=\u20090.0002, urothelial bladder carcinoma: HR\u2009=\u20090.74 [0.59-0.93], p\u2009=\u20090.01, and ovarian carcinoma: HR\u2009=\u20090.80 [0.70-0.93], p\u2009=\u20090.003. High TEMMB was associated with decreased survival in colorectal adenocarcinoma: HR\u2009=\u20091.32 [1.00-1.74], p\u2009<\u20090.05. We identified that TEMMB survival effects were governed by the balance of recurrent and non-recurrent mutations. In cancers with a low RS, high TEMMB was correlated with better survival outcomes (r\u2009=\u20090.49, p\u2009=\u20090.02). In conclusion, TEMMB effects on survival depend on recurrent mutation enrichment; tumor types that are highly enriched in passenger mutations show a survival benefit in the setting of high tumor mutational burden.",
			"category": 2,
			"name": "Klebanov Nikolai,2020"
		},
		{
			"PMID": 30871030,
			"title": "Synthetic Lethality in Lung Cancer-From the Perspective of Cancer Genomics.",
			"journal": "Medicines (Basel, Switzerland)",
			"authorList": [
				"Shimomura Iwao",
				"Yamamoto Yusuke",
				"Ochiya Takahiro"
			],
			"DOI": "10.3390/medicines6010038",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a genetic disease, and this concept is now widely exploited by both scientists and clinicians to develop new genotype-selective anticancer therapeutics. Although the quest of cancer genomics is in its dawn, recognition of the widespread applicability of genetic interactions with biological processes of tumorigenesis is propelling research throughout academic fields. Lung cancer is the most common cause of cancer death worldwide, with an estimated 1.6 million deaths each year. Despite the development of targeted therapies that inhibit oncogenic mutations of lung cancer cases, continued research into new therapeutic approaches is required for untreatable lung cancer patients, and the development of therapeutic modalities has proven elusive. The \"synthetic lethal\" approach holds the promise of delivering a therapeutic regimen that preferentially targets malignant cells while sparing normal cells. We highlight the potential challenges in synthetic lethal anticancer therapeutics that target untreatable genetic alterations in lung cancer. We also discuss both challenges and opportunities regarding the application of new synthetic lethal interactions in lung cancer.",
			"category": 2,
			"name": "Shimomura Iwao,2020"
		},
		{
			"PMID": 30856168,
			"title": "Modeling differentiation-state transitions linked to therapeutic escape in triple-negative breast cancer.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Chapman Margaret P",
				"Risom Tyler",
				"Aswani Anil J",
				"Langer Ellen M",
				"Sears Rosalie C",
				"Tomlin Claire J"
			],
			"DOI": "10.1371/journal.pcbi.1006840",
			"date": "2019-04-29",
			"PMC": "",
			"citation": "",
			"abstract": "Drug resistance in breast cancer cell populations has been shown to arise through phenotypic transition of cancer cells to a drug-tolerant state, for example through epithelial-to-mesenchymal transition or transition to a cancer stem cell state. However, many breast tumors are a heterogeneous mixture of cell types with numerous epigenetic states in addition to stem-like and mesenchymal phenotypes, and the dynamic behavior of this heterogeneous mixture in response to drug treatment is not well-understood. Recently, we showed that plasticity between differentiation states, as identified with intracellular markers such as cytokeratins, is linked to resistance to specific targeted therapeutics. Understanding the dynamics of differentiation-state transitions in this context could facilitate the development of more effective treatments for cancers that exhibit phenotypic heterogeneity and plasticity. In this work, we develop computational models of a drug-treated, phenotypically heterogeneous triple-negative breast cancer (TNBC) cell line to elucidate the feasibility of differentiation-state transition as a mechanism for therapeutic escape in this tumor subtype. Specifically, we use modeling to predict the changes in differentiation-state transitions that underlie specific therapy-induced changes in differentiation-state marker expression that we recently observed in the HCC1143 cell line. We report several statistically significant therapy-induced changes in transition rates between basal, luminal, mesenchymal, and non-basal/non-luminal/non-mesenchymal differentiation states in HCC1143 cell populations. Moreover, we validate model predictions on cell division and cell death empirically, and we test our models on an independent data set. Overall, we demonstrate that changes in differentiation-state transition rates induced by targeted therapy can provoke distinct differentiation-state aggregations of drug-resistant cells, which may be fundamental to the design of improved therapeutic regimens for cancers with phenotypic heterogeneity.",
			"category": 2,
			"name": "Chapman Margaret P,2019"
		},
		{
			"PMID": 30854468,
			"title": "Accumulation of genetic and epigenetic alterations in normal cells and cancer risk.",
			"journal": "NPJ precision oncology",
			"authorList": [
				"Takeshima Hideyuki",
				"Ushijima Toshikazu"
			],
			"DOI": "10.1038/s41698-019-0079-0",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "Cancers develop due to the accumulation of genetic and epigenetic alterations. Genetic alterations are induced by aging, mutagenic chemicals, ultraviolet light, and other factors; whereas, epigenetic alterations are mainly by aging and chronic inflammation. The accumulation and patterns of alterations in normal cells reflect our past exposure levels and life history. Most accumulated alterations are considered as passengers, but their accumulation is correlated with cancer drivers. This has been shown for aberrant DNA methylation but has only been speculated for genetic alterations. However, recent technological advancements have enabled measurement of rare point mutations, and studies have shown that their accumulation levels are indeed correlated with cancer risk. When the accumulation levels of aberrant DNA methylation and point mutations are combined, risk prediction becomes even more accurate. When high levels of alterations accumulate, the tissue has a high risk of developing cancer or even multiple cancers and is considered as a \"cancerization field\", with or without expansion of physiological patches of clonal cells. In this review, we describe the formation of a cancerization field and how we can apply its detection in precision cancer risk diagnosis.",
			"category": 2,
			"name": "Takeshima Hideyuki,2020"
		},
		{
			"PMID": 30854067,
			"title": "Molecular mechanism of triple-negative breast cancer-associated BRCA1 and the identification of signaling pathways.",
			"journal": "Oncology letters",
			"authorList": [
				"Qi Feng",
				"Qin Wen-Xing",
				"Zang Yuan-Sheng"
			],
			"DOI": "10.3892/ol.2019.9884",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "BRAC1 has multiple important interactions with triple-negative breast cancer, the specific molecular characteristics of this interaction, however, have not yet been completely elucidated. By examining cell signaling pathways, important information for comprehending the potential mechanisms of this cancer may become known. The aim of the present study was to identify the effects of BRAC1 and to find the signaling pathway(s) involved in the pathogenic mechanism of triple-negative breast cancer. In this study, GSE27447 microarray data were obtained from the Gene Expression Omnibus (GEO) database of the National Center for Biotechnology Information, and differentially expressed genes (DEGs) from GSE27447 were distinguished by Significant Analysis of Microarray. Gene ontology (GO) analysis was carried out on 132 upregulated and 198 downregulated genes with DAVID. The signaling was forecast by the Kyoto Encyclopedia of Genes and Genomes (KEGG). Transcription factors were recognized by TFatS. The BRAC1 relevant protein-protein interaction networks (PPI) were fixed by STRING and visualized by CytoScape. Overall, the upregulated DEGs, which included CR2, IGHM, PRKCB, CARD11, PLCG2, CD79A, IGKC and CD27, were primarily enriched in the terms associated with immune responses, and the downregulated DEGs, which included STARD3, ALDH8A1, SRD5A3, CACNA1H, UGT2B4, SDR16C5 and MED1, were primarily enriched in the hormone metabolic process. In addition, 13 pathways, such as the B-cell receptor-signaling pathway, the hormone synthesis signaling pathway and the oxytocin-signaling pathway, were chosen. MYC, SP1 and CTNNB1 were determined to be enriched in triple-negative breast cancer. A total of 8 genes were identified to be downregulated in the BRAC1-related PPI network. The results of the present study show a fresh angle on the molecular mechanism of triple-negative breast cancer and indicate a possible target for its treatment.",
			"category": 2,
			"name": "Qi Feng,2020"
		},
		{
			"PMID": 30849372,
			"title": "Characterizing Mutational Signatures in Human Cancer Cell Lines Reveals Episodic APOBEC Mutagenesis.",
			"journal": "Cell",
			"authorList": [
				"Petljak Mia",
				"Alexandrov Ludmil B",
				"Brammeld Jonathan S",
				"Price Stacey",
				"Wedge David C",
				"Grossmann Sebastian",
				"Dawson Kevin J",
				"Ju Young Seok",
				"Iorio Francesco",
				"Tubio Jose M C",
				"Koh Ching Chiek",
				"Georgakopoulos-Soares Ilias",
				"Rodr\u00edguez-Mart\u00edn Bernardo",
				"Otlu Bur\u00e7ak",
				"O'Meara Sarah",
				"Butler Adam P",
				"Menzies Andrew",
				"Bhosle Shriram G",
				"Raine Keiran",
				"Jones David R",
				"Teague Jon W",
				"Beal Kathryn",
				"Latimer Calli",
				"O'Neill Laura",
				"Zamora Jorge",
				"Anderson Elizabeth",
				"Patel Nikita",
				"Maddison Mark",
				"Ng Bee Ling",
				"Graham Jennifer",
				"Garnett Mathew J",
				"McDermott Ultan",
				"Nik-Zainal Serena",
				"Campbell Peter J",
				"Stratton Michael R"
			],
			"DOI": "10.1016/j.cell.2019.02.012",
			"date": "2020-01-06",
			"PMC": "",
			"citation": "",
			"abstract": "Multiple signatures of somatic mutations have been identified in cancer genomes. Exome sequences of 1,001 human cancer cell lines and 577 xenografts revealed most common mutational signatures, indicating past activity of the underlying processes, usually in appropriate cancer types. To investigate ongoing patterns of mutational-signature generation, cell lines were cultured for extended periods and subsequently DNA sequenced. Signatures of discontinued exposures, including tobacco smoke and ultraviolet light, were not generated in\u00a0vitro. Signatures of normal and defective DNA repair and replication continued to be generated at roughly stable mutation rates. Signatures of APOBEC cytidine deaminase DNA-editing exhibited substantial fluctuations in mutation rate over time with episodic bursts of mutations. The initiating factors for the bursts are\u00a0unclear, although retrotransposon mobilization may\u00a0contribute. The examined cell lines constitute a resource of live experimental models of mutational processes, which potentially retain patterns of activity and regulation operative in primary human cancers.",
			"category": 2,
			"name": "Petljak Mia,2020"
		},
		{
			"PMID": 30842677,
			"title": "Genomic correlates of response to immune checkpoint blockade.",
			"journal": "Nature medicine",
			"authorList": [
				"Keenan Tanya E",
				"Burke Kelly P",
				"Van Allen Eliezer M"
			],
			"DOI": "10.1038/s41591-019-0382-x",
			"date": "2019-05-13",
			"PMC": "",
			"citation": "",
			"abstract": "Despite impressive durable responses, immune checkpoint inhibitors do not provide a long-term benefit to the majority of patients with cancer. Understanding genomic correlates of response and resistance to checkpoint blockade may enhance benefits for patients with cancer by elucidating biomarkers for patient stratification and resistance mechanisms for therapeutic targeting. Here we review emerging genomic markers of checkpoint blockade response, including those related to neoantigens, antigen presentation, DNA repair, and oncogenic pathways. Compelling evidence also points to a role for T cell functionality, checkpoint regulators, chromatin modifiers, and copy-number alterations in mediating selective response to immune checkpoint blockade. Ultimately, efforts to contextualize genomic correlates of response into the larger understanding of tumor immune biology will build a foundation for the development of novel biomarkers and therapies to overcome resistance to checkpoint blockade.",
			"category": 2,
			"name": "Keenan Tanya E,2019"
		},
		{
			"PMID": 30833487,
			"title": "Referrals to a Phase I Clinic and Trial Enrollment in the Molecular Screening Era.",
			"journal": "The oncologist",
			"authorList": [
				"Tan Tira",
				"Rheaume Michael",
				"Wang Lisa",
				"Chow Helen",
				"Spreafico Anna",
				"Hansen Aaron R",
				"Razak Albiruni R A",
				"Siu Lillian L",
				"Bedard Philippe L"
			],
			"DOI": "10.1634/theoncologist.2018-0808",
			"date": "2020-06-30",
			"PMC": "",
			"citation": "",
			"abstract": "Enrichment of patients based on molecular biomarkers is increasingly used in early phase clinical trials. Molecular profiling of patients with advanced cancers can identify specific genomic alterations to inform decisions about investigational treatment(s). Our aim was to evaluate the outcomes of new patient referrals to a large academic solid tumor phase I clinical trial program after the implementation of molecular profiling.",
			"category": 2,
			"name": "Tan Tira,2020"
		},
		{
			"PMID": 30828525,
			"title": "Prediction of Driver Modules via Balancing Exclusive Coverages of Mutations in Cancer Samples.",
			"journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)",
			"authorList": [
				"Gao Bo",
				"Zhao Yue",
				"Li Yang",
				"Liu Juntao",
				"Wang Lushan",
				"Li Guojun",
				"Su Zhengchang"
			],
			"DOI": "10.1002/advs.201801384",
			"date": "2024-07-14",
			"PMC": "",
			"citation": "",
			"abstract": "Mutual exclusivity of cancer driving mutations is a frequently observed phenomenon in the mutational landscape of cancer. The long tail of rare mutations complicates the discovery of mutually exclusive driver modules. The existing methods usually suffer from the problem that only few genes in some identified modules cover most of the cancer samples. To overcome this hurdle, an efficient method UniCovEx is presented via identifying mutually exclusive driver modules of balanced exclusive coverages. UniCovEx first searches for candidate driver modules with a strong topological relationship in signaling networks using a greedy strategy. It then evaluates the candidate modules by considering their coverage, exclusivity, and balance of coverage, using a novel metric termed exclusive entropy of modules, which measures how balanced the modules are. Finally, UniCovEx predicts sample-specific driver modules by solving a minimum set cover problem using a greedy strategy. When tested on 12 The Cancer Genome Atlas datasets of different cancer types, UniCovEx shows a significant superiority over the previous methods. The software is available at: https://sourceforge.net/projects/cancer-pathway/files/.",
			"category": 2,
			"name": "Gao Bo,2024"
		},
		{
			"PMID": 30803482,
			"title": "Somatic mutations in early metazoan genes disrupt regulatory links between unicellular and multicellular genes in cancer.",
			"journal": "eLife",
			"authorList": [
				"Trigos Anna S",
				"Pearson Richard B",
				"Papenfuss Anthony T",
				"Goode David L"
			],
			"DOI": "10.7554/eLife.40947",
			"date": "2020-03-24",
			"PMC": "",
			"citation": "",
			"abstract": "Extensive transcriptional alterations are observed in cancer, many of which activate core biological processes established in unicellular organisms or suppress differentiation pathways formed in metazoans. Through rigorous, integrative analysis of genomics data from a range of solid tumors, we show many transcriptional changes in tumors are tied to mutations disrupting regulatory interactions between unicellular and multicellular genes within human gene regulatory networks (GRNs). Recurrent point mutations were enriched in regulator genes linking unicellular and multicellular subnetworks, while copy-number alterations affected downstream target genes in distinctly unicellular and multicellular regions of the GRN. Our results depict drivers of tumourigenesis as genes that created key regulatory links during the evolution of early multicellular life, whose dysfunction creates widespread dysregulation of primitive elements of the GRN. Several genes we identified as important in this process were associated with drug response, demonstrating the potential clinical value of our approach.",
			"category": 2,
			"name": "Trigos Anna S,2020"
		},
		{
			"PMID": 30796309,
			"title": "Phylostratigraphic analysis of gene co-expression network reveals the evolution of functional modules for ovarian cancer.",
			"journal": "Scientific reports",
			"authorList": [
				"Zhang Luoyan",
				"Tan Yi",
				"Fan Shoujin",
				"Zhang Xuejie",
				"Zhang Zhen"
			],
			"DOI": "10.1038/s41598-019-40023-9",
			"date": "2020-09-09",
			"PMC": "",
			"citation": "",
			"abstract": "Ovarian cancer (OV) is an extremely lethal disease. However, the evolutionary machineries of OV are still largely unknown. Here, we used a method that combines phylostratigraphy information with gene co-expression networks to extensively study the evolutionary compositions of OV. The present co-expression network construction yielded 18,549 nodes and 114,985 edges based on 307 OV expression samples obtained from the Genome Data Analysis Centers database. A total of 20 modules were identified as OV related clusters. The human genome sequences were divided into 19 phylostrata (PS), the majority (67.45%) of OV genes was already present in the eukaryotic ancestor. There were two strong peaks of the emergence of OV genes screened by hypergeometric test: the evolution of the multicellular metazoan organisms (PS5 and PS6, P value\u2009=\u20090.002) and the emergence of bony fish (PS11 and PS12, P value\u2009=\u20090.009). Hence, the origin of OV is far earlier than its emergence. The integrated analysis of the topology of OV modules and the phylogenetic data revealed an evolutionary pattern of OV in human, namely, OV modules have arisen step by step during the evolution of the respective lineages. New genes have evolved and become locked into a pathway, where more and more biological pathways are fixed into OV modules by recruiting new genes during human evolution.",
			"category": 2,
			"name": "Zhang Luoyan,2020"
		},
		{
			"PMID": 30789293,
			"title": "Measuring DNA Copy Number Variation Using High-Density Methylation Microarrays.",
			"journal": "Journal of computational biology : a journal of computational molecular cell biology",
			"authorList": [
				"Cho Soonweng",
				"Kim Hyun-Seok",
				"Zeiger Martha A",
				"Umbricht Christopher B",
				"Cope Leslie M"
			],
			"DOI": "10.1089/cmb.2018.0143",
			"date": "2020-06-22",
			"PMC": "",
			"citation": "",
			"abstract": "Genetic and epigenetic changes drive carcinogenesis, and their integrated analysis provides insights into mechanisms of cancer development. Computational methods have been developed to measure copy number variation (CNV) from methylation array data, including ChAMP-CNV, CN450K, and, introduced here, Epicopy. Using paired single nucleotide polymorphism (SNP) and methylation array data from the public The Cancer Genome Atlas repository, we optimized CNV calling and benchmarked the performance of these methods. We optimized the thresholds of all three methods and showed comparable performance across methods. Using Epicopy as a representative analysis of Illumina450K array, we show that Illumina450K-derived CNV methods achieve a sensitivity of 0.7 and a positive predictive value of 0.75 in identifying CNVs, which is similar to results achieved when comparing competing SNP microarray platforms with each other.",
			"category": 2,
			"name": "Cho Soonweng,2020"
		},
		{
			"PMID": 30787564,
			"title": "Chromosomal aberrations in renal cell carcinoma: An overview with implications for clinical practice.",
			"journal": "Urology annals",
			"authorList": [
				"Quddus Muhammad Bilal",
				"Pratt Norman",
				"Nabi Ghulam"
			],
			"DOI": "10.4103/UA.UA_32_18",
			"date": "2020-09-29",
			"PMC": "",
			"citation": "",
			"abstract": "Chromosomal instability and aberrations are known in many cancers including renal cell carcinoma. Detailed understanding of these changes has led to an improved drug discovery and continued developments in other therapeutic options. Chromosomal aberrations have a potential to be used to monitor disease including prognostication. There has been a growing experience in cytogenetic techniques and gap between clinic and laboratory has narrowed significantly in the recent past. Nevertheless, more work on validation of these techniques, establishing threshold and interobserver agreement needs to be carried out for these diagnostic/prognostic tests before utilizing them in clinics as a part of \"personalized medicine\" care. The review presented here is a summary of common genetic disorders in renal cancer and some of acquired genetic changes which can be used as biomarkers. The review also describes basics of commonly used genetic techniques for wider clinical community involved in the management of renal cancer.",
			"category": 2,
			"name": "Quddus Muhammad Bilal,2020"
		},
		{
			"PMID": 30777857,
			"title": null,
			"journal": "Cancer prevention research (Philadelphia, Pa.)",
			"authorList": [
				"Guerrero-Preston Rafael",
				"Lawson Fahcina",
				"Rodriguez-Torres Sebastian",
				"Noordhuis Maartje G",
				"Pirini Francesca",
				"Manuel Laura",
				"Valle Blanca L",
				"Hadar Tal",
				"Rivera Bianca",
				"Folawiyo Oluwasina",
				"Baez Adriana",
				"Marchionni Luigi",
				"Koch Wayne M",
				"Westra William H",
				"Kim Young J",
				"Eshleman James R",
				"Sidransky David"
			],
			"DOI": "10.1158/1940-6207.CAPR-17-0356",
			"date": "2020-07-13",
			"PMC": "",
			"citation": "",
			"abstract": "To inform novel personalized medicine approaches for race and socioeconomic disparities in head and neck cancer, we examined germline and somatic mutations, immune signatures, and epigenetic alterations linked to neighborhood determinants of health in Black and non-Latino White (NLW) patients with head and neck cancer. Cox proportional hazards revealed that Black patients with squamous cell carcinoma of head and neck (HNSCC) with ",
			"category": 2,
			"name": "Guerrero-Preston Rafael,2020"
		},
		{
			"PMID": 30773592,
			"title": "DriverML: a machine learning algorithm for identifying driver genes in cancer sequencing studies.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Han Yi",
				"Yang Juze",
				"Qian Xinyi",
				"Cheng Wei-Chung",
				"Liu Shu-Hsuan",
				"Hua Xing",
				"Zhou Liyuan",
				"Yang Yaning",
				"Wu Qingbiao",
				"Liu Pengyuan",
				"Lu Yan"
			],
			"DOI": "10.1093/nar/gkz096",
			"date": "2019-11-25",
			"PMC": "",
			"citation": "",
			"abstract": "Although rapid progress has been made in computational approaches for prioritizing cancer driver genes, research is far from achieving the ultimate goal of discovering a complete catalog of genes truly associated with cancer. Driver gene lists predicted from these computational tools lack consistency and are prone to false positives. Here, we developed an approach (DriverML) integrating Rao's score test and supervised machine learning to identify cancer driver genes. The weight parameters in the score statistics quantified the functional impacts of mutations on the protein. To obtain optimized weight parameters, the score statistics of prior driver genes were maximized on pan-cancer training data. We conducted rigorous and unbiased benchmark analysis and comparisons of DriverML with 20 other existing tools in 31 independent datasets from The Cancer Genome Atlas (TCGA). Our comprehensive evaluations demonstrated that DriverML was robust and powerful among various datasets and outperformed the other tools with a better balance of precision and sensitivity. In vitro cell-based assays further proved the validity of the DriverML prediction of novel driver genes. In summary, DriverML uses an innovative, machine learning-based approach to prioritize cancer driver genes and provides dramatic improvements over currently existing methods. Its source code is available at https://github.com/HelloYiHan/DriverML.",
			"category": 2,
			"name": "Han Yi,2019"
		},
		{
			"PMID": 30759076,
			"title": "Convergent perturbation of the human domain-resolved interactome by viruses and mutations inducing similar disease phenotypes.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Chen Yangchun Frank",
				"Xia Yu"
			],
			"DOI": "10.1371/journal.pcbi.1006762",
			"date": "2019-03-12",
			"PMC": "",
			"citation": "",
			"abstract": "An important goal of systems medicine is to study disease in the context of genetic and environmental perturbations to the human interactome network. For diseases with both genetic and infectious contributors, a key postulate is that similar perturbations of the human interactome by either disease mutations or pathogens can have similar disease consequences. This postulate has so far only been tested for a few viral species at the level of whole proteins. Here, we expand the scope of viral species examined, and test this postulate more rigorously at the higher resolution of protein domains. Focusing on diseases with both genetic and viral contributors, we found significant convergent perturbation of the human domain-resolved interactome by endogenous genetic mutations and exogenous viral proteins inducing similar disease phenotypes. Pan-cancer, pan-oncovirus analysis further revealed that domains of human oncoproteins either physically targeted or structurally mimicked by oncoviruses are enriched for cancer driver rather than passenger mutations, suggesting convergent targeting of cancer driver pathways by diverse oncoviruses. Our study provides a framework for high-resolution, network-based comparison of various disease factors, both genetic and environmental, in terms of their impacts on the human interactome.",
			"category": 2,
			"name": "Chen Yangchun Frank,2019"
		},
		{
			"PMID": 30736482,
			"title": "Cell Fusion in Human Cancer: The Dark Matter Hypothesis.",
			"journal": "Cells",
			"authorList": [
				"Weiler Julian",
				"Dittmar Thomas"
			],
			"DOI": "10.3390/cells8020132",
			"date": "2019-11-27",
			"PMC": "",
			"citation": "",
			"abstract": "Current strategies to determine tumor \u00d7 normal (TN)-hybrid cells among human cancer cells include the detection of hematopoietic markers and other mesodermal markers on tumor cells or the presence of donor DNA in cancer samples from patients who had previously received an allogenic bone marrow transplant. By doing so, several studies have demonstrated that TN-hybrid cells could be found in human cancers. However, a prerequisite of this cell fusion search strategy is that such markers are stably expressed by TN-hybrid cells over time. However, cell fusion is a potent inducer of genomic instability, and TN-hybrid cells may lose these cell fusion markers, thereby becoming indistinguishable from nonfused tumor cells. In addition, hybrid cells can evolve from homotypic fusion events between tumor cells or from heterotypic fusion events between tumor cells and normal cells possessing similar markers, which would also be indistinguishable from nonfused tumor cells. Such indistinguishable or invisible hybrid cells will be referred to as dark matter hybrids, which cannot as yet be detected and quantified, but which contribute to tumor growth and progression.",
			"category": 2,
			"name": "Weiler Julian,2019"
		},
		{
			"PMID": 30728902,
			"title": "Polymorphism of DNA repair genes in breast cancer.",
			"journal": "Oncotarget",
			"authorList": [
				"Smolarz Beata",
				"Michalska Magdalena M",
				"Samulak Dariusz",
				"Romanowicz Hanna",
				"W\u00f3jcik Luiza"
			],
			"DOI": "10.18632/oncotarget.26568",
			"date": "2022-04-01",
			"PMC": "",
			"citation": "",
			"abstract": "The aim of the study was to determine the relationship between single nucleotide polymorphisms (SNPs) of DNA repair genes and modulation of the risk of breast cancer. The following SNPs were analysed: XRCC1-Arg399Gln (rs25487), hMSH2-Gly322Asp (rs4987188), ",
			"category": 2,
			"name": "Smolarz Beata,2022"
		},
		{
			"PMID": 30728898,
			"title": "Imbalanced sphingolipid signaling is maintained as a core proponent of a cancerous phenotype in spite of metabolic pressure and epigenetic drift.",
			"journal": "Oncotarget",
			"authorList": [
				"Speirs Monique M P",
				"Swensen Adam C",
				"Chan Tsz Y",
				"Jones Peter M",
				"Holman John C",
				"Harris McCall B",
				"Maschek John A",
				"Cox James E",
				"Carson Richard H",
				"Hill Jonathon T",
				"Andersen Joshua L",
				"Prince John T",
				"Price John C"
			],
			"DOI": "10.18632/oncotarget.26533",
			"date": "2020-02-25",
			"PMC": "",
			"citation": "",
			"abstract": "Tumor heterogeneity may arise through genetic drift and environmentally driven clonal selection for metabolic fitness. This would promote subpopulations derived from single cancer cells that exhibit distinct phenotypes while conserving vital pro-survival pathways. We aimed to identify significant drivers of cell fitness in pancreatic adenocarcinoma (PDAC) creating subclones in different nutrient formulations to encourage differential metabolic reprogramming. The genetic and phenotypic expression profiles of each subclone were analyzed relative to a healthy control cell line (hTert-HPNE). The subclones exhibited distinct variations in protein expression and lipid metabolism. Relative to hTert-HPNE, PSN-1 subclones uniformly maintained modified sphingolipid signaling and specifically retained elevated sphingosine-1-phosphate (S1P) relative to C16 ceramide (C16 Cer) ratios. Each clone utilized a different perturbation to this pathway, but maintained this modified signaling to preserve cancerous phenotypes, such as rapid proliferation and defense against mitochondria-mediated apoptosis. Although the subclones were unique in their sensitivity, inhibition of S1P synthesis significantly reduced the ratio of S1P/C16 Cer, slowed cell proliferation, and enhanced sensitivity to apoptotic signals. This reliance on S1P signaling identifies this pathway as a promising drug-sensitizing target that may be used to eliminate cancerous cells consistently across uniquely reprogrammed PDAC clones.",
			"category": 2,
			"name": "Speirs Monique M P,2020"
		},
		{
			"PMID": 30718964,
			"title": "Overview of the genetic basis toward early detection of breast cancer.",
			"journal": "Breast cancer (Dove Medical Press)",
			"authorList": [
				"De Silva Sumadee",
				"Tennekoon Kamani Hemamala",
				"Karunanayake Eric Hamilton"
			],
			"DOI": "10.2147/BCTT.S185870",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a socioeconomical burden in any nation. Out of that, breast cancer is identified as the most common malignancy worldwide among women irrespective of age. As women are an important segment in a community, the weakening of their strength toward the development of a nation is a critical problem in each nation. In this review, it was aimed to discuss the characteristics of cancer genome, cancer genetics, and cancer epigenetics in general and then focus on discussing both genetic and nongenetic factors responsible for the predisposition of breast cancer in humans. More emphasis was placed on genes responsible for the early onset of the disease and which can be used as genetic tools in the identification of the disease at an early stage. Then the context of genetic involvement toward the breast cancer occurrence before age of 40 years was highlighted accordingly. In addition to genetic testing, the review paid adequate attention to mention novel liquid biopsy techniques and other clinical, laboratory, and radiologic assessments. These techniques can be used in early detection and recurrence as well as the surveillance of the patients after primary therapies.",
			"category": 2,
			"name": "De Silva Sumadee,2020"
		},
		{
			"PMID": 30718408,
			"title": "Defining the impact of mutation accumulation on replicative lifespan in yeast using cancer-associated mutator phenotypes.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Lee Mitchell B",
				"Dowsett Ian T",
				"Carr Daniel T",
				"Wasko Brian M",
				"Stanton Sarah G",
				"Chung Michael S",
				"Ghodsian Niloufar",
				"Bode Anna",
				"Kiflezghi Michael G",
				"Uppal Priya A",
				"Grayden Katherine A",
				"Elala Yordanos C",
				"Tang Thao T",
				"Tran Ngoc H B",
				"Tran Thu H B",
				"Diep Anh B",
				"Hope Michael",
				"Promislow Daniel E L",
				"Kennedy Scott R",
				"Kaeberlein Matt",
				"Herr Alan J"
			],
			"DOI": "10.1073/pnas.1815966116",
			"date": "2019-05-03",
			"PMC": "",
			"citation": "",
			"abstract": "Mutations accumulate within somatic cells and have been proposed to contribute to aging. It is unclear what level of mutation burden may be required to consistently reduce cellular lifespan. Human cancers driven by a mutator phenotype represent an intriguing model to test this hypothesis, since they carry the highest mutation burdens of any human cell. However, it remains technically challenging to measure the replicative lifespan of individual mammalian cells. Here, we modeled the consequences of cancer-related mutator phenotypes on lifespan using yeast defective for mismatch repair (MMR) and/or leading strand (Pol\u03b5) or lagging strand (Pol\u03b4) DNA polymerase proofreading. Only haploid mutator cells with significant lifetime mutation accumulation (MA) exhibited shorter lifespans. Diploid strains, derived by mating haploids of various genotypes, carried variable numbers of fixed mutations and a range of mutator phenotypes. Some diploid strains with fewer than two mutations per megabase displayed a 25% decrease in lifespan, suggesting that moderate numbers of random heterozygous mutations can increase mortality rate. As mutation rates and burdens climbed, lifespan steadily eroded. Strong diploid mutator phenotypes produced a form of genetic anticipation with regard to aging, where the longer a lineage persisted, the shorter lived cells became. Using MA lines, we established a relationship between mutation burden and lifespan, as well as population doubling time. Our observations define a threshold of random mutation burden that consistently decreases cellular longevity in diploid yeast cells. Many human cancers carry comparable mutation burdens, suggesting that while cancers appear immortal, individual cancer cells may suffer diminished lifespan due to accrued mutation burden.",
			"category": 2,
			"name": "Lee Mitchell B,2019"
		},
		{
			"PMID": 30700008,
			"title": "Mitochondrial DNA Integrity: Role in Health and Disease.",
			"journal": "Cells",
			"authorList": [
				"Sharma Priyanka",
				"Sampath Harini"
			],
			"DOI": "10.3390/cells8020100",
			"date": "2019-12-03",
			"PMC": "",
			"citation": "",
			"abstract": "As the primary cellular location for respiration and energy production, mitochondria serve in a critical capacity to the cell. Yet, by virtue of this very function of respiration, mitochondria are subject to constant oxidative stress that can damage one of the unique features of this organelle, its distinct genome. Damage to mitochondrial DNA (mtDNA) and loss of mitochondrial genome integrity is increasingly understood to play a role in the development of both severe early-onset maladies and chronic age-related diseases. In this article, we review the processes by which mtDNA integrity is maintained, with an emphasis on the repair of oxidative DNA lesions, and the cellular consequences of diminished mitochondrial genome stability.",
			"category": 2,
			"name": "Sharma Priyanka,2019"
		},
		{
			"PMID": 30687641,
			"title": "Strategies of the War on Cancer: To Kill or to Neutralize?",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Lichtenstein Anatoly V"
			],
			"DOI": "10.3389/fonc.2018.00667",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Lichtenstein Anatoly V,2020"
		},
		{
			"PMID": 30675185,
			"title": "Use case driven evaluation of open databases for pediatric cancer research.",
			"journal": "BioData mining",
			"authorList": [
				"Jeanquartier Fleur",
				"Jean-Quartier Claire",
				"Holzinger Andreas"
			],
			"DOI": "10.1186/s13040-018-0190-8",
			"date": "2023-10-05",
			"PMC": "",
			"citation": "",
			"abstract": "A plethora of Web resources are available offering information on clinical, pre-clinical, genomic and theoretical aspects of cancer, including not only the comprehensive cancer projects as ICGC and TCGA, but also less-known and more specialized projects on pediatric diseases such as PCGP. However, in case of data on childhood cancer there is very little information openly available. Several web-based resources and tools offer general biomedical data which are not purpose-built, for neither pediatric nor cancer analysis. Additionally, many Web resources on cancer focus on incidence data and statistical social characteristics as well as self-regulating communities.",
			"category": 2,
			"name": "Jeanquartier Fleur,2023"
		},
		{
			"PMID": 30664300,
			"title": "Tumor mutational burden standardization initiatives: Recommendations for consistent tumor mutational burden assessment in clinical samples to guide immunotherapy treatment decisions.",
			"journal": "Genes, chromosomes & cancer",
			"authorList": [
				"Stenzinger Albrecht",
				"Allen Jeffrey D",
				"Maas J\u00f6rg",
				"Stewart Mark D",
				"Merino Diana M",
				"Wempe Madison M",
				"Dietel Manfred"
			],
			"DOI": "10.1002/gcc.22733",
			"date": "2020-01-09",
			"PMC": "",
			"citation": "",
			"abstract": "Characterization of tumors utilizing next-generation sequencing methods, including assessment of the number of somatic mutations (tumor mutational burden [TMB]), is currently at the forefront of the field of personalized medicine. Recent clinical studies have associated high TMB with improved patient response rates and survival benefit from immune checkpoint inhibitors; hence, TMB is emerging as a biomarker of response for these immunotherapy agents. However, variability in current methods for TMB estimation and reporting is evident, demonstrating a need for standardization and harmonization of TMB assessment methodology across assays and centers. Two uniquely placed organizations, Friends of Cancer Research (Friends) and the Quality Assurance Initiative Pathology (QuIP), have collaborated to coordinate efforts for international multistakeholder initiatives to address this need. Friends and QuIP, who have partnered with several academic centers, pharmaceutical organizations, and diagnostic companies, have adopted complementary, multidisciplinary approaches toward the goal of proposing evidence-based recommendations for achieving consistent TMB estimation and reporting in clinical samples across assays and centers. Many factors influence TMB assessment, including preanalytical factors, choice of assay, and methods of reporting. Preliminary analyses highlight the importance of targeted gene panel size and composition, and bioinformatic parameters for reliable TMB estimation. Herein, Friends and QuIP propose recommendations toward consistent TMB estimation and reporting methods in clinical samples across assays and centers. These recommendations should be followed to minimize variability in TMB estimation and reporting, which will ensure reliable and reproducible identification of patients who are likely to benefit from immune checkpoint inhibitors.",
			"category": 2,
			"name": "Stenzinger Albrecht,2020"
		},
		{
			"PMID": 30655888,
			"title": "Deletion of C9orf53 promotes the growth of head and neck squamous cell carcinoma and is associated with poor prognosis of patients with head and neck squamous cell carcinoma.",
			"journal": "Oncology letters",
			"authorList": [
				"Wang Guo Dong",
				"Huang Jian Tao",
				"Liu Yuan",
				"Wu Yang",
				"Chen Xiao Qing",
				"Zhao Yun Fu",
				"Wang Da Lin"
			],
			"DOI": "10.3892/ol.2018.9675",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "Head and neck squamous cell carcinoma (HNSCC) is the fifth most common carcinoma worldwide, and accounts for ~600,000 new cases every year. The information on the molecular carcinogenesis of HNSCC is very limited. In the present study, the role of C9orf53 in HNSCC was investigated. The levels of C9orf53 were assayed by reverse transcription-quantitative polymerase chain reaction. The levels of C9orf53 in cells were overexpressed by overexpression plasmid and inhibited by small-interfering RNA. Cell proliferation was assayed by MTT, and cell apoptosis was assessed by FACS analysis. It was demonstrated that C9orf53 deletion was associated with a decreased survival of patients. The level of C9orf53 in HNSCC tissues was lower compared with the matched normal tissues adjacent to tumors. A lower expression of C9orf53 promoted cell proliferation, and the overexpression of C9orf53 induced cell apoptosis. In conclusion, a low level of C9orf53 in HNSCC promoted the growth of HNSCC cells, which might be associated with the low survival rate of patients with HNSCC.",
			"category": 2,
			"name": "Wang Guo Dong,2020"
		},
		{
			"PMID": 30610579,
			"title": "Precision medicine review: rare driver mutations and their biophysical classification.",
			"journal": "Biophysical reviews",
			"authorList": [
				"Nussinov Ruth",
				"Jang Hyunbum",
				"Tsai Chung-Jung",
				"Cheng Feixiong"
			],
			"DOI": "10.1007/s12551-018-0496-2",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "How can biophysical principles help precision medicine identify rare driver mutations? A major tenet of pragmatic approaches to precision oncology and pharmacology is that driver mutations are very frequent. However, frequency is a statistical attribute, not a mechanistic one. Rare mutations can also act through the same mechanism, and as we discuss below, \"latent driver\" mutations may also follow the same route, with \"helper\" mutations. Here, we review how biophysics provides mechanistic guidelines that extend precision medicine. We outline principles and strategies, especially focusing on mutations that drive cancer. Biophysics has contributed profoundly to deciphering biological processes. However, driven by data science, precision medicine has skirted some of its major tenets. Data science embodies genomics, tissue- and cell-specific expression levels, making it capable of defining genome- and systems-wide molecular disease signatures. It classifies cancer driver genes/mutations and affected pathways, and its associated protein structural data guide drug discovery. Biophysics complements data science. It considers structures and their heterogeneous ensembles, explains how mutational variants can signal through distinct pathways, and how allo-network drugs can be harnessed. Biophysics clarifies how one mutation-frequent or rare-can affect multiple phenotypic traits by populating conformations that favor interactions with other network modules. It also suggests how to identify such mutations and their signaling consequences. Biophysics offers principles and strategies that can help precision medicine push the boundaries to transform our insight into biological processes and the practice of personalized medicine. By contrast, \"phenotypic drug discovery,\" which capitalizes on physiological cellular conditions and first-in-class drug discovery, may not capture the proper molecular variant. This is because variants of the same protein can express more than one phenotype, and a phenotype can be encoded by several variants.",
			"category": 2,
			"name": "Nussinov Ruth,2020"
		},
		{
			"PMID": 30588296,
			"title": "A comprehensive review of available omics data resources and molecular profiling for precision glioma studies.",
			"journal": "Biomedical reports",
			"authorList": [
				"Zhao Zheng",
				"Zhang Kenan",
				"Wang Zhiliang",
				"Wang Kuanyu",
				"Liu Xing",
				"Wu Fan",
				"Chen Jing"
			],
			"DOI": "10.3892/br.2018.1168",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "Gliomas are the most common and lethal type of primary malignant central nervous system tumors, with an extremely poor prognosis. The latest progression in the technological development of sequencing/microarray and bioinformatics has provided insights into the glioma genome. These technologies have generated large amounts of easily accessible biological omics data, providing an unprecedented opportunity to study glioma formation. According to the 2016 WHO organization classification of brain tumors, gliomas are currently diagnosed with respect to morphological and molecular tumor alterations, especially for isocitrate dehydrogenase and 1p/19q codeletions. In the present study, the comprehensive molecular profiling and available omics data resources for malignant gliomas were reviewed for novel insights into the biology and classification of these tumors. These molecular profiling resources may be useful for improving the understanding of malignant gliomas, and to accelerate the clinical, experimental and epidemiological studies that may lead to improvements in the lives of patients with glioma.",
			"category": 2,
			"name": "Zhao Zheng,2020"
		},
		{
			"PMID": 30588243,
			"title": "Decoding Somatic Driver Gene Mutations and Affected Signaling Pathways in Human Medulloblastoma Subgroups.",
			"journal": "Journal of Cancer",
			"authorList": [
				"Robbins Charles J",
				"Bou-Dargham Mayassa J",
				"Sanchez Kevin",
				"Rosen Matthew C",
				"Sang Qing-Xiang Amy"
			],
			"DOI": "10.7150/jca.27993",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "Medulloblastoma is the most common malignant pediatric brain tumor. Prior studies have concentrated their efforts studying the four molecular subgroups: SHH, Wnt, group 3, and group 4. SHH and Wnt are driven by their canonical pathways. Groups 3 and 4 are highly metastatic and associated with aberrations in epigenetic regulators. Recent developments in the field have revealed that these subgroups are not as homogenous as previously believed. The objective of this study is to investigate the involvement of somatic driver gene mutations in these medulloblastoma subgroups. We obtained medulloblastoma data from the Catalogue of Somatic Mutations in Cancer (COSMIC), which contains distinct samples that were not previously studied in a large cohort. We identified somatic driver gene mutations and the signaling pathways affected by these driver genes for medulloblastoma subgroups using bioinformatics tools. We have revealed novel infrequent drivers in these subgroups that contribute to our understanding of tumor heterogeneity in medulloblastoma. Normally SHH signaling is activated in the SHH subgroup, however, we determined gain-of-function mutations in ubiquitin ligase (",
			"category": 2,
			"name": "Robbins Charles J,2020"
		},
		{
			"PMID": 30577475,
			"title": "Recent Development of pH-Responsive Polymers for Cancer Nanomedicine.",
			"journal": "Molecules (Basel, Switzerland)",
			"authorList": [
				"Tang Houliang",
				"Zhao Weilong",
				"Yu Jinming",
				"Li Yang",
				"Zhao Chao"
			],
			"DOI": "10.3390/molecules24010004",
			"date": "2019-02-19",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer remains a leading cause of death worldwide with more than 10 million new cases every year. Tumor-targeted nanomedicines have shown substantial improvements of the therapeutic index of anticancer agents, addressing the deficiencies of conventional chemotherapy, and have had a tremendous growth over past several decades. Due to the pathophysiological characteristics that almost all tumor tissues have lower pH in comparison to normal healthy tissues, among various tumor-targeted nanomaterials, pH-responsive polymeric materials have been one of the most prevalent approaches for cancer diagnosis and treatment. In this review, we summarized the types of pH-responsive polymers, describing their chemical structures and pH-response mechanisms; we illustrated the structure-property relationships of pH-responsive polymers and introduced the approaches to regulating their pH-responsive behaviors; we also highlighted the most representative applications of pH-responsive polymers in cancer imaging and therapy. This review article aims to provide general guidelines for the rational design of more effective pH-responsive nanomaterials for cancer diagnosis and treatment.",
			"category": 2,
			"name": "Tang Houliang,2019"
		},
		{
			"PMID": 30563957,
			"title": "Histone Deacetylase Inhibitor-Induced Autophagy in Tumor Cells: Implications for p53.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Mrakovcic Maria",
				"Kleinheinz Johannes",
				"Fr\u00f6hlich Leopold F"
			],
			"DOI": "10.3390/ijms18091883",
			"date": "2019-03-18",
			"PMC": "",
			"citation": "",
			"abstract": "Autophagy is an essential process of the eukaryotic cell allowing degradation and recycling of dysfunctional cellular components in response to either physiological or pathological changes. Inhibition of autophagy in combination with chemotherapeutic treatment has emerged as a novel approach in cancer treatment leading to cell cycle arrest, differentiation, and apoptosis. Suberoyl hydroxamic acid (SAHA) is a broad-spectrum histone deacetylase inhibitor (HDACi) suppressing family members in multiple HDAC classes. Increasing evidence indicates that SAHA and other HDACi can, in addition to mitochondria-mediated apoptosis, also promote caspase-independent autophagy. SAHA-induced mTOR inactivation as a major regulator of autophagy activating the remaining autophagic core machinery is by far the most reported pathway in several tumor models. However, the question of which upstream mechanisms regulate SAHA-induced mTOR inactivation that consequently initiate autophagy has been mainly left unexplored. To elucidate this issue, we recently initiated a study clarifying different modes of SAHA-induced cell death in two human uterine sarcoma cell lines which led to the conclusion that the tumor suppressor protein p53 could act as a molecular switch between SAHA-triggered autophagic or apoptotic cell death. In this review, we present current research evidence about HDACi-mediated apoptotic and autophagic pathways, in particular with regard to p53 and its therapeutic implications.",
			"category": 2,
			"name": "Mrakovcic Maria,2019"
		},
		{
			"PMID": 30562346,
			"title": "Single-cell copy number variant detection reveals the dynamics and diversity of adaptation.",
			"journal": "PLoS biology",
			"authorList": [
				"Lauer Stephanie",
				"Avecilla Grace",
				"Spealman Pieter",
				"Sethia Gunjan",
				"Brandt Nathan",
				"Levy Sasha F",
				"Gresham David"
			],
			"DOI": "10.1371/journal.pbio.3000069",
			"date": "2019-06-17",
			"PMC": "",
			"citation": "",
			"abstract": "Copy number variants (CNVs) are a pervasive source of genetic variation and evolutionary potential, but the dynamics and diversity of CNVs within evolving populations remain unclear. Long-term evolution experiments in chemostats provide an ideal system for studying the molecular processes underlying CNV formation and the temporal dynamics with which they are generated, selected, and maintained. Here, we developed a fluorescent CNV reporter to detect de novo gene amplifications and deletions in individual cells. We used the CNV reporter in Saccharomyces cerevisiae to study CNV formation at the GAP1 locus, which encodes the general amino acid permease, in different nutrient-limited chemostat conditions. We find that under strong selection, GAP1 CNVs are repeatedly generated and selected during the early stages of adaptive evolution, resulting in predictable dynamics. Molecular characterization of CNV-containing lineages shows that the CNV reporter detects different classes of CNVs, including aneuploidies, nonreciprocal translocations, tandem duplications, and complex CNVs. Despite GAP1's proximity to repeat sequences that facilitate intrachromosomal recombination, breakpoint analysis revealed that short inverted repeat sequences mediate formation of at least 50% of GAP1 CNVs. Inverted repeat sequences are also found at breakpoints at the DUR3 locus, where CNVs are selected in urea-limited chemostats. Analysis of 28 CNV breakpoints indicates that inverted repeats are typically 8 nucleotides in length and separated by 40 bases. The features of these CNVs are consistent with origin-dependent inverted-repeat amplification (ODIRA), suggesting that replication-based mechanisms of CNV formation may be a common source of gene amplification. We combined the CNV reporter with barcode lineage tracking and found that 102-104 independent CNV-containing lineages initially compete within populations, resulting in extreme clonal interference. However, only a small number (18-21) of CNV lineages ever constitute more than 1% of the CNV subpopulation, and as selection progresses, the diversity of CNV lineages declines. Our study introduces a novel means of studying CNVs in heterogeneous cell populations and provides insight into their dynamics, diversity, and formation mechanisms in the context of adaptive evolution.",
			"category": 2,
			"name": "Lauer Stephanie,2019"
		},
		{
			"PMID": 30552234,
			"title": "Unraveling the Cellular Mechanism of Assembling Cholesterols for Selective Cancer Cell Death.",
			"journal": "Molecular cancer research : MCR",
			"authorList": [
				"Wang Huaimin",
				"Feng Zhaoqianqi",
				"Yang Cuihong",
				"Liu Jinjian",
				"Medina Jamie E",
				"Aghvami S Ali",
				"Dinulescu Daniela M",
				"Liu Jianfeng",
				"Fraden Seth",
				"Xu Bing"
			],
			"DOI": "10.1158/1541-7786.MCR-18-0931",
			"date": "2020-01-09",
			"PMC": "",
			"citation": "",
			"abstract": "Acquired drug resistance remains a challenge in chemotherapy. Here we show enzymatic, ",
			"category": 2,
			"name": "Wang Huaimin,2020"
		},
		{
			"PMID": 30545857,
			"title": "Comprehensive functional genomic resource and integrative model for the human brain.",
			"journal": "Science (New York, N.Y.)",
			"authorList": [
				"Wang Daifeng",
				"Liu Shuang",
				"Warrell Jonathan",
				"Won Hyejung",
				"Shi Xu",
				"Navarro Fabio C P",
				"Clarke Declan",
				"Gu Mengting",
				"Emani Prashant",
				"Yang Yucheng T",
				"Xu Min",
				"Gandal Michael J",
				"Lou Shaoke",
				"Zhang Jing",
				"Park Jonathan J",
				"Yan Chengfei",
				"Rhie Suhn Kyong",
				"Manakongtreecheep Kasidet",
				"Zhou Holly",
				"Nathan Aparna",
				"Peters Mette",
				"Mattei Eugenio",
				"Fitzgerald Dominic",
				"Brunetti Tonya",
				"Moore Jill",
				"Jiang Yan",
				"Girdhar Kiran",
				"Hoffman Gabriel E",
				"Kalayci Selim",
				"G\u00fcm\u00fc\u015f Zeynep H",
				"Crawford Gregory E",
				"PsychENCODE Consortium",
				"Roussos Panos",
				"Akbarian Schahram",
				"Jaffe Andrew E",
				"White Kevin P",
				"Weng Zhiping",
				"Sestan Nenad",
				"Geschwind Daniel H",
				"Knowles James A",
				"Gerstein Mark B"
			],
			"DOI": "10.1126/science.aat8464",
			"date": "2019-01-14",
			"PMC": "",
			"citation": "",
			"abstract": "Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource for the adult brain across 1866 individuals. The PsychENCODE resource contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles for many cell types; expression quantitative-trait loci (QTLs); and further QTLs associated with chromatin, splicing, and cell-type proportions. Integration shows that varying cell-type proportions largely account for the cross-population variation in expression (with >88% reconstruction accuracy). It also allows building of a gene regulatory network, linking genome-wide association study variants to genes (e.g., 321 for schizophrenia). We embed this network into an interpretable deep-learning model, which improves disease prediction by ~6-fold versus polygenic risk scores and identifies key genes and pathways in psychiatric disorders.",
			"category": 2,
			"name": "Wang Daifeng,2019"
		},
		{
			"PMID": 30522449,
			"title": "Different mutational characteristics of the subsets of EGFR-tyrosine kinase inhibitor sensitizing mutation-positive lung adenocarcinoma.",
			"journal": "BMC cancer",
			"authorList": [
				"Kim Eun Young",
				"Kim Arum",
				"Lee Gaeun",
				"Lee Hangsuck",
				"Chang Yoon Soo"
			],
			"DOI": "10.1186/s12885-018-5116-9",
			"date": "2019-03-25",
			"PMC": "",
			"citation": "",
			"abstract": "A subset of lung adenocarcinoma with EGFR-tyrosine kinase inhibitor sensitizing mutations (mEGFR) is common in non-smokers and women, suggesting that mutational stressors other than smoking are involved.",
			"category": 2,
			"name": "Kim Eun Young,2019"
		},
		{
			"PMID": 30519450,
			"title": "Breaking point: the genesis and impact of structural variation in tumours.",
			"journal": "F1000Research",
			"authorList": [
				"Ewing Ailith",
				"Semple Colin"
			],
			"DOI": "10.12688/f1000research.16079.1",
			"date": "2019-03-06",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic structural variants undoubtedly play important roles in driving tumourigenesis. This is evident despite the substantial technical challenges that remain in accurately detecting structural variants and their breakpoints in tumours and in spite of our incomplete understanding of the impact of structural variants on cellular function. Developments in these areas of research contribute to the ongoing discovery of structural variation with a clear impact on the evolution of the tumour and on the clinical importance to the patient. Recent large whole genome sequencing studies have reinforced our impression of each tumour as a unique combination of mutations but paradoxically have also discovered similar genome-wide patterns of single-nucleotide and structural variation between tumours. Statistical methods have been developed to deconvolute mutation patterns, or signatures, that recur across samples, providing information about the mutagens and repair processes that may be active in a given tumour. These signatures can guide treatment by, for example, highlighting vulnerabilities in a particular tumour to a particular chemotherapy. Thus, although the complete reconstruction of the full evolutionary trajectory of a tumour genome remains currently out of reach, valuable data are already emerging to improve the treatment of cancer.",
			"category": 2,
			"name": "Ewing Ailith,2019"
		},
		{
			"PMID": 30515675,
			"title": "Next-generation sequencing-based clinical sequencing: toward precision medicine in solid tumors.",
			"journal": "International journal of clinical oncology",
			"authorList": [
				"Wakai Toshifumi",
				"Prasoon Pankaj",
				"Hirose Yuki",
				"Shimada Yoshifumi",
				"Ichikawa Hiroshi",
				"Nagahashi Masayuki"
			],
			"DOI": "10.1007/s10147-018-1375-3",
			"date": "2019-03-13",
			"PMC": "",
			"citation": "",
			"abstract": "Numerous technical and functional advances in next-generation sequencing (NGS) have led to the adoption of this technique in conventional clinical practice. Recently, large-scale genomic research and NGS technological innovation have revealed many more details of somatic and germline mutations in solid tumors. This development is allowing for the classification of tumor type sub-categories based on genetic alterations in solid tumors, and based on this information, new drugs and targeted therapies are being administered to patients. This has largely been facilitated by gene panel testing, which allows for a better understanding of the genetic basis for an individual's response to therapy. NGS-based comprehensive gene panel testing is a clinically useful approach to investigate genomic mechanisms, including therapy-related signaling pathways, microsatellite instability, hypermutated phenotypes, and tumor mutation burden. In this review, we describe the concept of precision medicine in solid tumors using NGS-based comprehensive gene panel testing, as well as the importance of quality control of tissue sample handling in routine NGS-based genomic testing, and we discuss issues for the future adoption of this technique in Japan.",
			"category": 2,
			"name": "Wakai Toshifumi,2019"
		},
		{
			"PMID": 30514790,
			"title": "Clinical outcomes after whole-genome sequencing in patients with metastatic non-small-cell lung cancer.",
			"journal": "Cold Spring Harbor molecular case studies",
			"authorList": [
				"Tsang Erica S",
				"Shen Yaoqing",
				"Chooback Negar",
				"Ho Cheryl",
				"Jones Martin",
				"Renouf Daniel J",
				"Lim Howard",
				"Sun Sophie",
				"Yip Stephen",
				"Pleasance Erin",
				"Ionescu Diana N",
				"Mungall Karen",
				"Kasaian Katayoon",
				"Ma Yussanne",
				"Zhao Yongjun",
				"Mungall Andrew",
				"Moore Richard",
				"Jones Steven J M",
				"Marra Marco",
				"Laskin Janessa"
			],
			"DOI": "10.1101/mcs.a002659",
			"date": "2020-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "The Personalized Onco-Genomics (POG) program at BC Cancer integrates whole-genome (DNA) and RNA sequencing into practice for metastatic malignancies. We examined the subgroup of patients with metastatic non-small-cell lung cancer (NSCLC) and report the prevalence of actionable targets, treatments, and outcomes. We identified patients who were enrolled in the POG program between 2012 and 2016 who had a tumor biopsy and blood samples with comprehensive DNA (80\u00d7, 40\u00d7 normal) and RNA sequencing followed by in-depth bioinformatics to identify potential cancer drivers and actionable targets. In NSCLC cases, we compared the progression-free survival (PFS) of \"POG-informed therapies\" with the PFS of the last regimen prior to POG (PFS ratio). In 29 NSCLC cases, 11 were male (38%), the median age was 60.2 yr (range: 39.4-72.6), and histologies included were adenocarcinoma (93%) and squamous cell carcinoma (7%). Potential molecular targets (i.e., cancer drivers including ",
			"category": 2,
			"name": "Tsang Erica S,2020"
		},
		{
			"PMID": 30505711,
			"title": "Measuring tumor mutation burden in non-small cell lung cancer: tissue versus liquid biopsy.",
			"journal": "Translational lung cancer research",
			"authorList": [
				"Fenizia Francesca",
				"Pasquale Raffaella",
				"Roma Cristin",
				"Bergantino Francesca",
				"Iannaccone Alessia",
				"Normanno Nicola"
			],
			"DOI": "10.21037/tlcr.2018.09.23",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "The introduction in the clinic of immune checkpoint inhibitors (IOs) has represented an important improvement for the treatment of patients with advanced non-small cell lung cancer (NSCLC). These drugs have shown a higher activity as compared with chemotherapy in both first- and second-line of treatment, with some patients experiencing a long-lasting response. More recently, combinations of IOs have entered clinical trials in different tumor types including NSCLC. Nevertheless, IOs are active only in a subgroup of patients and biomarkers for appropriate patients' selection are urgently needed to offer the patients an effective therapy, and also to manage the costs. Tumor mutation burden (TMB) has powerfully emerged as a potential biomarker for immunotherapy and might enter the clinic in the next months, although different challenges are still unsolved. Different methods exist to evaluate TMB in tissue, ranging from whole exome sequencing (WES) to targeted sequencing of smaller sets of genes, which need to be fully standardized to ensure that patients receive an appropriate TMB test with clear clinical interpretation. In addition, as already happened for the implementation of liquid biopsy testing from NSCLC patients to identify targetable alterations, researchers are also evaluating the possibility to calculate TMB in blood, to further enlarge the number of NSCLC patients who may benefit from immunotherapy. Preliminary data highlight the difficulty to develop targeted sequencing panels for the assessment of TMB starting from the circulating cell free DNA (cfDNA). The applicability of TMB testing on liquid biopsy needs further investigation and may be clarified within the ongoing clinical trials.",
			"category": 2,
			"name": "Fenizia Francesca,2020"
		},
		{
			"PMID": 30505709,
			"title": "Clinical utility of tumor mutational burden in patients with non-small cell lung cancer treated with immunotherapy.",
			"journal": "Translational lung cancer research",
			"authorList": [
				"Hendriks Lizza E",
				"Rouleau Etienne",
				"Besse Benjamin"
			],
			"DOI": "10.21037/tlcr.2018.09.22",
			"date": "2023-10-04",
			"PMC": "",
			"citation": "",
			"abstract": "Anti-programmed death (ligand)-1 [anti-PD-(L)1] therapies such as pembrolizumab, nivolumab or atezolizumab have become standard of care for non-small cell lung cancer (NSCLC) patients either in first line or beyond. PD-L1 expression level allows enriching the treated population with responders, but it is still not an optimal biomarker. Even in patients with PD-L1 tumor proportion score (TPS) levels of \u226550% treated with first line pembrolizumab overall response rate (ORR) is only 44.8% and overall survival at one year is 70%. Moreover, in combination trials with chemotherapy and anti-PD-(L)1 therapy, a significant proportion of patients does not respond (ORR ranges from 45.3% to 64.0%), regardless of PD-L1 expression. Furthermore, PD-L1 expression level is not associated with improved benefit in patients treated with combinations of anti-PD-(L)1 and anti-cytotoxic T-lymphocyte-associated antigen (anti-CTLA4) therapy. One of the new promising biomarkers is tumor mutational burden (TMB). It has been discovered that especially tumor types with a known high mutation rate such as NSCLC and melanoma respond best to immune checkpoint inhibitors (ICIs). An explanation is that this high mutation rate makes it more likely that neoantigens arise that are targeted by activated immune cells, but it is not feasible to determine neoantigen load in daily practice. However, TMB of a certain tumor type is associated with neoantigen load and outcome on ICIs. In this comprehensive review, we discuss the TMB analysis methods, the rationale to use TMB as a predictive biomarker and the clinical utility of TMB in NSCLC patients treated with ICIs.",
			"category": 2,
			"name": "Hendriks Lizza E,2023"
		},
		{
			"PMID": 30485801,
			"title": "Somatic Mutations Reveal Lineage Relationships and Age-Related Mutagenesis in Human Hematopoiesis.",
			"journal": "Cell reports",
			"authorList": [
				"Osorio Fernando G",
				"Rosendahl Huber Axel",
				"Oka Rurika",
				"Verheul Mark",
				"Patel Sachin H",
				"Hasaart Karlijn",
				"de la Fonteijne Lisanne",
				"Varela Ignacio",
				"Camargo Fernando D",
				"van Boxtel Ruben"
			],
			"DOI": "10.1016/j.celrep.2018.11.014",
			"date": "2019-12-11",
			"PMC": "",
			"citation": "",
			"abstract": "Mutation accumulation during life can contribute to hematopoietic dysfunction; however, the underlying dynamics are unknown. Somatic mutations in blood progenitors can provide insight into the rate and processes underlying this accumulation, as well as the developmental lineage tree and stem cell division numbers. Here, we catalog mutations in the genomes of human-bone-marrow-derived and umbilical-cord-blood-derived hematopoietic stem and progenitor cells (HSPCs). We find that mutations accumulate gradually during life with approximately 14 base substitutions per year. The majority of mutations were acquired after birth and could be explained by the constant activity of various endogenous mutagenic processes, which also explains the mutation load in acute myeloid leukemia (AML). Using these mutations, we construct a developmental lineage tree of human hematopoiesis, revealing a polyclonal architecture and providing evidence that developmental clones exhibit multipotency. Our approach highlights features of human native hematopoiesis and its implications for leukemogenesis.",
			"category": 2,
			"name": "Osorio Fernando G,2019"
		},
		{
			"PMID": 30440635,
			"title": "Micro-Inversions In Human Cancer Genomes.",
			"journal": "Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference",
			"authorList": [
				"Qu Li",
				"Zhu Huaiqiu",
				"Wang May"
			],
			"DOI": "10.1109/EMBC.2018.8512514",
			"date": "2019-10-24",
			"PMC": "",
			"citation": "",
			"abstract": "During the past few years, although scientists and researchers have studied variations in the cancer genomes, our current knowledge about the function of Micro-inversions (MIs) in cancer are still limited. MIs are generally defined as small inversions in DNA segments shorter than 100 bp. To expand our knowledge of their roles in cancer, we analyzed the MIs of 209 samples from four types of cancer, including hepatocellular carcinoma, lung cancer, pancreatic cancer, and bladder cancer. Within all the 209 samples, we identified 2,925 MIs, of which 1,519 (51.93%) are in gene regions. Of the 1,519 MIs in the gene regions, 106 (6.98%) are in the exon regions. We also analyzed 209 healthy samples as the control samples. We further analyzed the distribution of MIs in the four types of cancer among 24 chromosomes. Besides the chromosome preference, different cancers also have different preference for various genes. The MIs preference for different genes among four types of cancer may provide a guidance for the treatment and diagnosis on the four types of cancer. Medical doctors should concentrate more on chromosomes and the genes that MIs prefer to locate on. We also calculated the average count of MIs per individual among each cancer. From this result, we found that the bladder cancer has the most average count of MIs per individual, which means MIs may be more likely to exist in bladder cancer. According to our analysis, MIs play an important role in cancer and should be considered for further analysis.",
			"category": 2,
			"name": "Qu Li,2019"
		},
		{
			"PMID": 30420667,
			"title": "Challenges in the introduction of next-generation sequencing (NGS) for diagnostics of myeloid malignancies into clinical routine use.",
			"journal": "Blood cancer journal",
			"authorList": [
				"Bacher Ulrike",
				"Shumilov Evgenii",
				"Flach Johanna",
				"Porret Naomi",
				"Joncourt Raphael",
				"Wiedemann Gertrud",
				"Fiedler Martin",
				"Novak Urban",
				"Amstutz Ursula",
				"Pabst Thomas"
			],
			"DOI": "10.1038/s41408-018-0148-6",
			"date": "2019-05-01",
			"PMC": "",
			"citation": "",
			"abstract": "Given the vast phenotypic and genetic heterogeneity of acute and chronic myeloid malignancies, hematologists have eagerly awaited the introduction of next-generation sequencing (NGS) into the routine diagnostic armamentarium to enable a more differentiated disease classification, risk stratification, and improved therapeutic decisions. At present, an increasing number of hematologic laboratories are in the process of integrating NGS procedures into the diagnostic algorithms of patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs). Inevitably accompanying such developments, physicians and molecular biologists are facing unexpected challenges regarding the interpretation and implementation of molecular genetic results derived from NGS in myeloid malignancies. This article summarizes typical challenges that may arise in the context of NGS-based analyses at diagnosis and during follow-up of myeloid malignancies.",
			"category": 2,
			"name": "Bacher Ulrike,2019"
		},
		{
			"PMID": 30412573,
			"title": "Analysis of 7,815 cancer exomes reveals associations between mutational processes and somatic driver mutations.",
			"journal": "PLoS genetics",
			"authorList": [
				"Poulos Rebecca C",
				"Wong Yuen T",
				"Ryan Regina",
				"Pang Herbert",
				"Wong Jason W H"
			],
			"DOI": "10.1371/journal.pgen.1007779",
			"date": "2019-02-26",
			"PMC": "",
			"citation": "",
			"abstract": "Driver mutations are the genetic variants responsible for oncogenesis, but how specific somatic mutational events arise in cells remains poorly understood. Mutational signatures derive from the frequency of mutated trinucleotides in a given cancer sample, and they provide an avenue for investigating the underlying mutational processes that operate in cancer. Here we analyse somatic mutations from 7,815 cancer exomes from The Cancer Genome Atlas (TCGA) across 26 cancer types. We curate a list of 50 known cancer driver mutations by analysing recurrence in our cohort and annotations of known cancer-associated genes from the Cancer Gene Census, IntOGen database and Cancer Genome Interpreter. We then use these datasets to perform binary univariate logistic regression and establish the statistical relationship between individual driver mutations and known mutational signatures across different cancer types. Our analysis led to the identification of 39 significant associations between driver mutations and mutational signatures (P < 0.004, with a false discovery rate of < 5%). We first validate our methodology by establishing statistical links for known and novel associations between driver mutations and the mutational signature arising from Polymerase Epsilon proofreading deficiency. We then examine associations between driver mutations and mutational signatures for AID/APOBEC enzyme activity and deficient mismatch repair. We also identify negative associations (odds ratio < 1) between mutational signatures and driver mutations, and here we examine the role of aging and cigarette smoke mutagenesis in the generation of driver mutations in IDH1 and KRAS in brain cancers and lung adenocarcinomas respectively. Our study provides statistical foundations for hypothesised links between otherwise independent biological processes and we uncover previously unexplored relationships between driver mutations and mutagenic processes during cancer development. These associations give insights into how cancers acquire advantageous mutations and can provide direction to guide further mechanistic studies into cancer pathogenesis.",
			"category": 2,
			"name": "Poulos Rebecca C,2019"
		},
		{
			"PMID": 30410595,
			"title": "Identifying a Novel Biomarker ",
			"journal": "Journal of Cancer",
			"authorList": [
				"Xiong Yaoyi",
				"Yuan Lushun",
				"Chen Liang",
				"Zhu Yuan",
				"Zhang Shanshan",
				"Liu Xuefeng",
				"Xiao Yu",
				"Wang Xinghuan"
			],
			"DOI": "10.7150/jca.25900",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "Although it is well known that smoking is one of pathogenesis of clear cell renal cell carcinoma (ccRCC), the underlying molecular mechanism is still unclear. In our study, the microarray dataset GSE46699 is analyzed by weighted gene co-expression network analysis (WGCNA). Then we identify 15 co-expressed gene modules in which the lightcyan module (R",
			"category": 2,
			"name": "Xiong Yaoyi,2020"
		},
		{
			"PMID": 30375428,
			"title": "A novel somatic mutation of SIN3A detected in breast cancer by whole-exome sequencing enhances cell proliferation through ER\u03b1 expression.",
			"journal": "Scientific reports",
			"authorList": [
				"Watanabe Kenji",
				"Yamamoto Shigeru",
				"Sakaguti Syuiti",
				"Isayama Keishiro",
				"Oka Masaaki",
				"Nagano Hiroaki",
				"Mizukami Yoichi"
			],
			"DOI": "10.1038/s41598-018-34290-1",
			"date": "2019-10-24",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer is the most frequent tumor in women, and in nearly two-thirds of cases, the tumors express estrogen receptor \u03b1 (ER\u03b1, encoded by ESR1). Here, we performed whole-exome sequencing of 16 breast cancer tissues classified according to ESR1 expression and 12 samples of whole blood, and detected 310 somatic mutations in cancer tissues with high levels of ESR1 expression. Of the somatic mutations validated by a different deep sequencer, a novel nonsense somatic mutation, c.2830\u2009C>T; p.Gln944*, in transcriptional regulator switch-independent 3 family member A (SIN3A) was detected in breast cancer of a patient. Part of the mutant protein localized in the cytoplasm in contrast to the nuclear localization of ER\u03b1, and induced a significant increase in ESR1 mRNA. The SIN3A mutation obviously enhanced MCF7 cell proliferation. In tissue sections from the breast cancer patient with the SIN3A c.2830\u2009C>T mutation, cytoplasmic SIN3A localization was detected within the tumor regions where nuclear enlargement was observed. The reduction in SIN3A mRNA correlates with the recurrence of ER-positive breast cancers on Kaplan-Meier plots. These observations reveal that the SIN3A mutation has lost its transcriptional repression function due to its cytoplasmic localization, and that this repression may contribute to the progression of breast cancer.",
			"category": 2,
			"name": "Watanabe Kenji,2019"
		},
		{
			"PMID": 30337457,
			"title": "Somatic mutant clones colonize the human esophagus with age.",
			"journal": "Science (New York, N.Y.)",
			"authorList": [
				"Martincorena I\u00f1igo",
				"Fowler Joanna C",
				"Wabik Agnieszka",
				"Lawson Andrew R J",
				"Abascal Federico",
				"Hall Michael W J",
				"Cagan Alex",
				"Murai Kasumi",
				"Mahbubani Krishnaa",
				"Stratton Michael R",
				"Fitzgerald Rebecca C",
				"Handford Penny A",
				"Campbell Peter J",
				"Saeb-Parsy Kourosh",
				"Jones Philip H"
			],
			"DOI": "10.1126/science.aau3879",
			"date": "2019-04-08",
			"PMC": "",
			"citation": "",
			"abstract": "The extent to which cells in normal tissues accumulate mutations throughout life is poorly understood. Some mutant cells expand into clones that can be detected by genome sequencing. We mapped mutant clones in normal esophageal epithelium from nine donors (age range, 20 to 75 years). Somatic mutations accumulated with age and were caused mainly by intrinsic mutational processes. We found strong positive selection of clones carrying mutations in 14 cancer genes, with tens to hundreds of clones per square centimeter. In middle-aged and elderly donors, clones with cancer-associated mutations covered much of the epithelium, with ",
			"category": 2,
			"name": "Martincorena I\u00f1igo,2019"
		},
		{
			"PMID": 30295189,
			"title": "EZH2 RIP-seq Identifies Tissue-specific Long Non-coding RNAs.",
			"journal": "Current gene therapy",
			"authorList": [
				"Wang Yan",
				"Xie Yinping",
				"Li Lili",
				"He Yuan",
				"Zheng Di",
				"Yu Pengcheng",
				"Yu Ling",
				"Tang Lixu",
				"Wang Yibin",
				"Wang Zhihua"
			],
			"DOI": "10.2174/1566523218666181008125010",
			"date": "2019-10-09",
			"PMC": "",
			"citation": "",
			"abstract": "Polycomb Repressive Complex 2 (PRC2) catalyzes histone methylation at H3 Lys27, and plays crucial roles during development and diseases in numerous systems. Its catalytic subunit EZH2 represents a key nuclear target for long non-coding RNAs (lncRNAs) that emerging to be a novel class of epigenetic regulator and participate in diverse cellular processes. LncRNAs are characterized by high tissue-specificity; however, little is known about the tissue profile of the EZH2- interacting lncRNAs.",
			"category": 2,
			"name": "Wang Yan,2019"
		},
		{
			"PMID": 30289602,
			"title": "Using microarray-based subtyping methods for breast cancer in the era of high-throughput RNA sequencing.",
			"journal": "Molecular oncology",
			"authorList": [
				"Pedersen Christina Bligaard",
				"Nielsen Finn Cilius",
				"Rossing Maria",
				"Olsen Lars R\u00f8nn"
			],
			"DOI": "10.1002/1878-0261.12389",
			"date": "2019-08-23",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer is a highly heterogeneous disease that can be classified into multiple subtypes based on the tumor transcriptome. Most of the subtyping schemes used in clinics today are derived from analyses of microarray data from thousands of different tumors together with clinical data for the patients from which the tumors were isolated. However, RNA sequencing (RNA-Seq) is gradually replacing microarrays as the preferred transcriptomics platform, and although transcript abundances measured by the two different technologies are largely compatible, subtyping methods developed for probe-based microarray data are incompatible with RNA-Seq as input data. Here, we present an RNA-Seq data processing pipeline, which relies on the mapping of sequencing reads to the probe set target sequences instead of the human reference genome, thereby enabling probe-based subtyping of breast cancer tumor tissue using sequencing-based transcriptomics. By analyzing 66 breast cancer tumors for which gene expression was measured using both microarrays and RNA-Seq, we show that RNA-Seq data can be directly compared to microarray data using our pipeline. Additionally, we demonstrate that the established subtyping method CITBCMST (Guedj et\u00a0al., ), which relies on a 375 probe set-signature to classify samples into the six subtypes basL, lumA, lumB, lumC, mApo, and normL, can be applied without further modifications. This pipeline enables a seamless transition to sequencing-based transcriptomics for future clinical purposes.",
			"category": 2,
			"name": "Pedersen Christina Bligaard,2019"
		},
		{
			"PMID": 30288353,
			"title": "MUC16 mutations improve patients' prognosis by enhancing the infiltration and antitumor immunity of cytotoxic T lymphocytes in the endometrial cancer microenvironment.",
			"journal": "Oncoimmunology",
			"authorList": [
				"Hu Jing",
				"Sun Jing"
			],
			"DOI": "10.1080/2162402X.2018.1487914",
			"date": "2024-04-02",
			"PMC": "",
			"citation": "",
			"abstract": "The incidence and mortality rates of endometrial cancer are increasing during recent years. CA125 (gene symbol MUC16) is a well-known diagnostic and prognostic serum marker of endometrial cancer. High serum CA125 level is associated with poor prognosis. MUC16 is one of the most frequently mutated genes in endometrial cancer. However, the potential relationship and underlying mechanism between MUC16 mutations and endometrial cancer patients' prognosis and disease progression remain unclear. In present study, we analyzed the whole exome sequencing data, RNA sequencing data and patients' clinical information in TCGA database and demonstrated that MUC16 mutational status was an independent prognostic factor for endometrial cancer patients. Patients with somatic MUC16 mutations had a prolonged overall survival time. MUC16 mutations promoted patients' antitumor immune responses. Cytotoxic immune cells mediated pathways were enriched in endometrial cancer samples with MUC16 mutations. Elevation of two pathways, NO2-dependent IL 12 pathway in NK cells and T cytotoxic cell surface molecules, significantly correlated with a higher rate of MUC16 mutations and a significantly favorable patients' prognosis. An increased level of cytotoxic T lymphocytes, not NK cells, infiltration was observed in the tumor microenvironment of patients with MUC16 mutations. High expression of molecular markers of T cells and CD8",
			"category": 2,
			"name": "Hu Jing,2024"
		},
		{
			"PMID": 30250803,
			"title": "MaxMIF: A New Method for Identifying Cancer Driver Genes through Effective Data Integration.",
			"journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)",
			"authorList": [
				"Hou Yingnan",
				"Gao Bo",
				"Li Guojun",
				"Su Zhengchang"
			],
			"DOI": "10.1002/advs.201800640",
			"date": "2023-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Identification of a few cancer driver mutation genes from a much larger number of passenger mutation genes in cancer samples remains a highly challenging task. Here, a novel method for distinguishing the driver genes from the passenger genes by effective integration of somatic mutation data and molecular interaction data using a maximal mutational impact function (MaxMIF) is presented. When evaluated on six somatic mutation datasets of Pan-Cancer and 19 datasets of different cancer types from TCGA, MaxMIF almost always significantly outperforms all the existing state-of-the-art methods in terms of predictive accuracy, sensitivity, and specificity. It recovers about 30% more known cancer genes in 500 top-ranked candidate genes than the best among the other tools evaluated. MaxMIF is also highly robust to data perturbation. Intriguingly, MaxMIF is able to identify potential cancer driver genes, with strong experimental data support. Therefore, MaxMIF can be very useful for identifying or prioritizing cancer driver genes in the increasing number of available cancer genomic data.",
			"category": 2,
			"name": "Hou Yingnan,2023"
		},
		{
			"PMID": 30238071,
			"title": "SMART Cancer Navigator: A Framework for Implementing ASCO Workshop Recommendations to Enable Precision Cancer Medicine.",
			"journal": "JCO precision oncology",
			"authorList": [
				"Warner Jeremy L",
				"Prasad Ishaan",
				"Bennett Makiah",
				"Arniella Monica",
				"Beeghly-Fadiel Alicia",
				"Mandl Kenneth D",
				"Alterovitz Gil"
			],
			"DOI": "10.1200/PO.17.00292",
			"date": "2022-03-21",
			"PMC": "",
			"citation": "",
			"abstract": "Data standards and interoperability are critical for improving care for patients with cancer. Recent efforts by ASCO include the Data Standards and Interoperability Summit in 2016, which led to the Omics and Precision Oncology and Advancing Interoperability workshops. To facilitate improved patient care, several recommendations for data sharing and standardization were made to the community.",
			"category": 2,
			"name": "Warner Jeremy L,2022"
		},
		{
			"PMID": 30228934,
			"title": "Losses of cytokines and chemokines are common genetic features of human cancers: the somatic copy number alterations are correlated with patient prognoses and therapeutic resistance.",
			"journal": "Oncoimmunology",
			"authorList": [
				"Wong Henry Sung-Ching",
				"Chang Wei-Chiao"
			],
			"DOI": "10.1080/2162402X.2018.1468951",
			"date": "2021-01-12",
			"PMC": "",
			"citation": "",
			"abstract": "Intricate relationships among cytokines (including chemokines) shape the tumor microenvironment (TME) and reflect cell-cell interactions between malignant cells and other cells from the TME. Although our previous study indicated the transcriptional landscape of cytokines in 19 cancer types, the global pattern somatic copy number (SCN) alterations and the clinical relevance of cytokines have not been systematically investigated. Here, we reported a significant negative selection on cytokine genes. We also linked the SCN losses of cytokine genes to the abundance of immune infiltrates which affects cancer progression and patient prognoses. We also demonstrated and validated the correlations between SCN alterations of cytokine-containing loci and drug sensitivity. The results indicated the genomic loss of cytokines in malignant cells as a crucial theme for interrogating cancer progression, malignant cell-TME interactions, and therapeutics.",
			"category": 2,
			"name": "Wong Henry Sung-Ching,2021"
		},
		{
			"PMID": 30217017,
			"title": "Targeted Genomic Screen Reveals Focal Long Non-Coding RNA Copy Number Alterations in Cancer Cell Lines.",
			"journal": "Non-coding RNA",
			"authorList": [
				"Volders Pieter-Jan",
				"Lefever Steve",
				"Baute Shalina",
				"Nuytens Justine",
				"Vanderheyden Katrien",
				"Menten Bj\u00f6rn",
				"Mestdagh Pieter",
				"Vandesompele Jo"
			],
			"DOI": "10.3390/ncrna4030021",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "The landscape of somatic copy-number alterations (SCNAs) affecting long non-coding RNAs (lncRNAs) in human cancers remains largely unexplored. While the majority of lncRNAs remain to be functionally characterized, several have been implicated in cancer development and metastasis. Considering the plethora of lncRNAs genes that have been currently reported, it is conceivable that many more lncRNAs might function as oncogenes or tumor suppressor genes. We devised a strategy to detect focal lncRNA SCNAs using a custom DNA microarray platform probing 10,519 lncRNA genes. By screening a panel of 80 cancer cell lines, we detected numerous focal aberrations targeting one or multiple lncRNAs without affecting neighboring protein-coding genes. These focal aberrations are highly suggestive for a tumor suppressive or oncogenic role of the targeted lncRNA gene. Although functional validation remains an essential step in the further characterization of the involved candidate cancer lncRNAs, our results provide a direct way of prioritizing candidate lncRNAs that are involved in cancer pathogenesis.",
			"category": 2,
			"name": "Volders Pieter-Jan,2020"
		},
		{
			"PMID": 30212483,
			"title": "Prevalence and spectrum of AKT1, PIK3CA, PTEN and TP53 somatic mutations in Chinese breast cancer patients.",
			"journal": "PloS one",
			"authorList": [
				"Li Guoli",
				"Guo Xinwu",
				"Chen Ming",
				"Tang Lili",
				"Jiang Hui",
				"Day Julia X",
				"Xie Yueliang",
				"Peng Limin",
				"Xu Xunxun",
				"Li Jinliang",
				"Wang Shouman",
				"Xiao Zhi",
				"Dai Lizhong",
				"Wang Jun"
			],
			"DOI": "10.1371/journal.pone.0203495",
			"date": "2019-02-19",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer, one of the most frequently occurring cancers worldwide, is the leading cause of cancer-related death among women. AKT1, PIK3CA, PTEN and TP53 mutations were common observed in breast cancer representing potential clinical biomarkers for cancer classification and treatment. A comprehensive knowledge of AKT1, PIK3CA, PTEN and TP53 mutations in breast cancer was still insufficient in Chinese population. In this study, the complete coding regions and exon-intron boundaries of AKT1, PIK3CA, PTEN and TP53 genes were sequenced in paired breast tumor and normal tissues from 313 Chinese breast cancer patients using microfluidic PCR-based target enrichment and next-generation sequencing technology. Total 120 somatic mutations were identified in 190 of the 313 patients (60.7%), with the mutation frequency of AKT1 as 3.2%, PIK3CA as 36.4%, PTEN as 4.8%, and TP53 as 33.9%. Among these mutations, 1 in PIK3CA (p.I69N), 3 in PTEN (p.K62X, c.635-12_636delTTAACCATGCAGAT and p.N340IfsTer4) and 5 in TP53 (p.Q136AfsTer5, p.K139_P142del, p.Y234dup, p.V274LfsTer31 and p.N310TfsTer35) were novel. Notably, PIK3CA somatic mutations were significantly associated with ER-positive or PR-positive tumors. TP53 somatic mutations were significantly associated with ER-negative, PR-negative, HER2-positive, BRCA1 mutation, Ki67 high expression and basal-like tumors. Our findings provided a comprehensive mutation profiling of AKT1, PIK3CA, PTEN and TP53 genes in Chinese breast cancer patients, which have potential implications in clinical management.",
			"category": 2,
			"name": "Li Guoli,2019"
		},
		{
			"PMID": 30197175,
			"title": "Cancer-Associated PIK3CA Mutations in Overgrowth Disorders.",
			"journal": "Trends in molecular medicine",
			"authorList": [
				"Madsen Ralitsa R",
				"Vanhaesebroeck Bart",
				"Semple Robert K"
			],
			"DOI": "10.1016/j.molmed.2018.08.003",
			"date": "2019-04-25",
			"PMC": "",
			"citation": "",
			"abstract": "PIK3CA is one of the most commonly mutated genes in solid cancers. PIK3CA mutations are also found in benign overgrowth syndromes, collectively known as PIK3CA-related overgrowth spectrum (PROS). As in cancer, PIK3CA mutations in PROS arise postzygotically, but unlike in cancer, these mutations arise during embryonic development, with their timing and location critically influencing the resulting disease phenotype. Recent evidence indicates that phosphoinositide 3-kinase (PI3K) pathway inhibitors undergoing trials in cancer can provide a therapy for PROS. Conversely, PROS highlights gaps in our understanding of PI3K's role during embryogenesis and in cancer development. Here, we summarize current knowledge of PROS, evaluate challenges and strategies for disease modeling, and consider the implications of PROS as a paradigm for understanding activating PIK3CA mutations in human development and cancer.",
			"category": 2,
			"name": "Madsen Ralitsa R,2019"
		},
		{
			"PMID": 30190968,
			"title": "The biological and clinical challenge of liver cancer heterogeneity.",
			"journal": "Hepatic oncology",
			"authorList": [
				"Wang Xin Wei",
				"Thorgeirsson Snorri S"
			],
			"DOI": "10.2217/hep.14.18",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Wang Xin Wei,2020"
		},
		{
			"PMID": 30152517,
			"title": "PARP inhibitors synergize with gemcitabine by potentiating DNA damage in non-small-cell lung cancer.",
			"journal": "International journal of cancer",
			"authorList": [
				"Jiang Yu",
				"Dai Hui",
				"Li Yang",
				"Yin Jun",
				"Guo Shuliang",
				"Lin Shiaw-Yih",
				"McGrail Daniel J"
			],
			"DOI": "10.1002/ijc.31770",
			"date": "2019-05-03",
			"PMC": "",
			"citation": "",
			"abstract": "Poly (ADP-ribose) polymerase (PARP) inhibitors have demonstrated great promise in the treatment of patients with deficiencies in homologous recombination (HR) DNA repair, such as those with loss of BRCA1 or BRCA2 function. However, emerging studies suggest that PARP inhibition can also target HR-competent cancers, such as non-small-cell lung cancer (NSCLC), and that the therapeutic effect of PARP inhibition may be improved by combination with chemotherapy agents. In our study, it was found that PARP inhibitors talazoparib (BMN-673) and olaparib (AZD-2281) both had synergistic activity with the common first-line chemotherapeutic gemcitabine in a panel of lung cancer cell lines. Furthermore, the combination demonstrated significant in vivo antitumor activity in an H23 xenograft model of NSCLC compared to either agent as monotherapy. This synergism occurred without loss of HR repair efficiency. Instead, the combination induced synergistic single-strand DNA breaks, leading to accumulation of toxic double-strand DNA lesions in vitro and in vivo. Our study elucidates the underlying mechanisms of synergistic activity of PARP inhibitors and gemcitabine, providing a strong motivation to pursue this combination as an improved therapeutic regimen.",
			"category": 2,
			"name": "Jiang Yu,2019"
		},
		{
			"PMID": 30148624,
			"title": "Redox Signaling by Reactive Electrophiles and Oxidants.",
			"journal": "Chemical reviews",
			"authorList": [
				"Parvez Saba",
				"Long Marcus J C",
				"Poganik Jesse R",
				"Aye Yimon"
			],
			"DOI": "10.1021/acs.chemrev.7b00698",
			"date": "2019-08-07",
			"PMC": "",
			"citation": "",
			"abstract": "The concept of cell signaling in the context of nonenzyme-assisted protein modifications by reactive electrophilic and oxidative species, broadly known as redox signaling, is a uniquely complex topic that has been approached from numerous different and multidisciplinary angles. Our Review reflects on five aspects critical for understanding how nature harnesses these noncanonical post-translational modifications to coordinate distinct cellular activities: (1) specific players and their generation, (2) physicochemical properties, (3) mechanisms of action, (4) methods of interrogation, and (5) functional roles in health and disease. Emphasis is primarily placed on the latest progress in the field, but several aspects of classical work likely forgotten/lost are also recollected. For researchers with interests in getting into the field, our Review is anticipated to function as a primer. For the expert, we aim to stimulate thought and discussion about fundamentals of redox signaling mechanisms and nuances of specificity/selectivity and timing in this sophisticated yet fascinating arena at the crossroads of chemistry and biology.",
			"category": 2,
			"name": "Parvez Saba,2019"
		},
		{
			"PMID": 30128050,
			"title": "Personalized cancer neoantigen vaccines come of age.",
			"journal": "Theranostics",
			"authorList": [
				"Chu Yanhong",
				"Liu Qin",
				"Wei Jia",
				"Liu Baorui"
			],
			"DOI": "10.7150/thno.24387",
			"date": "2019-09-04",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer vaccines have encountered their ideal personalized partner along with evidence for great breakthroughs in the identification and synthesis of neoantigens. Individual cancer neoantigen vaccines are capable of eliciting robust T-cell responses and have been demonstrated to achieve striking clinical efficacy due to their high immunogenicity and central thymic tolerance escape of neoantigens. Two recent phase I clinical trials have provided support for the hypothesis and have heralded a nascent era of personalized vaccines in the field of immunotherapy. This review aims to address the identification of neoepitopes and describes advances made in personalized vaccines. In addition, this review discusses the challenges related to the exploitation of vaccine therapy, and provides potential thoughts for the improvement of vaccine design and applications.",
			"category": 2,
			"name": "Chu Yanhong,2019"
		},
		{
			"PMID": 30089796,
			"title": "Patterns and mechanisms of structural variations in human cancer.",
			"journal": "Experimental & molecular medicine",
			"authorList": [
				"Yi Kijong",
				"Ju Young Seok"
			],
			"DOI": "10.1038/s12276-018-0112-3",
			"date": "2019-05-17",
			"PMC": "",
			"citation": "",
			"abstract": "Next-generation sequencing technology has enabled the comprehensive detection of genomic alterations in human somatic cells, including point mutations, chromosomal rearrangements, and structural variations (SVs). Using sophisticated bioinformatics algorithms, unbiased catalogs of SVs are emerging from thousands of human cancer genomes for the first time. Via careful examination of SV breakpoints at single-nucleotide resolution as well as local DNA copy number changes, diverse patterns of genomic rearrangements are being revealed. These \"SV signatures\" provide deep insight into the mutational processes that have shaped genome changes in human somatic cells. This review summarizes the characteristics of recently identified complex SVs, including chromothripsis, chromoplexy, microhomology-mediated breakage-induced replication (MMBIR), and others, to provide a holistic snapshot of the current knowledge on genomic rearrangements in somatic cells.",
			"category": 2,
			"name": "Yi Kijong,2019"
		},
		{
			"PMID": 30082874,
			"title": "Estimation of the cancer risk induced by therapies targeting stem cell replication and treatment recommendations.",
			"journal": "Scientific reports",
			"authorList": [
				"Meyer-Hermann Michael"
			],
			"DOI": "10.1038/s41598-018-29967-6",
			"date": "2019-10-18",
			"PMC": "",
			"citation": "",
			"abstract": "Rejuvenation of stem cell activity might increase life expectancy by prolonging functionality of organs. Higher stem cell replication rates also bear the risk of cancer. The extent of this risk is not known. While it is difficult to evaluate this cancer risk in experiments, it can be estimated using a mathematical model for tissue homeostasis by stem cell replication and associated cancer risk. The model recapitulates the observation that treatments targeting stem cell replication can induce a substantial delay of organ failure. The model predicts that the cancer risk is minor under particular conditions. It depends on the assumed implications for cell damage repair during treatment. The benefit of rejuvenation therapy and its impact on cancer risk depend on the biological age at the time of treatment and on the overall cell turnover rate of the organs. Different organs have to be considered separately in the planning of systemic treatments. In recent years, the transfer of blood from young to old individuals was shown to bear the potential of rejuvenation of stem cell activity. In this context, the model predicts that the treatment schedule is critical for success and that schedules successful in animal experiments are not transferable to humans. Guidelines for successful protocols are proposed. The model presented here may be used as a guidance for the development of stem cell rejuvenation treatment protocols and the identification of critical parameters for cancer risk.",
			"category": 2,
			"name": "Meyer-Hermann Michael,2019"
		},
		{
			"PMID": 30065701,
			"title": "Landscape of CDKN1B Mutations in Luminal Breast Cancer and Other Hormone-Driven Human Tumors.",
			"journal": "Frontiers in endocrinology",
			"authorList": [
				"Cusan Martina",
				"Mungo Giorgia",
				"De Marco Zompit Mara",
				"Segatto Ilenia",
				"Belletti Barbara",
				"Baldassarre Gustavo"
			],
			"DOI": "10.3389/fendo.2018.00393",
			"date": "2024-03-28",
			"PMC": "",
			"citation": "",
			"abstract": "The ",
			"category": 2,
			"name": "Cusan Martina,2024"
		},
		{
			"PMID": 30061703,
			"title": "Explaining cancer type specific mutations with transcriptomic and epigenomic features in normal tissues.",
			"journal": "Scientific reports",
			"authorList": [
				"Tiong Khong-Loon",
				"Yeang Chen-Hsiang"
			],
			"DOI": "10.1038/s41598-018-29861-1",
			"date": "2019-10-18",
			"PMC": "",
			"citation": "",
			"abstract": "Most cancer driver genes are involved in generic cellular processes such as DNA repair, cell proliferation and cell adhesion, yet their mutations are often confined to specific cancer types. To resolve this paradox, we explained mutation frequencies of selected genes across tumor types with four features in the corresponding normal tissues from cancer-free subjects: mRNA expression and chromatin accessibility of mutated genes, mRNA expressions of their neighbors in curated pathways and the protein-protein interaction network. Encouragingly, these transcriptomic/epigenomic features in normal tissues were closely associated with mutational/functional characteristics in tumors. First, chromatin accessibility was a necessary but not sufficient condition for frequent mutations. Second, variations of mutation frequencies in selected genes across tissue types were significantly associated with all four features. Third, the genes possessing significant associations between mutation frequency variations and pathway gene expression were enriched with documented cancer genes. We further proposed a novel bivariate gene set enrichment analysis and confirmed that the pathway gene expression was the dominant factor in cancer gene enrichment. These findings shed lights on the functional roles of genes in normal tissues in shaping the mutational landscape during tumor genome evolution.",
			"category": 2,
			"name": "Tiong Khong-Loon,2019"
		},
		{
			"PMID": 30044985,
			"title": "Insights into the Mutational Burden of Human Induced Pluripotent Stem Cells from an Integrative Multi-Omics Approach.",
			"journal": "Cell reports",
			"authorList": [
				"D'Antonio Matteo",
				"Benaglio Paola",
				"Jakubosky David",
				"Greenwald William W",
				"Matsui Hiroko",
				"Donovan Margaret K R",
				"Li He",
				"Smith Erin N",
				"D'Antonio-Chronowska Agnieszka",
				"Frazer Kelly A"
			],
			"DOI": "10.1016/j.celrep.2018.06.091",
			"date": "2020-01-07",
			"PMC": "",
			"citation": "",
			"abstract": "To understand the mutational burden of human induced pluripotent stem cells (iPSCs), we sequenced genomes of 18 fibroblast-derived iPSC lines and identified different classes of somatic mutations based on structure, origin, and frequency. Copy-number alterations affected 295 kb in each sample and strongly impacted gene expression. UV-damage mutations were present in \u223c45% of the iPSCs and accounted for most of the observed heterogeneity in mutation rates across lines. Subclonal mutations (not present in all iPSCs within a line) composed 10% of point mutations and, compared with clonal variants, showed an enrichment in active promoters and increased association with altered gene expression. Our study shows that, by combining WGS, transcriptome, and epigenome data, we can understand the mutational burden of each iPSC line on an individual basis and suggests that this information could be used to prioritize iPSC lines for models of specific human diseases and/or transplantation therapy.",
			"category": 2,
			"name": "D'Antonio Matteo,2020"
		},
		{
			"PMID": 30041675,
			"title": "Timing somatic events in the evolution of cancer.",
			"journal": "Genome biology",
			"authorList": [
				"Jolly Clemency",
				"Van Loo Peter"
			],
			"DOI": "10.1186/s13059-018-1476-3",
			"date": "2018-11-19",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer arises through the accumulation of somatic mutations over time. An understanding of the sequence of events during this process should allow both earlier diagnosis and better prediction of cancer progression. However, the pathways of tumor evolution have not yet been comprehensively characterized. With the advent of whole genome sequencing, it is now possible to infer the evolutionary history of single tumors from the snapshot of their genome taken at diagnosis, giving new insights into the biology of tumorigenesis.",
			"category": 2,
			"name": "Jolly Clemency,2018"
		},
		{
			"PMID": 30012096,
			"title": "Germline and somatic variations influence the somatic mutational signatures of esophageal squamous cell carcinomas in a Chinese population.",
			"journal": "BMC genomics",
			"authorList": [
				"Guo Jintao",
				"Huang Jiankun",
				"Zhou Ying",
				"Zhou Yulin",
				"Yu Liying",
				"Li Huili",
				"Hou Lingyun",
				"Zhu Liuwei",
				"Ge Dandan",
				"Zeng Yuanyuan",
				"Guleng Bayasi",
				"Li Qiyuan"
			],
			"DOI": "10.1186/s12864-018-4906-4",
			"date": "2018-12-18",
			"PMC": "",
			"citation": "",
			"abstract": "Esophageal squamous cell carcinomas (ESCC) is the fourth most lethal cancer in China. Previous studies reveal several highly conserved mutational processes in ESCC. However, it remains unclear what are the true regulators of the mutational processes.",
			"category": 2,
			"name": "Guo Jintao,2018"
		},
		{
			"PMID": 30007283,
			"title": "The Biology of Normal Zona Glomerulosa and Aldosterone-Producing Adenoma: Pathological Implications.",
			"journal": "Endocrine reviews",
			"authorList": [
				"Seccia Teresa M",
				"Caroccia Brasilina",
				"Gomez-Sanchez Elise P",
				"Gomez-Sanchez Celso E",
				"Rossi Gian Paolo"
			],
			"DOI": "10.1210/er.2018-00060",
			"date": "2019-03-21",
			"PMC": "",
			"citation": "",
			"abstract": "The identification of several germline and somatic ion channel mutations in aldosterone-producing adenomas (APAs) and detection of cell clusters that can be responsible for excess aldosterone production, as well as the isolation of autoantibodies activating the angiotensin II type 1 receptor, have rapidly advanced the understanding of the biology of primary aldosteronism (PA), particularly that of APA. Hence, the main purpose of this review is to discuss how discoveries of the last decade could affect histopathology analysis and clinical practice. The structural remodeling through development and aging of the human adrenal cortex, particularly of the zona glomerulosa, and the complex regulation of aldosterone, with emphasis on the concepts of zonation and channelopathies, will be addressed. Finally, the diagnostic workup for PA and its subtyping to optimize treatment are reviewed.",
			"category": 2,
			"name": "Seccia Teresa M,2019"
		},
		{
			"PMID": 29983986,
			"title": "Drug conjugates-an emerging approach to treat breast cancer.",
			"journal": "Pharmacology research & perspectives",
			"authorList": [
				"Hasan Mahmud",
				"Leak Rehana K",
				"Stratford Robert E",
				"Zlotos Darius P",
				"Witt-Enderby Paula A"
			],
			"DOI": "10.1002/prp2.417",
			"date": "2018-12-31",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer treatment using a single drug is associated with a high failure rate due, in part, to the heterogeneity of drug response within individuals, nonspecific target action, drug toxicity, and/or development of resistance. Use of dual-drug therapies, including drug conjugates, may help overcome some of these roadblocks by more selective targeting of the cancer cell and by acting at multiple drug targets rather than one. Drug-conjugate approaches include linking drugs to antibodies (antibody-drug conjugates), radionuclides (radioimmunoconjugates), nanoparticles (nanoparticle-drug conjugates), or to other drugs (drug-drug conjugates). Although all of these conjugates might be designed as effective treatments against breast cancer, the focus of this review will be on drug-drug conjugates because of the increase in versatility of these types of drugs with respect to mode of action at the level of the cancer cell either by creating a novel pharmacophore or by increasing the potency and/or efficacy of the drugs' effects at their respective molecular targets. The development, synthesis, and pharmacological characteristics of drug-drug conjugates will be discussed in the context of breast cancer with the hope of enhancing drug efficacy and reducing toxicities to improve patient quality of life.",
			"category": 2,
			"name": "Hasan Mahmud,2018"
		},
		{
			"PMID": 29978435,
			"title": "Tetz's theory and law of longevity.",
			"journal": "Theory in biosciences = Theorie in den Biowissenschaften",
			"authorList": [
				"Tetz George",
				"Tetz Victor"
			],
			"DOI": "10.1007/s12064-018-0267-4",
			"date": "2019-01-07",
			"PMC": "",
			"citation": "",
			"abstract": "Here, we present new theory and law of longevity intended to evaluate fundamental factors that control lifespan. This theory is based on the fact that genes affecting host organism longevity are represented by subpopulations: genes of host eukaryotic cells, commensal microbiota, and non-living genetic elements. Based on Tetz's theory of longevity, we propose that lifespan and aging are defined by the accumulation of alterations over all genes of macroorganism and microbiome and the non-living genetic elements associated with them. Tetz's law of longevity states that longevity is limited by the accumulation of alterations to the limiting value that is not compatible with life. Based on theory and law, we also propose a novel model to calculate several parameters, including the rate of aging and the remaining lifespan of individuals. We suggest that this theory and model have explanatory and predictive potential to eukaryotic organisms, allowing the influence of diseases, medication, and medical procedures to be re-examined in relation to longevity. Such estimates also provide a framework to evaluate new fundamental aspects that control aging and lifespan.",
			"category": 2,
			"name": "Tetz George,2019"
		},
		{
			"PMID": 29968906,
			"title": "Epithelial-to-mesenchymal transition and cancer stem cells contribute to breast cancer heterogeneity.",
			"journal": "Journal of cellular physiology",
			"authorList": [
				"Hong Deli",
				"Fritz Andrew J",
				"Zaidi Sayyed K",
				"van Wijnen Andre J",
				"Nickerson Jeffrey A",
				"Imbalzano Anthony N",
				"Lian Jane B",
				"Stein Janet L",
				"Stein Gary S"
			],
			"DOI": "10.1002/jcp.26847",
			"date": "2019-09-25",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer is the most common cancer in women, and accounts for ~30% of new cancer cases and 15% of cancer-related deaths. Tumor relapse and metastasis are primary factors contributing to breast cancer-related deaths. Therefore, the challenge for breast cancer treatment is to sustain remission. A driving force behind tumor relapse is breast cancer heterogeneity (both intertumor, between different patients, and intratumor, within the same tumor). Understanding breast cancer heterogeneity is necessary to develop preventive interventions and targeted therapies. A recently emerging concept is that intratumor heterogeneity is driven by cancer stem cells (CSCs) that are capable of giving rise to a multitude of different cells within a tumor. Studies have highlighted linkage of CSC formation with epithelial-to-mesenchymal transition (EMT). In this review, we summarize the current understanding of breast cancer heterogeneity, links between EMT and CSCs, regulation of EMT by Runx transcription factors, and potential therapeutic strategies targeting these processes.",
			"category": 2,
			"name": "Hong Deli,2019"
		},
		{
			"PMID": 29967379,
			"title": "A high-risk, Double-Hit, group of newly diagnosed myeloma identified by genomic analysis.",
			"journal": "Leukemia",
			"authorList": [
				"Walker Brian A",
				"Mavrommatis Konstantinos",
				"Wardell Christopher P",
				"Ashby T Cody",
				"Bauer Michael",
				"Davies Faith",
				"Rosenthal Adam",
				"Wang Hongwei",
				"Qu Pingping",
				"Hoering Antje",
				"Samur Mehmet",
				"Towfic Fadi",
				"Ortiz Maria",
				"Flynt Erin",
				"Yu Zhinuan",
				"Yang Zhihong",
				"Rozelle Dan",
				"Obenauer John",
				"Trotter Matthew",
				"Auclair Daniel",
				"Keats Jonathan",
				"Bolli Niccolo",
				"Fulciniti Mariateresa",
				"Szalat Raphael",
				"Moreau Phillipe",
				"Durie Brian",
				"Stewart A Keith",
				"Goldschmidt Hartmut",
				"Raab Marc S",
				"Einsele Hermann",
				"Sonneveld Pieter",
				"San Miguel Jesus",
				"Lonial Sagar",
				"Jackson Graham H",
				"Anderson Kenneth C",
				"Avet-Loiseau Herve",
				"Munshi Nikhil",
				"Thakurta Anjan",
				"Morgan Gareth"
			],
			"DOI": "10.1038/s41375-018-0196-8",
			"date": "2019-05-30",
			"PMC": "",
			"citation": "",
			"abstract": "Patients with newly diagnosed multiple myeloma (NDMM) with high-risk disease are in need of new treatment strategies to improve the outcomes. Multiple clinical, cytogenetic, or gene expression features have been used to identify high-risk patients, each of which has significant weaknesses. Inclusion of molecular features into risk stratification could resolve the current challenges. In a genome-wide analysis of the largest set of molecular and clinical data established to date from NDMM, as part of the Myeloma Genome Project, we have defined DNA drivers of aggressive clinical behavior. Whole-genome and exome data from 1273 NDMM patients identified genetic factors that contribute significantly to progression free survival (PFS) and overall survival (OS) (cumulative R",
			"category": 2,
			"name": "Walker Brian A,2019"
		},
		{
			"PMID": 29942026,
			"title": "A genome-wide mutation analysis method enabling high-throughput identification of chemical mutagen signatures.",
			"journal": "Scientific reports",
			"authorList": [
				"Matsumura Shoji",
				"Fujita Yurika",
				"Yamane Masayuki",
				"Morita Osamu",
				"Honda Hiroshi"
			],
			"DOI": "10.1038/s41598-018-27755-w",
			"date": "2019-10-21",
			"PMC": "",
			"citation": "",
			"abstract": "Trinucleotide mutational signatures extracted from cancer genomes provide clues useful in understanding the roles of mutagens and mutagenic mechanisms in cancer development. The lack of a simple method for genome-wide analysis of alterations induced by mutagens hampers the identification of trinucleotide signatures of mutagen exposure and evaluation of their relationships with human cancers. Here, we describe a novel approach to facilitate analysis of chemically induced mutations in bacterial cells by detection of increased frequencies of base substitutions after mutagen exposure, using paired-end overlapping next-generation sequencing. DNA samples from Salmonella typhimurium strain TA100, exposed to three alkylating agents, ethylnitrosourea (ENU), methylnitrosourea (MNU), and ethyl methansulphonate (EMS), were analysed. The G:C\u2009>\u2009A:T mutation frequency was increased in all samples, whereas A:T base pair substitution frequencies were increased specifically in samples exposed to ENU, consistent with previous reports. Mutation patterns in the context of 96 possible trinucleotide formats in these samples exhibited a sharp peak corresponding to an NpCpY consensus sequence, which is similar to the mutational signature of alkylating agents in human cancer. These results indicate that our approach can be useful in facilitating the understanding of mechanisms underlying chemical mutagenicity and for identification of unknown causal mutagens in human cancer.",
			"category": 2,
			"name": "Matsumura Shoji,2019"
		},
		{
			"PMID": 29934362,
			"title": "Role of RNF20 in cancer development and progression - a comprehensive review.",
			"journal": "Bioscience reports",
			"authorList": [
				"Sethi Gautam",
				"Shanmugam Muthu K",
				"Arfuso Frank",
				"Kumar Alan Prem"
			],
			"DOI": "10.1042/BSR20171287",
			"date": "2019-04-19",
			"PMC": "",
			"citation": "",
			"abstract": "Evolving strategies to counter cancer initiation and progression rely on the identification of novel therapeutic targets that exploit the aberrant genetic changes driving oncogenesis. Several chromatin associated enzymes have been shown to influence post-translational modification (PTM) in DNA, histones, and non-histone proteins. Any deregulation of this core group of enzymes often leads to cancer development. Ubiquitylation of histone H2B in mammalian cells was identified over three decades ago. An exciting really interesting new gene (RING) family of E3 ubiquitin ligases, known as RNF20 and RNF40, monoubiquitinates histone H2A at K119 or H2B at K120, is known to function in transcriptional elongation, DNA double-strand break (DSB) repair processes, maintenance of chromatin differentiation, and exerting tumor suppressor activity. RNF20 is somatically altered in breast, lung, prostate cancer, clear cell renal cell carcinoma (ccRCC), and mixed lineage leukemia, and its reduced expression is a key factor in initiating genome instability; and it also functions as one of the significant driving factors of oncogenesis. Loss of RNF20/40 and H2B monoubiquitination (H2Bub1) is found in several cancers and is linked to an aggressive phenotype, and is also an indicator of poor prognosis. In this review, we summarized the current knowledge of RNF20 in chronic inflammation-driven cancers, DNA DSBs, and apoptosis, and its impact on chromatin structure beyond the single nucleosome level.",
			"category": 2,
			"name": "Sethi Gautam,2019"
		},
		{
			"PMID": 29925861,
			"title": "The homeostasis-maintaining metabolites from bacterial stress response to bacteriophage infection suppress tumor metastasis.",
			"journal": "Oncogene",
			"authorList": [
				"He Tianliang",
				"Jin Min",
				"Xu Chenxi",
				"Ma Zhongjun",
				"Wu Fufang",
				"Zhang Xiaobo"
			],
			"DOI": "10.1038/s41388-018-0376-z",
			"date": "2019-07-02",
			"PMC": "",
			"citation": "",
			"abstract": "The antiviral metabolites from bacterial stress response to bacteriophage infection can maintain homeostasis of host cells, while metabolism disorder is a remarkable characteristic of tumorigenesis. In the aspect of metabolic homeostasis, therefore, the antiviral homeostasis-maintaining metabolites of bacteria may possess anti-tumor activity. However, this issue has not been addressed. Here we show that the homeostasis-challenged maintaining metabolites from deep-sea bacteriophage-challenged thermophile can suppress tumor metastasis. The results indicated that the metabolic profiles of the bacteriophage GVE2-infected and virus-free thermophile Geobacillus sp. E263 from a deep-sea hydrothermal vent were remarkably different. Thirteen metabolites were significantly elevated and two metabolites were downregulated in thermophile stress response to GVE2 infection. As an example, the upregulated L-norleucine was characterized. The data showed that L-norleucine had antiviral activity in thermophile. Furthermore, the in vitro and in vivo assays revealed that L-norleucine, as well as its derivative, significantly suppressed metastasis of gastric and breast cancer cells. L-norleucine interacted with hnRNPA2/B1 protein to inhibit the expressions of Twist1 and Snail, two inhibitors of E-cadherin, and promote the E-cadherin expression, leading to the inhibition of tumor metastasis. Therefore, our study presented that antiviral homeostasis-maintaining metabolites of microbes might be a promising source for anti-tumor drugs.",
			"category": 2,
			"name": "He Tianliang,2019"
		},
		{
			"PMID": 29912344,
			"title": "Prioritizing predictive biomarkers for gene essentiality in cancer cells with mRNA expression data and DNA copy number profile.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Guan Yuanfang",
				"Li Tingyang",
				"Zhang Hongjiu",
				"Zhu Fan",
				"Omenn Gilbert S"
			],
			"DOI": "10.1093/bioinformatics/bty467",
			"date": "2019-10-22",
			"PMC": "",
			"citation": "",
			"abstract": "Finding driver genes that are responsible for the aberrant proliferation rate of cancer cells is informative for both cancer research and the development of targeted drugs. The established experimental and computational methods are labor-intensive. To make algorithms feasible in real clinical settings, methods that can predict driver genes using less experimental data are urgently needed.",
			"category": 2,
			"name": "Guan Yuanfang,2019"
		},
		{
			"PMID": 29907142,
			"title": "MALBAC-based chromosomal imbalance analysis: a novel technique enabling effective non-invasive diagnosis and monitoring of bladder cancer.",
			"journal": "BMC cancer",
			"authorList": [
				"Liu Hao",
				"He Wang",
				"Wang Bo",
				"Xu Kewei",
				"Han Jinli",
				"Zheng Junjiong",
				"Ren Jun",
				"Shao Lin",
				"Bo Shiping",
				"Lu Sijia",
				"Lin Tianxin",
				"Huang Jian"
			],
			"DOI": "10.1186/s12885-018-4571-7",
			"date": "2019-02-08",
			"PMC": "",
			"citation": "",
			"abstract": "The gold standard for bladder cancer detection is cystoscopy, which is an invasive procedure that causes discomfort in patients. The currently available non-invasive approaches either show limited sensitivity in low-grade tumours or possess unsatisfying specificity. The aim of the present study is to develop a new non-invasive strategy based on chromosomal imbalance levels to detect bladder cancer effectively.",
			"category": 2,
			"name": "Liu Hao,2019"
		},
		{
			"PMID": 29901861,
			"title": "Rapid proteomic analysis for solid tumors reveals LSD1 as a drug target in an end-stage cancer patient.",
			"journal": "Molecular oncology",
			"authorList": [
				"Doll Sophia",
				"Kriegmair Maximilian C",
				"Santos Alberto",
				"Wierer Michael",
				"Coscia Fabian",
				"Neil Helen Michele",
				"Porubsky Stefan",
				"Geyer Philipp E",
				"Mund Andreas",
				"Nuhn Philipp",
				"Mann Matthias"
			],
			"DOI": "10.1002/1878-0261.12326",
			"date": "2019-07-01",
			"PMC": "",
			"citation": "",
			"abstract": "Recent advances in mass spectrometry (MS)-based technologies are now set to transform translational cancer proteomics from an idea to a practice. Here, we present a robust proteomic workflow for the analysis of clinically relevant human cancer tissues that allows quantitation of thousands of tumor proteins in several hours of measuring time and a total turnaround of a few days. We applied it to a chemorefractory metastatic case of the extremely rare urachal carcinoma. Quantitative comparison of lung metastases and surrounding tissue revealed several significantly upregulated proteins, among them lysine-specific histone demethylase 1 (LSD1/KDM1A). LSD1 is an epigenetic regulator and the target of active development efforts in oncology. Thus, clinical cancer proteomics can rapidly and efficiently identify actionable therapeutic options. While currently described for a single case study, we envision that it can be applied broadly to other patients in a similar condition.",
			"category": 2,
			"name": "Doll Sophia,2019"
		},
		{
			"PMID": 29895971,
			"title": "\u03b2-catenin/TCF activity regulates IGF-1R tyrosine kinase inhibitor sensitivity in colon cancer.",
			"journal": "Oncogene",
			"authorList": [
				"Lee Hani",
				"Kim Nayoung",
				"Yoo Young Ji",
				"Kim Hyejin",
				"Jeong Euna",
				"Choi SeokGyeong",
				"Moon Sung Un",
				"Oh Seung Hyun",
				"Mills Gordon B",
				"Yoon Sukjoon",
				"Kim Woo-Young"
			],
			"DOI": "10.1038/s41388-018-0362-5",
			"date": "2019-02-21",
			"PMC": "",
			"citation": "",
			"abstract": "The availability of large-scale drug screening data on cell line panels provides a unique opportunity to identify predictive biomarkers for targeted drug efficacy. Analysis of diverse drug data on ~990 cancer cell lines revealed enhanced sensitivity of insulin-like growth factor 1 receptor/ Insulin Receptor (IGF-1R/IR) tyrosine kinase inhibitors (TKIs) in colon cancer cells. Interestingly, \u03b2-catenin/TCF(T cell factor)-responsive promoter activity exhibited a significant positive association with IGF-1R/IR TKI response, while the mutational status of direct upstream genes, such as CTNNB1 and APC, was not significantly associated with the response. The \u03b2-catenin/TCF activity high cell lines express components of IGF-1R/IR signaling more than the low cell lines explaining their enhanced sensitivity against IGF-1R/IR TKI. Reinforcing \u03b2-catenin/TCF responsive promoter activity by introducing CTNNB1 gain-of-function mutations into IGF-1R/IR TKI-resistant cells increased the expression and activity of IGF-1R/IR signaling components and also sensitized the cells to IGF-1R/IR TKIs in vitro and in vivo. Analysis of TCGA data revealed that the stronger \u03b2-catenin/TCF responsive promoter activity was associated with higher IGF-1R and IGF2 transcription in human colon cancer specimens as well. Collectively, compared to the mutational status of upstream genes, \u03b2-catenin/TCF responsive promoter activity has potential to be a stronger predictive positive biomarker for IGF-1R/IR TKI responses in colon cancer cells. The present study highlights the potential of transcriptional activity as therapeutic biomarkers for targeted therapies, overcoming the limited ability of upstream genetic mutations to predict responses.",
			"category": 2,
			"name": "Lee Hani,2019"
		},
		{
			"PMID": 29891981,
			"title": "Cancer Drug Response Profile scan (CDRscan): A Deep Learning Model That Predicts Drug Effectiveness from Cancer Genomic Signature.",
			"journal": "Scientific reports",
			"authorList": [
				"Chang Yoosup",
				"Park Hyejin",
				"Yang Hyun-Jin",
				"Lee Seungju",
				"Lee Kwee-Yum",
				"Kim Tae Soon",
				"Jung Jongsun",
				"Shin Jae-Min"
			],
			"DOI": "10.1038/s41598-018-27214-6",
			"date": "2019-11-04",
			"PMC": "",
			"citation": "",
			"abstract": "In the era of precision medicine, cancer therapy can be tailored to an individual patient based on the genomic profile of a tumour. Despite the ever-increasing abundance of cancer genomic data, linking mutation profiles to drug efficacy remains a challenge. Herein, we report Cancer Drug Response profile scan (CDRscan) a novel deep learning model that predicts anticancer drug responsiveness based on a large-scale drug screening assay data encompassing genomic profiles of 787 human cancer cell lines and structural profiles of 244 drugs. CDRscan employs a two-step convolution architecture, where the genomic mutational fingerprints of cell lines and the molecular fingerprints of drugs are processed individually, then merged by 'virtual docking', an in silico modelling of drug treatment. Analysis of the goodness-of-fit between observed and predicted drug response revealed a high prediction accuracy of CDRscan (R",
			"category": 2,
			"name": "Chang Yoosup,2019"
		},
		{
			"PMID": 29889312,
			"title": "DNA adducts: Formation, biological effects, and new biospecimens for mass spectrometric measurements in humans.",
			"journal": "Mass spectrometry reviews",
			"authorList": [
				"Hwa Yun Byeong",
				"Guo Jingshu",
				"Bellamri Medjda",
				"Turesky Robert J"
			],
			"DOI": "10.1002/mas.21570",
			"date": "2021-07-27",
			"PMC": "",
			"citation": "",
			"abstract": "Hazardous chemicals in the environment and diet or their electrophilic metabolites can form adducts with genomic DNA, which can lead to mutations and the initiation of cancer. In addition, reactive intermediates can be generated in the body through oxidative stress and damage the genome. The identification and measurement of DNA adducts are required for understanding exposure and the causal role of a genotoxic chemical in cancer risk. Over the past three decades, ",
			"category": 2,
			"name": "Hwa Yun Byeong,2021"
		},
		{
			"PMID": 29875994,
			"title": "Computational modeling of methionine cycle-based metabolism and DNA methylation and the implications for anti-cancer drug response prediction.",
			"journal": "Oncotarget",
			"authorList": [
				"Zhang Mengying",
				"Saad Christian",
				"Le Lien",
				"Halfter Kathrin",
				"Bauer Bernhard",
				"Mansmann Ulrich R",
				"Li Jian"
			],
			"DOI": "10.18632/oncotarget.24547",
			"date": "2019-11-20",
			"PMC": "",
			"citation": "",
			"abstract": "The relationship between metabolism and methylation is considered to be an important aspect of cancer development and drug efficacy. However, it remains poorly defined how to apply this aspect to improve preclinical disease characterization and clinical treatment outcome. Using available molecular information from Kyoto Encyclopedia of Genes and Genomes (KEGG) and literature, we constructed a large-scale knowledge-based metabolic ",
			"category": 2,
			"name": "Zhang Mengying,2019"
		},
		{
			"PMID": 29865161,
			"title": "Formalin-Fixed Paraffin-Embedded Tissues-An Untapped Biospecimen for Biomonitoring DNA Adducts by Mass Spectrometry.",
			"journal": "Toxics",
			"authorList": [
				"Yun Byeong Hwa",
				"Guo Jingshu",
				"Turesky Robert J"
			],
			"DOI": "10.3390/toxics6020030",
			"date": "2023-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "The measurement of DNA adducts provides important information about human exposure to genotoxic chemicals and can be employed to elucidate mechanisms of DNA damage and repair. DNA adducts can serve as biomarkers for interspecies comparisons of the biologically effective dose of procarcinogens and permit extrapolation of genotoxicity data from animal studies for human risk assessment. One major challenge in DNA adduct biomarker research is the paucity of fresh frozen biopsy samples available for study. However, archived formalin-fixed paraffin-embedded (FFPE) tissues with clinical diagnosis of disease are often available. We have established robust methods to recover DNA free of crosslinks from FFPE tissues under mild conditions which permit quantitative measurements of DNA adducts by liquid chromatography-mass spectrometry. The technology is versatile and can be employed to screen for DNA adducts formed with a wide range of environmental and dietary carcinogens, some of which were retrieved from section-cuts of FFPE blocks stored at ambient temperature for up to nine years. The ability to retrospectively analyze FFPE tissues for DNA adducts for which there is clinical diagnosis of disease opens a previously untapped source of biospecimens for molecular epidemiology studies that seek to assess the causal role of environmental chemicals in cancer etiology.",
			"category": 2,
			"name": "Yun Byeong Hwa,2023"
		},
		{
			"PMID": 29864749,
			"title": "Lung Cancer: One Disease or Many.",
			"journal": "Human heredity",
			"authorList": [
				"O'Brien Timothy D",
				"Jia Peilin",
				"Aldrich Melinda C",
				"Zhao Zhongming"
			],
			"DOI": "10.1159/000488942",
			"date": "2019-03-22",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer is classified as a single entity comprised of multiple histological subtypes. But how similar are these subtypes on a genetic level? This paper aims to address this question through a concise overview of germline and somatic differences between small cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma.",
			"category": 2,
			"name": "O'Brien Timothy D,2019"
		},
		{
			"PMID": 29856501,
			"title": "Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like family genes activation and regulation during tumorigenesis.",
			"journal": "Cancer science",
			"authorList": [
				"Gao Jianlong",
				"Choudhry Hani",
				"Cao Wei"
			],
			"DOI": "10.1111/cas.13658",
			"date": "2018-09-04",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is currently viewed as a disease of evolving genomic instability and abnormal epigenomic modifications. Most solid cancers harbor oncogenic gene mutations driven by both extrinsic and intrinsic factors. Apolipoprotein B mRNA editing catalytic polypeptide-like family (APOBEC) enzymes have an intrinsic deamination activity to convert cytosine to uracil during RNA editing and retrovirus or retrotransposon restriction. Beyond their natural defense in innate immunity, compelling evidence showed that a subclass of APOBEC3 can cause high mutation burden in various types of cancer genomes, and high expression subtypes of APOBEC3 may contribute to drug resistance and associate with clinical outcomes. The underlying molecular mechanisms of APOBEC-mediated hypermutation phenotype are poorly understood. In this review, we discuss the linkage of activation-induced deaminase (AID)/APOBEC3 enzymes to tumorigenesis, highlight the dysregulatory mechanisms of APOBEC3 activities during cancer development, and propose potential approaches to targeting APOBEC3-mediated mutagenesis for cancer interventions.",
			"category": 2,
			"name": "Gao Jianlong,2018"
		},
		{
			"PMID": 29844133,
			"title": "Loss of Elongation-Like Factor 1 Spontaneously Induces Diverse, RNase H-Related Suppressor Mutations in ",
			"journal": "Genetics",
			"authorList": [
				"Marayati Bahjat F",
				"Drayton Alena L",
				"Tucker James F",
				"Huckabee Reid H",
				"Anderson Alicia M",
				"Pease James B",
				"Zeyl Clifford W",
				"Zhang Ke"
			],
			"DOI": "10.1534/genetics.118.301055",
			"date": "2018-10-09",
			"PMC": "",
			"citation": "",
			"abstract": "A healthy individual may carry a detrimental genetic trait that is masked by another genetic mutation. Such suppressive genetic interactions, in which a mutant allele either partially or completely restores the fitness defect of a particular mutant, tend to occur between genes that have a confined functional connection. Here we investigate a self-recovery phenotype in ",
			"category": 2,
			"name": "Marayati Bahjat F,2018"
		},
		{
			"PMID": 29805750,
			"title": "Identification of ",
			"journal": "Oncotarget",
			"authorList": [
				"Kumari Rashmi",
				"Silic Martin R",
				"Jones-Hall Yava L",
				"Nin-Velez Alexandra",
				"Yang Jer-Yen",
				"Mittal Suresh K",
				"Zhang GuangJun"
			],
			"DOI": "10.18632/oncotarget.25236",
			"date": "2019-11-20",
			"PMC": "",
			"citation": "",
			"abstract": "Malignant peripheral nerve sheath tumors (MPNSTs) are a type of sarcoma with poor prognosis due to their complex genetic changes, invasive growth, and insensitivity to chemo- and radiotherapies. One of the most frequently lost chromosome arms in human MPNSTs is chromosome 9p. However, the cancer driver genes located on it remain largely unknown, except the tumor suppressor gene, p16 ",
			"category": 2,
			"name": "Kumari Rashmi,2019"
		},
		{
			"PMID": 29790943,
			"title": "Mutalisk: a web-based somatic MUTation AnaLyIS toolKit for genomic, transcriptional and epigenomic signatures.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Lee Jongkeun",
				"Lee Andy Jinseok",
				"Lee June-Koo",
				"Park Jongkeun",
				"Kwon Youngoh",
				"Park Seongyeol",
				"Chun Hyonho",
				"Ju Young Seok",
				"Hong Dongwan"
			],
			"DOI": "10.1093/nar/gky406",
			"date": "2019-08-08",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic genome mutations occur due to combinations of various intrinsic/extrinsic mutational processes and DNA repair mechanisms. Different molecular processes frequently generate different signatures of somatic mutations in their own favored contexts. As a result, the regional somatic mutation rate is dependent on the local DNA sequence, the DNA replication/RNA transcription dynamics and epigenomic chromatin organization landscape in the genome. Here, we propose an online computational framework, termed Mutalisk, which correlates somatic mutations with various genomic, transcriptional and epigenomic features in order to understand mutational processes that contribute to the generation of the mutations. This user-friendly tool explores the presence of localized hypermutations (kataegis), dissects the spectrum of mutations into the maximum likelihood combination of known mutational signatures and associates the mutation density with numerous regulatory elements in the genome. As a result, global patterns of somatic mutations in any query sample can be efficiently screened, thus enabling a deeper understanding of various mutagenic factors. This tool will facilitate more effective downstream analyses of cancer genome sequences to elucidate the diversity of mutational processes underlying the development and clonal evolution of cancer cells. Mutalisk is freely available at http://mutalisk.org.",
			"category": 2,
			"name": "Lee Jongkeun,2019"
		},
		{
			"PMID": 29769662,
			"title": "Novel internal regulators and candidate miRNAs within miR-379/miR-656 miRNA cluster can alter cellular phenotype of human glioblastoma.",
			"journal": "Scientific reports",
			"authorList": [
				"Nayak Subhashree",
				"Aich Meghali",
				"Kumar Anupam",
				"Sengupta Suman",
				"Bajad Prajakta",
				"Dhapola Parashar",
				"Paul Deepanjan",
				"Narta Kiran",
				"Purkrait Suvendu",
				"Mehani Bharati",
				"Suri Ashish",
				"Chakraborty Debojyoti",
				"Mukhopadhyay Arijit",
				"Sarkar Chitra"
			],
			"DOI": "10.1038/s41598-018-26000-8",
			"date": "2019-10-23",
			"PMC": "",
			"citation": "",
			"abstract": "Clustered miRNAs can affect functioning of downstream pathways due to possible coordinated function. We observed 78-88% of the miR-379/miR-656 cluster (C14MC) miRNAs were downregulated in three sub-types of diffuse gliomas, which was also corroborated with analysis from The Cancer Genome Atlas (TCGA) datasets. The miRNA expression levels decreased with increasing tumor grade, indicating this downregulation as an early event in gliomagenesis. Higher expression of the C14MC miRNAs significantly improved glioblastioma prognosis (Pearson's r\u2009=\u20090.62; p\u2009<\u20093.08e-22). ENCODE meta-data analysis, followed by reporter assays validated existence of two novel internal regulators within C14MC. CRISPR activation of the most efficient internal regulator specifically induced members of the downstream miRNA sub-cluster and apoptosis in glioblastoma cells. Luciferase assays validated novel targets for miR-134 and miR-485-5p, two miRNAs from C14MC with the most number of target genes relevant for glioma. Overexpression of miR-134 and miR-485-5p in human glioblastoma cells suppressed invasion and proliferation, respectively. Furthermore, apoptosis was induced by both miRs, individually and in combination. The results emphasize the tumor suppressive role of C14MC in diffuse gliomas, and identifies two specific miRNAs with potential therapeutic value and towards better disease management and therapy.",
			"category": 2,
			"name": "Nayak Subhashree,2019"
		},
		{
			"PMID": 29755661,
			"title": "Identification of copy number alterations in colon cancer from analysis of amplicon-based next generation sequencing data.",
			"journal": "Oncotarget",
			"authorList": [
				"Oliveira Duarte Mendes",
				"Santamaria Gianluca",
				"Laudanna Carmelo",
				"Migliozzi Simona",
				"Zoppoli Pietro",
				"Quist Michael",
				"Grasso Catie",
				"Mignogna Chiara",
				"Elia Laura",
				"Faniello Maria Concetta",
				"Marinaro Cinzia",
				"Sacco Rosario",
				"Corcione Francesco",
				"Viglietto Giuseppe",
				"Malanga Donatella",
				"Rizzuto Antonia"
			],
			"DOI": "10.18632/oncotarget.24912",
			"date": "2023-11-05",
			"PMC": "",
			"citation": "",
			"abstract": "The objective of this study was to determine the feasibility to detect copy number alterations in colon cancer samples using Next Generation Sequencing data and to elucidate the association between copy number alterations in specific genes and the development of cancer in different colon segments. We report the successful detection of somatic changes in gene copy number in 37 colon cancer patients by analysis of sequencing data through Amplicon CNA Algorithm. Overall, we have found a total of 748 significant copy number alterations in 230 significant genes, of which 143 showed CN losses and 87 showed CN gains. Validation of results was performed on 20 representative genes by quantitative qPCR and/or immunostaining. By this analysis, we have identified 4 genes that were subjected to copy number alterations in tumors arising in all colon segments (defined \"common genes\") and the presence of copy number alterations in 14 genes that were significantly associated to one specific site (defined \"site-associated genes\"). Finally, copy number alterations in ASXL1, TSC1 and IL7R turned out to be clinically relevant since the loss of TSC1 and IL7R was associated with advanced stages and/or reduced survival whereas copy number gain of ASXL1 was associated with good prognosis.",
			"category": 2,
			"name": "Oliveira Duarte Mendes,2023"
		},
		{
			"PMID": 29751586,
			"title": "Telomere Maintenance Mechanisms in Cancer.",
			"journal": "Genes",
			"authorList": [
				"Gaspar Tiago Bordeira",
				"S\u00e1 Ana",
				"Lopes Jos\u00e9 Manuel",
				"Sobrinho-Sim\u00f5es Manuel",
				"Soares Paula",
				"Vinagre Jo\u00e3o"
			],
			"DOI": "10.3390/genes9050241",
			"date": "2023-11-05",
			"PMC": "",
			"citation": "",
			"abstract": "Tumour cells can adopt telomere maintenance mechanisms (TMMs) to avoid telomere shortening, an inevitable process due to successive cell divisions. In most tumour cells, telomere length (TL) is maintained by reactivation of telomerase, while a small part acquires immortality through the telomerase-independent alternative lengthening of telomeres (ALT) mechanism. In the last years, a great amount of data was generated, and different TMMs were reported and explained in detail, benefiting from genome-scale studies of major importance. In this review, we address seven different TMMs in tumour cells: mutations of the ",
			"category": 2,
			"name": "Gaspar Tiago Bordeira,2023"
		},
		{
			"PMID": 29738578,
			"title": "Cancer driver mutation prediction through Bayesian integration of multi-omic data.",
			"journal": "PloS one",
			"authorList": [
				"Wang Zixing",
				"Ng Kwok-Shing",
				"Chen Tenghui",
				"Kim Tae-Beom",
				"Wang Fang",
				"Shaw Kenna",
				"Scott Kenneth L",
				"Meric-Bernstam Funda",
				"Mills Gordon B",
				"Chen Ken"
			],
			"DOI": "10.1371/journal.pone.0196939",
			"date": "2018-08-01",
			"PMC": "",
			"citation": "",
			"abstract": "Identification of cancer driver mutations is critical for advancing cancer research and personalized medicine. Due to inter-tumor genetic heterogeneity, many driver mutations occur at low frequencies, which make it challenging to distinguish them from passenger mutations. Here, we show that a novel Bayesian hierarchical modeling approach, named rDriver can achieve enhanced prediction accuracy by identifying mutations that not only have high functional impact scores but also are associated with systemic variation in gene expression levels. In examining 3,080 tumor samples from 8 cancer types in The Cancer Genome Atlas, rDriver predicted 1,389 driver mutations. Compared with existing tools, rDriver identified more low frequency mutations associated with lineage specific functional properties, timing of occurrence and patient survival. Evaluation of rDriver predictions using engineered cell-line models resulted in a positive predictive value of 0.94 in PIK3CA genes. Our study highlights the importance of integrating multi-omic data in predicting cancer driver mutations and provides a statistically rigorous solution for cancer target discovery and development.",
			"category": 2,
			"name": "Wang Zixing,2018"
		},
		{
			"PMID": 29726113,
			"title": "Targeting RNA in mammalian systems with small molecules.",
			"journal": "Wiley interdisciplinary reviews. RNA",
			"authorList": [
				"Donlic Anita",
				"Hargrove Amanda E"
			],
			"DOI": "10.1002/wrna.1477",
			"date": "2018-10-05",
			"PMC": "",
			"citation": "",
			"abstract": "The recognition of RNA functions beyond canonical protein synthesis has challenged the central dogma of molecular biology. Indeed, RNA is now known to directly regulate many important cellular processes, including transcription, splicing, translation, and epigenetic modifications. The misregulation of these processes in disease has led to an appreciation of RNA as a therapeutic target. This potential was first recognized in bacteria and viruses, but discoveries of new RNA classes following the sequencing of the human genome have invigorated exploration of its disease-related functions in mammals. As stable structure formation is evolving as a hallmark of mammalian RNAs, the prospect of utilizing small molecules to specifically probe the function of RNA structural domains and their interactions is gaining increased recognition. To date, researchers have discovered bioactive small molecules that modulate phenotypes by binding to expanded repeats, microRNAs, G-quadruplex structures, and RNA splice sites in neurological disorders, cancers, and other diseases. The lessons learned from achieving these successes both call for additional studies and encourage exploration of the plethora of mammalian RNAs whose precise mechanisms of action remain to be elucidated. Efforts toward understanding fundamental principles of small molecule-RNA recognition combined with advances in methodology development should pave the way toward targeting emerging RNA classes such as long noncoding RNAs. Together, these endeavors can unlock the full potential of small molecule-based probing of RNA-regulated processes and enable us to discover new biology and underexplored avenues for therapeutic intervention in human disease. This article is categorized under: RNA Methods > RNA Analyses In Vitro and In Silico RNA Interactions with Proteins and Other Molecules > Small Molecule-RNA Interactions RNA in Disease and Development > RNA in Disease.",
			"category": 2,
			"name": "Donlic Anita,2018"
		},
		{
			"PMID": 29720900,
			"title": "Update on Sporadic Colorectal Cancer Genetics.",
			"journal": "Clinics in colon and rectal surgery",
			"authorList": [
				"Hardiman Karin M"
			],
			"DOI": "10.1055/s-0037-1602234",
			"date": "2021-04-08",
			"PMC": "",
			"citation": "",
			"abstract": "Our understanding of the genetics of colorectal cancer has changed dramatically over recent years. Colorectal cancer can be classified in multiple different ways. Along with the advent of whole-exome sequencing, we have gained an understanding of the scale of the genetic changes found in sporadic colorectal cancer. We now know that there are multiple pathways that are commonly involved in the evolution of colorectal cancer including Wnt/\u03b2-catenin, RAS, EGFR, and PIK3 kinase. Another recent leap in our understanding of colorectal cancer genetics is the recognition that many, if not all tumors, are actually genetically heterogeneous within individual tumors and also between tumors. Recent research has revealed the prognostic and possibly therapeutic implications of various specific mutations, including specific mutations in ",
			"category": 2,
			"name": "Hardiman Karin M,2021"
		},
		{
			"PMID": 29717121,
			"title": "Validating the concept of mutational signatures with isogenic cell models.",
			"journal": "Nature communications",
			"authorList": [
				"Zou Xueqing",
				"Owusu Michel",
				"Harris Rebecca",
				"Jackson Stephen P",
				"Loizou Joanna I",
				"Nik-Zainal Serena"
			],
			"DOI": "10.1038/s41467-018-04052-8",
			"date": "2018-12-11",
			"PMC": "",
			"citation": "",
			"abstract": "The diversity of somatic mutations in human cancers can be decomposed into individual mutational signatures, patterns of mutagenesis that arise because of DNA damage and DNA repair processes that have occurred in cells as they evolved towards malignancy. Correlations between mutational signatures and environmental exposures, enzymatic activities and genetic defects have been described, but human cancers are not ideal experimental systems-the exposures to different mutational processes in a patient's lifetime are uncontrolled and any relationships observed can only be described as an association. Here, we demonstrate the proof-of-principle that it is possible to recreate cancer mutational signatures in vitro using CRISPR-Cas9-based gene-editing experiments in an isogenic human-cell system. We provide experimental and algorithmic methods to discover mutational signatures generated under highly experimentally-controlled conditions. Our in vitro findings strikingly recapitulate in vivo observations of cancer data, fundamentally validating the concept of (particularly) endogenously-arising mutational signatures.",
			"category": 2,
			"name": "Zou Xueqing,2018"
		},
		{
			"PMID": 29713164,
			"title": "Global trends in nanomedicine research on triple negative breast cancer: a bibliometric analysis.",
			"journal": "International journal of nanomedicine",
			"authorList": [
				"Teles Ramon Handerson Gomes",
				"Moralles Herick Fernando",
				"Cominetti M\u00e1rcia Regina"
			],
			"DOI": "10.2147/IJN.S164355",
			"date": "2018-06-11",
			"PMC": "",
			"citation": "",
			"abstract": "Nanotechnology has emerged as a promising tool in the clinic to combat several difficult-to-manage diseases, such as cancer, which is the second leading cause of death worldwide. Chemotherapeutic drugs present several limitations such as undesired side effects, low specificity, resistance, and high relapse rates. Triple negative breast cancer (TNBC) is caused by cells that lack specific receptors in their membrane, such as estrogen (ER+) and progesterone (PR+) receptors, or by cells that do not express the amplification of human epidermal growth factor receptor-2 (HER-2+). This cancer type has poor prognosis, high relapse rates, and no targeted therapies. Thus, this study aimed to investigate the trends of nanotechnology research in TNBC and compare the contribution of research from different regions, institutions, and authors. A search of the studies published between 2012 and 2017, related to nanotechnology and TNBC, with different keyword combinations, was performed in the Scopus database. The keywords found in this search were grouped into four clusters, in which \"breast cancer\" was the most mentioned (1,133 times) and the word \"MCF-7 cell line\" is one of the latest hotspots that appeared in the year 2016. A total of 1,932 articles, which were cited 26,450 times, were identified. The USA accounted for 28.36% of the articles and 27.61% of the citations; however, none of its centers appeared in the list of 10 most productive ones in terms of publications. The journals ",
			"category": 2,
			"name": "Teles Ramon Handerson Gomes,2018"
		},
		{
			"PMID": 29713020,
			"title": "Pathway-based dissection of the genomic heterogeneity of cancer hallmarks' acquisition with SLAPenrich.",
			"journal": "Scientific reports",
			"authorList": [
				"Iorio Francesco",
				"Garcia-Alonso Luz",
				"Brammeld Jonathan S",
				"Martincorena I\u0148igo",
				"Wille David R",
				"McDermott Ultan",
				"Saez-Rodriguez Julio"
			],
			"DOI": "10.1038/s41598-018-25076-6",
			"date": "2019-10-03",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer hallmarks are evolutionary traits required by a tumour to develop. While extensively characterised, the way these traits are achieved through the accumulation of somatic mutations in key biological pathways is not fully understood. To shed light on this subject, we characterised the landscape of pathway alterations associated with somatic mutations observed in 4,415 patients across ten cancer types, using 374 orthogonal pathway gene-sets mapped onto canonical cancer hallmarks. Towards this end, we developed SLAPenrich: a computational method based on population-level statistics, freely available as an open source R package. Assembling the identified pathway alterations into sets of hallmark signatures allowed us to connect somatic mutations to clinically interpretable cancer mechanisms. Further, we explored the heterogeneity of these signatures, in terms of ratio of altered pathways associated with each individual hallmark, assuming that this is reflective of the extent of selective advantage provided to the cancer type under consideration. Our analysis revealed the predominance of certain hallmarks in specific cancer types, thus suggesting different evolutionary trajectories across cancer lineages. Finally, although many pathway alteration enrichments are guided by somatic mutations in frequently altered high-confidence cancer genes, excluding these driver mutations preserves the hallmark heterogeneity signatures, thus the detected hallmarks' predominance across cancer types. As a consequence, we propose the hallmark signatures as a ground truth to characterise tails of infrequent genomic alterations and identify potential novel cancer driver genes and networks.",
			"category": 2,
			"name": "Iorio Francesco,2019"
		},
		{
			"PMID": 29697749,
			"title": "How to talk about genome editing.",
			"journal": "British medical bulletin",
			"authorList": [
				"Starr Sandy"
			],
			"DOI": "10.1093/bmb/ldy015",
			"date": "2019-07-22",
			"PMC": "",
			"citation": "",
			"abstract": "Human genome editing is an area of growing prominence, with many potential therapeutic applications.",
			"category": 2,
			"name": "Starr Sandy,2019"
		},
		{
			"PMID": 29697361,
			"title": "Mut2Vec: distributed representation of cancerous mutations.",
			"journal": "BMC medical genomics",
			"authorList": [
				"Kim Sunkyu",
				"Lee Heewon",
				"Kim Keonwoo",
				"Kang Jaewoo"
			],
			"DOI": "10.1186/s12920-018-0349-7",
			"date": "2019-05-29",
			"PMC": "",
			"citation": "",
			"abstract": "Embedding techniques for converting high-dimensional sparse data into low-dimensional distributed representations have been gaining popularity in various fields of research. In deep learning models, embedding is commonly used and proven to be more effective than naive binary representation. However, yet no attempt has been made to embed highly sparse mutation profiles into densely distributed representations. Since binary representation does not capture biological context, its use is limited in many applications such as discovering novel driver mutations. Additionally, training distributed representations of mutations is challenging due to a relatively small amount of available biological data compared with the large amount of text corpus data in text mining fields.",
			"category": 2,
			"name": "Kim Sunkyu,2019"
		},
		{
			"PMID": 29695914,
			"title": "Role of the NF\u03baB-signaling pathway in cancer.",
			"journal": "OncoTargets and therapy",
			"authorList": [
				"Xia Longzheng",
				"Tan Shiming",
				"Zhou Yujuan",
				"Lin Jingguan",
				"Wang Heran",
				"Oyang Linda",
				"Tian Yutong",
				"Liu Lu",
				"Su Min",
				"Wang Hui",
				"Cao Deliang",
				"Liao Qianjin"
			],
			"DOI": "10.2147/OTT.S161109",
			"date": "2024-03-23",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a group of cells that malignantly grow and proliferate uncontrollably. At present, treatment modes for cancer mainly comprise surgery, chemotherapy, radiotherapy, molecularly targeted therapy, gene therapy, and immunotherapy. However, the curative effects of these treatments have been limited thus far by specific characteristics of tumors. Abnormal activation of signaling pathways is involved in tumor pathogenesis and plays critical roles in growth, progression, and relapse of cancers. Targeted therapies against effectors in oncogenic signaling have improved the outcomes of cancer patients. NF\u03baB is an important signaling pathway involved in pathogenesis and treatment of cancers. Excessive activation of the NF\u03baB-signaling pathway has been documented in various tumor tissues, and studies on this signaling pathway for targeted cancer therapy have become a hot topic. In this review, we update current understanding of the NF\u03baB-signaling pathway in cancer.",
			"category": 2,
			"name": "Xia Longzheng,2024"
		},
		{
			"PMID": 29693804,
			"title": "Synergistic Growth Inhibitory Effects of Chrysin and Metformin Combination on Breast Cancer Cells through hTERT and Cyclin D1 Suppression.",
			"journal": "Asian Pacific journal of cancer prevention : APJCP",
			"authorList": [
				"Rasouli Sara",
				"Zarghami Nosratollah"
			],
			"DOI": "",
			"date": "2018-09-26",
			"PMC": "",
			"citation": "",
			"abstract": "Objective: To explore the possibility of a novel chemopreventive strategy for improving breast cancer treatment, the anticancer effects of a combination two natural compounds, Chrysin and Metformin, against T47D breast cancer cells were investigated. Materials and Methods: After treatment of T47D cells with Metformin, Chrysin and the two drugs in combination, toxicity to cancer cells was evaluated by MTT assay. Real time PCR was then used to determine the expression levels of hTERT and cyclin D1 genes. Results: The MTT test findings showed that the combination of metformin and chrysin had high synergistic effects in killing cancer cells. In addition PCR demonstrated a significant decrease in cyclin D1 and hTERT gene expression in the T47D breast cancer cell line. Conclusion: The conmbination of metformin and chrysin suppressing hTERT and cyclin D1 gene expression might offer an appropriate approach for breast cancer therapy.",
			"category": 2,
			"name": "Rasouli Sara,2018"
		},
		{
			"PMID": 29673314,
			"title": "A site specific model and analysis of the neutral somatic mutation rate in whole-genome cancer data.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"Bertl Johanna",
				"Guo Qianyun",
				"Juul Malene",
				"Besenbacher S\u00f8ren",
				"Nielsen Morten Muhlig",
				"Hornsh\u00f8j Henrik",
				"Pedersen Jakob Skou",
				"Hobolth Asger"
			],
			"DOI": "10.1186/s12859-018-2141-2",
			"date": "2018-10-29",
			"PMC": "",
			"citation": "",
			"abstract": "Detailed modelling of the neutral mutational process in cancer cells is crucial for identifying driver mutations and understanding the mutational mechanisms that act during cancer development. The neutral mutational process is very complex: whole-genome analyses have revealed that the mutation rate differs between cancer types, between patients and along the genome depending on the genetic and epigenetic context. Therefore, methods that predict the number of different types of mutations in regions or specific genomic elements must consider local genomic explanatory variables. A major drawback of most methods is the need to average the explanatory variables across the entire region or genomic element. This procedure is particularly problematic if the explanatory variable varies dramatically in the element under consideration.",
			"category": 2,
			"name": "Bertl Johanna,2018"
		},
		{
			"PMID": 29657279,
			"title": "oncoNcRNA: A Web Portal for Exploring the Non-Coding RNAs with Oncogenic Potentials in Human Cancers.",
			"journal": "Non-coding RNA",
			"authorList": [
				"Wang Ze-Lin",
				"Zhang Xiao-Qin",
				"Zhou Hui",
				"Yang Jian-Hua",
				"Qu Liang-Hu"
			],
			"DOI": "10.3390/ncrna3010007",
			"date": "2020-09-29",
			"PMC": "",
			"citation": "",
			"abstract": "Non-coding RNAs (ncRNAs) have been shown to contribute to tumorigenesis and progression. However, the functions of the majority of ncRNAs remain unclear. Through integrating published large-scale somatic copy number alterations (SCNAs) data from various human cancer types, we have developed oncoNcRNA, a user-friendly web portal to explore ncRNAs with oncogenic potential in human cancers. The portal characterizes the SCNAs of over 58,000 long non-coding RNAs (lncRNAs), 34,000 piwi-interacting RNAs (piRNAs), 2700 microRNAs (miRNAs), 600 transfer RNAs (tRNAs) and 400 small nucleolar RNAs (snoRNAs) in 64 human cancer types. It enables researchers to rapidly and intuitively analyze the oncogenic potential of ncRNAs of interest. Indeed, we have discovered a large number of ncRNAs which are frequently amplified or deleted within and across tumor types. Moreover, we built a web-based tool, Correlations, to explore the relationships between gene expression and copy number from ~10,000 tumor samples in 36 cancer types identified by The Cancer Genome Atlas (TCGA). oncoNcRNA is a valuable tool for investigating the function and clinical relevance of ncRNAs in human cancers. oncoNcRNA is freely available at http://rna.sysu.edu.cn/onconcrna/.",
			"category": 2,
			"name": "Wang Ze-Lin,2020"
		},
		{
			"PMID": 29581875,
			"title": "Vive la radior\u00e9sistance!: converging research in radiobiology and biogerontology to enhance human radioresistance for deep space exploration and colonization.",
			"journal": "Oncotarget",
			"authorList": [
				"Cortese Franco",
				"Klokov Dmitry",
				"Osipov Andreyan",
				"Stefaniak Jakub",
				"Moskalev Alexey",
				"Schastnaya Jane",
				"Cantor Charles",
				"Aliper Alexander",
				"Mamoshina Polina",
				"Ushakov Igor",
				"Sapetsky Alex",
				"Vanhaelen Quentin",
				"Alchinova Irina",
				"Karganov Mikhail",
				"Kovalchuk Olga",
				"Wilkins Ruth",
				"Shtemberg Andrey",
				"Moreels Marjan",
				"Baatout Sarah",
				"Izumchenko Evgeny",
				"de Magalh\u00e3es Jo\u00e3o Pedro",
				"Artemov Artem V",
				"Costes Sylvain V",
				"Beheshti Afshin",
				"Mao Xiao Wen",
				"Pecaut Michael J",
				"Kaminskiy Dmitry",
				"Ozerov Ivan V",
				"Scheibye-Knudsen Morten",
				"Zhavoronkov Alex"
			],
			"DOI": "10.18632/oncotarget.24461",
			"date": "2023-11-12",
			"PMC": "",
			"citation": "",
			"abstract": "While many efforts have been made to pave the way toward human space colonization, little consideration has been given to the methods of protecting spacefarers against harsh cosmic and local radioactive environments and the high costs associated with protection from the deleterious physiological effects of exposure to high-Linear energy transfer (high-LET) radiation. Herein, we lay the foundations of a roadmap toward enhancing human radioresistance for the purposes of deep space colonization and exploration. We outline future research directions toward the goal of enhancing human radioresistance, including upregulation of endogenous repair and radioprotective mechanisms, possible leeways into gene therapy in order to enhance radioresistance via the translation of exogenous and engineered DNA repair and radioprotective mechanisms, the substitution of organic molecules with fortified isoforms, and methods of slowing metabolic activity while preserving cognitive function. We conclude by presenting the known associations between radioresistance and longevity, and articulating the position that enhancing human radioresistance is likely to extend the healthspan of human spacefarers as well.",
			"category": 2,
			"name": "Cortese Franco,2023"
		},
		{
			"PMID": 29576621,
			"title": "The mechanism study of lentiviral vector carrying methioninase enhances the sensitivity of drug-resistant gastric cancer cells to Cisplatin.",
			"journal": "British journal of cancer",
			"authorList": [
				"Xin Lin",
				"Yang Wei-Feng",
				"Zhang Hou-Ting",
				"Li Yi-Fan",
				"Liu Chuan"
			],
			"DOI": "10.1038/s41416-018-0043-8",
			"date": "2019-06-10",
			"PMC": "",
			"citation": "",
			"abstract": "To investigate the mechanism of lentiviral vector carrying methioninase enhances the sensitivity of drug-resistant gastric cancer cells to Cisplatin.",
			"category": 2,
			"name": "Xin Lin,2019"
		},
		{
			"PMID": 29567676,
			"title": "Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA ",
			"journal": "Genome research",
			"authorList": [
				"Shah Maitri Y",
				"Ferracin Manuela",
				"Pileczki Valentina",
				"Chen Baoqing",
				"Redis Roxana",
				"Fabris Linda",
				"Zhang Xinna",
				"Ivan Cristina",
				"Shimizu Masayoshi",
				"Rodriguez-Aguayo Cristian",
				"Dragomir Mihnea",
				"Van Roosbroeck Katrien",
				"Almeida Maria Ines",
				"Ciccone Maria",
				"Nedelcu Daniela",
				"Cortez Maria Angelica",
				"Manshouri Taghi",
				"Calin Steliana",
				"Muftuoglu Muharrem",
				"Banerjee Pinaki P",
				"Badiwi Mustafa H",
				"Parker-Thornburg Jan",
				"Multani Asha",
				"Welsh James William",
				"Estecio Marcos Roberto",
				"Ling Hui",
				"Tomuleasa Ciprian",
				"Dima Delia",
				"Yang Hui",
				"Alvarez Hector",
				"You M James",
				"Radovich Milan",
				"Shpall Elizabeth",
				"Fabbri Muller",
				"Rezvani Katy",
				"Girnita Leonard",
				"Berindan-Neagoe Ioana",
				"Maitra Anirban",
				"Verstovsek Srdan",
				"Fodde Riccardo",
				"Bueso-Ramos Carlos",
				"Gagea Mihai",
				"Manero Guillermo Garcia",
				"Calin George A"
			],
			"DOI": "10.1101/gr.225128.117",
			"date": "2018-10-05",
			"PMC": "",
			"citation": "",
			"abstract": "The cancer-risk-associated rs6983267 single nucleotide polymorphism (SNP) and the accompanying long noncoding RNA ",
			"category": 2,
			"name": "Shah Maitri Y,2018"
		},
		{
			"PMID": 29560343,
			"title": "Phenotypic Plasticity, Bet-Hedging, and Androgen Independence in Prostate Cancer: Role of Non-Genetic Heterogeneity.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Jolly Mohit Kumar",
				"Kulkarni Prakash",
				"Weninger Keith",
				"Orban John",
				"Levine Herbert"
			],
			"DOI": "10.3389/fonc.2018.00050",
			"date": "2024-03-18",
			"PMC": "",
			"citation": "",
			"abstract": "It is well known that genetic mutations can drive drug resistance and lead to tumor relapse. Here, we focus on alternate mechanisms-those without mutations, such as phenotypic plasticity and stochastic cell-to-cell variability that can also evade drug attacks by giving rise to drug-tolerant persisters. The phenomenon of persistence has been well-studied in bacteria and has also recently garnered attention in cancer. We draw a parallel between bacterial persistence and resistance against androgen deprivation therapy in prostate cancer (PCa), the primary standard care for metastatic disease. We illustrate how phenotypic plasticity and consequent mutation-independent or non-genetic heterogeneity possibly driven by protein conformational dynamics can stochastically give rise to androgen independence in PCa, and suggest that dynamic phenotypic plasticity should be considered in devising therapeutic dosing strategies designed to treat and manage PCa.",
			"category": 2,
			"name": "Jolly Mohit Kumar,2024"
		},
		{
			"PMID": 29535811,
			"title": "Thyroid follicular adenomas and carcinomas: molecular profiling provides evidence for a continuous evolution.",
			"journal": "Oncotarget",
			"authorList": [
				"Dom Genevi\u00e8ve",
				"Frank Sandra",
				"Floor Sebastien",
				"Kehagias Pashalina",
				"Libert Frederick",
				"Hoang Catherine",
				"Andry Guy",
				"Spinette Alex",
				"Craciun Ligia",
				"de Saint Aubin Nicolas",
				"Tresallet Christophe",
				"Tissier Frederique",
				"Savagner Frederique",
				"Majjaj Samira",
				"Gutierrez-Roelens Ilse",
				"Marbaix Etienne",
				"Dumont Jacques E",
				"Maenhaut Carine"
			],
			"DOI": "10.18632/oncotarget.23130",
			"date": "2023-11-05",
			"PMC": "",
			"citation": "",
			"abstract": "Non-autonomous thyroid nodules are common in the general population with a proportion found to be cancerous. A current challenge in the field is to be able to distinguish benign adenoma (FA) from preoperatively malignant thyroid follicular carcinoma (FTC), which are very similar both histologically and genetically. One controversial issue, which is currently not understood, is whether both tumor types represent different molecular entities or rather a biological continuum. To gain a better insight into FA and FTC tumorigenesis, we defined their molecular profiles by mRNA and miRNA microarray. Expression data were analyzed, validated by qRT-PCR and compared with previously published data sets. The majority of deregulated mRNAs were common between FA and FTC and were downregulated, however FTC showed additional deregulated mRNA. Both types of tumors share deregulated pathways, molecular functions and biological processes. The additional deregulations in FTC include the lipid transport process that may be involved in tumor progression. The strongest candidate genes which may be able to discriminate follicular adenomas and carcinomas, CRABP1, FABP4 and HMGA2, were validated in independent samples by qRT-PCR and immunohistochemistry. However, they were not able to adequately classify FA or FTC, supporting the notion of continuous evolving tumors, whereby FA and FTC appear to show quantitative rather than qualitative changes. Conversely, miRNA expression profiles showed few dysregulations in FTC, and even fewer in FA, suggesting that miRNA play a minor, if any, role in tumor progression.",
			"category": 2,
			"name": "Dom Genevi\u00e8ve,2023"
		},
		{
			"PMID": 29515689,
			"title": "The crucial role of multiomic approach in cancer research and clinically relevant outcomes.",
			"journal": "The EPMA journal",
			"authorList": [
				"Lu Miaolong",
				"Zhan Xianquan"
			],
			"DOI": "10.1007/s13167-018-0128-8",
			"date": "2023-11-05",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer with heavily economic and social burden is the hot point in the field of medical research. Some remarkable achievements have been made; however, the exact mechanisms of tumor initiation and development remain unclear. Cancer is a complex, whole-body disease that involves multiple abnormalities in the levels of DNA, RNA, protein, metabolite and medical imaging. Biological omics including genomics, transcriptomics, proteomics, metabolomics and radiomics aims to systematically understand carcinogenesis in different biological levels, which is driving the shift of cancer research paradigm from single parameter model to multi-parameter systematical model. The rapid development of various omics technologies is driving one to conveniently get multi-omics data, which accelerates predictive, preventive and personalized medicine (PPPM) practice allowing prediction of response with substantially increased accuracy, stratification of particular patients and eventual personalization of medicine. This review article describes the methodology, advances, and clinically relevant outcomes of different \"omics\" technologies in cancer research, and especially emphasizes the importance and scientific merit of integrating multi-omics in cancer research and clinically relevant outcomes.",
			"category": 2,
			"name": "Lu Miaolong,2023"
		},
		{
			"PMID": 29504908,
			"title": "Exome analysis of carotid body tumor.",
			"journal": "BMC medical genomics",
			"authorList": [
				"Snezhkina Anastasiya V",
				"Lukyanova Elena N",
				"Kalinin Dmitry V",
				"Pokrovsky Anatoly V",
				"Dmitriev Alexey A",
				"Koroban Nadezhda V",
				"Pudova Elena A",
				"Fedorova Maria S",
				"Volchenko Nadezhda N",
				"Stepanov Oleg A",
				"Zhevelyuk Ekaterina A",
				"Kharitonov Sergey L",
				"Lipatova Anastasiya V",
				"Abramov Ivan S",
				"Golovyuk Alexander V",
				"Yegorov Yegor E",
				"Vishnyakova Khava S",
				"Moskalev Alexey A",
				"Krasnov George S",
				"Melnikova Nataliya V",
				"Shcherbo Dmitry S",
				"Kiseleva Marina V",
				"Kaprin Andrey D",
				"Alekseev Boris Y",
				"Zaretsky Andrew R",
				"Kudryavtseva Anna V"
			],
			"DOI": "10.1186/s12920-018-0327-0",
			"date": "2019-06-07",
			"PMC": "",
			"citation": "",
			"abstract": "Carotid body tumor (CBT) is a form of head and neck paragangliomas (HNPGLs) arising at the bifurcation of carotid arteries. Paragangliomas are commonly associated with germline and somatic mutations involving at least one of more than thirty causative genes. However, the specific functionality of a number of these genes involved in\u00a0the formation of paragangliomas has not yet been fully investigated.",
			"category": 2,
			"name": "Snezhkina Anastasiya V,2019"
		},
		{
			"PMID": 29503867,
			"title": "Mapping a functional cancer genome atlas of tumor suppressors in mouse liver using AAV-CRISPR-mediated direct in vivo screening.",
			"journal": "Science advances",
			"authorList": [
				"Wang Guangchuan",
				"Chow Ryan D",
				"Ye Lupeng",
				"Guzman Christopher D",
				"Dai Xiaoyun",
				"Dong Matthew B",
				"Zhang Feng",
				"Sharp Phillip A",
				"Platt Randall J",
				"Chen Sidi"
			],
			"DOI": "10.1126/sciadv.aao5508",
			"date": "2019-09-04",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer genomics consortia have charted the landscapes of numerous human cancers. Whereas some mutations were found in classical oncogenes and tumor suppressors, others have not yet been functionally studied in vivo. To date, a comprehensive assessment of how these genes influence oncogenesis is lacking. We performed direct high-throughput in vivo mapping of functional variants in an autochthonous mouse model of cancer. Using adeno-associated viruses (AAVs) carrying a single-guide RNA (sgRNA) library targeting putative tumor suppressor genes significantly mutated in human cancers, we directly pool-mutagenized the livers of Cre-inducible CRISPR (clustered regularly interspaced short palindromic repeats)-associated protein 9 (Cas9) mice. All mice that received the AAV-mTSG library developed liver cancer and died within 4 months. We used molecular inversion probe sequencing of the sgRNA target sites to chart the mutational landscape of these tumors, revealing the functional consequence of multiple variants in driving liver tumorigenesis in immunocompetent mice. AAV-mediated autochthonous CRISPR screens provide a powerful means for mapping a provisional functional cancer genome atlas of tumor suppressors in vivo.",
			"category": 2,
			"name": "Wang Guangchuan,2019"
		},
		{
			"PMID": 29499836,
			"title": "New tools for old drugs: Functional genetic screens to optimize current chemotherapy.",
			"journal": "Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy",
			"authorList": [
				"Gerhards Nora M",
				"Rottenberg Sven"
			],
			"DOI": "10.1016/j.drup.2018.01.001",
			"date": "2018-12-11",
			"PMC": "",
			"citation": "",
			"abstract": "Despite substantial advances in the treatment of various cancers, many patients still receive anti-cancer therapies that hardly eradicate tumor cells but inflict considerable side effects. To provide the best treatment regimen for an individual patient, a major goal in molecular oncology is to identify predictive markers for a personalized therapeutic strategy. Regarding novel targeted anti-cancer therapies, there are usually good markers available. Unfortunately, however, targeted therapies alone often result in rather short remissions and little cytotoxic effect on the cancer cells. Therefore, classical chemotherapy with frequent long remissions, cures, and a clear effect on cancer cell eradication remains a corner stone in current anti-cancer therapy. Reliable biomarkers which predict the response of tumors to classical chemotherapy are rare, in contrast to the situation for targeted therapy. For the bulk of cytotoxic therapeutic agents, including DNA-damaging drugs, drugs targeting microtubules or antimetabolites, there are still no reliable biomarkers used in the clinic to predict tumor response. To make progress in this direction, meticulous studies of classical chemotherapeutic drug action and resistance mechanisms are required. For this purpose, novel functional screening technologies have emerged as successful technologies to study chemotherapeutic drug response in a variety of models. They allow a systematic analysis of genetic contributions to a drug-responsive or -sensitive phenotype and facilitate a better understanding of the mode of action of these drugs. These functional genomic approaches are not only useful for the development of novel targeted anti-cancer drugs but may also guide the use of classical chemotherapeutic drugs by deciphering novel mechanisms influencing a tumor's drug response. Moreover, due to the advances of 3D organoid cultures from patient tumors and in vivo screens in mice, these genetic screens can be applied using conditions that are more representative of the clinical setting. Patient-derived 3D organoid lines furthermore allow the characterization of the \"essentialome\", the specific set of genes required for survival of these cells, of an individual tumor, which could be monitored over the course of treatment and help understanding how drug resistance evolves in clinical tumors. Thus, we expect that these functional screens will enable the discovery of novel cancer-specific vulnerabilities, and through clinical validation, move the field of predictive biomarkers forward. This review focuses on novel advanced techniques to decipher the interplay between genetic alterations and drug response.",
			"category": 2,
			"name": "Gerhards Nora M,2018"
		},
		{
			"PMID": 29485617,
			"title": "Applying Expression Profile Similarity for Discovery of Patient-Specific Functional Mutations.",
			"journal": "High-throughput",
			"authorList": [
				"Meng Guofeng"
			],
			"DOI": "10.3390/ht7010006",
			"date": "2023-11-05",
			"PMC": "",
			"citation": "",
			"abstract": "The progress of cancer genome sequencing projects yields unprecedented information of mutations for numerous patients. However, the complexity of mutation profiles of cancer patients hinders the further understanding to mechanisms of oncogenesis. One basic question is how to find mutations with functional impacts. In this work, we introduce a computational method to predict functional somatic mutations of each patient by integrating mutation recurrence with expression profile similarity. With this method, the functional mutations are determined by checking the mutation enrichment among a group of patients with similar expression profiles. We applied this method to three cancer types and identified the functional mutations. Comparison of the predictions for three cancer types suggested that most of the functional mutations were cancer-type-specific with one exception to ",
			"category": 2,
			"name": "Meng Guofeng,2023"
		},
		{
			"PMID": 29479084,
			"title": "Stretching the limits: from homeostasis to stem cell plasticity in wound healing and cancer.",
			"journal": "Nature reviews. Genetics",
			"authorList": [
				"Ge Yejing",
				"Fuchs Elaine"
			],
			"DOI": "10.1038/nrg.2018.9",
			"date": "2019-07-16",
			"PMC": "",
			"citation": "",
			"abstract": "Stem cells (SCs) govern tissue homeostasis and wound repair. They reside within niches, the special microenvironments within tissues that control SC lineage outputs. Upon injury or stress, new signals emanating from damaged tissue can divert nearby cells into adopting behaviours that are not part of their homeostatic repertoire. This behaviour, known as SC plasticity, typically resolves as wounds heal. However, in cancer, it can endure. Recent studies have yielded insights into the orchestrators of maintenance and lineage commitment for SCs belonging to three mammalian tissues: the haematopoietic system, the skin epithelium and the intestinal epithelium. We delineate the multifactorial determinants and general principles underlying the remarkable facets of SC plasticity, which lend promise for regenerative medicine and cancer therapeutics.",
			"category": 2,
			"name": "Ge Yejing,2019"
		},
		{
			"PMID": 29471004,
			"title": "Prostate cancer chemoprevention by natural agents: Clinical evidence and potential implications.",
			"journal": "Cancer letters",
			"authorList": [
				"Chhabra Gagan",
				"Singh Chandra K",
				"Ndiaye Mary Ann",
				"Fedorowicz Samantha",
				"Molot Arielle",
				"Ahmad Nihal"
			],
			"DOI": "10.1016/j.canlet.2018.02.025",
			"date": "2019-05-21",
			"PMC": "",
			"citation": "",
			"abstract": "Prostate cancer (PCa) is the most common non-skin cancer and the second leading cause of cancer-related deaths in American men. Due to its long latency period, PCa is considered as an ideal cancer type for chemopreventive interventions. Chemopreventive agents include various natural or synthetic agents that prevent or delay cancer development, progression and/or recurrence. Pre-clinical studies suggest that many natural products and dietary agents have chemopreventive properties. However, a limited number of these agents have been tested in clinical trials, with varying success. In this review, we have discussed the available clinical studies regarding the efficacy of natural chemopreventive agents against PCa, including tea polyphenols, selenium, soy proteins, vitamins and resveratrol. We have also provided a discussion on the clinical challenges and opportunities for the potential use of chemopreventive agents against PCa. Based on available literature, it appears that the variable outcomes of the chemopreventive clinical studies necessitate a need for additional studies with more rigorous designs and methodical interpretations in order to measure the potential of the natural agents against PCa.",
			"category": 2,
			"name": "Chhabra Gagan,2019"
		},
		{
			"PMID": 29468138,
			"title": "Editorial: Inter-Organelle Calcium Communication in Cancer.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Cardenas Cesar",
				"Pinton Paolo",
				"Bultynck Geert"
			],
			"DOI": "10.3389/fonc.2018.00014",
			"date": "2024-03-13",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Cardenas Cesar,2024"
		},
		{
			"PMID": 29467476,
			"title": "A Simple 3-Parameter Model for Cancer Incidences.",
			"journal": "Scientific reports",
			"authorList": [
				"Zhang Xiaoxiao",
				"Fr\u00f6hlich Holger",
				"Grigoriev Dima",
				"Vakulenko Sergey",
				"Zimmermann J\u00f6rg",
				"Weber Andreas G\u00fcnter"
			],
			"DOI": "10.1038/s41598-018-21734-x",
			"date": "2019-09-06",
			"PMC": "",
			"citation": "",
			"abstract": "We propose a simple 3-parameter model that provides very good fits for incidence curves of 18 common solid cancers even when variations due to different locations, races, or periods are taken into account. From a data perspective, we use model selection (Akaike information criterion) to show that this model, which is based on the Weibull distribution, outperforms other simple models like the Gamma distribution. From a modeling perspective, the Weibull distribution can be justified as modeling the accumulation of driver events, which establishes a link to stem cell division based cancer development models and a connection to a recursion formula for intrinsic cancer risk published by Wu et al. For the recursion formula a closed form solution is given, which will help to simplify future analyses. Additionally, we perform a sensitivity analysis for the parameters, showing that two of the three parameters can vary over several orders of magnitude. However, the shape parameter of the Weibull distribution, which corresponds to the number of driver mutations required for cancer onset, can be robustly estimated from epidemiological data.",
			"category": 2,
			"name": "Zhang Xiaoxiao,2019"
		},
		{
			"PMID": 29467187,
			"title": null,
			"journal": "G3 (Bethesda, Md.)",
			"authorList": [
				"Rossi Fabrizio",
				"Attolini Camille Stephan-Otto",
				"Mosquera Jose Luis",
				"Gonzalez Cayetano"
			],
			"DOI": "10.1534/g3.117.300489",
			"date": "2018-11-06",
			"PMC": "",
			"citation": "",
			"abstract": "Single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) are found at different rates in human cancer. To determine if these genetic lesions appear in Drosophila tumors we have sequenced the genomes of 17 malignant neoplasms caused by mutations ",
			"category": 2,
			"name": "Rossi Fabrizio,2018"
		},
		{
			"PMID": 29458961,
			"title": "The Genetic/Non-genetic Duality of Drug 'Resistance' in Cancer.",
			"journal": "Trends in cancer",
			"authorList": [
				"Salgia Ravi",
				"Kulkarni Prakash"
			],
			"DOI": "10.1016/j.trecan.2018.01.001",
			"date": "2018-12-11",
			"PMC": "",
			"citation": "",
			"abstract": "Drug resistance is a serious impediment to the treatment of cancer. However, the mechanisms involved remain poorly understood. While it is widely held that the phenomenon is genetic in nature, emerging evidence suggests that non-genetic mechanisms may also be important. Furthermore, at least in some cases, refractoriness to treatment can be reversed by epigenetic reprogramming, and combination and intermittent therapies, as opposed to sustained monotherapy, appear more effective in attenuating it. Here we iterate the confusion in understanding the phenomenon by which cancer cells evade drug response and underscore the need to recognize the genetic/non-genetic duality of drug resistance in cancer. We discuss how ecological and evolutionary principles may help to reconcile the duality and may even offer new treatment strategies.",
			"category": 2,
			"name": "Salgia Ravi,2018"
		},
		{
			"PMID": 29434197,
			"title": "BRD4 regulates cellular senescence in gastric cancer cells via E2F/miR-106b/p21 axis.",
			"journal": "Cell death & disease",
			"authorList": [
				"Dong Xingchen",
				"Hu Xiangming",
				"Chen Jinjing",
				"Hu Dan",
				"Chen Lin-Feng"
			],
			"DOI": "10.1038/s41419-017-0181-6",
			"date": "2019-09-16",
			"PMC": "",
			"citation": "",
			"abstract": "Small molecules targeting bromodomains of BET proteins possess strong anti-tumor activities and have emerged as potential therapeutics for cancer. However, the underlying mechanisms for the anti-proliferative activity of these inhibitors are still not fully characterized. In this study, we demonstrated that BET inhibitor JQ1 suppressed the proliferation and invasiveness of gastric cancer cells by inducing cellular senescence. Depletion of BRD4, which was overexpressed in gastric cancer tissues, but not other BET proteins recapitulated JQ1-induced cellular senescence with increased cellular SA-\u03b2-Gal activity and elevated p21 levels. In addition, we showed that the levels of p21 were regulated at the post-transcriptional level by BRD4-dependent expression of miR-106b-5p, which targets the 3'-UTR of p21 mRNA. Overexpression of miR-106b-5p prevented JQ1-induced p21 expression and BRD4 inhibition-associated cellular senescence, whereas miR-106b-5p inhibitor up-regulated p21 and induced cellular senescence. Finally, we demonstrated that inhibition of E2F suppressed the binding of BRD4 to the promoter of miR-106b-5p and inhibited its transcription, leading to the increased p21 levels and cellular senescence in gastric cancer cells. Our results reveal a novel mechanism by which BRD4 regulates cancer cell proliferation by modulating the cellular senescence through E2F/miR-106b-5p/p21 axis and provide new insights into using BET inhibitors as potential anticancer drugs.",
			"category": 2,
			"name": "Dong Xingchen,2019"
		},
		{
			"PMID": 29433427,
			"title": "MethCNA: a database for integrating genomic and epigenomic data in human cancer.",
			"journal": "BMC genomics",
			"authorList": [
				"Deng Gaofeng",
				"Yang Jian",
				"Zhang Qing",
				"Xiao Zhi-Xiong",
				"Cai Haoyang"
			],
			"DOI": "10.1186/s12864-018-4525-0",
			"date": "2018-08-20",
			"PMC": "",
			"citation": "",
			"abstract": "The integration of DNA methylation and copy number alteration data promises to provide valuable insight into the underlying molecular mechanisms responsible for cancer initiation and progression. However, the generation and processing of these datasets are costly and time-consuming if carried out separately. The Illumina Infinium HumanMethylation450 BeadChip, initially designed for the evaluation of DNA methylation levels, allows copy number variant calling using bioinformatics tools.",
			"category": 2,
			"name": "Deng Gaofeng,2018"
		},
		{
			"PMID": 29417354,
			"title": "Clonal dynamics in a case of acute monoblastic leukemia that later developed myeloproliferative neoplasm.",
			"journal": "International journal of hematology",
			"authorList": [
				"Sato Shinya",
				"Itonaga Hidehiro",
				"Taguchi Masataka",
				"Sawayama Yasushi",
				"Imanishi Daisuke",
				"Tsushima Hideki",
				"Hata Tomoko",
				"Moriuchi Yukiyoshi",
				"Mishima Hiroyuki",
				"Kinoshita Akira",
				"Yoshiura Koh-Ichiro",
				"Miyazaki Yasushi"
			],
			"DOI": "10.1007/s12185-018-2419-1",
			"date": "2018-09-06",
			"PMC": "",
			"citation": "",
			"abstract": "In acute myeloid leukemia (AML), patients may harbor pre-leukemic hematopoietic stem cells (HSCs) containing some, but not all, of the mutations observed in the leukemic cells. These pre-leukemic HSCs may survive induction chemotherapy and contribute to AML relapse by obtaining additional mutations. We report here an acute monoblastic leukemia (AMoL) patient who later developed an unclassifiable myeloproliferative neoplasm (MPN-U). Whole-exome sequencing and cluster analysis demonstrated the presence of three distinct major clones during the clinical course: (1) an AMoL clone with ASXL1, CBL, and NPM1 somatic mutations, likely associated with the pathogenesis, and GATA2, SRSF2, and TET2 mutations, (2) an AMoL remission clone, with mutated GATA2, SRSF2, and TET2 only (possibly the founding clone (pre-leukemic HSC) that survived chemotherapy), (3) a small subclone which had JAK2 mutation during the AMoL remission, appearing at MPN-U manifestation with additional mutations. These findings suggest that pre-leukemic HSCs in AML patients may give rise to non-AML myeloid malignancies. This is the first report to analyze the clonal evolution from AMoL to MPN-U, which may provide new insight into the development of myeloid malignancies.",
			"category": 2,
			"name": "Sato Shinya,2018"
		},
		{
			"PMID": 29416919,
			"title": "Mechanism of action of the atypical retinoid ST1926 in colorectal cancer: DNA damage and DNA polymerase \u03b1.",
			"journal": "American journal of cancer research",
			"authorList": [
				"Abdel-Samad Rana",
				"Aouad Patrick",
				"Gali-Muhtasib Hala",
				"Sweidan Zeinab",
				"Hmadi Raed",
				"Kadara Humam",
				"D'Andrea Egildo Luca",
				"Fucci Alessandra",
				"Pisano Claudio",
				"Darwiche Nadine"
			],
			"DOI": "",
			"date": "2020-09-29",
			"PMC": "",
			"citation": "",
			"abstract": "Despite advances in therapeutic strategies, colorectal cancer (CRC) remains the third cause of cancer-related deaths with a relatively low survival rate. Resistance to standard chemotherapy represents a major hurdle in disease management; therefore, developing new therapeutic agents demands a thorough understanding of their mechanisms of action. One of these compounds is ST1926, an adamantyl retinoid that has shown potent antitumor activities in several human cancer models. Here, we show that ST1926 selectively suppressed the proliferation of CRC cells while sparing normal counterparts, and significantly reduced tumor volume in a xenograft cancer mouse model. Next, we investigated the effects of ST1926 in CRC cells and observed early DNA damage, S-phase arrest, dissipation of mitochondrial membrane potential, and apoptosis induction, in a ",
			"category": 2,
			"name": "Abdel-Samad Rana,2020"
		},
		{
			"PMID": 29416824,
			"title": "The dawn of the liquid biopsy in the fight against cancer.",
			"journal": "Oncotarget",
			"authorList": [
				"Dom\u00ednguez-Vigil Irma G",
				"Moreno-Mart\u00ednez Ana K",
				"Wang Julia Y",
				"Roehrl Michael H A",
				"Barrera-Salda\u00f1a Hugo A"
			],
			"DOI": "10.18632/oncotarget.23131",
			"date": "2024-06-06",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a molecular disease associated with alterations in the genome, which, thanks to the highly improved sensitivity of mutation detection techniques, can be identified in cell-free DNA (cfDNA) circulating in blood, a method also called liquid biopsy. This is a non-invasive alternative to surgical biopsy and has the potential of revealing the molecular signature of tumors to aid in the individualization of treatments. In this review, we focus on cfDNA analysis, its advantages, and clinical applications employing genomic tools (NGS and dPCR) particularly in the field of oncology, and highlight its valuable contributions to early detection, prognosis, and prediction of treatment response.",
			"category": 2,
			"name": "Dom\u00ednguez-Vigil Irma G,2024"
		},
		{
			"PMID": 29358879,
			"title": "Construction of an oesophageal cancer-specific ceRNA network based on miRNA, lncRNA, and mRNA expression data.",
			"journal": "World journal of gastroenterology",
			"authorList": [
				"Xue Wen-Hua",
				"Fan Zhi-Rui",
				"Li Li-Feng",
				"Lu Jing-Li",
				"Ma Bing-Jun",
				"Kan Quan-Cheng",
				"Zhao Jie"
			],
			"DOI": "10.3748/wjg.v24.i1.23",
			"date": "2018-08-27",
			"PMC": "",
			"citation": "",
			"abstract": "To explore the expression profiles of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and mRNAs in oesophageal squamous cell carcinoma (ESCC) in order to construct an oesophageal cancer-specific competing endogenous RNA (ceRNA) network.",
			"category": 2,
			"name": "Xue Wen-Hua,2018"
		},
		{
			"PMID": 29358395,
			"title": "Genetic and epigenetic alterations in normal tissues have differential impacts on cancer risk among tissues.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Yamashita Satoshi",
				"Kishino Takayoshi",
				"Takahashi Takamasa",
				"Shimazu Taichi",
				"Charvat Hadrien",
				"Kakugawa Yasuo",
				"Nakajima Takeshi",
				"Lee Yi-Chia",
				"Iida Naoko",
				"Maeda Masahiro",
				"Hattori Naoko",
				"Takeshima Hideyuki",
				"Nagano Reiko",
				"Oda Ichiro",
				"Tsugane Shoichiro",
				"Wu Ming-Shiang",
				"Ushijima Toshikazu"
			],
			"DOI": "10.1073/pnas.1717340115",
			"date": "2018-08-01",
			"PMC": "",
			"citation": "",
			"abstract": "Genetic and epigenetic alterations are both involved in carcinogenesis, and their low-level accumulation in normal tissues constitutes cancer risk. However, their relative importance has never been examined, as measurement of low-level mutations has been difficult. Here, we measured low-level accumulations of genetic and epigenetic alterations in normal tissues with low, intermediate, and high cancer risk and analyzed their relative effects on cancer risk in the esophagus and stomach. Accumulation of genetic alterations, estimated as a frequency of rare base substitution mutations, significantly increased according to cancer risk in esophageal mucosae, but not in gastric mucosae. The mutation patterns reflected the exposure to lifestyle risk factors. In contrast, the accumulation of epigenetic alterations, measured as DNA methylation levels of marker genes, significantly increased according to cancer risk in both tissues. Patients with cancer (high-risk individuals) were precisely discriminated from healthy individuals with exposure to risk factors (intermediate-risk individuals) by a combination of alterations in the esophagus (odds ratio, 18.2; 95% confidence interval, 3.69-89.9) and by only epigenetic alterations in the stomach (odds ratio, 7.67; 95% confidence interval, 2.52-23.3). The relative importance of epigenetic alterations upon genetic alterations was 1.04 in the esophagus and 2.31 in the stomach. The differential impacts among tissues will be critically important for effective cancer prevention and precision cancer risk diagnosis.",
			"category": 2,
			"name": "Yamashita Satoshi,2018"
		},
		{
			"PMID": 29349042,
			"title": "An optimized targeted Next-Generation Sequencing approach for sensitive detection of single nucleotide variants.",
			"journal": "Biomolecular detection and quantification",
			"authorList": [
				"Stasik S",
				"Schuster C",
				"Ortlepp C",
				"Platzbecker U",
				"Bornh\u00e4user M",
				"Schetelig J",
				"Ehninger G",
				"Folprecht G",
				"Thiede C"
			],
			"DOI": "10.1016/j.bdq.2017.12.001",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "Monitoring of minimal residual disease (MRD) has become an important clinical aspect for early relapse detection during follow-up care after cancer treatment. Still, the sensitive detection of single base pair point mutations via Next-Generation Sequencing (NGS) is hampered mainly due to high substitution error rates. We evaluated the use of NGS for the detection of low-level variants on an Ion Torrent PGM system. As a model case we used the c.1849G\u202f>\u202fT (p.Val617Phe) mutation of the ",
			"category": 2,
			"name": "Stasik S,2020"
		},
		{
			"PMID": 29347918,
			"title": "Somatic evolutionary timings of driver mutations.",
			"journal": "BMC cancer",
			"authorList": [
				"Gomez Karen",
				"Miura Sayaka",
				"Huuki Louise A",
				"Spell Brianna S",
				"Townsend Jeffrey P",
				"Kumar Sudhir"
			],
			"DOI": "10.1186/s12885-017-3977-y",
			"date": "2018-08-07",
			"PMC": "",
			"citation": "",
			"abstract": "A unified analysis of DNA sequences from hundreds of tumors concluded that the driver mutations primarily occur in the earliest stages of cancer formation, with relatively few driver mutation events detected in the late-arising subclones. However, emerging evidence from the sequencing of multiple tumors and tumor regions per individual suggests that late-arising subclones with additional driver mutations are underestimated in single-sample analyses.",
			"category": 2,
			"name": "Gomez Karen,2018"
		},
		{
			"PMID": 29345757,
			"title": "Whole genome sequencing analysis for cancer genomics and precision medicine.",
			"journal": "Cancer science",
			"authorList": [
				"Nakagawa Hidewaki",
				"Fujita Masashi"
			],
			"DOI": "10.1111/cas.13505",
			"date": "2018-03-12",
			"PMC": "",
			"citation": "",
			"abstract": "Explosive advances in next-generation sequencer (NGS) and computational analyses have enabled exploration of somatic protein-altered mutations in most cancer types, with coding mutation data intensively accumulated. However, there is limited information on somatic mutations in non-coding regions, including introns, regulatory elements and non-coding RNA. Structural variants and pathogen in cancer genomes remain widely unexplored. Whole genome sequencing (WGS) approaches can be used to comprehensively explore all types of genomic alterations in cancer and help us to better understand the whole landscape of driver mutations and mutational signatures in cancer genomes and elucidate the functional or clinical implications of these unexplored genomic regions and mutational signatures. This review describes recently developed technical approaches for cancer WGS and the future direction of cancer WGS, and discusses its utility and limitations as an analysis platform and for mutation interpretation for cancer genomics and cancer precision medicine. Taking into account the diversity of cancer genomes and phenotypes, interpretation of abundant mutation information from WGS, especially non-coding and structure variants, requires the analysis of large-scale WGS data integrated with RNA-Seq, epigenomics, immuno-genomic and clinic-pathological information.",
			"category": 2,
			"name": "Nakagawa Hidewaki,2018"
		},
		{
			"PMID": 29343880,
			"title": "Novel Application of Loop-mediated Isothermal Amplification for Rapid Detection of Gene Translocation.",
			"journal": "Acta histochemica et cytochemica",
			"authorList": [
				"Matsuzaki Ibu",
				"Iguchi Hideto",
				"Mikasa Yurina",
				"Morishita Hiromu",
				"Okuda Katsuya",
				"Nakaguchi Keita",
				"Mori Yuki",
				"Iwahashi Yoshifumi",
				"Warigaya Kenji",
				"Fujimoto Masakazu",
				"Kojima Fumiyoshi",
				"Murata Shin-Ichi"
			],
			"DOI": "10.1267/ahc.17024",
			"date": "2024-03-13",
			"PMC": "",
			"citation": "",
			"abstract": "Identification of fusion genes in cancer is essential for pathological diagnosis and clinical therapy. Although methods for detection of fusion genes, such as fluorescence ",
			"category": 2,
			"name": "Matsuzaki Ibu,2024"
		},
		{
			"PMID": 29334356,
			"title": "p53 orchestrates DNA replication restart homeostasis by suppressing mutagenic RAD52 and POL\u03b8 pathways.",
			"journal": "eLife",
			"authorList": [
				"Roy Sunetra",
				"Tomaszowski Karl-Heinz",
				"Luzwick Jessica W",
				"Park Soyoung",
				"Li Jun",
				"Murphy Maureen",
				"Schlacher Katharina"
			],
			"DOI": "10.7554/eLife.31723",
			"date": "2019-08-16",
			"PMC": "",
			"citation": "",
			"abstract": "Classically, p53 tumor suppressor acts in transcription, apoptosis, and cell cycle arrest. Yet, replication-mediated genomic instability is integral to oncogenesis, and p53 mutations promote tumor progression and drug-resistance. By delineating human and murine separation-of-function p53 alleles, we find that p53 null and gain-of-function (GOF) mutations exhibit defects in restart of stalled or damaged DNA replication forks that drive genomic instability, which isgenetically separable from transcription activation. By assaying protein-DNA fork interactions in single cells, we unveil a p53-MLL3-enabled recruitment of MRE11 DNA replication restart nuclease. Importantly, p53 defects or depletion unexpectedly allow mutagenic RAD52 and POL\u03b8 pathways to hijack stalled forks, which we find reflected in p53 defective breast-cancer patient COSMIC mutational signatures. These data uncover p53 as a keystone regulator of replication homeostasis within a DNA restart network. Mechanistically, this has important implications for development of resistance in cancer therapy. Combined, these results define an unexpected role for p53-mediated suppression of replication genome instability.",
			"category": 2,
			"name": "Roy Sunetra,2019"
		},
		{
			"PMID": 29304754,
			"title": "Integration of multiple networks and pathways identifies cancer driver genes in pan-cancer analysis.",
			"journal": "BMC genomics",
			"authorList": [
				"Cava Claudia",
				"Bertoli Gloria",
				"Colaprico Antonio",
				"Olsen Catharina",
				"Bontempi Gianluca",
				"Castiglioni Isabella"
			],
			"DOI": "10.1186/s12864-017-4423-x",
			"date": "2018-09-05",
			"PMC": "",
			"citation": "",
			"abstract": "Modern high-throughput genomic technologies represent a comprehensive hallmark of molecular changes in pan-cancer studies. Although different cancer gene signatures have been revealed, the mechanism of tumourigenesis has yet to be completely understood. Pathways and networks are important tools to explain the role of genes in functional genomic studies. However, few methods consider the functional non-equal roles of genes in pathways and the complex gene-gene interactions in a network.",
			"category": 2,
			"name": "Cava Claudia,2018"
		},
		{
			"PMID": 29302629,
			"title": "Growth Inhibition and DNA Damage Induced by X-Phenols in Yeast: A Quantitative Structure-Activity Relationship Study.",
			"journal": "ACS omega",
			"authorList": [
				"Negritto M Cristina",
				"Valdez Clarissa",
				"Sharma Jasmine",
				"Rosenberg Christa",
				"Selassie Cynthia R"
			],
			"DOI": "10.1021/acsomega.7b01200",
			"date": "2022-03-21",
			"PMC": "",
			"citation": "",
			"abstract": "Phenolic compounds and their derivatives are ubiquitous constituents of numerous synthetic and natural chemicals that exist in the environment. Their toxicity is mostly attributed to their hydrophobicity and/or the formation of free radicals. In a continuation of the study of phenolic toxicity in a systematic manner, we have examined the biological responses of ",
			"category": 2,
			"name": "Negritto M Cristina,2022"
		},
		{
			"PMID": 29296225,
			"title": "Significance of the E3 ubiquitin protein UBR5 as an oncogene and a prognostic biomarker in colorectal cancer.",
			"journal": "Oncotarget",
			"authorList": [
				"Xie Zhongdong",
				"Liang Han",
				"Wang Jinmeng",
				"Xu Xiaowen",
				"Zhu Yan",
				"Guo Aizhen",
				"Shen Xian",
				"Cao Fuao",
				"Chang Wenjun"
			],
			"DOI": "10.18632/oncotarget.22531",
			"date": "2019-11-20",
			"PMC": "",
			"citation": "",
			"abstract": "The E3 ubiquitin protein UBR5 has been implicated in the regulation of multiple biological functions and has recently emerged as a key regulator of the ubiquitin-proteasome system (UPS) in cancer. However, the clinical significance and biological function of UBR5 in colorectal cancer (CRC) are poorly understood. In this study, we compared the expression pattern of UBR5 between CRC and adjacent normal tissues and found that UBR5 expression was frequently elevated in CRC, possibly through chromosomal gains. Using three CRC patient cohorts, we found that patients with high UBR5 mRNA levels, UBR5 gene amplification, or high nuclear UBR5 protein levels had poor prognoses. Multivariate analysis showed that the alterations in UBR5 were independent predictors of CRC prognosis with the TNM stage as a confounding factor. Furthermore, knockdown of UBR5 prevented the proliferation, colony formation, migration, and invasion of CRC cells in cell culture models. An ",
			"category": 2,
			"name": "Xie Zhongdong,2019"
		},
		{
			"PMID": 29289569,
			"title": "Simultaneous Multiplexed Imaging of mRNA and Proteins with Subcellular Resolution in Breast Cancer Tissue Samples by Mass Cytometry.",
			"journal": "Cell systems",
			"authorList": [
				"Schulz Daniel",
				"Zanotelli Vito Riccardo Tomaso",
				"Fischer Jana Raja",
				"Schapiro Denis",
				"Engler Stefanie",
				"Lun Xiao-Kang",
				"Jackson Hartland Warren",
				"Bodenmiller Bernd"
			],
			"DOI": "10.1016/j.cels.2017.12.001",
			"date": "2019-09-23",
			"PMC": "",
			"citation": "",
			"abstract": "To build comprehensive models of cellular states and interactions in normal and diseased tissue, genetic and proteomic information must be extracted with single-cell and spatial resolution. Here, we extended imaging mass cytometry to enable multiplexed detection of mRNA and proteins in tissues. Three mRNA target species were detected by\u00a0RNAscope-based metal in situ hybridization with simultaneous antibody detection of 16 proteins. Analysis of 70 breast cancer samples showed that HER2 and CK19 mRNA and protein levels are moderately correlated on the single-cell level, but that only HER2, and not CK19, has strong mRNA-to-protein correlation on\u00a0the cell population level. The chemoattractant CXCL10 was expressed in stromal cell clusters, and the frequency of CXCL10-expressing cells correlated with T\u00a0cell presence. Our flexible and expandable method will allow an increase in the information content retrieved from patient samples for biomedical purposes, enable detailed studies of tumor biology, and serve as a tool to bridge comprehensive genomic and proteomic tissue analysis.",
			"category": 2,
			"name": "Schulz Daniel,2019"
		},
		{
			"PMID": 29276510,
			"title": "Recent Successes and Future Directions in Immunotherapy of Cutaneous Melanoma.",
			"journal": "Frontiers in immunology",
			"authorList": [
				"Sadozai Hassan",
				"Gruber Thomas",
				"Hunger Robert Emil",
				"Schenk Mirjam"
			],
			"DOI": "10.3389/fimmu.2017.01617",
			"date": "2024-06-06",
			"PMC": "",
			"citation": "",
			"abstract": "The global health burden associated with melanoma continues to increase while treatment options for metastatic melanoma are limited. Nevertheless, in the past decade, the field of cancer immunotherapy has witnessed remarkable advances for the treatment of a number of malignancies including metastatic melanoma. Although the earliest observations of an immunological antitumor response were made nearly a century ago, it was only in the past 30\u2009years, that immunotherapy emerged as a viable therapeutic option, in particular for cutaneous melanoma. As such, melanoma remains the focus of various preclinical and clinical studies to understand the immunobiology of cancer and to test various tumor immunotherapies. Here, we review key recent developments in the field of immune-mediated therapy of melanoma. Our primary focus is on therapies that have received regulatory approval. Thus, a brief overview of the pathophysiology of melanoma is provided. The purported functions of various tumor-infiltrating immune cell subsets are described, in particular the recently described roles of intratumoral dendritic cells. The section on immunotherapies focuses on strategies that have proved to be the most clinically successful such as immune checkpoint blockade. Prospects for novel therapeutics and the potential for combinatorial approaches are delineated. Finally, we briefly discuss nanotechnology-based platforms which can in theory, activate multiple arms of immune system to fight cancer. The promising advances in the field of immunotherapy signal the dawn of a new era in cancer treatment and warrant further investigation to understand the opportunities and barriers for future progress.",
			"category": 2,
			"name": "Sadozai Hassan,2024"
		},
		{
			"PMID": 29273096,
			"title": "Genetic variation in human drug-related genes.",
			"journal": "Genome medicine",
			"authorList": [
				"Sch\u00e4rfe Charlotta Pauline Irmgard",
				"Tremmel Roman",
				"Schwab Matthias",
				"Kohlbacher Oliver",
				"Marks Debora Susan"
			],
			"DOI": "10.1186/s13073-017-0502-5",
			"date": "2018-11-08",
			"PMC": "",
			"citation": "",
			"abstract": "Variability in drug efficacy and adverse effects are observed in clinical practice. While the extent of genetic variability in classic pharmacokinetic genes is rather well understood, the role of genetic variation in drug targets is typically less studied.",
			"category": 2,
			"name": "Sch\u00e4rfe Charlotta Pauline Irmgard,2018"
		},
		{
			"PMID": 29270870,
			"title": "FGFR1 gene amplification in squamous cell carcinomas of the lung: a potential favorable prognostic marker for women and for patients with advanced cancer.",
			"journal": "Virchows Archiv : an international journal of pathology",
			"authorList": [
				"Flockerzi Fidelis Andrea",
				"Roggia Cristiana",
				"Langer Frank",
				"Holleczek Bernd",
				"Bohle Rainer M"
			],
			"DOI": "10.1007/s00428-017-2282-0",
			"date": "2018-05-29",
			"PMC": "",
			"citation": "",
			"abstract": "In squamous cell carcinoma (SCC) of the lung, mutations within the genes of fibroblast growth factor receptors (FGFR) such as K660N/K660E in FGFR2 and R248C/S249C in FGFR3 and FGFR1 gene amplification have been described, but their prognostic relevance still remains unclear. In order to detect the mutation frequencies and to define their prognostic value for associated clinicopathologic features and survival of patients, resected \u0394Np63/p40-positive SCC of the lung (n\u2009=\u2009101) were screened for FGFR1 gene amplification by fluorescence in situ hybridization performed on formalin-fixed paraffin embedded tissues and for the presumed driver mutations in genes of FGFR2 and FGFR3 by PCR and Sanger sequencing. Twenty-two of 101 SCCs (22%) were positive for amplification based on a FGFR1/centromere (chromosome 8) ratio >\u20092.0 or higher. In advanced tumor stages (III-IV), the overall survival of patients carrying FGFR1 gene amplification was significantly higher (p\u2009=\u20090.006). Among women, FGFR1 gene amplification was significantly associated with longer overall survival (p\u2009=\u20090.023). The presence of FGFR1 gene amplification was associated with patient age (65 versus 69\u00a0years, p\u2009=\u20090.046), but not with gender, tumor stage, histologic subtype, tumor grade, or \u0394Np63/p40 immunoreactivity. The S249C mutation in the FGFR3 gene was identified in one out of 101 SCCs (1%); the K600N, K660E, or R248C mutations were not identified. These results suggest that FGFR1 gene amplification is a frequent alteration in SCC of the lung and appears not to be a negative but rather a favorable prognostic marker for women and particularly for patients with advanced SCC of the lung (stage III-IV).",
			"category": 2,
			"name": "Flockerzi Fidelis Andrea,2018"
		},
		{
			"PMID": 29254236,
			"title": "The ubiquitous 'cancer mutational signature' 5 occurs specifically in cancers with deleted ",
			"journal": "Oncotarget",
			"authorList": [
				"Volinia Stefano",
				"Druck Teresa",
				"Paisie Carolyn A",
				"Schrock Morgan S",
				"Huebner Kay"
			],
			"DOI": "10.18632/oncotarget.22321",
			"date": "2019-11-20",
			"PMC": "",
			"citation": "",
			"abstract": "The ",
			"category": 2,
			"name": "Volinia Stefano,2019"
		},
		{
			"PMID": 29253114,
			"title": "Informatics for cancer immunotherapy.",
			"journal": "Annals of oncology : official journal of the European Society for Medical Oncology",
			"authorList": [
				"Hammerbacher J",
				"Snyder A"
			],
			"DOI": "10.1093/annonc/mdx682",
			"date": "2018-07-05",
			"PMC": "",
			"citation": "",
			"abstract": "The rapid development of immunomodulatory cancer therapies has led to a concurrent increase in the application of informatics techniques to the analysis of tumors, the tumor microenvironment, and measures of systemic immunity. In this review, the use of tumors to gather genetic and expression data will first be explored. Next, techniques to assess tumor immunity are reviewed, including HLA status, predicted neoantigens, immune microenvironment deconvolution, and T-cell receptor sequencing. Attempts to integrate these data are in early stages of development and are discussed in this review. Finally, we review the application of these informatics strategies to therapy development, with a focus on vaccines, adoptive cell transfer, and checkpoint blockade therapies.",
			"category": 2,
			"name": "Hammerbacher J,2018"
		},
		{
			"PMID": 29240787,
			"title": "BRD3/4 inhibition and FLT3-ligand deprivation target pathways that are essential for the survival of human MLL-AF9+ leukemic cells.",
			"journal": "PloS one",
			"authorList": [
				"Carretta Marco",
				"Brouwers-Vos Annet Z",
				"Bosman Matthieu",
				"Horton Sarah J",
				"Martens Joost H A",
				"Vellenga Edo",
				"Schuringa Jan Jacob"
			],
			"DOI": "10.1371/journal.pone.0189102",
			"date": "2018-01-16",
			"PMC": "",
			"citation": "",
			"abstract": "In the present work we aimed to identify targetable signaling networks in human MLL-AF9 leukemias. We show that MLL-AF9 cells critically depend on FLT3-ligand induced pathways as well as on BRD3/4 for their survival. We evaluated the in vitro and in vivo efficacy of the BRD3/4 inhibitor I-BET151 in various human MLL-AF9 (primary) models and patient samples and analyzed the transcriptome changes following treatment. To further understand the mode of action of BRD3/4 inhibition, we performed ChIP-seq experiments on the MLL-AF9 complex in THP1 cells and compared it to RNA-seq data of I-BET151 treated cells. While we could confirm a consistent and specific downregulation of key-oncogenic drivers such as MYC and BCL2, we found that the majority of I-BET151-responsive genes were not direct MLL-AF9 targets. In fact, MLL-AF9 specific targets such as the HOXA cluster, MEIS1 and other cell cycle regulators such as CDK6 were not affected by I-BET151 treatment. Furthermore, we also highlight how MLL-AF9 transformed cells are dependent on the function of non-mutated hematopoietic transcription factors and tyrosine kinases such as the FLT3-TAK1/NF-kB pathway, again impacting on BCL2 but not on the HOXA cluster. We conclude that BRD3/4 and the FLT3-TAK1/NF-kB pathways collectively control a set of targets that are critically important for the survival of human MLL-AF9 cells.",
			"category": 2,
			"name": "Carretta Marco,2018"
		},
		{
			"PMID": 29230567,
			"title": "Cancer nanomedicine: a review of recent success in drug delivery.",
			"journal": "Clinical and translational medicine",
			"authorList": [
				"Tran Stephanie",
				"DeGiovanni Peter-Joseph",
				"Piel Brandon",
				"Rai Prakash"
			],
			"DOI": "10.1186/s40169-017-0175-0",
			"date": "2023-11-05",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer continues to be one of the most difficult global healthcare problems. Although there is a large library of drugs that can be used in cancer treatment, the problem is selectively killing all the cancer cells while reducing collateral toxicity to healthy cells. There are several biological barriers to effective drug delivery in cancer such as renal, hepatic, or immune clearance. Nanoparticles loaded with drugs can be designed to overcome these biological barriers to improve efficacy while reducing morbidity. Nanomedicine has ushered in a new era for drug delivery by improving the therapeutic indices of the active pharmaceutical ingredients engineered within nanoparticles. First generation nanomedicines have received widespread clinical approval over the past two decades, from Doxil",
			"category": 2,
			"name": "Tran Stephanie,2023"
		},
		{
			"PMID": 29221206,
			"title": "Single nucleotide polymorphisms rs701848 and rs2735343 in PTEN increases cancer risks in an Asian population.",
			"journal": "Oncotarget",
			"authorList": [
				"Song Dan-Dan",
				"Zhang Qian",
				"Li Jing-Hua",
				"Hao Rui-Min",
				"Ma Ying",
				"Wang Ping-Yu",
				"Xie Shu-Yang"
			],
			"DOI": "10.18632/oncotarget.22019",
			"date": "2024-03-27",
			"PMC": "",
			"citation": "",
			"abstract": "We performed this meta-analysis to analyze the cancer risk to individuals carrying the rs701848 and rs2735343 single nucleotide polymorphisms (SNPs) in the phosphatase and tensin homolog (",
			"category": 2,
			"name": "Song Dan-Dan,2024"
		},
		{
			"PMID": 29217838,
			"title": "An evolutionary perspective on field cancerization.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Curtius Kit",
				"Wright Nicholas A",
				"Graham Trevor A"
			],
			"DOI": "10.1038/nrc.2017.102",
			"date": "2017-12-27",
			"PMC": "",
			"citation": "",
			"abstract": "Tumorigenesis begins long before the growth of a clinically detectable lesion and, indeed, even before any of the usual morphological correlates of pre-malignancy are recognizable. Field cancerization, which is the replacement of the normal cell population by a cancer-primed cell population that may show no morphological change, is now recognized to underlie the development of many types of cancer, including the common carcinomas of the lung, colon, skin, prostate and bladder. Field cancerization is the consequence of the evolution of somatic cells in the body that results in cells that carry some but not all phenotypes required for malignancy. Here, we review the evidence of field cancerization across organs and examine the biological mechanisms that drive the evolutionary process that results in field creation. We discuss the clinical implications, principally, how measurements of the cancerized field could improve cancer risk prediction in patients with pre-malignant disease.",
			"category": 2,
			"name": "Curtius Kit,2017"
		},
		{
			"PMID": 29216366,
			"title": "LncRNA lnc-RI regulates homologous recombination repair of DNA double-strand breaks by stabilizing RAD51 mRNA as a competitive endogenous RNA.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Shen Liping",
				"Wang Qi",
				"Liu Ruixue",
				"Chen Zhongmin",
				"Zhang Xueqing",
				"Zhou Pingkun",
				"Wang Zhidong"
			],
			"DOI": "10.1093/nar/gkx1224",
			"date": "2019-07-22",
			"PMC": "",
			"citation": "",
			"abstract": "DNA double-strand break (DSB) repair is critical for the maintenance of genome stability. The current models of the mechanism of DSB repair are based on studies of DNA repair proteins. Long non-coding RNAs (lncRNAs) have recently emerged as new regulatory molecules, with diverse functions in biological processes. In the present study, we found that expression of the ionizing radiation-inducible lncRNA, lnc-RI, was correlate negatively with micronucleus frequencies in human peripheral blood lymphocytes. Knockdown of lnc-RI significantly increased spontaneous DSBs levels, which was confirmed to be associated with the decreased efficiency of homologous recombination (HR) repair of DSBs. The expression of RAD51, a key recombinase in the HR pathway, decreased sharply in lnc-RI-depressed cells. In a further investigation, we demonstrated that miR-193a-3p could bind with both lnc-RI and RAD51 mRNA and depressed the expression of lnc-RI and RAD51 mRNA. Lnc-RI acted as a competitive endogenous RNA (ceRNA) to stabilize RAD51 mRNA via competitive binding with miR-193a-3p and release of its inhibition of RAD51 expression. To our knowledge, this is the first study to demonstrate the role of lnc-RI in regulating HR repair of DSBs. The feedback loop established in the current study suggests that lnc-RI is critical for the maintenance of genomic stability.",
			"category": 2,
			"name": "Shen Liping,2019"
		},
		{
			"PMID": 29198524,
			"title": "Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer.",
			"journal": "Cell",
			"authorList": [
				"Puram Sidharth V",
				"Tirosh Itay",
				"Parikh Anuraag S",
				"Patel Anoop P",
				"Yizhak Keren",
				"Gillespie Shawn",
				"Rodman Christopher",
				"Luo Christina L",
				"Mroz Edmund A",
				"Emerick Kevin S",
				"Deschler Daniel G",
				"Varvares Mark A",
				"Mylvaganam Ravi",
				"Rozenblatt-Rosen Orit",
				"Rocco James W",
				"Faquin William C",
				"Lin Derrick T",
				"Regev Aviv",
				"Bernstein Bradley E"
			],
			"DOI": "10.1016/j.cell.2017.10.044",
			"date": "2017-12-28",
			"PMC": "",
			"citation": "",
			"abstract": "The diverse malignant, stromal, and immune cells in tumors affect growth, metastasis, and response to therapy. We profiled transcriptomes of \u223c6,000 single cells from 18 head and neck squamous cell carcinoma (HNSCC) patients, including five matched pairs of primary tumors and lymph node metastases. Stromal and immune cells had consistent expression programs across patients. Conversely, malignant cells varied within and between tumors in their expression of signatures related to cell cycle, stress, hypoxia, epithelial differentiation, and partial epithelial-to-mesenchymal transition (p-EMT). Cells expressing the p-EMT program spatially localized to the leading edge of primary tumors. By integrating single-cell transcriptomes with bulk expression profiles for hundreds of tumors, we refined HNSCC subtypes by their malignant and stromal composition and established p-EMT as an independent predictor of nodal metastasis, grade, and adverse pathologic features. Our results provide insight into the HNSCC ecosystem and define stromal interactions and a p-EMT program associated with metastasis.",
			"category": 2,
			"name": "Puram Sidharth V,2017"
		},
		{
			"PMID": 29191787,
			"title": "Post-translational regulation of metabolism in fumarate hydratase deficient cancer cells.",
			"journal": "Metabolic engineering",
			"authorList": [
				"Gon\u00e7alves Emanuel",
				"Sciacovelli Marco",
				"Costa Ana S H",
				"Tran Maxine Gia Binh",
				"Johnson Timothy Isaac",
				"Machado Daniel",
				"Frezza Christian",
				"Saez-Rodriguez Julio"
			],
			"DOI": "10.1016/j.ymben.2017.11.011",
			"date": "2019-01-23",
			"PMC": "",
			"citation": "",
			"abstract": "Deregulated signal transduction and energy metabolism are hallmarks of cancer and both play a fundamental role in tumorigenesis. While it is increasingly recognised that signalling and metabolism are highly interconnected, the underpinning mechanisms of their co-regulation are still largely unknown. Here we designed and acquired proteomics, phosphoproteomics, and metabolomics experiments in fumarate hydratase (FH) deficient cells and developed a computational modelling approach to identify putative regulatory phosphorylation-sites of metabolic enzymes. We identified previously reported functionally relevant phosphosites and potentially novel regulatory residues in enzymes of the central carbon metabolism. In particular, we showed that pyruvate dehydrogenase (PDHA1) enzymatic activity is inhibited by increased phosphorylation in FH-deficient cells, restricting carbon entry from glucose to the tricarboxylic acid cycle. Moreover, we confirmed PDHA1 phosphorylation in human FH-deficient tumours. Our work provides a novel approach to investigate how post-translational modifications of enzymes regulate metabolism and could have important implications for understanding the metabolic transformation of FH-deficient cancers with potential clinical applications.",
			"category": 2,
			"name": "Gon\u00e7alves Emanuel,2019"
		},
		{
			"PMID": 29187807,
			"title": "Characteristic miRNA expression signature and random forest survival analysis identify potential cancer-driving miRNAs in a broad range of head and neck squamous cell carcinoma subtypes.",
			"journal": "Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology",
			"authorList": [
				"Nunez Lopez Yury O",
				"Victoria Berta",
				"Golusinski Pawel",
				"Golusinski Wojciech",
				"Masternak Michal M"
			],
			"DOI": "10.1016/j.rpor.2017.10.003",
			"date": "2024-03-18",
			"PMC": "",
			"citation": "",
			"abstract": "To characterize the miRNA expression profile in head and neck squamous cell carcinoma (HNSSC) accounting for a broad range of cancer subtypes and consequently identify an optimal miRNA signature with prognostic value.",
			"category": 2,
			"name": "Nunez Lopez Yury O,2024"
		},
		{
			"PMID": 29170717,
			"title": "Stochasticity and determinism in cancer creation and progression.",
			"journal": "Convergent science physical oncology",
			"authorList": [
				"Davies Paul C",
				"Agus David B"
			],
			"DOI": "10.1088/2057-1739/1/2/026003",
			"date": "2020-09-29",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Davies Paul C,2020"
		},
		{
			"PMID": 29168077,
			"title": "Progress and challenges of sequencing and analyzing circulating tumor cells.",
			"journal": "Cell biology and toxicology",
			"authorList": [
				"Zhu Zhongyi",
				"Qiu Si",
				"Shao Kang",
				"Hou Yong"
			],
			"DOI": "10.1007/s10565-017-9418-5",
			"date": "2019-06-14",
			"PMC": "",
			"citation": "",
			"abstract": "Circulating tumor cells (CTCs) slough off primary tumor tissues and are swept away by the circulatory system. These CTCs can remain in circulation or colonize new sites, forming metastatic clones in distant organs. Recently, CTC analyses have been successfully used as effective clinical tools to monitor tumor progression and prognosis. With advances in next-generation sequencing (NGS) and single-cell sequencing (SCS) technologies, scientists can obtain the complete genome of a CTC and compare it with corresponding primary and metastatic tumors. CTC sequencing has been successfully applied to monitor genomic variations in metastatic and recurrent tumors, infer tumor evolution during treatment, and examine gene expression as well as the mechanism of the epithelial-mesenchymal transition. However, compared with cancer biopsy sequencing and circulating tumor DNA sequencing, the sequencing of CTC genomes and transcriptomes is more complex and technically difficult. Challenges include enriching pure tumor cells from a background of white blood cells, isolating and collecting cells without damaging or losing DNA and RNA, obtaining unbiased and even whole-genome and transcriptome amplification material, and accurately analyzing CTC sequencing data. Here, we review and summarize recent studies using NGS on CTCs. We mainly focus on CTC genome and transcriptome sequencing and the biological and potential clinical applications of these methodologies. Finally, we discuss challenges and future perspectives of CTC sequencing.",
			"category": 2,
			"name": "Zhu Zhongyi,2019"
		},
		{
			"PMID": 29164061,
			"title": "The Landscape of mtDNA Modifications in Cancer: A Tale of Two Cities.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Hertweck Kate L",
				"Dasgupta Santanu"
			],
			"DOI": "10.3389/fonc.2017.00262",
			"date": "2020-09-29",
			"PMC": "",
			"citation": "",
			"abstract": "Mitochondria from normal and cancerous cells represent a tale of two cities, wherein both execute similar processes but with different cellular and molecular effects. Given the number of reviews currently available which describe the functional implications of mitochondrial mutations in cancer, this article focuses on documenting current knowledge in the abundance and distribution of somatic mitochondrial mutations, followed by elucidation of processes which affect the fate of mutations in cancer cells. The conclusion includes an overview of translational implications for mtDNA mutations, as well as recommendations for future research uniting mitochondrial variants and tumorigenesis.",
			"category": 2,
			"name": "Hertweck Kate L,2020"
		},
		{
			"PMID": 29163852,
			"title": "Melatonin as a potential inhibitory agent in head and neck cancer.",
			"journal": "Oncotarget",
			"authorList": [
				"Yeh Chia-Ming",
				"Su Shih-Chi",
				"Lin Chiao-Wen",
				"Yang Wei-En",
				"Chien Ming-Hsien",
				"Reiter Russel J",
				"Yang Shun-Fa"
			],
			"DOI": "10.18632/oncotarget.20079",
			"date": "2019-11-20",
			"PMC": "",
			"citation": "",
			"abstract": "Melatonin is a molecule secreted by the pineal gland; it is an important regulator of sleep and circadian rhythms. Through multiple interrelated mechanisms, melatonin exhibits various inhibitory properties at different stages of tumor progression. Many studies have explored the oncostatic effects of melatonin on hormone-dependent tumors. In this review, we highlight recent advances in understanding the effects of melatonin on the development of head and neck cancers, including molecular mechanisms identified through experimental and clinical observations. Because melatonin exerts a wide range of effects, melatonin may influence many mechanisms that influence the development of cancer. These include cell proliferation, apoptosis, angiogenesis, extracellular matrix remodeling through matrix metalloproteinases, and genetic polymorphism. Thus, the evidence discussed in this article will serve as a basis for basic and clinical research to promote the use of melatonin for understanding and controlling the development of head and neck cancers.",
			"category": 2,
			"name": "Yeh Chia-Ming,2019"
		},
		{
			"PMID": 29159069,
			"title": "Co-expression network analysis identified six hub genes in association with progression and prognosis in human clear cell renal cell carcinoma (ccRCC).",
			"journal": "Genomics data",
			"authorList": [
				"Yuan Lushun",
				"Chen Liang",
				"Qian Kaiyu",
				"Qian Guofeng",
				"Wu Chin-Lee",
				"Wang Xinghuan",
				"Xiao Yu"
			],
			"DOI": "10.1016/j.gdata.2017.10.006",
			"date": "2022-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "Human clear cell renal cell carcinoma (ccRCC) is one of the most common types of malignant adult kidney tumors. We constructed a weighted gene co-expression network to identify gene modules associated with clinical features of ccRCC (",
			"category": 2,
			"name": "Yuan Lushun,2022"
		},
		{
			"PMID": 29141951,
			"title": "Selector genes display tumor cooperation and inhibition in ",
			"journal": "Biology open",
			"authorList": [
				"Gupta Ram Prakash",
				"Bajpai Anjali",
				"Sinha Pradip"
			],
			"DOI": "10.1242/bio.027821",
			"date": "2019-11-20",
			"PMC": "",
			"citation": "",
			"abstract": "During animal development, selector genes determine identities of body segments and those of individual organs. Selector genes are also misexpressed in cancers, although their contributions to tumor progression per se remain poorly understood. Using a model of cooperative tumorigenesis, we show that gain of selector genes results in tumor cooperation, but in only select developmental domains of the wing, haltere and eye-antennal imaginal discs of ",
			"category": 2,
			"name": "Gupta Ram Prakash,2019"
		},
		{
			"PMID": 29137657,
			"title": "p53 aberrations in low grade endometrioid carcinoma of the endometrium with nodal metastases: possible insights on pathogenesis discerned from immunohistochemistry.",
			"journal": "Diagnostic pathology",
			"authorList": [
				"Fadare Oluwole",
				"Parkash Vinita"
			],
			"DOI": "10.1186/s13000-017-0668-6",
			"date": "2018-08-08",
			"PMC": "",
			"citation": "",
			"abstract": "TP53 mutations are rarely identified in low grade endometrioid carcinoma of the endometrium, and their pathogenic significance in such tumors is evidenced by the fact that TP53 aberrations have been associated with reduced recurrence-free survival in this subset of tumors. However, TP53 aberrations may not always represent a driving molecular event in a given endometrial cancer with a mutation. In this case study, the immunophenotype of a distinctive low grade endometrioid adenocarcinoma with an unusual pattern of lymph node metastases is used to explore the possible roles for underlying TP53-related molecular events in its pathogenesis.",
			"category": 2,
			"name": "Fadare Oluwole,2018"
		},
		{
			"PMID": 29129848,
			"title": "Significance of functional disease-causal/susceptible variants identified by whole-genome analyses for the understanding of human diseases.",
			"journal": "Proceedings of the Japan Academy. Series B, Physical and biological sciences",
			"authorList": [
				"Hitomi Yuki",
				"Tokunaga Katsushi"
			],
			"DOI": "10.2183/pjab.93.042",
			"date": "2018-06-18",
			"PMC": "",
			"citation": "",
			"abstract": "Human genome variation may cause differences in traits and disease risks. Disease-causal/susceptible genes and variants for both common and rare diseases can be detected by comprehensive whole-genome analyses, such as whole-genome sequencing (WGS), using next-generation sequencing (NGS) technology and genome-wide association studies (GWAS). Here, in addition to the application of an NGS as a whole-genome analysis method, we summarize approaches for the identification of functional disease-causal/susceptible variants from abundant genetic variants in the human genome and methods for evaluating their functional effects in human diseases, using an NGS and in silico and in vitro functional analyses. We also discuss the clinical applications of the functional disease causal/susceptible variants to personalized medicine.",
			"category": 2,
			"name": "Hitomi Yuki,2018"
		},
		{
			"PMID": 29109099,
			"title": "Targeted Gene Sequencing of Gallbladder Carcinoma Identifies High-impact Somatic and Rare Germline Mutations.",
			"journal": "Cancer genomics & proteomics",
			"authorList": [
				"Yadav Saurabh",
				"DE Sarkar Navonil",
				"Kumari Niraj",
				"Krishnani Narendra",
				"Kumar Ashok",
				"Mittal Balraj"
			],
			"DOI": "",
			"date": "2018-07-03",
			"PMC": "",
			"citation": "",
			"abstract": "Gallbladder carcinoma (GBC) is a subtype of biliary tract malignancy with poor prognosis and high fatality rate. The present study was designed to uncover somatic and rare germline mutations in GBC to reveal the disease biology and understand the clinical importance of mutation profile in terms of prognostics and actionability.",
			"category": 2,
			"name": "Yadav Saurabh,2018"
		},
		{
			"PMID": 29089486,
			"title": "Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors.",
			"journal": "Nature communications",
			"authorList": [
				"Cheng Jiqiu",
				"Demeulemeester Jonas",
				"Wedge David C",
				"Vollan Hans Kristian M",
				"Pitt Jason J",
				"Russnes Hege G",
				"Pandey Bina P",
				"Nilsen Gro",
				"Nord Silje",
				"Bignell Graham R",
				"White Kevin P",
				"B\u00f8rresen-Dale Anne-Lise",
				"Campbell Peter J",
				"Kristensen Vessela N",
				"Stratton Michael R",
				"Lingj\u00e6rde Ole Christian",
				"Moreau Yves",
				"Van Loo Peter"
			],
			"DOI": "10.1038/s41467-017-01355-0",
			"date": "2018-08-27",
			"PMC": "",
			"citation": "",
			"abstract": "Homozygous deletions are rare in cancers and often target tumour suppressor genes. Here, we build a compendium of 2218 primary tumours across 12 human cancer types and systematically screen for homozygous deletions, aiming to identify rare tumour suppressors. Our analysis defines 96 genomic regions recurrently targeted by homozygous deletions. These recurrent homozygous deletions occur either over tumour suppressors or over fragile sites, regions of increased genomic instability. We construct a statistical model that separates fragile sites from regions showing signatures of positive selection for homozygous deletions and identify candidate tumour suppressors within those regions. We find 16 established tumour suppressors and propose 27 candidate tumour suppressors. Several of these genes (including MGMT, RAD17, and USP44) show prior evidence of a tumour suppressive function. Other candidate tumour suppressors, such as MAFTRR, KIAA1551, and IGF2BP2,\u00a0are novel. Our study demonstrates how rare tumour suppressors can be identified through copy number meta-analysis.",
			"category": 2,
			"name": "Cheng Jiqiu,2018"
		},
		{
			"PMID": 29057328,
			"title": "Cancer Prevention and Treatment by Wholistic Nutrition.",
			"journal": "Journal of nature and science",
			"authorList": [
				"Campbell T Colin"
			],
			"DOI": "",
			"date": "2024-06-10",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is traditionally considered a genetic disease. It starts with a gene mutation, often caused by environmental carcinogens that are enzymatically activated to metabolites that covalently bind to DNA. If these now-damaged carcinogen-DNA adducts are not repaired before the cell replicates, they result in a mutation, which is inherited by daughter cells and their subsequent progeny. Still more mutations are added that are thought to advance cellular independence, metastasis, and drug resistance, among other characteristics typically observed for advanced cancer. The stages of initiation, promotion and progression of cancer by mutations infer irreversibility because back mutations are exceedingly rare. Thus, treatment protocols typically are designed to remove or kill cancer cells by surgery, chemotherapy, immunotherapy and/or radiotherapy. However, empirical evidence has existed to show a fundamentally different treatment option. For example, the promotion of cancer growth and development in laboratory animals initiated by a powerful mutagen/carcinogen can be repetitively turned on and off by non-mutagenic mechanisms, even completely, by modifying the consumption of protein at relevant levels of intake. Similar but less substantiated evidence also exists for other nutrients and other cancer types. This suggests that ultimate cancer development is primarily a nutrition-responsive disease rather than a genetic disease, with the understanding that nutrition is a comprehensive, wholistic biological effect that reflects the natural contents of nutrients and related substances in whole, intact food. This perspective sharply contrasts with the contemporary inference that nutrition is the summation of individual nutrients acting independently. The spelling of 'holism' with the 'w' is meant to emphasize the empirical basis for this function. The proposition that wholistic nutrition controls and even reverses disease development suggests that cancer may be treated by nutritional intervention.",
			"category": 2,
			"name": "Campbell T Colin,2024"
		},
		{
			"PMID": 29056344,
			"title": "Comprehensive Analysis of Hypermutation in Human Cancer.",
			"journal": "Cell",
			"authorList": [
				"Campbell Brittany B",
				"Light Nicholas",
				"Fabrizio David",
				"Zatzman Matthew",
				"Fuligni Fabio",
				"de Borja Richard",
				"Davidson Scott",
				"Edwards Melissa",
				"Elvin Julia A",
				"Hodel Karl P",
				"Zahurancik Walter J",
				"Suo Zucai",
				"Lipman Tatiana",
				"Wimmer Katharina",
				"Kratz Christian P",
				"Bowers Daniel C",
				"Laetsch Theodore W",
				"Dunn Gavin P",
				"Johanns Tanner M",
				"Grimmer Matthew R",
				"Smirnov Ivan V",
				"Larouche Val\u00e9rie",
				"Samuel David",
				"Bronsema Annika",
				"Osborn Michael",
				"Stearns Duncan",
				"Raman Pichai",
				"Cole Kristina A",
				"Storm Phillip B",
				"Yalon Michal",
				"Opocher Enrico",
				"Mason Gary",
				"Thomas Gregory A",
				"Sabel Magnus",
				"George Ben",
				"Ziegler David S",
				"Lindhorst Scott",
				"Issai Vanan Magimairajan",
				"Constantini Shlomi",
				"Toledano Helen",
				"Elhasid Ronit",
				"Farah Roula",
				"Dvir Rina",
				"Dirks Peter",
				"Huang Annie",
				"Galati Melissa A",
				"Chung Jiil",
				"Ramaswamy Vijay",
				"Irwin Meredith S",
				"Aronson Melyssa",
				"Durno Carol",
				"Taylor Michael D",
				"Rechavi Gideon",
				"Maris John M",
				"Bouffet Eric",
				"Hawkins Cynthia",
				"Costello Joseph F",
				"Meyn M Stephen",
				"Pursell Zachary F",
				"Malkin David",
				"Tabori Uri",
				"Shlien Adam"
			],
			"DOI": "10.1016/j.cell.2017.09.048",
			"date": "2017-12-15",
			"PMC": "",
			"citation": "",
			"abstract": "We present an extensive assessment of mutation burden through sequencing analysis of >81,000 tumors from pediatric and adult patients, including tumors with hypermutation caused by chemotherapy, carcinogens, or germline alterations. Hypermutation was detected in tumor types not previously associated with high mutation burden. Replication repair deficiency was a major contributing factor. We uncovered new driver mutations in the replication-repair-associated DNA polymerases and a distinct impact of microsatellite instability and replication repair deficiency on the scale of mutation load. Unbiased clustering, based on mutational context, revealed clinically relevant subgroups regardless of the tumors' tissue of origin, highlighting similarities in evolutionary dynamics leading to hypermutation. Mutagens, such as UV light, were implicated in unexpected cancers, including sarcomas and lung tumors. The order of mutational signatures identified previous treatment and germline replication repair deficiency, which improved management of\u00a0patients and families. These data will inform tumor classification, genetic testing, and clinical trial design.",
			"category": 2,
			"name": "Campbell Brittany B,2017"
		},
		{
			"PMID": 29042409,
			"title": "RECQ-like helicases Sgs1 and BLM regulate R-loop-associated genome instability.",
			"journal": "The Journal of cell biology",
			"authorList": [
				"Chang Emily Yun-Chia",
				"Novoa Carolina A",
				"Aristizabal Maria J",
				"Coulombe Yan",
				"Segovia Romulo",
				"Chaturvedi Richa",
				"Shen Yaoqing",
				"Keong Christelle",
				"Tam Annie S",
				"Jones Steven J M",
				"Masson Jean-Yves",
				"Kobor Michael S",
				"Stirling Peter C"
			],
			"DOI": "10.1083/jcb.201703168",
			"date": "2017-12-06",
			"PMC": "",
			"citation": "",
			"abstract": "Sgs1, the orthologue of human Bloom's syndrome helicase BLM, is a yeast DNA helicase functioning in DNA replication and repair. We show that ",
			"category": 2,
			"name": "Chang Emily Yun-Chia,2017"
		},
		{
			"PMID": 29030609,
			"title": "Signatures of positive selection reveal a universal role of chromatin modifiers as cancer driver genes.",
			"journal": "Scientific reports",
			"authorList": [
				"Zapata Luis",
				"Susak Hana",
				"Drechsel Oliver",
				"Friedl\u00e4nder Marc R",
				"Estivill Xavier",
				"Ossowski Stephan"
			],
			"DOI": "10.1038/s41598-017-12888-1",
			"date": "2019-07-01",
			"PMC": "",
			"citation": "",
			"abstract": "Tumors are composed of an evolving population of cells subjected to tissue-specific selection, which fuels tumor heterogeneity and ultimately complicates cancer driver gene identification. Here, we integrate cancer cell fraction, population recurrence, and functional impact of somatic mutations as signatures of selection into a Bayesian model for driver prediction. We demonstrate that our model, cDriver, outperforms competing methods when analyzing solid tumors, hematological malignancies, and pan-cancer datasets. Applying cDriver to exome sequencing data of 21 cancer types from 6,870 individuals revealed 98 unreported tumor type-driver gene connections. These novel connections are highly enriched for chromatin-modifying proteins, hinting at a universal role of chromatin regulation in cancer etiology. Although infrequently mutated as single genes, we show that chromatin modifiers are altered in a large fraction of cancer patients. In summary, we demonstrate that integration of evolutionary signatures is key for identifying mutational driver genes, thereby facilitating the discovery of novel therapeutic targets for cancer treatment.",
			"category": 2,
			"name": "Zapata Luis,2019"
		},
		{
			"PMID": 29025907,
			"title": "Depletion of SIRT6 enzymatic activity increases acute myeloid leukemia cells' vulnerability to DNA-damaging agents.",
			"journal": "Haematologica",
			"authorList": [
				"Cagnetta Antonia",
				"Soncini Debora",
				"Orecchioni Stefania",
				"Talarico Giovanna",
				"Minetto Paola",
				"Guolo Fabio",
				"Retali Veronica",
				"Colombo Nicoletta",
				"Carminati Enrico",
				"Clavio Marino",
				"Miglino Maurizio",
				"Bergamaschi Micaela",
				"Nahimana Aimable",
				"Duchosal Michel",
				"Todoerti Katia",
				"Neri Antonino",
				"Passalacqua Mario",
				"Bruzzone Santina",
				"Nencioni Alessio",
				"Bertolini Francesco",
				"Gobbi Marco",
				"Lemoli Roberto M",
				"Cea Michele"
			],
			"DOI": "10.3324/haematol.2017.176248",
			"date": "2019-07-24",
			"PMC": "",
			"citation": "",
			"abstract": "Genomic instability plays a pathological role in various malignancies, including acute myeloid leukemia (AML), and thus represents a potential therapeutic target. Recent studies demonstrate that SIRT6, a NAD",
			"category": 2,
			"name": "Cagnetta Antonia,2019"
		},
		{
			"PMID": 29018192,
			"title": "Simultaneous evolutionary expansion and constraint of genomic heterogeneity in multifocal lung cancer.",
			"journal": "Nature communications",
			"authorList": [
				"Ma Pengfei",
				"Fu Yujie",
				"Cai Mei-Chun",
				"Yan Ying",
				"Jing Ying",
				"Zhang Shengzhe",
				"Chen Minjiang",
				"Wu Jie",
				"Shen Ying",
				"Zhu Liang",
				"Chen Hong-Zhuan",
				"Gao Wei-Qiang",
				"Wang Mengzhao",
				"Gu Zhenyu",
				"Bivona Trever G",
				"Zhao Xiaojing",
				"Zhuang Guanglei"
			],
			"DOI": "10.1038/s41467-017-00963-0",
			"date": "2018-09-04",
			"PMC": "",
			"citation": "",
			"abstract": "Recent genomic analyses have revealed substantial tumor heterogeneity across various cancers. However, it remains unclear whether and how genomic heterogeneity is constrained during tumor evolution. Here, we sequence a unique cohort of multiple synchronous lung cancers (MSLCs) to determine the relative diversity and uniformity of genetic drivers upon identical germline and environmental background. We find that each multicentric primary tumor harbors distinct oncogenic alterations, including novel mutations that are experimentally demonstrated to be functional and therapeutically targetable. However, functional studies show a strikingly constrained tumorigenic pathway underlying heterogeneous genetic variants. These results suggest that although the mutation-specific routes that cells take during oncogenesis are stochastic, genetic trajectories may be constrained by selection for functional convergence on key signaling pathways. Our findings highlight the robust evolutionary pressures that simultaneously shape the expansion and constraint of genomic diversity, a principle that holds important implications for understanding tumor evolution and optimizing therapeutic strategies.Across cancer types tumor heterogeneity has been observed, but how this relates to tumor evolution is unclear. Here, the authors sequence multiple synchronous lung cancers, highlighting the evolutionary pressures that simultaneously shape the expansion and constraint of genomic heterogeneity.",
			"category": 2,
			"name": "Ma Pengfei,2018"
		},
		{
			"PMID": 28984200,
			"title": "Incorporating genomic, transcriptomic and clinical data: a prognostic and stem cell-like MYC and PRC imbalance in high-risk neuroblastoma.",
			"journal": "BMC systems biology",
			"authorList": [
				"Yang Xinan Holly",
				"Tang Fangming",
				"Shin Jisu",
				"Cunningham John M"
			],
			"DOI": "10.1186/s12918-017-0466-5",
			"date": "2018-05-17",
			"PMC": "",
			"citation": "",
			"abstract": "Previous studies suggested that cancer cells possess traits reminiscent of the biological mechanisms ascribed to normal embryonic stem cells (ESCs) regulated by MYC and Polycomb repressive complex 2 (PRC2). Several poorly differentiated adult tumors showed preferentially high expression levels in targets of MYC, coincident with low expression levels in targets of PRC2. This paper will reveal this ESC-like cancer signature in high-risk neuroblastoma (HR-NB), the most common extracranial solid tumor in children.",
			"category": 2,
			"name": "Yang Xinan Holly,2018"
		},
		{
			"PMID": 28981122,
			"title": "Base-resolution stratification of cancer mutations using functional variomics.",
			"journal": "Nature protocols",
			"authorList": [
				"Yi Song",
				"Liu Ning-Ning",
				"Hu Limei",
				"Wang Hui",
				"Sahni Nidhi"
			],
			"DOI": "10.1038/nprot.2017.086",
			"date": "2017-10-13",
			"PMC": "",
			"citation": "",
			"abstract": "A complete understanding of human cancer variants requires new methods to systematically and efficiently assess the functional effects of genomic mutations at a large scale. Here, we describe a set of tools to rapidly clone and stratify thousands of cancer mutations at base resolution. This protocol provides a massively parallel pipeline to achieve high stringency and throughput. The approach includes high-throughput generation of mutant clones by Gateway, confirmation of variant identity by barcoding and next-generation sequencing, and stratification of cancer variants by multiplexed interaction profiling. Compared with alternative site-directed mutagenesis methods, our protocol requires less sequencing effort and enables robust statistical calling of allele-specific effects. To ensure the precision of variant interaction profiling, we further describe two complementary methods-a high-throughput enhanced yeast two-hybrid (HT-eY2H) assay and a mammalian-cell-based Gaussia princeps luciferase protein-fragment complementation assay (GPCA). These independent assays with standard controls validate mutational interaction profiles with high quality. This protocol provides experimentally derived guidelines for classifying candidate cancer alleles emerging from whole-genome or whole-exome sequencing projects as 'drivers' or 'passengers'. For \u223c100 genomic mutations, the protocol-including target primer design, variant library construction, and sequence verification-can be completed within as little as 2-3 weeks, and cancer variant stratification can be completed within 2 weeks.",
			"category": 2,
			"name": "Yi Song,2017"
		},
		{
			"PMID": 28967881,
			"title": "Nuclear topology modulates the mutational landscapes of cancer genomes.",
			"journal": "Nature structural & molecular biology",
			"authorList": [
				"Smith Kyle S",
				"Liu Lin L",
				"Ganesan Shridar",
				"Michor Franziska",
				"De Subhajyoti"
			],
			"DOI": "10.1038/nsmb.3474",
			"date": "2017-11-13",
			"PMC": "",
			"citation": "",
			"abstract": "Nuclear organization of genomic DNA affects processes of DNA damage and repair, yet its effects on mutational landscapes in cancer genomes remain unclear. Here we analyzed genome-wide somatic mutations from 366 samples of six cancer types. We found that lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core. This effect was observed even after adjustment for features such as GC percentage, chromatin, and replication timing. Furthermore, mutational signatures differed between the nuclear core and periphery, thus indicating differences in the patterns of DNA-damage or DNA-repair processes. For instance, smoking and UV-related signatures, as well as substitutions at certain motifs, were more enriched in the nuclear periphery. Thus, the nuclear architecture may influence mutational landscapes in cancer genomes beyond the previously described effects of chromatin structure and replication timing.",
			"category": 2,
			"name": "Smith Kyle S,2017"
		},
		{
			"PMID": 28957656,
			"title": "Network-Based Coverage of Mutational Profiles Reveals Cancer Genes.",
			"journal": "Cell systems",
			"authorList": [
				"Hristov Borislav H",
				"Singh Mona"
			],
			"DOI": "10.1016/j.cels.2017.09.003",
			"date": "2019-07-01",
			"PMC": "",
			"citation": "",
			"abstract": "A central goal in cancer genomics is to identify the somatic alterations that underpin tumor initiation and progression. While commonly mutated cancer genes are readily identifiable, those that are rarely mutated across samples are difficult to distinguish from the large numbers of other infrequently mutated genes. We introduce a method, nCOP, that considers per-individual mutational profiles within the context of protein-protein interaction networks in order to identify small connected subnetworks of genes that, while not individually frequently mutated, comprise pathways that are altered across (i.e., \"cover\") a large fraction of individuals. By analyzing 6,038 samples across 24 different cancer types, we demonstrate that nCOP is highly effective in identifying cancer genes, including those with low mutation frequencies. Overall, our work demonstrates that combining per-individual mutational information with interaction networks is a powerful approach for tackling the mutational heterogeneity observed across cancers.",
			"category": 2,
			"name": "Hristov Borislav H,2019"
		},
		{
			"PMID": 28914620,
			"title": "New Developments in the Molecular Mechanisms of Pancreatic Tumorigenesis.",
			"journal": "Advances in anatomic pathology",
			"authorList": [
				"Felsenstein Matth\u00e4us",
				"Hruban Ralph H",
				"Wood Laura D"
			],
			"DOI": "10.1097/PAP.0000000000000172",
			"date": "2018-08-21",
			"PMC": "",
			"citation": "",
			"abstract": "Pancreatic cancer is an aggressive disease with a dismal prognosis in dire need of novel diagnostic and therapeutic approaches. The past decade has witnessed an explosion of data on the genetic alterations that occur in pancreatic cancer, as comprehensive next-generation sequencing analyses have been performed on samples from large cohorts of patients. These studies have defined the genomic landscape of this disease and identified novel candidates whose mutations contribute to pancreatic tumorigenesis. They have also clarified the genetic alterations that underlie multistep tumorigenesis in precursor lesions and provided insights into clonal evolution in pancreatic neoplasia. In addition to these important insights into pancreatic cancer biology, these large scale genomic studies have also provided a foundation for the development of novel early detection strategies and targeted therapies. In this review, we discuss the results of these comprehensive sequencing studies of pancreatic neoplasms, with a particular focus on how their results will impact the clinical care of patients with pancreatic cancer.",
			"category": 2,
			"name": "Felsenstein Matth\u00e4us,2018"
		},
		{
			"PMID": 28870239,
			"title": "Evaluating somatic tumor mutation detection without matched normal samples.",
			"journal": "Human genomics",
			"authorList": [
				"Teer Jamie K",
				"Zhang Yonghong",
				"Chen Lu",
				"Welsh Eric A",
				"Cress W Douglas",
				"Eschrich Steven A",
				"Berglund Anders E"
			],
			"DOI": "10.1186/s40246-017-0118-2",
			"date": "2018-07-18",
			"PMC": "",
			"citation": "",
			"abstract": "Observations of recurrent somatic mutations in tumors have led to identification and definition of signaling and other pathways that are important for cancer progression and therapeutic targeting. As tumor cells contain both an individual's inherited genetic variants and somatic mutations, challenges arise in distinguishing these events in massively parallel sequencing datasets. Typically, both a tumor sample and a \"normal\" sample from the same individual are sequenced and compared; variants observed only in the tumor are considered to be somatic mutations. However, this approach requires two samples for each individual.",
			"category": 2,
			"name": "Teer Jamie K,2018"
		},
		{
			"PMID": 28849200,
			"title": "Individualized drug screening based on next generation sequencing and patient derived xenograft model for pancreatic cancer with bone metastasis.",
			"journal": "Molecular medicine reports",
			"authorList": [
				"Guan Zhonghai",
				"Lan Huanrong",
				"Chen Xiangheng",
				"Jiang Xiaoxia",
				"Wang Xuanwei",
				"Jin Ketao"
			],
			"DOI": "10.3892/mmr.2017.7213",
			"date": "2018-05-21",
			"PMC": "",
			"citation": "",
			"abstract": "The efficacy of traditional chemoradiotherapies for pancreatic cancer remains limited, and no effective targeted therapies or screening tests are currently available. Therefore more individualized drug screening is warranted for the clinical treatment of pancreatic cancer. A patient\u2011derived xenograft (PDX) model of pancreatic cancer bone metastasis was established, and next\u2011generation sequencing (NGS) was used to investigate the molecular characteristics of the cancer and screen for potential drugs. Immunohistochemical analysis was performed to validate that the PDX retained the molecular characteristics from the patient. Using NGS technology, 13\u00a0pancreatic\u2011cancer\u2011associated polymorphisms/mutations were identified out of 416 genes sequenced. Based on the sequencing results and associated literatures, AZD6244, a highly selective inhibitor against mitogen\u2011activated protein kinase kinase\u00a01 (MEK1), was chosen as a potential therapy. AZD6244, a highly selective MEK1 inhibitor, was evaluated as effective for the pancreatic cancer PDX model, and thus may provide potential efficacy in the clinical treatment of the patient with pancreatic cancer investigated in the present study. The feasibility of the novel NGS\u2011PDX based drug\u2011screening pattern was demonstrated, and has a potential to improve individua-lized treatment for cancer.",
			"category": 2,
			"name": "Guan Zhonghai,2018"
		},
		{
			"PMID": 28840016,
			"title": "Lung adenocarcinoma: from molecular basis to genome-guided therapy and immunotherapy.",
			"journal": "Journal of thoracic disease",
			"authorList": [
				"Chalela Roberto",
				"Curull V\u00edctor",
				"Enr\u00edquez C\u00e9sar",
				"Pijuan Lara",
				"Bellosillo Beatriz",
				"Gea Joaquim"
			],
			"DOI": "10.21037/jtd.2017.06.20",
			"date": "2024-03-26",
			"PMC": "",
			"citation": "",
			"abstract": "Although adenocarcinoma (ADC) is the most frequent lung cancer, its diagnosis is often late, when the local invasion is important and/or the metastases have already appeared. Therefore, the mortality at 5 years is still very high, ranging from 51% to 99%, depending on the stage. The implementation of different molecular techniques has allowed genomic studies even in relatively small histological samples such as obtained with non-invasive or minimally invasive techniques, facilitating a better phenotyping of lung ADC. Thus, current classification differentiates between preinvasive lesions (atypical adenomatous hyperplasia and in situ ADC), minimally invasive ADC (MIA) and invasive ADC. 'Field cancerization' is a concept that refers to progressive loco-regional changes occurring in tissues exposed to carcinogens, due to the interaction of the latter with a predisposing genetic background and an appropriate tissue microenvironment. Somatic genetic alterations, including mutations but also other changes, are necessary for oncogenesis, being especially frequent in lung ADC. Changes in the epidermal growth factor receptor (",
			"category": 2,
			"name": "Chalela Roberto,2024"
		},
		{
			"PMID": 28837838,
			"title": "Single nucleotide variations in cultured cancer cells: Effect of mismatch repair.",
			"journal": "Mutation research",
			"authorList": [
				"Panyutin Igor G",
				"Panyutin Irina V",
				"Powell-Castilla Ian",
				"Felix Laura",
				"Neumann Ronald D"
			],
			"DOI": "10.1016/j.mrfmmm.2017.07.003",
			"date": "2017-10-11",
			"PMC": "",
			"citation": "",
			"abstract": "We assessed single nucleotide variations (SNVs) between individual cells in two cancer cell lines; DU145, from brain metastasis of prostate tumor with deficient mismatch repair; and HT1080, a fibrosarcoma cell line. Clones of individual cells were isolated, and sequenced using Ion Ampliseq comprehensive cancer panel that covered the exomes of 409 oncogenes and tumor suppressor genes. Five clones of DU145 and four clones of HT1080 cells were analyzed. We found from 7 to 12 unique SNVs between DU145 clones, while HT1080 clones showed no more than one unique SNV. We then sub-cloned individual cells from some of these isolated clones of DU145 and HT1080 cells. The sub-clones were expanded from a single cell to approximately one million cells after about 20 cell divisions. The sub-clones of DU145 cells had from one to four new unique SNVs within the sequenced regions. No unique SNVs were found between sub-clones of HT1080 cells. Our data demonstrate that the extent of genetic variation at the single nucleotide level in cultured cancer cells is significantly affected by the status of the DNA mismatch repair system.",
			"category": 2,
			"name": "Panyutin Igor G,2017"
		},
		{
			"PMID": 28836096,
			"title": "DNA helix: the importance of being AT-rich.",
			"journal": "Mammalian genome : official journal of the International Mammalian Genome Society",
			"authorList": [
				"Vinogradov A E",
				"Anatskaya O V"
			],
			"DOI": "10.1007/s00335-017-9713-8",
			"date": "2018-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "The AT-rich DNA is mostly associated with condensed chromatin, whereas the GC-rich sequence is preferably located in the dispersed chromatin. The AT-rich genes are prone to be tissue-specific (silenced in most tissues), while the GC-rich genes tend to be housekeeping (expressed in many tissues). This paper reports another important property of DNA base composition, which can affect repertoire of genes with high AT content. The GC-rich sequence is more liable to mutation. We found that Spearman correlation between human gene GC content and mutation probability is above 0.9. The change of base composition even in synonymous sites affects mutation probability of nonsynonymous sites and thus of encoded proteins. There is a unique type of housekeeping genes, which are especially unsafe when prone to mutation. Natural selection which usually removes deleterious mutations, in the case of these genes only increases the hazard because it can descend to suborganismal (cellular) level. These are cell cycle-related genes. In accordance with the proposed concept, they have low GC content of synonymous sites (despite them being housekeeping). The gene-centred protein interaction enrichment analysis (PIEA) showed the core clusters of genes whose interactants are modularly enriched in genes with AT-rich synonymous codons. This interconnected network is involved in double-strand break repair, DNA integrity checkpoints and chromosome pairing at mitosis. The damage of these genes results in genome and chromosome instability leading to cancer and other 'error catastrophes'. Reducing the nonsynonymous mutations, the usage of AT-rich synonymous codons can decrease probability of cancer by above 20-fold.",
			"category": 2,
			"name": "Vinogradov A E,2018"
		},
		{
			"PMID": 28823142,
			"title": "Oncogenes, mitochondrial metabolism, and quality control in differentiated thyroid cancer.",
			"journal": "The Korean journal of internal medicine",
			"authorList": [
				"Yi Hyon-Seung",
				"Chang Joon Young",
				"Kim Koon Soon",
				"Shong Minho"
			],
			"DOI": "10.3904/kjim.2016.420",
			"date": "2018-05-21",
			"PMC": "",
			"citation": "",
			"abstract": "Thyroid cancer is one of the most common malignancies of endocrine organs, and its incidence rate has increased steadily over the past several decades. Most differentiated thyroid tumors derived from thyroid epithelial cells exhibit slow-growing cancers, and patients with these tumors can achieve a good prognosis with surgical removal and radioiodine treatment. However, a small proportion of patients present with advanced thyroid cancer and are unusually resistant to current drug treatment modalities. Thyroid tumorigenesis is a complex process that is regulated by the activation of oncogenes, inactivation of tumor suppressors, and alterations in programmed cell death. Mitochondria play an essential role during tumor formation, progression, and metastasis of thyroid cancer. Recent studies have successfully observed the mitochondrial etiology of thyroid carcinogenesis. This review focuses on the recent progress in understanding the molecular mechanisms of thyroid cancer relating to altered mitochondrial metabolism.",
			"category": 2,
			"name": "Yi Hyon-Seung,2018"
		},
		{
			"PMID": 28813639,
			"title": "Exploitation of Gene Expression and Cancer Biomarkers in Paving the Path to Era of Personalized Medicine.",
			"journal": "Genomics, proteomics & bioinformatics",
			"authorList": [
				"Kamel Hala Fawzy Mohamed",
				"Al-Amodi Hiba Saeed A Bagader"
			],
			"DOI": "10.1016/j.gpb.2016.11.005",
			"date": "2017-12-19",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer therapy agents have been used extensively as cytotoxic drugs against tissue or organ of a specific type of cancer. With the better understanding of molecular mechanisms underlying carcinogenesis and cellular events during cancer progression and metastasis, it is now possible to use targeted therapy for these molecular events. Targeted therapy is able to identify cancer patients with dissimilar genetic defects at cellular level for the same cancer type and consequently requires individualized approach for treatment. Cancer therapy begins to shift steadily from the traditional approach of \"one regimen for all patients\" to a more individualized approach, through which each patient will be treated specifically according to their specific genetic defects. Personalized medicine accordingly requires identification of indicators or markers that guide in the decision making of such therapy to the chosen patients for more effective therapy. Cancer biomarkers are frequently used in clinical practice for diagnosis and prognosis, as well as identification of responsive patients and prediction of treatment response of cancer patient. The rapid breakthrough and development of microarray and sequencing technologies is probably the main tool for paving the way toward \"individualized biomarker-driven cancer therapy\" or \"personalized medicine\". In this review, we aim to provide an updated knowledge and overview of the current landscape of cancer biomarkers and their role in personalized medicine, emphasizing the impact of genomics on the implementation of new potential targeted therapies and development of novel cancer biomarkers in improving the outcome of cancer therapy.",
			"category": 2,
			"name": "Kamel Hala Fawzy Mohamed,2017"
		},
		{
			"PMID": 28810879,
			"title": "Quantification of mutant SPOP proteins in prostate cancer using mass spectrometry-based targeted proteomics.",
			"journal": "Journal of translational medicine",
			"authorList": [
				"Wang Hui",
				"Barbieri Christopher E",
				"He Jintang",
				"Gao Yuqian",
				"Shi Tujin",
				"Wu Chaochao",
				"Schepmoes Athena A",
				"Fillmore Thomas L",
				"Chae Sung-Suk",
				"Huang Dennis",
				"Mosquera Juan Miguel",
				"Qian Wei-Jun",
				"Smith Richard D",
				"Srivastava Sudhir",
				"Kagan Jacob",
				"Camp David G",
				"Rodland Karin D",
				"Rubin Mark A",
				"Liu Tao"
			],
			"DOI": "10.1186/s12967-017-1276-7",
			"date": "2018-05-07",
			"PMC": "",
			"citation": "",
			"abstract": "Speckle-type POZ protein (SPOP) is an E3 ubiquitin ligase adaptor protein that functions as a potential tumor suppressor, and SPOP mutations have been identified in ~10% of human prostate cancers. However, it remains unclear if mutant SPOP proteins can be utilized as biomarkers for early detection, diagnosis, prognosis or targeted therapy of prostate cancer. Moreover, the SPOP mutation sites are distributed in a relatively short region with multiple lysine residues, posing significant challenges for bottom-up proteomics analysis of the SPOP mutations.",
			"category": 2,
			"name": "Wang Hui,2018"
		},
		{
			"PMID": 28794467,
			"title": "TDP2 suppresses chromosomal translocations induced by DNA topoisomerase II during gene transcription.",
			"journal": "Nature communications",
			"authorList": [
				"G\u00f3mez-Herreros Fernando",
				"Zagnoli-Vieira Guido",
				"Ntai Ioanna",
				"Mart\u00ednez-Mac\u00edas Mar\u00eda Isabel",
				"Anderson Rhona M",
				"Herrero-Ru\u00edz Andr\u00e9s",
				"Caldecott Keith W"
			],
			"DOI": "10.1038/s41467-017-00307-y",
			"date": "2017-12-12",
			"PMC": "",
			"citation": "",
			"abstract": "DNA double-strand breaks (DSBs) induced by abortive topoisomerase II (TOP2) activity are a potential source of genome instability and chromosome translocation. TOP2-induced DNA double-strand breaks are rejoined in part by tyrosyl-DNA phosphodiesterase 2 (TDP2)-dependent non-homologous end-joining (NHEJ), but whether this process suppresses or promotes TOP2-induced translocations is unclear. Here, we show that TDP2 rejoins DSBs induced during transcription-dependent TOP2 activity in breast cancer cells and at the translocation 'hotspot', MLL. Moreover, we find that TDP2 suppresses chromosome rearrangements induced by TOP2 and reduces TOP2-induced chromosome translocations that arise during gene transcription. Interestingly, however, we implicate TDP2-dependent NHEJ in the formation of a rare subclass of translocations associated previously with therapy-related leukemia and characterized by junction sequences with 4-bp of perfect homology. Collectively, these data highlight the threat posed by TOP2-induced DSBs during transcription and demonstrate the importance of TDP2-dependent non-homologous end-joining in protecting both gene transcription and genome stability.DNA double-strand breaks (DSBs) induced by topoisomerase II (TOP2) are rejoined by TDP2-dependent non-homologous end-joining (NHEJ) but whether this promotes or suppresses translocations is not clear. Here the authors show that TDP2 suppresses chromosome translocations from DSBs introduced during gene transcription.",
			"category": 2,
			"name": "G\u00f3mez-Herreros Fernando,2017"
		},
		{
			"PMID": 28768687,
			"title": "HIT'nDRIVE: patient-specific multidriver gene prioritization for precision oncology.",
			"journal": "Genome research",
			"authorList": [
				"Shrestha Raunak",
				"Hodzic Ermin",
				"Sauerwald Thomas",
				"Dao Phuong",
				"Wang Kendric",
				"Yeung Jake",
				"Anderson Shawn",
				"Vandin Fabio",
				"Haffari Gholamreza",
				"Collins Colin C",
				"Sahinalp S Cenk"
			],
			"DOI": "10.1101/gr.221218.117",
			"date": "2018-05-03",
			"PMC": "",
			"citation": "",
			"abstract": "Prioritizing molecular alterations that act as drivers of cancer remains a crucial bottleneck in therapeutic development. Here we introduce HIT'nDRIVE, a computational method that integrates genomic and transcriptomic data to identify a set of patient-specific, sequence-altered genes, with sufficient collective influence over dysregulated transcripts. HIT'nDRIVE aims to solve the \"random walk facility location\" (RWFL) problem in a gene (or protein) interaction network, which differs from the standard facility location problem by its use of an alternative distance measure: \"multihitting time,\" the expected length of the shortest random walk from any one of the set of sequence-altered genes to an expression-altered target gene. When applied to 2200 tumors from four major cancer types, HIT'nDRIVE revealed many potentially clinically actionable driver genes. We also demonstrated that it is possible to perform accurate phenotype prediction for tumor samples by only using HIT'nDRIVE-seeded driver gene modules from gene interaction networks. In addition, we identified a number of breast cancer subtype-specific driver modules that are associated with patients' survival outcome. Furthermore, HIT'nDRIVE, when applied to a large panel of pan-cancer cell lines, accurately predicted drug efficacy using the driver genes and their seeded gene modules. Overall, HIT'nDRIVE may help clinicians contextualize massive multiomics data in therapeutic decision making, enabling widespread implementation of precision oncology.",
			"category": 2,
			"name": "Shrestha Raunak,2018"
		},
		{
			"PMID": 28753846,
			"title": "The Landscape of Whole-genome Alterations and Pathologic Features in Genitourinary Malignancies: An Analysis of the Cancer Genome Atlas.",
			"journal": "European urology focus",
			"authorList": [
				"Ball Mark W",
				"Gorin Michael A",
				"Drake Charles G",
				"Hammers Hans J",
				"Allaf Mohamad E"
			],
			"DOI": "10.1016/j.euf.2017.01.007",
			"date": "2019-01-24",
			"PMC": "",
			"citation": "",
			"abstract": "The accumulation of somatic genetic alterations drives carcinogenesis. Little is known, however, about how the level of genetic alteration across an entire cancer genome affects tumor grade, stage or survival.",
			"category": 2,
			"name": "Ball Mark W,2019"
		},
		{
			"PMID": 28748501,
			"title": "A step-by-step microRNA guide to cancer development and metastasis.",
			"journal": "Cellular oncology (Dordrecht, Netherlands)",
			"authorList": [
				"Markopoulos Georgios S",
				"Roupakia Eugenia",
				"Tokamani Maria",
				"Chavdoula Evangelia",
				"Hatziapostolou Maria",
				"Polytarchou Christos",
				"Marcu Kenneth B",
				"Papavassiliou Athanasios G",
				"Sandaltzopoulos Raphael",
				"Kolettas Evangelos"
			],
			"DOI": "10.1007/s13402-017-0341-9",
			"date": "2018-04-23",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is one of the leading causes of mortality. The neoplastic transformation of normal cells to cancer cells is caused by a progressive accumulation of genetic and epigenetic alterations in oncogenes, tumor suppressor genes and epigenetic regulators, providing cells with new properties, collectively known as the hallmarks of cancer. During the process of neoplastic transformation cells progressively acquire novel characteristics such as unlimited growth potential, increased motility and the ability to migrate and invade adjacent tissues, the ability to spread from the tumor of origin to distant sites, and increased resistance to various types of stresses, mostly attributed to the activation of genetic stress-response programs. Accumulating evidence indicates a crucial role of microRNAs (miRNAs or miRs) in the initiation and progression of cancer, acting either as oncogenes (oncomirs) or as tumor suppressors via several molecular mechanisms. MiRNAs comprise a class of small ~22\u00a0bp long noncoding RNAs that play a key role in the regulation of gene expression at the post-transcriptional level, acting as negative regulators of mRNA translation and/or stability. MiRNAs are involved in the regulation of a variety of biological processes including cell cycle progression, DNA damage responses and apoptosis, epithelial-to-mesenchymal cell transitions, cell motility and stemness through complex and interactive transcription factor-miRNA regulatory networks.",
			"category": 2,
			"name": "Markopoulos Georgios S,2018"
		},
		{
			"PMID": 28733365,
			"title": "Contrasting Determinants of Mutation Rates in Germline and Soma.",
			"journal": "Genetics",
			"authorList": [
				"Chen Chen",
				"Qi Hongjian",
				"Shen Yufeng",
				"Pickrell Joseph",
				"Przeworski Molly"
			],
			"DOI": "10.1534/genetics.117.1114",
			"date": "2017-12-07",
			"PMC": "",
			"citation": "",
			"abstract": "Recent studies of somatic and germline mutations have led to the identification of a number of factors that influence point mutation rates, including CpG methylation, expression levels, replication timing, and GC content. Intriguingly, some of the effects appear to differ between soma and germline: in particular, whereas mutation rates have been reported to decrease with expression levels in tumors, no clear effect has been detected in the germline. Distinct approaches were taken to analyze the data, however, so it is hard to know whether these apparent differences are real. To enable a cleaner comparison, we considered a statistical model in which the mutation rate of a coding region is predicted by GC content, expression levels, replication timing, and two histone repressive marks. We applied this model to both a set of germline mutations identified in exomes and to exonic somatic mutations in four types of tumors. Most determinants of mutations are shared: notably, we detected an effect of expression levels on both germline and somatic mutation rates. Moreover, in all tissues considered, higher expression levels are associated with greater strand asymmetry of mutations. However, mutation rates increase with expression levels in testis (and, more tentatively, in ovary), whereas they decrease with expression levels in somatic tissues. This contrast points to differences in damage or repair rates during transcription in soma and germline.",
			"category": 2,
			"name": "Chen Chen,2017"
		},
		{
			"PMID": 28716121,
			"title": "Identification of trunk mutations in gastric carcinoma: a case study.",
			"journal": "BMC medical genomics",
			"authorList": [
				"Zhou Zhan",
				"Wu Shanshan",
				"Lai Jun",
				"Shi Yuan",
				"Qiu Chixiao",
				"Chen Zhe",
				"Wang Yufeng",
				"Gu Xun",
				"Zhou Jie",
				"Chen Shuqing"
			],
			"DOI": "10.1186/s12920-017-0285-y",
			"date": "2018-02-26",
			"PMC": "",
			"citation": "",
			"abstract": "Intratumor heterogeneity (ITH) poses an urgent challenge for cancer precision medicine because it can cause drug resistance against cancer target therapy and immunotherapy. The search for trunk mutations that are present in all cancer cells is therefore critical for each patient.",
			"category": 2,
			"name": "Zhou Zhan,2018"
		},
		{
			"PMID": 28685150,
			"title": "Genetic Mutations and Epigenetic Modifications: Driving Cancer and Informing Precision Medicine.",
			"journal": "BioMed research international",
			"authorList": [
				"Coyle Krysta Mila",
				"Boudreau Jeanette E",
				"Marcato Paola"
			],
			"DOI": "10.1155/2017/9620870",
			"date": "2018-03-21",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer treatment is undergoing a significant revolution from \"one-size-fits-all\" cytotoxic therapies to tailored approaches that precisely target molecular alterations. Precision strategies for drug development and patient stratification, based on the molecular features of tumors, are the next logical step in a long history of approaches to cancer therapy. In this review, we discuss the history of cancer treatment from generic natural extracts and radical surgical procedures to site-specific and combinatorial treatment regimens, which have incrementally improved patient outcomes. We discuss the related contributions of genetics and epigenetics to cancer progression and the response to targeted therapies and identify challenges and opportunities for the success of precision medicine. The identification of patients who will benefit from targeted therapies is more complex than simply identifying patients whose tumors harbour the targeted aberration, and intratumoral heterogeneity makes it difficult to determine if a precision therapy is successful during treatment. This heterogeneity enables tumors to develop resistance to targeted approaches; therefore, the rational combination of therapeutic agents will limit the threat of acquired resistance to therapeutic success. By incorporating the view of malignant transformation modulated by networks of genetic and epigenetic interactions, molecular strategies will enable precision medicine for effective treatment across cancer subtypes.",
			"category": 2,
			"name": "Coyle Krysta Mila,2018"
		},
		{
			"PMID": 28680959,
			"title": "DNA Mutations May Not Be the Cause of Cancer.",
			"journal": "Oncology and therapy",
			"authorList": [
				"Adjiri Adouda"
			],
			"DOI": "10.1007/s40487-017-0047-1",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is the most challenging disease of our time with increasing numbers of new cases each year, worldwide. Great achievements have been reached in cancer research through deep sequencing which helped define druggable targets. However, the still-evolving targeted therapy suffers resistance suggesting that DNA mutations considered as drivers may not have a role in tumor initiation. The present work discusses the role of DNA mutations as drivers and passengers in cancer initiation and development. First, it is important to discern the role of these DNA mutations as initiating events causing cancer or as contributors crucial for the development of a tumor once it has initiated. Second, breast cancer shown here illustrates how identification of DNA mutations in cancerous cells has influenced our approach for anti-cancer drug design. The cancer trilogy we have reached and described as: initial drug; resistance/recurrence; drug/treatment combinations, calls for a paradigm shift. To design more effective cancer drugs with durable and positive outcome, future cancer research needs to move beyond the sequencing era and explore changes which are taking place in cancer cells at levels other than the DNA. Evolutionary constraints may be acting as a barrier to preserve the human species from being transformed and, for that matter, all multi-cellular species which can incur cancer. Furthermore, mutations in the DNA do occur and for a multitude of reasons but without necessarily causing cancer. New directions will draw themselves when more focus is given to the event responsible for the switch of a cell from normalcy to malignancy. Until then, targeted therapy will certainly continue to improve the outcome of patients; however, it is unlikely to eradicate breast cancer depicted here.",
			"category": 2,
			"name": "Adjiri Adouda,2020"
		},
		{
			"PMID": 28669404,
			"title": "Ultra-sensitive Sequencing Identifies High Prevalence of Clonal Hematopoiesis-Associated Mutations throughout Adult Life.",
			"journal": "American journal of human genetics",
			"authorList": [
				"Acuna-Hidalgo Rocio",
				"Sengul Hilal",
				"Steehouwer Marloes",
				"van de Vorst Maartje",
				"Vermeulen Sita H",
				"Kiemeney Lambertus A L M",
				"Veltman Joris A",
				"Gilissen Christian",
				"Hoischen Alexander"
			],
			"DOI": "10.1016/j.ajhg.2017.05.013",
			"date": "2017-08-02",
			"PMC": "",
			"citation": "",
			"abstract": "Clonal hematopoiesis results from somatic mutations in hematopoietic stem cells, which give an advantage to mutant cells, driving their clonal expansion and potentially leading to leukemia. The acquisition of clonal hematopoiesis-driver mutations (CHDMs) occurs with normal aging and these mutations have been detected in more than 10% of individuals \u226565 years. We aimed to examine the prevalence and characteristics of CHDMs throughout adult life. We developed a targeted re-sequencing assay combining high-throughput with ultra-high sensitivity based on single-molecule molecular inversion probes (smMIPs). Using smMIPs, we screened more than 100 loci for CHDMs in more than 2,000 blood DNA samples from population controls between 20 and 69 years of age. Loci screened included 40 regions known to drive clonal hematopoiesis when mutated and 64 novel candidate loci. We identified 224 somatic mutations throughout our cohort, of which 216 were coding mutations in known driver genes (DNMT3A, JAK2, GNAS, TET2, and ASXL1), including 196 point mutations and 20 indels. Our assay's improved sensitivity allowed us to detect mutations with variant allele frequencies as low as 0.001. CHDMs were identified in more than 20% of individuals 60 to 69 years of age and in 3% of individuals 20 to 29 years of age, approximately double the previously reported prevalence despite screening a limited set of loci. Our findings support the occurrence of clonal hematopoiesis-associated mutations as a widespread mechanism linked with aging, suggesting that mosaicism as a result of clonal evolution of cells harboring somatic mutations is a universal mechanism occurring at all ages in healthy humans.",
			"category": 2,
			"name": "Acuna-Hidalgo Rocio,2017"
		},
		{
			"PMID": 28652432,
			"title": "Chromosome 7 Multiplication in EGFR-positive Lung Carcinomas Based on Tissue Microarray Analysis.",
			"journal": "In vivo (Athens, Greece)",
			"authorList": [
				"Tsiambas Evangelos",
				"Mastronikolis Nicholas S",
				"Lefas Alicia Y",
				"Georgiannos Stavros N",
				"Ragos Vasileios",
				"Fotiades Panagiotis P",
				"Tsoukalas Nikolaos",
				"Kavantzas Nikolaos",
				"Karameris Andreas",
				"Peschos Dimitrios",
				"Patsouris Efstratios",
				"Syrigos Konstantinos"
			],
			"DOI": "",
			"date": "2018-03-26",
			"PMC": "",
			"citation": "",
			"abstract": "Epidermal growth factor receptor (EGFR) over-activation is observed in significant proportions of non-small cell lung carcinomas (NSCLC). Our aim was to investigate the role of chromosome 7 multiplication with regard to its influence in EGFR expression, combined or not with gene amplification.",
			"category": 2,
			"name": "Tsiambas Evangelos,2018"
		},
		{
			"PMID": 28650955,
			"title": "NetNorM: Capturing cancer-relevant information in somatic exome mutation data with gene networks for cancer stratification and prognosis.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Le Morvan Marine",
				"Zinovyev Andrei",
				"Vert Jean-Philippe"
			],
			"DOI": "10.1371/journal.pcbi.1005573",
			"date": "2017-08-18",
			"PMC": "",
			"citation": "",
			"abstract": "Genome-wide somatic mutation profiles of tumours can now be assessed efficiently and promise to move precision medicine forward. Statistical analysis of mutation profiles is however challenging due to the low frequency of most mutations, the varying mutation rates across tumours, and the presence of a majority of passenger events that hide the contribution of driver events. Here we propose a method, NetNorM, to represent whole-exome somatic mutation data in a form that enhances cancer-relevant information using a gene network as background knowledge. We evaluate its relevance for two tasks: survival prediction and unsupervised patient stratification. Using data from 8 cancer types from The Cancer Genome Atlas (TCGA), we show that it improves over the raw binary mutation data and network diffusion for these two tasks. In doing so, we also provide a thorough assessment of somatic mutations prognostic power which has been overlooked by previous studies because of the sparse and binary nature of mutations.",
			"category": 2,
			"name": "Le Morvan Marine,2017"
		},
		{
			"PMID": 28637487,
			"title": "The NF1 somatic mutational landscape in sporadic human cancers.",
			"journal": "Human genomics",
			"authorList": [
				"Philpott Charlotte",
				"Tovell Hannah",
				"Frayling Ian M",
				"Cooper David N",
				"Upadhyaya Meena"
			],
			"DOI": "10.1186/s40246-017-0109-3",
			"date": "2018-05-23",
			"PMC": "",
			"citation": "",
			"abstract": "Neurofibromatosis type 1 (NF1: Online Mendelian Inheritance in Man (OMIM) #162200) is an autosomal dominantly inherited tumour predisposition syndrome. Heritable constitutional mutations in the NF1 gene result in dysregulation of the RAS/MAPK pathway and are causative of NF1. The major known function of the NF1 gene product neurofibromin is to downregulate RAS. NF1 exhibits variable clinical expression and is characterized by benign cutaneous lesions including neurofibromas and caf\u00e9-au-lait macules, as well as a predisposition to various types of malignancy, such as breast cancer and leukaemia. However, acquired somatic mutations in NF1 are also found in a wide variety of malignant neoplasms that are not associated with NF1.",
			"category": 2,
			"name": "Philpott Charlotte,2018"
		},
		{
			"PMID": 28623259,
			"title": "MicroRNA-34a Encapsulated in Hyaluronic Acid Nanoparticles Induces Epigenetic Changes with Altered Mitochondrial Bioenergetics and Apoptosis in Non-Small-Cell Lung Cancer Cells.",
			"journal": "Scientific reports",
			"authorList": [
				"Trivedi Malav",
				"Singh Amit",
				"Talekar Meghna",
				"Pawar Grishma",
				"Shah Parin",
				"Amiji Mansoor"
			],
			"DOI": "10.1038/s41598-017-02816-8",
			"date": "2019-06-10",
			"PMC": "",
			"citation": "",
			"abstract": "Therapies targeting epigenetic changes for cancer treatment are in Phase I/II trials; however, all of these target\u00a0only nuclear DNA. Emerging evidence suggests presence of methylation marks on mitochondrial DNA (mtDNA); but their contribution in cancer is unidentified. Expression of genes encoded on mtDNA are altered in cancer cells, along with increased glycolytic flux. Such glycolytic flux and elevated reactive oxygen species is supported by increased antioxidant; glutathione. MicroRNA-34a can translocate to mitochondria, mediate downstream apoptotic effects of tumor suppressor P53, and inhibit the antioxidant response element Nrf-2, resulting in depleted glutathione levels. Based on such strong rationale, we encapsulated microRNA-34a in our well-established Hyaluronic-Acid nanoparticles and delivered to cisplatin-sensitive and cisplatin-resistant A549-lung adenocarcinoma cells. Successful delivery and uptake in cells resulted in altered ATP levels, decreased glycolytic flux, Nrf-2 and glutathione levels, ultimately resulting in caspase-3 activation and apoptosis. Most important were the concurrent underlying molecular changes in epigenetic status of D-loop on the mtDNA and transcription of mtDNA-encoded genes. Although preliminary, we provide a novel therapeutic approach in form of altered mitochondrial bioenergetics and redox status of cancer cells with underlying changes in epigenetic status of mtDNA that can subsequently results in induction of cancer cell apoptosis.",
			"category": 2,
			"name": "Trivedi Malav,2019"
		},
		{
			"PMID": 28572256,
			"title": "Mutational Signatures in Breast Cancer: The Problem at the DNA Level.",
			"journal": "Clinical cancer research : an official journal of the American Association for Cancer Research",
			"authorList": [
				"Nik-Zainal Serena",
				"Morganella Sandro"
			],
			"DOI": "10.1158/1078-0432.CCR-16-2810",
			"date": "2018-03-16",
			"PMC": "",
			"citation": "",
			"abstract": "A breast cancer genome is a record of the historic mutagenic activity that has occurred throughout the development of the tumor. Indeed, every mutation may be informative. Although driver mutations were the main focus of cancer research for a long time, passenger mutational signatures, the imprints of DNA damage and DNA repair processes that have been operative during tumorigenesis, are also biologically illuminating. This review is a chronicle of how the concept of mutational signatures arose and brings the reader up-to-date on this field, particularly in breast cancer. Mutational signatures have now been advanced to include mutational processes that involve rearrangements, and novel cancer biological insights have been gained through studying these in great detail. Furthermore, there are efforts to take this field into the clinical sphere. If validated, mutational signatures could thus form an additional weapon in the arsenal of cancer precision diagnostics and therapeutic stratification in the modern war against cancer. ",
			"category": 2,
			"name": "Nik-Zainal Serena,2018"
		},
		{
			"PMID": 28569140,
			"title": "An evaluation of copy number variation detection tools for cancer using whole exome sequencing data.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"Zare Fatima",
				"Dow Michelle",
				"Monteleone Nicholas",
				"Hosny Abdelrahman",
				"Nabavi Sheida"
			],
			"DOI": "10.1186/s12859-017-1705-x",
			"date": "2017-11-16",
			"PMC": "",
			"citation": "",
			"abstract": "Recently copy number variation (CNV) has gained considerable interest as a type of genomic/genetic variation that plays an important role in disease susceptibility. Advances in sequencing technology have created an opportunity for detecting CNVs more accurately. Recently whole exome sequencing (WES) has become primary strategy for sequencing patient samples and study their genomics aberrations. However, compared to whole genome sequencing, WES introduces more biases and noise that make CNV detection very challenging. Additionally, tumors' complexity makes the detection of cancer specific CNVs even more difficult. Although many CNV detection tools have been developed since introducing NGS data, there are few tools for somatic CNV detection for WES data in cancer.",
			"category": 2,
			"name": "Zare Fatima,2017"
		},
		{
			"PMID": 28529482,
			"title": "Mode of Action Analyses of Neferine, a Bisbenzylisoquinoline Alkaloid of Lotus (",
			"journal": "Frontiers in pharmacology",
			"authorList": [
				"Kadioglu Onat",
				"Law Betty Y K",
				"Mok Simon W F",
				"Xu Su-Wei",
				"Efferth Thomas",
				"Wong Vincent K W"
			],
			"DOI": "10.3389/fphar.2017.00238",
			"date": "2024-03-26",
			"PMC": "",
			"citation": "",
			"abstract": "Neferine, a bisbenzylisoquinoline alkaloid isolated from the green seed embryos of Lotus (",
			"category": 2,
			"name": "Kadioglu Onat,2024"
		},
		{
			"PMID": 28528721,
			"title": "Perspectives on Gene Regulatory Network Evolution.",
			"journal": "Trends in genetics : TIG",
			"authorList": [
				"Halfon Marc S"
			],
			"DOI": "10.1016/j.tig.2017.04.005",
			"date": "2018-02-23",
			"PMC": "",
			"citation": "",
			"abstract": "Animal development proceeds through the activity of genes and their cis-regulatory modules (CRMs) working together in sets of gene regulatory networks (GRNs). The emergence of species-specific traits and novel structures results from evolutionary changes in GRNs. Recent work in a wide variety of animal models, and particularly in insects, has started to reveal the modes and mechanisms of GRN evolution. I discuss here various aspects of GRN evolution and argue that developmental system drift (DSD), in which conserved phenotype is nevertheless a result of changed genetic interactions, should regularly be viewed from the perspective of GRN evolution. Advances in methods to discover related CRMs in diverse insect species, a critical requirement for detailed GRN characterization, are also described.",
			"category": 2,
			"name": "Halfon Marc S,2018"
		},
		{
			"PMID": 28526679,
			"title": "Succession of transiently active tumor-initiating cell clones in human pancreatic cancer xenografts.",
			"journal": "EMBO molecular medicine",
			"authorList": [
				"Ball Claudia R",
				"Oppel Felix",
				"Ehrenberg Karl Roland",
				"Dubash Taronish D",
				"Dieter Sebastian M",
				"Hoffmann Christopher M",
				"Abel Ulrich",
				"Herbst Friederike",
				"Koch Moritz",
				"Werner Jens",
				"Bergmann Frank",
				"Ishaque Naveed",
				"Schmidt Manfred",
				"von Kalle Christof",
				"Scholl Claudia",
				"Fr\u00f6hling Stefan",
				"Brors Benedikt",
				"Weichert Wilko",
				"Weitz J\u00fcrgen",
				"Glimm Hanno"
			],
			"DOI": "10.15252/emmm.201607354",
			"date": "2018-03-12",
			"PMC": "",
			"citation": "",
			"abstract": "Although tumor-initiating cell (TIC) self-renewal has been postulated to be essential in progression and metastasis formation of human pancreatic adenocarcinoma (PDAC), clonal dynamics of TICs within PDAC tumors are yet unknown. Here, we show that long-term progression of PDAC in serial xenotransplantation is driven by a succession of transiently active TICs producing tumor cells in temporally restricted bursts. Clonal tracking of individual, genetically marked TICs revealed that individual tumors are generated by distinct sets of TICs with very little overlap between subsequent xenograft generations. An unexpected functional and phenotypic plasticity of pancreatic TICs ",
			"category": 2,
			"name": "Ball Claudia R,2018"
		},
		{
			"PMID": 28498882,
			"title": "Mutational signatures and mutable motifs in cancer genomes.",
			"journal": "Briefings in bioinformatics",
			"authorList": [
				"Rogozin Igor B",
				"Pavlov Youri I",
				"Goncearenco Alexander",
				"De Subhajyoti",
				"Lada Artem G",
				"Poliakov Eugenia",
				"Panchenko Anna R",
				"Cooper David N"
			],
			"DOI": "10.1093/bib/bbx049",
			"date": "2019-07-05",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a genetic disorder, meaning that a plethora of different mutations, whether somatic or germ line, underlie the etiology of the 'Emperor of Maladies'. Point mutations, chromosomal rearrangements and copy number changes, whether they have occurred spontaneously in predisposed individuals or have been induced by intrinsic or extrinsic (environmental) mutagens, lead to the activation of oncogenes and inactivation of tumor suppressor genes, thereby promoting malignancy. This scenario has now been recognized and experimentally confirmed in a wide range of different contexts. Over the past decade, a surge in available sequencing technologies has allowed the sequencing of whole genomes from liquid malignancies and solid tumors belonging to different types and stages of cancer, giving birth to the new field of cancer genomics. One of the most striking discoveries has been that cancer genomes are highly enriched with mutations of specific kinds. It has been suggested that these mutations can be classified into 'families' based on their mutational signatures. A mutational signature may be regarded as a type of base substitution (e.g. C:G to T:A) within a particular context of neighboring nucleotide sequence (the bases upstream and/or downstream of the mutation). These mutational signatures, supplemented by mutable motifs (a wider mutational context), promise to help us to understand the nature of the mutational processes that operate during tumor evolution because they represent the footprints of interactions between DNA, mutagens and the enzymes of the repair/replication/modification pathways.",
			"category": 2,
			"name": "Rogozin Igor B,2019"
		},
		{
			"PMID": 28490961,
			"title": "Radiofrequency radiations induced genotoxic and carcinogenic effects on chickpea (",
			"journal": "Saudi journal of biological sciences",
			"authorList": [
				"Qureshi Sadaf Tabasum",
				"Memon Sajjad Ahmed",
				"Abassi Abdul Rasool",
				"Sial Mahboob Ali",
				"Bughio Farooque Ali"
			],
			"DOI": "10.1016/j.sjbs.2016.02.011",
			"date": "2023-11-04",
			"PMC": "",
			"citation": "",
			"abstract": "Present study was under taken to predict the possible DNA damages (genotoxicity) and carcinogenicity caused by radiofrequency radiations (RF) to living tissue. Dry seeds of chickpea were treated with GSM cell phone (900\u00a0MHz) and laptop (3.31\u00a0GHz) as RF source for 24 and 48\u00a0h. Untreated seeds were used as (0\u00a0h) negative control and Gamma rays (250 Gray) as positive control. Plant chromosomal aberration assay was used as genotoxicity marker. All the treatment of RF inhibits seed germination percentage. 48\u00a0h laptop treatment has the most negative effect as compared to untreated control. A decrease was observed in mitotic index (M.I) and increase in abnormality index (A.I) with the increase in exposure duration and frequency in (Hz). Cell membrane damages were also observed only in 48\u00a0h exposure of cell phone and laptop (RF). Maximum nuclear membrane damages and ghost cells were again recorded in 48\u00a0h exposure of cell phone and laptop. The radiofrequency radiations (900\u00a0MHz and 3.31\u00a0GHz) are only genotoxic as they induce micronuclei, bi-nuclei, multi-nuclei and scattered nuclei but could be carcinogenic as 48\u00a0h incubation of RF induced fragmentation and ghost cells. Therefore cell phones and laptop should not be used unnecessarily to avoid possible genotoxic and carcinogenic effects.",
			"category": 2,
			"name": "Qureshi Sadaf Tabasum,2023"
		},
		{
			"PMID": 28489996,
			"title": "Cancer-Associated Mutations in Endometriosis without Cancer.",
			"journal": "The New England journal of medicine",
			"authorList": [
				"Anglesio Michael S",
				"Papadopoulos Nickolas",
				"Ayhan Ayse",
				"Nazeran Tayyebeh M",
				"No\u00eb Micha\u00ebl",
				"Horlings Hugo M",
				"Lum Amy",
				"Jones Si\u00e2n",
				"Senz Janine",
				"Seckin Tamer",
				"Ho Julie",
				"Wu Ren-Chin",
				"Lac Vivian",
				"Ogawa Hiroshi",
				"Tessier-Cloutier Basile",
				"Alhassan Rami",
				"Wang Amy",
				"Wang Yuxuan",
				"Cohen Joshua D",
				"Wong Fontayne",
				"Hasanovic Adnan",
				"Orr Natasha",
				"Zhang Ming",
				"Popoli Maria",
				"McMahon Wyatt",
				"Wood Laura D",
				"Mattox Austin",
				"Allaire Catherine",
				"Segars James",
				"Williams Christina",
				"Tomasetti Cristian",
				"Boyd Niki",
				"Kinzler Kenneth W",
				"Gilks C Blake",
				"Diaz Luis",
				"Wang Tian-Li",
				"Vogelstein Bert",
				"Yong Paul J",
				"Huntsman David G",
				"Shih Ie-Ming"
			],
			"DOI": "10.1056/NEJMoa1614814",
			"date": "2017-06-01",
			"PMC": "",
			"citation": "",
			"abstract": "Endometriosis, defined as the presence of ectopic endometrial stroma and epithelium, affects approximately 10% of reproductive-age women and can cause pelvic pain and infertility. Endometriotic lesions are considered to be benign inflammatory lesions but have cancerlike features such as local invasion and resistance to apoptosis.",
			"category": 2,
			"name": "Anglesio Michael S,2017"
		},
		{
			"PMID": 28489584,
			"title": "Transcriptional response profiles of paired tumor-normal samples offer novel perspectives in pan-cancer analysis.",
			"journal": "Oncotarget",
			"authorList": [
				"Hu Shuofeng",
				"Yuan Hanyu",
				"Li Zongcheng",
				"Zhang Jian",
				"Wu Jiaqi",
				"Chen Yaowen",
				"Shi Qiang",
				"Ren Wu",
				"Shao Ningsheng",
				"Ying Xiaomin"
			],
			"DOI": "10.18632/oncotarget.17295",
			"date": "2018-04-09",
			"PMC": "",
			"citation": "",
			"abstract": "Both tumor and adjacent normal tissues are valuable in cancer research. Transcriptional response profiles represent the changes of gene expression levels between paired tumor and adjacent normal tissues. In this study, we performed a pan-cancer analysis based on the transcriptional response profiles from 633 samples across 13 cancer types. We obtained two interesting results. Using consensus clustering method, we characterized ten clusters with distinct transcriptional response patterns and enriched pathways. Notably, head and neck squamous cell carcinoma was divided in two subtypes, enriched in cell cycle-related pathways and cell adhesion-related pathways respectively. The other interesting result is that we identified 92 potential pan-cancer genes that were consistently upregulated across multiple cancer types. Knockdown of FAM64A or TROAP inhibited the growth of cancer cells, suggesting that these genes may promote tumor development and are worthy of further validations. Our results suggest that transcriptional response profiles of paired tumor-normal tissues can provide novel perspectives in pan-cancer analysis.",
			"category": 2,
			"name": "Hu Shuofeng,2018"
		},
		{
			"PMID": 28484631,
			"title": "TSNAD: an integrated software for cancer somatic mutation and tumour-specific neoantigen detection.",
			"journal": "Royal Society open science",
			"authorList": [
				"Zhou Zhan",
				"Lyu Xingzheng",
				"Wu Jingcheng",
				"Yang Xiaoyue",
				"Wu Shanshan",
				"Zhou Jie",
				"Gu Xun",
				"Su Zhixi",
				"Chen Shuqing"
			],
			"DOI": "10.1098/rsos.170050",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "Tumour antigens have attracted much attention because of their importance to cancer diagnosis, prognosis and targeted therapy. With the development of cancer genomics, the identification of tumour-specific neoantigens became possible, which is a crucial step for cancer immunotherapy. In this study, we developed software called the tumour-specific neoantigen detector for detecting cancer somatic mutations following the best practices of the genome analysis toolkit and predicting potential tumour-specific neoantigens, which could be either extracellular mutations of membrane proteins or mutated peptides presented by class I major histocompatibility complex molecules. This pipeline was beneficial to the biologist with little programmatic background. We also applied the software to the somatic mutations from the International Cancer Genome Consortium database to predict numerous potential tumour-specific neoantigens. This software is freely available from https://github.com/jiujiezz/tsnad.",
			"category": 2,
			"name": "Zhou Zhan,2020"
		},
		{
			"PMID": 28484242,
			"title": "Regulation of CHK1 by mTOR contributes to the evasion of DNA damage barrier of cancer cells.",
			"journal": "Scientific reports",
			"authorList": [
				"Zhou Xinhui",
				"Liu Weijin",
				"Hu Xing",
				"Dorrance Adrienne",
				"Garzon Ramiro",
				"Houghton Peter J",
				"Shen Changxian"
			],
			"DOI": "10.1038/s41598-017-01729-w",
			"date": "2018-12-17",
			"PMC": "",
			"citation": "",
			"abstract": "Oncogenic transformation leads to dysregulated cell proliferation, nutrient deficiency, and hypoxia resulting in metabolic stress and increased DNA damage. In normal cells, such metabolic stress leads to inhibition of signaling through the mammalian Target of Rapamycin Complex 1 (mTORC1), reduction of protein translation, cell cycle arrest, and conservation of energy. In contrast, negative regulation of mTORC1 signaling by DNA damage is abrogated in many cancer cells, thus mTORC1 signaling remains active under microenvironmental conditions that potentially promote endogenous DNA damage. Here we report that mTORC1 signaling suppresses endogenous DNA damage and replication stress. Pharmacological inhibition of mTOR signaling resulted in phosphorylation of H2AX concomitant with the decrease of CHK1 levels both in cell culture and mouse rhadomyosarcoma xenografts. Further results demonstrated that mTORC1-S6K1 signaling controls transcription of CHK1 via Rb-E2F by upregulating cyclin D and E. Consistent with these results, downregulation of CHK1 by inhibition of mTOR kinase resulted in defects in the slow S phase progression following DNA damage. These results indicate that, under stressful conditions, maintained mTORC1 signaling in cancer cells promotes survival by suppressing endogenous DNA damage, and may control cell fate through the regulation of CHK1.",
			"category": 2,
			"name": "Zhou Xinhui,2018"
		},
		{
			"PMID": 28477017,
			"title": "Characterization of potential driver mutations involved in human breast cancer by computational approaches.",
			"journal": "Oncotarget",
			"authorList": [
				"Rajendran Barani Kumar",
				"Deng Chu-Xia"
			],
			"DOI": "10.18632/oncotarget.17225",
			"date": "2018-05-17",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer is the second most frequently occurring form of cancer and is also the second most lethal cancer in women worldwide. A genetic mutation is one of the key factors that alter multiple cellular regulatory pathways and drive breast cancer initiation and progression yet nature of these cancer drivers remains elusive. In this article, we have reviewed various computational perspectives and algorithms for exploring breast cancer driver mutation genes. Using both frequency based and mutational exclusivity based approaches, we identified 195 driver genes and shortlisted 63 of them as candidate drivers for breast cancer using various computational approaches. Finally, we conducted network and pathway analysis to explore their functions in breast tumorigenesis including tumor initiation, progression, and metastasis.",
			"category": 2,
			"name": "Rajendran Barani Kumar,2018"
		},
		{
			"PMID": 28445463,
			"title": "Stem cells: Subclone wars.",
			"journal": "Nature",
			"authorList": [
				"Chanock Stephen"
			],
			"DOI": "10.1038/nature22490",
			"date": "2017-08-09",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Chanock Stephen,2017"
		},
		{
			"PMID": 28427189,
			"title": "Identifying biomarkers of papillary renal cell carcinoma associated with pathological stage by weighted gene co-expression network analysis.",
			"journal": "Oncotarget",
			"authorList": [
				"He Zhongshi",
				"Sun Min",
				"Ke Yuan",
				"Lin Rongjie",
				"Xiao Youde",
				"Zhou Shuliang",
				"Zhao Hong",
				"Wang Yan",
				"Zhou Fuxiang",
				"Zhou Yunfeng"
			],
			"DOI": "10.18632/oncotarget.15842",
			"date": "2018-04-03",
			"PMC": "",
			"citation": "",
			"abstract": "Although papillary renal cell carcinoma (PRCC) accounts for 10%-15% of renal cell carcinoma (RCC), no predictive molecular biomarker is currently applicable to guiding disease stage of PRCC patients. The mRNASeq data of PRCC and adjacent normal tissue in The Cancer Genome Atlas was analyzed to identify 1148 differentially expressed genes, on which weighted gene co-expression network analysis was performed. Then 11 co-expressed gene modules were identified. The highest association was found between blue module and pathological stage (r = 0.45) by Pearson's correlation analysis. Functional enrichment analysis revealed that biological processes of blue module focused on nuclear division, cell cycle phase, and spindle (all P < 1e-10). All 40 hub genes in blue module can distinguish localized (pathological stage I, II) from non-localized (pathological stage III, IV) PRCC (P < 0.01). A good molecular biomarker for pathological stage of RCC must be a prognostic gene in clinical practice. Survival analysis was performed to reversely validate if hub genes were associated with pathological stage. Survival analysis unveiled that all hub genes were associated with patient prognosis (P < 0.01).The validation cohort GSE2748 verified that 30 hub genes can differentiate localized from non-localized PRCC (P < 0.01), and 18 hub genes are prognosis-associated (P < 0.01).ROC curve indicated that the 17 hub genes exhibited excellent diagnostic efficiency for localized and non-localized PRCC (AUC > 0.7). These hub genes may serve as a biomarker and help to distinguish different pathological stages for PRCC patients.",
			"category": 2,
			"name": "He Zhongshi,2018"
		},
		{
			"PMID": 28426665,
			"title": "Oncodomains: A protein domain-centric framework for analyzing rare variants in tumor samples.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Peterson Thomas A",
				"Gauran Iris Ivy M",
				"Park Junyong",
				"Park DoHwan",
				"Kann Maricel G"
			],
			"DOI": "10.1371/journal.pcbi.1005428",
			"date": "2017-06-26",
			"PMC": "",
			"citation": "",
			"abstract": "The fight against cancer is hindered by its highly heterogeneous nature. Genome-wide sequencing studies have shown that individual malignancies contain many mutations that range from those commonly found in tumor genomes to rare somatic variants present only in a small fraction of lesions. Such rare somatic variants dominate the landscape of genomic mutations in cancer, yet efforts to correlate somatic mutations found in one or few individuals with functional roles have been largely unsuccessful. Traditional methods for identifying somatic variants that drive cancer are 'gene-centric' in that they consider only somatic variants within a particular gene and make no comparison to other similar genes in the same family that may play a similar role in cancer. In this work, we present oncodomain hotspots, a new 'domain-centric' method for identifying clusters of somatic mutations across entire gene families using protein domain models. Our analysis confirms that our approach creates a framework for leveraging structural and functional information encapsulated by protein domains into the analysis of somatic variants in cancer, enabling the assessment of even rare somatic variants by comparison to similar genes. Our results reveal a vast landscape of somatic variants that act at the level of domain families altering pathways known to be involved with cancer such as protein phosphorylation, signaling, gene regulation, and cell metabolism. Due to oncodomain hotspots' unique ability to assess rare variants, we expect our method to become an important tool for the analysis of sequenced tumor genomes, complementing existing methods.",
			"category": 2,
			"name": "Peterson Thomas A,2017"
		},
		{
			"PMID": 28423713,
			"title": "Systematic analysis of gene expression alterations and clinical outcomes of adenylate cyclase-associated protein in cancer.",
			"journal": "Oncotarget",
			"authorList": [
				"Xie Shuanshuan",
				"Shen Changxing",
				"Tan Min",
				"Li Ming",
				"Song Xiaolian",
				"Wang Changhui"
			],
			"DOI": "10.18632/oncotarget.16111",
			"date": "2018-03-05",
			"PMC": "",
			"citation": "",
			"abstract": "Adenylate Cyclase-associated protein (CAP) is an evolutionarily conserved protein that regulates actin dynamics. Our previous study indicates that CAP1 is overexpressed in NSCLC tissues and correlated with poor clinical outcomes, but CAP1 in HeLa cells actually inhibited migration and invasion, the role of CAP was discrepancy in different cancer types. The present study aims to determine whether CAP can serve as a prognostic marker in human cancers. The CAP expression was assessed using Oncomine database to determine the gene alteration during carcinogenesis, the copy number alteration, or mutations of CAP using cBioPortal, International Cancer Genome Consortium, and Tumorscape database investigated, and the association between CAP expression and the survival of cancer patient using Kaplan-Meier plotter and PrognoScan database evaluated. Therefore, the functional correlation between CAP expression and cancer phenotypes can be established; wherein CAP might serve as a diagnostic marker or therapeutic target for certain types of cancers.",
			"category": 2,
			"name": "Xie Shuanshuan,2018"
		},
		{
			"PMID": 28416802,
			"title": "RNA editing-dependent epitranscriptome diversity in cancer stem cells.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Jiang Qingfei",
				"Crews Leslie A",
				"Holm Frida",
				"Jamieson Catriona H M"
			],
			"DOI": "10.1038/nrc.2017.23",
			"date": "2017-08-04",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer stem cells (CSCs) can regenerate all facets of a tumour as a result of their stem cell-like capacity to self-renew, survive and become dormant in protective microenvironments. CSCs evolve during tumour progression in a manner that conforms to Charles Darwin's principle of natural selection. Although somatic DNA mutations and epigenetic alterations promote evolution, post-transcriptional RNA modifications together with RNA binding protein activity (the 'epitranscriptome') might also contribute to clonal evolution through dynamic determination of RNA function and gene expression diversity in response to environmental stimuli. Deregulation of these epitranscriptomic events contributes to CSC generation and maintenance, which governs cancer progression and drug resistance. In this Review, we discuss the role of malignant RNA processing in CSC generation and maintenance, including mechanisms of RNA methylation, RNA editing and RNA splicing, and the functional consequences of their aberrant regulation in human malignancies. Finally, we highlight the potential of these events as novel CSC biomarkers as well as therapeutic targets.",
			"category": 2,
			"name": "Jiang Qingfei,2017"
		},
		{
			"PMID": 28416672,
			"title": "Bisulfite-converted duplexes for the strand-specific detection and quantification of rare mutations.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Mattox Austin K",
				"Wang Yuxuan",
				"Springer Simeon",
				"Cohen Joshua D",
				"Yegnasubramanian Srinivasan",
				"Nelson William G",
				"Kinzler Kenneth W",
				"Vogelstein Bert",
				"Papadopoulos Nickolas"
			],
			"DOI": "10.1073/pnas.1701382114",
			"date": "2018-04-23",
			"PMC": "",
			"citation": "",
			"abstract": "The identification of mutations that are present at low frequencies in clinical samples is an essential component of precision medicine. The development of molecular barcoding for next-generation sequencing has greatly enhanced the sensitivity of detecting such mutations by massively parallel sequencing. However, further improvements in specificity would be useful for a variety of applications. We herein describe a technology (BiSeqS) that can increase the specificity of sequencing by at least two orders of magnitude over and above that achieved with molecular barcoding and can be applied to any massively parallel sequencing instrument. BiSeqS employs bisulfite treatment to distinguish the two strands of molecularly barcoded DNA; its specificity arises from the requirement for the same mutation to be identified in both strands. Because no library preparation is required, the technology permits very efficient use of the template DNA as well as sequence reads, which are nearly all confined to the amplicons of interest. Such efficiency is critical for clinical samples, such as plasma, in which only tiny amounts of DNA are often available. We show here that BiSeqS can be applied to evaluate transversions, as well as small insertions or deletions, and can reliably detect one mutation among >10,000 wild-type molecules.",
			"category": 2,
			"name": "Mattox Austin K,2018"
		},
		{
			"PMID": 28386116,
			"title": "Cancer-associated noncoding mutations affect RNA G-quadruplex-mediated regulation of gene expression.",
			"journal": "Scientific reports",
			"authorList": [
				"Zeraati Mahdi",
				"Moye Aaron L",
				"Wong Jason W H",
				"Perera Dilmi",
				"Cowley Mark J",
				"Christ Daniel U",
				"Bryan Tracy M",
				"Dinger Marcel E"
			],
			"DOI": "10.1038/s41598-017-00739-y",
			"date": "2018-08-30",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a multifactorial disease driven by a combination of genetic and environmental factors. Many cancer driver mutations have been characterised in protein-coding regions of the genome. However, mutations in noncoding regions associated with cancer have been less investigated. G-quadruplex (G4) nucleic acids are four-stranded secondary structures formed in guanine-rich sequences and prevalent in the regulatory regions. In this study, we used published whole cancer genome sequence data to find mutations in cancer patients that overlap potential RNA G4-forming sequences in 5' UTRs. Using RNAfold, we assessed the effect of these mutations on the thermodynamic stability of predicted RNA G4s in the context of full-length 5' UTRs. Of the 217 identified mutations, we found that 33 are predicted to destabilise and 21 predicted to stabilise potential RNA G4s. We experimentally validated the effect of destabilising mutations in the 5' UTRs of BCL2 and CXCL14 and one stabilising mutation in the 5' UTR of TAOK2. These mutations resulted in an increase or a decrease in translation of these mRNAs, respectively. These findings suggest that mutations that modulate the G4 stability in the noncoding regions could act as cancer driver mutations, which present an opportunity for early cancer diagnosis using individual sequencing information.",
			"category": 2,
			"name": "Zeraati Mahdi,2018"
		},
		{
			"PMID": 28381299,
			"title": "Emerging concepts in liquid biopsies.",
			"journal": "BMC medicine",
			"authorList": [
				"Perakis Samantha",
				"Speicher Michael R"
			],
			"DOI": "10.1186/s12916-017-0840-6",
			"date": "2017-07-10",
			"PMC": "",
			"citation": "",
			"abstract": "Characterizing and monitoring tumor genomes with blood samples could achieve significant improvements in precision medicine. As tumors shed parts of themselves into the circulation, analyses of circulating tumor cells, circulating tumor DNA, and tumor-derived exosomes, often referred to as \"liquid biopsies\", may enable tumor genome characterization by minimally invasive means. Indeed, multiple studies have described how molecular information about parent tumors can be extracted from these components. Here, we briefly summarize current technologies and then elaborate on emerging novel concepts that may further propel the field. We address normal and detectable mutation levels in the context of our current knowledge regarding the gradual accumulation of mutations during aging and in light of technological limitations. Finally, we discuss whether liquid biopsies are ready to be used in routine clinical practice.",
			"category": 2,
			"name": "Perakis Samantha,2017"
		},
		{
			"PMID": 28362259,
			"title": "Non-coding cancer driver candidates identified with a sample- and position-specific model of the somatic mutation rate.",
			"journal": "eLife",
			"authorList": [
				"Juul Malene",
				"Bertl Johanna",
				"Guo Qianyun",
				"Nielsen Morten Muhlig",
				"\u015awitnicki Micha\u0142",
				"Hornsh\u00f8j Henrik",
				"Madsen Tobias",
				"Hobolth Asger",
				"Pedersen Jakob Skou"
			],
			"DOI": "10.7554/eLife.21778",
			"date": "2018-02-12",
			"PMC": "",
			"citation": "",
			"abstract": "Non-coding mutations may drive cancer development. Statistical detection of non-coding driver regions is challenged by a varying mutation rate and uncertainty of functional impact. Here, we develop a statistically founded non-coding driver-detection method, ncdDetect, which includes sample-specific mutational signatures, long-range mutation rate variation, and position-specific impact measures. Using ncdDetect, we screened non-coding regulatory regions of protein-coding genes across a pan-cancer set of whole-genomes (n = 505), which top-ranked known drivers and identified new candidates. For individual candidates, presence of non-coding mutations associates with altered expression or decreased patient survival across an independent pan-cancer sample set (n = 5454). This includes an antigen-presenting gene (",
			"category": 2,
			"name": "Juul Malene,2018"
		},
		{
			"PMID": 28344341,
			"title": "Functional variomics and network perturbation: connecting genotype to phenotype in cancer.",
			"journal": "Nature reviews. Genetics",
			"authorList": [
				"Yi Song",
				"Lin Shengda",
				"Li Yongsheng",
				"Zhao Wei",
				"Mills Gordon B",
				"Sahni Nidhi"
			],
			"DOI": "10.1038/nrg.2017.8",
			"date": "2017-07-27",
			"PMC": "",
			"citation": "",
			"abstract": "Proteins interact with other macromolecules in complex cellular networks for signal transduction and biological function. In cancer, genetic aberrations have been traditionally thought to disrupt the entire gene function. It has been increasingly appreciated that each mutation of a gene could have a subtle but unique effect on protein function or network rewiring, contributing to diverse phenotypic consequences across cancer patient populations. In this Review, we discuss the current understanding of cancer genetic variants, including the broad spectrum of mutation classes and the wide range of mechanistic effects on gene function in the context of signalling networks. We highlight recent advances in computational and experimental strategies to study the diverse functional and phenotypic consequences of mutations at the base-pair resolution. Such information is crucial to understanding the complex pleiotropic effect of cancer genes and provides a possible link between genotype and phenotype in cancer.",
			"category": 2,
			"name": "Yi Song,2017"
		},
		{
			"PMID": 28336671,
			"title": "Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention.",
			"journal": "Science (New York, N.Y.)",
			"authorList": [
				"Tomasetti Cristian",
				"Li Lu",
				"Vogelstein Bert"
			],
			"DOI": "10.1126/science.aaf9011",
			"date": "2017-11-03",
			"PMC": "",
			"citation": "",
			"abstract": "Cancers are caused by mutations that may be inherited, induced by environmental factors, or result from DNA replication errors (R). We studied the relationship between the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries throughout the world. The data revealed a strong correlation (median = 0.80) between cancer incidence and normal stem cell divisions in all countries, regardless of their environment. The major role of R mutations in cancer etiology was supported by an independent approach, based solely on cancer genome sequencing and epidemiological data, which suggested that R mutations are responsible for two-thirds of the mutations in human cancers. All of these results are consistent with epidemiological estimates of the fraction of cancers that can be prevented by changes in the environment. Moreover, they accentuate the importance of early detection and intervention to reduce deaths from the many cancers arising from unavoidable R mutations.",
			"category": 2,
			"name": "Tomasetti Cristian,2017"
		},
		{
			"PMID": 28333948,
			"title": "Epigenomic annotation of noncoding mutations identifies mutated pathways in primary liver cancer.",
			"journal": "PloS one",
			"authorList": [
				"Lowdon Rebecca F",
				"Wang Ting"
			],
			"DOI": "10.1371/journal.pone.0174032",
			"date": "2017-08-25",
			"PMC": "",
			"citation": "",
			"abstract": "Evidence that noncoding mutation can result in cancer driver events is mounting. However, it is more difficult to assign molecular biological consequences to noncoding mutations than to coding mutations, and a typical cancer genome contains many more noncoding mutations than protein-coding mutations. Accordingly, parsing functional noncoding mutation signal from noise remains an important challenge. Here we use an empirical approach to identify putatively functional noncoding somatic single nucleotide variants (SNVs) from liver cancer genomes. Annotation of candidate variants by publicly available epigenome datasets finds that 40.5% of SNVs fall in regulatory elements. When assigned to specific regulatory elements, we find that the distribution of regulatory element mutation mirrors that of nonsynonymous coding mutation, where few regulatory elements are recurrently mutated in a patient population but many are singly mutated. We find potential gain-of-binding site events among candidate SNVs, suggesting a mechanism of action for these variants. When aggregating noncoding somatic mutation in promoters, we find that genes in the ERBB signaling and MAPK signaling pathways are significantly enriched for promoter mutations. Altogether, our results suggest that functional somatic SNVs in cancer are sporadic, but occasionally occur in regulatory elements and may affect phenotype by creating binding sites for transcriptional regulators. Accordingly, we propose that noncoding mutation should be formally accounted for when determining gene- and pathway-mutation burden in cancer.",
			"category": 2,
			"name": "Lowdon Rebecca F,2017"
		},
		{
			"PMID": 28325298,
			"title": "Relevance of Fusion Genes in Pediatric Cancers: Toward Precision Medicine.",
			"journal": "Molecular therapy. Nucleic acids",
			"authorList": [
				"Dupain C\u00e9lia",
				"Harttrampf Anne Catherine",
				"Urbinati Giorgia",
				"Geoerger Birgit",
				"Massaad-Massade Liliane"
			],
			"DOI": "10.1016/j.omtn.2017.01.005",
			"date": "2020-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Pediatric cancers differ from adult tumors, especially by their very low mutational rate. Therefore, their etiology could be explained in part by other oncogenic mechanisms such as chromosomal rearrangements, supporting the possible implication of fusion genes in the development of pediatric cancers. Fusion genes result from chromosomal rearrangements leading to the juxtaposition of two genes. Consequently, an abnormal activation of one or both genes is observed. The detection of fusion genes has generated great interest in basic cancer research and in the clinical setting, since these genes can lead to better comprehension of the biological mechanisms of tumorigenesis and they can also be used as therapeutic targets and diagnostic or prognostic biomarkers. In this review, we discuss the molecular mechanisms of fusion genes and their particularities in pediatric cancers, as well as their relevance in murine models and in the clinical setting. We also point out the difficulties encountered in the discovery of fusion genes. Finally, we discuss future perspectives and priorities for finding new innovative therapies in childhood cancer.",
			"category": 2,
			"name": "Dupain C\u00e9lia,2020"
		},
		{
			"PMID": 28276478,
			"title": "B-Myb Induces APOBEC3B Expression Leading to Somatic Mutation in Multiple Cancers.",
			"journal": "Scientific reports",
			"authorList": [
				"Chou Wen-Cheng",
				"Chen Wei-Ting",
				"Hsiung Chia-Ni",
				"Hu Ling-Yueh",
				"Yu Jyh-Cherng",
				"Hsu Huan-Ming",
				"Shen Chen-Yang"
			],
			"DOI": "10.1038/srep44089",
			"date": "2018-11-08",
			"PMC": "",
			"citation": "",
			"abstract": "The key signature of cancer genomes is the accumulation of DNA mutations, the most abundant of which is the cytosine-to-thymine (C-to-T) transition that results from cytosine deamination. Analysis of The Cancer Genome Atlas (TCGA) database has demonstrated that this transition is caused mainly by upregulation of the cytosine deaminase APOBEC3B (A3B), but the mechanism has not been completely characterized. We found that B-Myb (encoded by MYBL2) binds the A3B promoter, causing transactivation, and this is responsible for the C-to-T transitions and DNA hypermutation in breast cancer cells. Analysis of TCGA database yielded similar results, supporting that MYBL2 and A3B are upregulated and putatively promote C-to-T transitions in multiple cancer types. Moreover, blockade of EGF receptor with afatinib attenuated B-Myb-A3B signaling, suggesting a clinically relevant means of suppressing mutagenesis. Our results suggest that B-Myb-A3B contributes to DNA damage and could be targeted by inhibiting EGF receptor.",
			"category": 2,
			"name": "Chou Wen-Cheng,2018"
		},
		{
			"PMID": 28270531,
			"title": "Principles of Reconstructing the Subclonal Architecture of Cancers.",
			"journal": "Cold Spring Harbor perspectives in medicine",
			"authorList": [
				"Dentro Stefan C",
				"Wedge David C",
				"Van Loo Peter"
			],
			"DOI": "10.1101/cshperspect.a026625",
			"date": "2018-04-25",
			"PMC": "",
			"citation": "",
			"abstract": "Most cancers evolve from a single founder cell through a series of clonal expansions that are driven by somatic mutations. These clonal expansions can lead to several coexisting subclones sharing subsets of mutations. Analysis of massively parallel sequencing data can infer a tumor's subclonal composition through the identification of populations of cells with shared mutations. We describe the principles that underlie subclonal reconstruction through single nucleotide variants (SNVs) or copy number alterations (CNAs) from bulk or single-cell sequencing. These principles include estimating the fraction of tumor cells for SNVs and CNAs, performing clustering of SNVs from single- and multisample cases, and single-cell sequencing. The application of subclonal reconstruction methods is providing key insights into tumor evolution, identifying subclonal driver mutations, patterns of parallel evolution and differences in mutational signatures between cellular populations, and characterizing the mechanisms of therapy resistance, spread, and metastasis.",
			"category": 2,
			"name": "Dentro Stefan C,2018"
		},
		{
			"PMID": 28246384,
			"title": "A c-Myc-regulated stem cell-like signature in high-risk neuroblastoma: A systematic discovery (Target neuroblastoma ESC-like signature).",
			"journal": "Scientific reports",
			"authorList": [
				"Yang Xinan Holly",
				"Tang Fangming",
				"Shin Jisu",
				"Cunningham John M"
			],
			"DOI": "10.1038/s41598-017-00122-x",
			"date": "2019-02-06",
			"PMC": "",
			"citation": "",
			"abstract": "c-Myc dysregulation is hypothesized to account for the 'stemness' - self-renewal and pluripotency - shared between embryonic stem cells (ESCs) and adult aggressive tumours. High-risk neuroblastoma (HR-NB) is the most frequent, aggressive, extracranial solid tumour in childhood. Using HR-NB as a platform, we performed a network analysis of transcriptome data and presented a c-Myc subnetwork enriched for genes previously reported as ESC-like cancer signatures. A subsequent drug-gene interaction analysis identified a pharmacogenomic agent that preferentially interacted with this HR-NB-specific, ESC-like signature. This agent, Roniciclib (BAY 1000394), inhibited neuroblastoma cell growth and induced apoptosis in vitro. It also repressed the expression of the oncogene c-Myc and the neural ESC marker CDK2 in vitro, which was accompanied by altered expression of the c-Myc-targeted cell cycle regulators CCND1, CDKN1A and CDKN2D in a time-dependent manner. Further investigation into this HR-NB-specific ESC-like signature in 295 and 243 independent patients revealed and validated the general prognostic index of CDK2 and CDKN3 compared with CDKN2D and CDKN1B. These findings highlight the very potent therapeutic benefits of Roniciclib in HR-NB through the targeting of c-Myc-regulated, ESC-like tumorigenesis. This work provides a hypothesis-driven systems computational model that facilitates the translation of genomic and transcriptomic signatures to molecular mechanisms underlying high-risk tumours.",
			"category": 2,
			"name": "Yang Xinan Holly,2019"
		},
		{
			"PMID": 28232730,
			"title": "Untangling the genetics from the epigenetics in pancreatic cancer metastasis.",
			"journal": "Nature genetics",
			"authorList": [
				"Vakoc Christopher R",
				"Tuveson David A"
			],
			"DOI": "10.1038/ng.3798",
			"date": "2017-07-20",
			"PMC": "",
			"citation": "",
			"abstract": "Comparative genomic analyses of primary tumors and metastases within individuals with pancreatic cancer have exposed the complex clonal dynamics that underlie the dissemination of cancer cells to distant sites. Recent studies implicate non-genetic mechanisms in this process, particularly fluctuations in chromatin states and metabolism, which can endow rare cells within a primary tumor with metastatic potential.",
			"category": 2,
			"name": "Vakoc Christopher R,2017"
		},
		{
			"PMID": 28223526,
			"title": "Hypermutation signature reveals a slippage and realignment model of translesion synthesis by Rev3 polymerase in cisplatin-treated yeast.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Segovia Romulo",
				"Shen Yaoqing",
				"Lujan Scott A",
				"Jones Steven J M",
				"Stirling Peter C"
			],
			"DOI": "10.1073/pnas.1618555114",
			"date": "2018-04-18",
			"PMC": "",
			"citation": "",
			"abstract": "Gene-gene or gene-drug interactions are typically quantified using fitness as a readout because the data are continuous and easily measured in high throughput. However, to what extent fitness captures the range of other phenotypes that show synergistic effects is usually unknown. Using ",
			"category": 2,
			"name": "Segovia Romulo,2018"
		},
		{
			"PMID": 28188128,
			"title": "Interaction Landscape of Inherited Polymorphisms with Somatic Events in Cancer.",
			"journal": "Cancer discovery",
			"authorList": [
				"Carter Hannah",
				"Marty Rachel",
				"Hofree Matan",
				"Gross Andrew M",
				"Jensen James",
				"Fisch Kathleen M",
				"Wu Xingyu",
				"DeBoever Christopher",
				"Van Nostrand Eric L",
				"Song Yan",
				"Wheeler Emily",
				"Kreisberg Jason F",
				"Lippman Scott M",
				"Yeo Gene W",
				"Gutkind J Silvio",
				"Ideker Trey"
			],
			"DOI": "10.1158/2159-8290.CD-16-1045",
			"date": "2017-11-20",
			"PMC": "",
			"citation": "",
			"abstract": "Recent studies have characterized the extensive somatic alterations that arise during cancer. However, the somatic evolution of a tumor may be significantly affected by inherited polymorphisms carried in the germline. Here, we analyze genomic data for 5,954 tumors to reveal and systematically validate 412 genetic interactions between germline polymorphisms and major somatic events, including tumor formation in specific tissues and alteration of specific cancer genes. Among germline-somatic interactions, we found germline variants in ",
			"category": 2,
			"name": "Carter Hannah,2017"
		},
		{
			"PMID": 28187285,
			"title": "Transcriptional Addiction in Cancer.",
			"journal": "Cell",
			"authorList": [
				"Bradner James E",
				"Hnisz Denes",
				"Young Richard A"
			],
			"DOI": "10.1016/j.cell.2016.12.013",
			"date": "2017-05-23",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer arises from genetic alterations that invariably lead to dysregulated transcriptional programs. These dysregulated programs can cause cancer cells to become highly dependent on certain regulators of gene expression. Here, we discuss how transcriptional control is disrupted by genetic alterations in cancer cells, why transcriptional dependencies can develop as a consequence of dysregulated programs, and how these dependencies provide opportunities for novel therapeutic interventions in cancer.",
			"category": 2,
			"name": "Bradner James E,2017"
		},
		{
			"PMID": 28184012,
			"title": "Chromosome 20q Amplification Defines a Subtype of Microsatellite Stable, Left-Sided Colon Cancers with Wild-type RAS/RAF and Better Overall Survival.",
			"journal": "Molecular cancer research : MCR",
			"authorList": [
				"Ptashkin Ryan N",
				"Pagan Carlos",
				"Yaeger Rona",
				"Middha Sumit",
				"Shia Jinru",
				"O'Rourke Kevin P",
				"Berger Michael F",
				"Wang Lu",
				"Cimera Robert",
				"Wang Jiajing",
				"Klimstra David S",
				"Saltz Leonard",
				"Ladanyi Marc",
				"Zehir Ahmet",
				"Hechtman Jaclyn F"
			],
			"DOI": "10.1158/1541-7786.MCR-16-0352",
			"date": "2018-03-26",
			"PMC": "",
			"citation": "",
			"abstract": "Here, comprehensive analysis was performed on the molecular and clinical features of colorectal carcinoma harboring chromosome 20q amplification. Tumor and normal DNA from patients with advanced colorectal carcinoma underwent next-generation sequencing via MSK-IMPACT, and a subset of case samples was subjected to high-resolution microarray (Oncoscan). Relationships between genomic copy number and transcript expression were assessed with The Cancer Genome Atlas (TCGA) colorectal carcinoma data. Of the colorectal carcinoma patients sequenced (",
			"category": 2,
			"name": "Ptashkin Ryan N,2018"
		},
		{
			"PMID": 28181482,
			"title": "Small genomic insertions form enhancers that misregulate oncogenes.",
			"journal": "Nature communications",
			"authorList": [
				"Abraham Brian J",
				"Hnisz Denes",
				"Weintraub Abraham S",
				"Kwiatkowski Nicholas",
				"Li Charles H",
				"Li Zhaodong",
				"Weichert-Leahey Nina",
				"Rahman Sunniyat",
				"Liu Yu",
				"Etchin Julia",
				"Li Benshang",
				"Shen Shuhong",
				"Lee Tong Ihn",
				"Zhang Jinghui",
				"Look A Thomas",
				"Mansour Marc R",
				"Young Richard A"
			],
			"DOI": "10.1038/ncomms14385",
			"date": "2018-11-09",
			"PMC": "",
			"citation": "",
			"abstract": "The non-coding regions of tumour cell genomes harbour a considerable fraction of total DNA sequence variation, but the functional contribution of these variants to tumorigenesis is ill-defined. Among these non-coding variants, somatic insertions are among the least well characterized due to challenges with interpreting short-read DNA sequences. Here, using a combination of Chip-seq to enrich enhancer DNA and a computational approach with multiple DNA alignment procedures, we identify enhancer-associated small insertion variants. Among the 102 tumour cell genomes we analyse, small insertions are frequently observed in enhancer DNA sequences near known oncogenes. Further study of one insertion, somatically acquired in primary leukaemia tumour genomes, reveals that it nucleates formation of an active enhancer that drives expression of the LMO2 oncogene. The approach described here to identify enhancer-associated small insertion variants provides a foundation for further study of these abnormalities across human cancers.",
			"category": 2,
			"name": "Abraham Brian J,2018"
		},
		{
			"PMID": 28168295,
			"title": "Discovery of cancer common and specific driver gene sets.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Zhang Junhua",
				"Zhang Shihua"
			],
			"DOI": "10.1093/nar/gkx089",
			"date": "2017-09-12",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is known as a disease mainly caused by gene alterations. Discovery of mutated driver pathways or gene sets is becoming an important step to understand molecular mechanisms of carcinogenesis. However, systematically investigating commonalities and specificities of driver gene sets among multiple cancer types is still a great challenge, but this investigation will undoubtedly benefit deciphering cancers and will be helpful for personalized therapy and precision medicine in cancer treatment. In this study, we propose two optimization models to de novo discover common driver gene sets among multiple cancer types (ComMDP) and specific driver gene sets of one certain or multiple cancer types to other cancers (SpeMDP), respectively. We first apply ComMDP and SpeMDP to simulated data to validate their efficiency. Then, we further apply these methods to 12 cancer types from The Cancer Genome Atlas (TCGA) and obtain several biologically meaningful driver pathways. As examples, we construct a common cancer pathway model for BRCA and OV, infer a complex driver pathway model for BRCA carcinogenesis based on common driver gene sets of BRCA with eight cancer types, and investigate specific driver pathways of the liquid cancer lymphoblastic acute myeloid leukemia (LAML) versus other solid cancer types. In these processes more candidate cancer genes are also found.",
			"category": 2,
			"name": "Zhang Junhua,2017"
		},
		{
			"PMID": 28167050,
			"title": "Changing mutational and adaptive landscapes and the genesis of cancer.",
			"journal": "Biochimica et biophysica acta. Reviews on cancer",
			"authorList": [
				"Liggett L Alexander",
				"DeGregori James"
			],
			"DOI": "10.1016/j.bbcan.2017.01.005",
			"date": "2017-08-24",
			"PMC": "",
			"citation": "",
			"abstract": "By the time the process of oncogenesis has produced an advanced cancer, tumor cells have undergone extensive evolution. The cellular phenotypes resulting from this evolution have been well studied, and include accelerated growth rates, apoptosis resistance, immortality, invasiveness, and immune evasion. Yet with all of our current knowledge of tumor biology, the details of early oncogenesis have been difficult to observe and understand. Where different oncogenic mutations may work together to enhance the survival of a tumor cell, in isolation they are often pro-apoptotic, pro-differentiative or pro-senescent, and therefore often, somewhat paradoxically, disadvantageous to a cell. It is also becoming clear that somatic mutations, including those in known oncogenic drivers, are common in tissues starting at a young age. These observations raise the question: how do we largely avoid cancer for most of our lives? Here we propose that evolutionary forces can help explain this paradox. As humans and other organisms age or experience external insults such as radiation or smoking, the structure and function of tissues progressively degrade, resulting in altered stem cell niche microenvironments. As tissue integrity declines, it becomes less capable of supporting and maintaining resident stem cells. These stem cells then find themselves in a microenvironment to which they are poorly adapted, providing a competitive advantage to those cells that can restore their functionality and fitness through mutations or epigenetic changes. The resulting oncogenic clonal expansions then increase the odds of further cancer progression. Understanding how the causes of cancer, such as aging or smoking, affect tissue microenvironments to control the impact of mutations on somatic cell fitness can help reconcile the discrepancy between marked mutation accumulation starting early in life and the somatic evolution that leads to cancer at advanced ages or following carcinogenic insults. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby.",
			"category": 2,
			"name": "Liggett L Alexander,2017"
		},
		{
			"PMID": 28159918,
			"title": "Protein drug target activation homogeneity in the face of intra-tumor heterogeneity: implications for precision medicine.",
			"journal": "Oncotarget",
			"authorList": [
				"Parasido Erika Maria",
				"Silvestri Alessandra",
				"Canzonieri Vincenzo",
				"Belluco Claudio",
				"Diodoro Maria Grazia",
				"Milione Massimo",
				"Melotti Flavia",
				"De Maria Ruggero",
				"Liotta Lance",
				"Petricoin Emanuel F",
				"Pierobon Mariaelena"
			],
			"DOI": "10.18632/oncotarget.14019",
			"date": "2018-04-23",
			"PMC": "",
			"citation": "",
			"abstract": "Recent studies indicated tumors may be comprised of heterogeneous molecular subtypes and incongruent molecular portraits may emerge if different areas of the tumor are sampled. This study explored the impact of intra-tumoral heterogeneity in terms of activation/phosphorylation of FDA approved drug targets and downstream kinase substrates.",
			"category": 2,
			"name": "Parasido Erika Maria,2018"
		},
		{
			"PMID": 28155908,
			"title": "Understanding cancer complexome using networks, spectral graph theory and multilayer framework.",
			"journal": "Scientific reports",
			"authorList": [
				"Rai Aparna",
				"Pradhan Priodyuti",
				"Nagraj Jyothi",
				"Lohitesh K",
				"Chowdhury Rajdeep",
				"Jalan Sarika"
			],
			"DOI": "10.1038/srep41676",
			"date": "2018-10-29",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer complexome comprises a heterogeneous and multifactorial milieu that varies in cytology, physiology, signaling mechanisms and response to therapy. The combined framework of network theory and spectral graph theory along with the multilayer analysis provides a comprehensive approach to analyze the proteomic data of seven different cancers, namely, breast, oral, ovarian, cervical, lung, colon and prostate. Our analysis demonstrates that the protein-protein interaction networks of the normal and the cancerous tissues associated with the seven cancers have overall similar structural and spectral properties. However, few of these properties implicate unsystematic changes from the normal to the disease networks depicting difference in the interactions and highlighting changes in the complexity of different cancers. Importantly, analysis of common proteins of all the cancer networks reveals few proteins namely the sensors, which not only occupy significant position in all the layers but also have direct involvement in causing cancer. The prediction and analysis of miRNAs targeting these sensor proteins hint towards the possible role of these proteins in tumorigenesis. This novel approach helps in understanding cancer at the fundamental level and provides a clue to develop promising and nascent concept of single drug therapy for multiple diseases as well as personalized medicine.",
			"category": 2,
			"name": "Rai Aparna,2018"
		},
		{
			"PMID": 28152008,
			"title": "Highly sensitive detection of a HER2 12-base pair duplicated insertion mutation in lung cancer using the Eprobe-PCR method.",
			"journal": "PloS one",
			"authorList": [
				"Takase Yoshiaki",
				"Usui Kengo",
				"Shimizu Kimihiro",
				"Kimura Yasumasa",
				"Ichihara Tatsuo",
				"Ohkawa Takahiro",
				"Atsumi Jun",
				"Enokida Yasuaki",
				"Nakazawa Seshiru",
				"Obayashi Kai",
				"Ohtaki Yoichi",
				"Nagashima Toshiteru",
				"Mitani Yasumasa",
				"Takeyoshi Izumi"
			],
			"DOI": "10.1371/journal.pone.0171225",
			"date": "2017-08-21",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic mutation in human epidermal growth factor receptor-related 2 gene (HER2) is one of the driver mutations in lung cancer. HER2 mutations are found in about 2% of lung adenocarcinomas (ADCs). Previous reports have been based mainly on diagnostic screening by Sanger sequencing or next-generation sequencing (NGS); however, these methods are time-consuming and complicated. We developed a rapid, simple, sensitive mutation detection assay for detecting HER2 12 base pair-duplicated insertion mutation based on the Eprobe-mediated PCR method (Eprobe-PCR) and validated the sensitivity of this assay system for clinical diagnostics. We examined 635 tumor samples and analyzed HER2 mutations using the Eprobe-PCR method, NGS, and Sanger sequencing. In a serial dilution study, the Eprobe-PCR was able to detect mutant plasmid DNA when its concentration was reduced to 0.1% by mixing with wild-type DNA. We also confirmed amplification of the mutated plasmid DNA with only 10 copies per reaction. In ADCs, Eprobe-PCR detected the HER2 mutation in 2.02% (9/446), while Sanger sequencing detected it in 1.57% (7/446). Eprobe-PCR was able to detect the mutation in two samples that were undetectable by Sanger sequencing. All non-ADC samples were wild-type. There were no discrepancies between frozen and formalin-fixed paraffin-embedded tissues in the nine samples. HER2 mutations detected by NGS data validated the high sensitivity of the method. Therefore, this new technique can lead to precise molecular-targeted therapies.",
			"category": 2,
			"name": "Takase Yoshiaki,2017"
		},
		{
			"PMID": 28146134,
			"title": "Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Kamps Rick",
				"Brand\u00e3o Rita D",
				"Bosch Bianca J van den",
				"Paulussen Aimee D C",
				"Xanthoulea Sofia",
				"Blok Marinus J",
				"Romano Andrea"
			],
			"DOI": "10.3390/ijms18020308",
			"date": "2017-04-20",
			"PMC": "",
			"citation": "",
			"abstract": "Next-generation sequencing (NGS) technology has expanded in the last decades with significant improvements in the reliability, sequencing chemistry, pipeline analyses, data interpretation and costs. Such advances make the use of NGS feasible in clinical practice today. This review describes the recent technological developments in NGS applied to the field of oncology. A number of clinical applications are reviewed, i.e., mutation detection in inherited cancer syndromes based on DNA-sequencing, detection of spliceogenic variants based on RNA-sequencing, DNA-sequencing to identify risk modifiers and application for pre-implantation genetic diagnosis, cancer somatic mutation analysis, pharmacogenetics and liquid biopsy. Conclusive remarks, clinical limitations, implications and ethical considerations that relate to the different applications are provided.",
			"category": 2,
			"name": "Kamps Rick,2017"
		},
		{
			"PMID": 28118322,
			"title": "Comparative mutational landscape analysis of patient-derived tumour xenografts.",
			"journal": "British journal of cancer",
			"authorList": [
				"Brait Mariana",
				"Izumchenko Evgeny",
				"Kagohara Luciane T",
				"Long Samuel",
				"Wysocki Piotr T",
				"Faherty Brian",
				"Fertig Elana J",
				"Khor Tin Oo",
				"Bruckheimer Elizabeth",
				"Baia Gilson",
				"Ciznadija Daniel",
				"Sloma Ido",
				"Ben-Zvi Ido",
				"Paz Keren",
				"Sidransky David"
			],
			"DOI": "10.1038/bjc.2016.450",
			"date": "2017-05-23",
			"PMC": "",
			"citation": "",
			"abstract": "Screening of patients for cancer-driving mutations is now used for cancer prognosis, remission scoring and treatment selection. Although recently emerged targeted next-generation sequencing-based approaches offer promising diagnostic capabilities, there are still limitations. There is a pressing clinical need for a well-validated, rapid, cost-effective mutation profiling system in patient specimens. Given their speed and cost-effectiveness, quantitative PCR mutation detection techniques are well suited for the clinical environment. The qBiomarker mutation PCR array has high sensitivity and shorter turnaround times compared with other methods. However, a direct comparison with existing viable alternatives are required to assess its true potential and limitations.",
			"category": 2,
			"name": "Brait Mariana,2017"
		},
		{
			"PMID": 28115009,
			"title": "3D clusters of somatic mutations in cancer reveal numerous rare mutations as functional targets.",
			"journal": "Genome medicine",
			"authorList": [
				"Gao Jianjiong",
				"Chang Matthew T",
				"Johnsen Hannah C",
				"Gao Sizhi Paul",
				"Sylvester Brooke E",
				"Sumer Selcuk Onur",
				"Zhang Hongxin",
				"Solit David B",
				"Taylor Barry S",
				"Schultz Nikolaus",
				"Sander Chris"
			],
			"DOI": "10.1186/s13073-016-0393-x",
			"date": "2017-08-07",
			"PMC": "",
			"citation": "",
			"abstract": "Many mutations in cancer are of unknown functional significance. Standard methods use statistically significant recurrence of mutations in tumor samples as an indicator of functional impact. We extend such analyses into the long tail of rare mutations by considering recurrence of mutations in clusters of spatially close residues in protein structures. Analyzing 10,000 tumor exomes, we identify more than 3000 rarely mutated residues in proteins as potentially functional and experimentally validate several in RAC1 and MAP2K1. These potential driver mutations (web resources: 3dhotspots.org and cBioPortal.org) can extend the scope of genomically informed clinical trials and of personalized choice of therapy.",
			"category": 2,
			"name": "Gao Jianjiong,2017"
		},
		{
			"PMID": 28091859,
			"title": "Cancer Genetic Counselors' Current Practices and Attitudes Related to the Use of Tumor Profiling.",
			"journal": "Journal of genetic counseling",
			"authorList": [
				"Goedde LeAnne Noelle",
				"Stupiansky Nathan W",
				"Lah Melissa",
				"Quaid Kimberly A",
				"Cohen Stephanie"
			],
			"DOI": "10.1007/s10897-017-0065-z",
			"date": "2018-09-10",
			"PMC": "",
			"citation": "",
			"abstract": "Tumor profiling (TP) is primarily used to identify driver mutations within a tumor for treatment purposes, but it may also identify germline mutations. Current involvement of cancer genetic counselors (GCs) in the TP process is not clear. Members of the National Society of Genetic Counselors Cancer Special Interest Group were invited to participate in a confidential, web-based survey to characterize current practices and attitudes related to the use of TP. Of 105 useable responses, 86.7% of GCs reported their institutions were using TP, although only 6.7% did this routinely. Although 63.7% reported personal involvement in the process, largely with result interpretation and follow-up germline testing, 69.7% reported seeing fewer than 5 patients for this reason and 97.9% desired further education on this topic. Work and regional setting were not predictors of involvement with TP; however, GCs in the academic setting were less aware of who obtains consent (p\u00a0=\u00a00.001). GCs reported they were not often utilized as a resource regarding TP. Overall, GCs believed TP is beneficial in identifying hereditary cancer syndromes, although most reported finding a germline mutation in <10% of cases. This study provides a snapshot of current GC involvement with TP, and documents the desire by GCs for additional education on tumor profiling.",
			"category": 2,
			"name": "Goedde LeAnne Noelle,2018"
		},
		{
			"PMID": 28083984,
			"title": "Whole genome sequencing analysis of lung adenocarcinoma in Xuanwei, China.",
			"journal": "Thoracic cancer",
			"authorList": [
				"Wang Xiao",
				"Li Jing",
				"Duan Yong",
				"Wu Huifei",
				"Xu Qiuyue",
				"Zhang Yanliang"
			],
			"DOI": "10.1111/1759-7714.12411",
			"date": "2017-10-30",
			"PMC": "",
			"citation": "",
			"abstract": "The lung cancer mortality rate in Xuanwei city is among the highest in China and adenocarcinoma is the major histological type. Lung cancer has been associated with exposure to indoor smoky coal emissions that contain high levels of polycyclic aromatic hydrocarbons; however, the pathogenesis of lung cancer has not yet been fully elucidated.",
			"category": 2,
			"name": "Wang Xiao,2017"
		},
		{
			"PMID": 28061765,
			"title": "miR-663a regulates growth of colon cancer cells, after administration of antimicrobial peptides, by targeting CXCR4-p21 pathway.",
			"journal": "BMC cancer",
			"authorList": [
				"Kuroda Kengo",
				"Fukuda Tomokazu",
				"Krstic-Demonacos Marija",
				"Demonacos Constantinos",
				"Okumura Kazuhiko",
				"Isogai Hiroshi",
				"Hayashi Miwa",
				"Saito Kazuki",
				"Isogai Emiko"
			],
			"DOI": "10.1186/s12885-016-3003-9",
			"date": "2018-01-16",
			"PMC": "",
			"citation": "",
			"abstract": "Antimicrobial peptides (AMPs) play important roles in the innate immune system of all life forms and recently have been characterized as multifunctional peptides that have a variety of biological roles such as anticancer agents. However, detailed mechanism of antimicrobial peptides on cancer cells is still largely unknown.",
			"category": 2,
			"name": "Kuroda Kengo,2018"
		},
		{
			"PMID": 28056774,
			"title": "Identification of coding and non-coding mutational hotspots in cancer genomes.",
			"journal": "BMC genomics",
			"authorList": [
				"Piraino Scott W",
				"Furney Simon J"
			],
			"DOI": "10.1186/s12864-016-3420-9",
			"date": "2017-09-11",
			"PMC": "",
			"citation": "",
			"abstract": "The identification of mutations that play a causal role in tumour development, so called \"driver\" mutations, is of critical importance for understanding how cancers form and how they might be treated. Several large cancer sequencing projects have identified genes that are recurrently mutated in cancer patients, suggesting a role in tumourigenesis. While the landscape of coding drivers has been extensively studied and many of the most prominent driver genes are well characterised, comparatively less is known about the role of mutations in the non-coding regions of the genome in cancer development. The continuing fall in genome sequencing costs has resulted in a concomitant increase in the number of cancer whole genome sequences being produced, facilitating systematic interrogation of both the coding and non-coding regions of cancer genomes.",
			"category": 2,
			"name": "Piraino Scott W,2017"
		},
		{
			"PMID": 28029147,
			"title": "SNP variants at the MAP3K1/SETD9 locus 5q11.2 associate with somatic PIK3CA variants in breast cancers.",
			"journal": "European journal of human genetics : EJHG",
			"authorList": [
				"Puzone Roberto",
				"Pfeffer Ulrich"
			],
			"DOI": "10.1038/ejhg.2016.179",
			"date": "2017-08-07",
			"PMC": "",
			"citation": "",
			"abstract": "Genome-wide association studies have revealed many breast cancer (BC) risk-associated genetic variants that might functionally interact with other molecular determinants of BC. We analysed the association of 21 known risk-associated single-nucleotide variants (SNVs) with recurrent somatic variants in two cohorts of 77 and 754 oestrogen receptor \u03b1-positive BCs. Four SNVs located at 5q11.2 were found to be associated with the somatic PIK3CA variant status in the pilot cohort of 77 cases with odds ratio (OR) up to 6.5 indicating strong effects, and were selected for the validation phase. Two of these SNVs, rs252913 and rs331499, located in the MAP3K1/SETD9 gene boundary, were confirmed to be associated with somatic PIK3CA variants in the large cohort with OR 2.97 (1.17-7.75) and 1.76 (1.11-2.77), respectively, notably higher than their BC risk-associated values, both around 1.1. In the presence of the SNV or of somatic PIK3CA variants, cancers express significantly elevated levels of MAP3K1 and SETD9, with synergy of SNV and PIK3CA variants in MAP3K1 gene overexpression, consistent with a preferential PIK3CA-dependent regulation of the variant alleles.",
			"category": 2,
			"name": "Puzone Roberto,2017"
		},
		{
			"PMID": 28027320,
			"title": "Genomic Analysis of Uterine Lavage Fluid Detects Early Endometrial Cancers and Reveals a Prevalent Landscape of Driver Mutations in Women without Histopathologic Evidence of Cancer: A Prospective Cross-Sectional Study.",
			"journal": "PLoS medicine",
			"authorList": [
				"Nair Navya",
				"Camacho-Vanegas Olga",
				"Rykunov Dmitry",
				"Dashkoff Matthew",
				"Camacho Sandra Catalina",
				"Schumacher Cassie A",
				"Irish Jonathan C",
				"Harkins Timothy T",
				"Freeman Elijah",
				"Garcia Isaac",
				"Pereira Elena",
				"Kendall Sviatoslav",
				"Belfer Rachel",
				"Kalir Tamara",
				"Sebra Robert",
				"Reva Boris",
				"Dottino Peter",
				"Martignetti John A"
			],
			"DOI": "10.1371/journal.pmed.1002206",
			"date": "2017-05-23",
			"PMC": "",
			"citation": "",
			"abstract": "Endometrial cancer is the most common gynecologic malignancy, and its incidence and associated mortality are increasing. Despite the immediate need to detect these cancers at an earlier stage, there is no effective screening methodology or protocol for endometrial cancer. The comprehensive, genomics-based analysis of endometrial cancer by The Cancer Genome Atlas (TCGA) revealed many of the molecular defects that define this cancer. Based on these cancer genome results, and in a prospective study, we hypothesized that the use of ultra-deep, targeted gene sequencing could detect somatic mutations in uterine lavage fluid obtained from women undergoing hysteroscopy as a means of molecular screening and diagnosis.",
			"category": 2,
			"name": "Nair Navya,2017"
		},
		{
			"PMID": 28007582,
			"title": "kMEn: Analyzing noisy and bidirectional transcriptional pathway responses in single subjects.",
			"journal": "Journal of biomedical informatics",
			"authorList": [
				"Li Qike",
				"Schissler A Grant",
				"Gardeux Vincent",
				"Berghout Joanne",
				"Achour Ikbel",
				"Kenost Colleen",
				"Li Haiquan",
				"Zhang Hao Helen",
				"Lussier Yves A"
			],
			"DOI": "10.1016/j.jbi.2016.12.009",
			"date": "2018-02-12",
			"PMC": "",
			"citation": "",
			"abstract": "Understanding dynamic, patient-level transcriptomic response to therapy is an important step forward for precision medicine. However, conventional transcriptome analysis aims to discover cohort-level change, lacking the capacity to unveil patient-specific response to therapy. To address this gap, we previously developed two N-of-1-pathways methods, Wilcoxon and Mahalanobis distance, to detect unidirectionally responsive transcripts within a pathway using a pair of samples from a single subject. Yet, these methods cannot recognize bidirectionally (up and down) responsive pathways. Further, our previous approaches have not been assessed in presence of background noise and are not designed to identify differentially expressed mRNAs between two samples of a patient taken in different contexts (e.g. cancer vs non cancer), which we termed responsive transcripts (RTs).",
			"category": 2,
			"name": "Li Qike,2018"
		},
		{
			"PMID": 28007024,
			"title": "iCAGES: integrated CAncer GEnome Score for comprehensively prioritizing driver genes in personal cancer genomes.",
			"journal": "Genome medicine",
			"authorList": [
				"Dong Chengliang",
				"Guo Yunfei",
				"Yang Hui",
				"He Zeyu",
				"Liu Xiaoming",
				"Wang Kai"
			],
			"DOI": "10.1186/s13073-016-0390-0",
			"date": "2017-03-17",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer results from the acquisition of somatic driver mutations. Several computational tools can predict driver genes from population-scale genomic data, but tools for analyzing personal cancer genomes are underdeveloped. Here we developed iCAGES, a novel statistical framework that infers driver variants by integrating contributions from coding, non-coding, and structural variants, identifies driver genes by combining genomic information and prior biological knowledge, then generates prioritized drug treatment. Analysis on The Cancer Genome Atlas (TCGA) data showed that iCAGES predicts whether patients respond to drug treatment (P\u2009=\u20090.006 by Fisher's exact test) and long-term survival (P\u2009=\u20090.003 from Cox regression). iCAGES is available at http://icages.wglab.org .",
			"category": 2,
			"name": "Dong Chengliang,2017"
		},
		{
			"PMID": 27999293,
			"title": "Antimutagenic Effects of Selenium-Enriched Polysaccharides from Pyracantha fortuneana through Suppression of Cytochrome P450 1A Subfamily in the Mouse Liver.",
			"journal": "Molecules (Basel, Switzerland)",
			"authorList": [
				"Peng Fan",
				"Guo Xin",
				"Li Zhihong",
				"Li Changzheng",
				"Wang Changdong",
				"Lv Weiran",
				"Wang Junjie",
				"Xiao Fangxiang",
				"Kamal Mohammad Amjad",
				"Yuan Chengfu"
			],
			"DOI": "10.3390/molecules21121731",
			"date": "2017-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "Both selenium (Se) and polysaccharides from ",
			"category": 2,
			"name": "Peng Fan,2017"
		},
		{
			"PMID": 27900322,
			"title": "Patterns of Transposable Element Expression and Insertion in Cancer.",
			"journal": "Frontiers in molecular biosciences",
			"authorList": [
				"Clayton Evan A",
				"Wang Lu",
				"Rishishwar Lavanya",
				"Wang Jianrong",
				"McDonald John F",
				"Jordan I King"
			],
			"DOI": "",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "Human transposable element (TE) activity in somatic tissues causes mutations that can contribute to tumorigenesis. Indeed, TE insertion mutations have been implicated in the etiology of a number of different cancer types. Nevertheless, the full extent of somatic TE activity, along with its relationship to tumorigenesis, have yet to be fully explored. Recent developments in bioinformatics software make it possible to analyze TE expression levels and TE insertional activity directly from transcriptome (RNA-seq) and whole genome (DNA-seq) next-generation sequence data. We applied these new sequence analysis techniques to matched normal and primary tumor patient samples from the Cancer Genome Atlas (TCGA) in order to analyze the patterns of TE expression and insertion for three cancer types: breast invasive carcinoma, head and neck squamous cell carcinoma, and lung adenocarcinoma. Our analysis focused on the three most abundant families of active human TEs: Alu, SVA, and L1. We found evidence for high levels of somatic TE activity for these three families in normal and cancer samples across diverse tissue types. Abundant transcripts for all three TE families were detected in both normal and cancer tissues along with an average of ~80 unique TE insertions per individual patient/tissue. We observed an increase in L1 transcript expression and L1 insertional activity in primary tumor samples for all three cancer types. Tumor-specific TE insertions are enriched for private mutations, consistent with a potentially causal role in tumorigenesis. We used genome feature analysis to investigate two specific cases of putative cancer-causing TE mutations in further detail. An Alu insertion in an upstream enhancer of the ",
			"category": 2,
			"name": "Clayton Evan A,2020"
		},
		{
			"PMID": 27896055,
			"title": "Phylooncogenomics: Examining the cancer genome in the context of vertebrate evolution.",
			"journal": "Applied & translational genomics",
			"authorList": [
				"Zhang GuangJun",
				"Vemulapalli Tracy H",
				"Yang Jer-Yen"
			],
			"DOI": "",
			"date": "2020-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "Currently, human cancer genomics is making great progress, and many mutations of new cancer driver genes have been detected at an unprecedented rate in a variety of human cancers. Many details of the genetic alterations in cancer cell genomes have been revealed by the massively parallel sequencing. Long-lasting aneuploidy caused large-scale somatic copy number alterations remains a difficulty as there are too many genes located on such big chromosomal fragments, and this cannot simply be solved by increasing sequencing depth and tumor sample numbers. Comparative oncogenomics may provide us with a solution to this problem. Here, we review some of the common animal cancer models and propose to analyze cancer cell genomics in vertebrate phylogenetic backgrounds. Thus phylooncogenomics may provide us with a unique perspective on he nature of cancer biology unattainable by single species studies.",
			"category": 2,
			"name": "Zhang GuangJun,2020"
		},
		{
			"PMID": 27880935,
			"title": "Evolutionary biologic changes of gut microbiota in an 'adenoma-carcinoma sequence' mouse colorectal cancer model induced by 1, 2-Dimethylhydrazine.",
			"journal": "Oncotarget",
			"authorList": [
				"Sun Teng",
				"Liu Shanglong",
				"Zhou Yanbing",
				"Yao Zengwu",
				"Zhang Dongfeng",
				"Cao Shougen",
				"Wei Zhiliang",
				"Tan Bin",
				"Li Yi",
				"Lian Zheng",
				"Wang Song"
			],
			"DOI": "10.18632/oncotarget.13443",
			"date": "2018-02-21",
			"PMC": "",
			"citation": "",
			"abstract": "The molecular biological mechanisms underlying the evolutionary biologic changes leading to carcinogenesis remain unclear. The main objective of our study was to explore the evolution of the microbiota community and molecules related with CRC in the dynamic transition from normal colon epithelium to premalignant adenoma with the aid of an 'adenoma-carcinoma sequence' mouse CRC model induced by DMH. We generated a modified mouse CRC model induced by DMH for DNA sequences, and characterized the molecular networks. Data from 454 pyrosequencing of the V3- V5 region of the 16S rDNA gene and immunohistochemical detection of APC, P53, K-RAS and BRAF genes were assessed with Principal coordinates, UniFrac, and Kruskal-Wallis rank sum test. The inflammatory group showed enrichment of Bacteroidetes and Porphyromonadaceae (P < 0.01). OTUs affiliated with Firmicutes were enriched in the hyperproliferative group (P < 0.01). Rikenellaceae and Ruminococcaceae showed an increasing trend during the CRC process while the opposite pattern was observed for Prevotellaceaeand Enterobacteriaceae. OTUs related to Alistipes finegoldii were significantly increased during CRC development, P53, K-RAS and BRAF, were gradually increased (P < 0.05). Conversely, expression of APC was decreased during the course of development of CRC. Our results demonstrate that the biological evolutionary shift of gut microbiota, characterized by a gradual decrease in 'driver' bacteria and an increase in DNA damage-causing bacteria, is accompanied by tumor development in the CRC model. The synergistic actions of microbiota dysbiosis and effects of bacterial metabolites on related molecular events are proposed to contribute to the progression of CRC tumorigenesis.",
			"category": 2,
			"name": "Sun Teng,2018"
		},
		{
			"PMID": 27874022,
			"title": "In-depth comparison of somatic point mutation callers based on different tumor next-generation sequencing depth data.",
			"journal": "Scientific reports",
			"authorList": [
				"Cai Lei",
				"Yuan Wei",
				"Zhang Zhou",
				"He Lin",
				"Chou Kuo-Chen"
			],
			"DOI": "10.1038/srep36540",
			"date": "2018-05-03",
			"PMC": "",
			"citation": "",
			"abstract": "Four popular somatic single nucleotide variant (SNV) calling methods (Varscan, SomaticSniper, Strelka and MuTect2) were carefully evaluated on the real whole exome sequencing (WES, depth of ~50X) and ultra-deep targeted sequencing (UDT-Seq, depth of ~370X) data. The four tools returned poor consensus on candidates (only 20% of calls were with multiple hits by the callers). For both WES and UDT-Seq, MuTect2 and Strelka obtained the largest proportion of COSMIC entries as well as the lowest rate of dbSNP presence and high-alternative-alleles-in-control calls, demonstrating their superior sensitivity and accuracy. Combining different callers does increase reliability of candidates, but narrows the list down to very limited range of tumor read depth and variant allele frequency. Calling SNV on UDT-Seq data, which were of much higher read-depth, discovered additional true-positive variations, despite an even more tremendous growth in false positive predictions. Our findings not only provide valuable benchmark for state-of-the-art SNV calling methods, but also shed light on the access to more accurate SNV identification in the future.",
			"category": 2,
			"name": "Cai Lei,2018"
		},
		{
			"PMID": 27863091,
			"title": "Computational approaches for the identification of cancer genes and pathways.",
			"journal": "Wiley interdisciplinary reviews. Systems biology and medicine",
			"authorList": [
				"Dimitrakopoulos Christos M",
				"Beerenwinkel Niko"
			],
			"DOI": "10.1002/wsbm.1364",
			"date": "2017-11-13",
			"PMC": "",
			"citation": "",
			"abstract": "High-throughput DNA sequencing techniques enable large-scale measurement of somatic mutations in tumors. Cancer genomics research aims at identifying all cancer-related genes and solid interpretation of their contribution to cancer initiation and development. However, this venture is characterized by various challenges, such as the high number of neutral passenger mutations and the complexity of the biological networks affected by driver mutations. Based on biological pathway and network information, sophisticated computational methods have been developed to facilitate the detection of cancer driver mutations and pathways. They can be categorized into (1) methods using known pathways from public databases, (2) network-based methods, and (3) methods learning cancer pathways de novo. Methods in the first two categories use and integrate different types of data, such as biological pathways, protein interaction networks, and gene expression measurements. The third category consists of de novo methods that detect combinatorial patterns of somatic mutations across tumor samples, such as mutual exclusivity and co-occurrence. In this review, we discuss recent advances, current limitations, and future challenges of these approaches for detecting cancer genes and pathways. We also discuss the most important current resources of cancer-related genes. WIREs Syst Biol Med 2017, 9:e1364. doi: 10.1002/wsbm.1364 For further resources related to this article, please visit the WIREs website.",
			"category": 2,
			"name": "Dimitrakopoulos Christos M,2017"
		},
		{
			"PMID": 27852048,
			"title": "IGFBP2 expression predicts IDH-mutant glioma patient survival.",
			"journal": "Oncotarget",
			"authorList": [
				"Huang Lin Eric",
				"Cohen Adam L",
				"Colman Howard",
				"Jensen Randy L",
				"Fults Daniel W",
				"Couldwell William T"
			],
			"DOI": "10.18632/oncotarget.13329",
			"date": "2018-03-05",
			"PMC": "",
			"citation": "",
			"abstract": "Mutations of the isocitrate dehydrogenase (IDH) 1 and 2 genes occur in ~80% of lower-grade (WHO grade II and grade III) gliomas. Mutant IDH produces (R)-2-hydroxyglutarate, which induces DNA hypermethylation and presumably drives tumorigenesis. Interestingly, IDH mutations are associated with improved survival in glioma patients, but the underlying mechanism for the difference in survival remains unclear. Through comparative analyses of 286 cases of IDH-wildtype and IDH-mutant lower-grade glioma from a TCGA data set, we report that IDH-mutant gliomas have increased expression of tumor-suppressor genes (NF1, PTEN, and PIK3R1) and decreased expression of oncogenes(AKT2, ARAF, ERBB2, FGFR3, and PDGFRB) and glioma progression genes (FOXM1, IGFBP2, and WWTR1) compared with IDH-wildtype gliomas. Furthermore, each of these genes is prognostic in overall gliomas; however, within the IDH-mutant group, none remains prognostic except IGFBP2 (encodinginsulin-like growth factor binding protein 2). Through validation in an independent cohort, we show that patients with low IGFBP2 expressiondisplay a clear advantage in overall and disease-free survival, whereas those with high IGFBP2 expressionhave worse median survival than IDH-wildtype patients. These observations hold true across different histological and molecular subtypes of lower-grade glioma. We propose therefore that an unexpected biological consequence of IDH mutations in glioma is to ameliorate patient survival by promoting tumor-suppressor signaling while inhibiting that of oncogenes, particularly IGFBP2.",
			"category": 2,
			"name": "Huang Lin Eric,2018"
		},
		{
			"PMID": 27797769,
			"title": "Cancer driver gene discovery through an integrative genomics approach in a non-parametric Bayesian framework.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Yang Hai",
				"Wei Qiang",
				"Zhong Xue",
				"Yang Hushan",
				"Li Bingshan"
			],
			"DOI": "10.1093/bioinformatics/btw662",
			"date": "2017-12-04",
			"PMC": "",
			"citation": "",
			"abstract": "Comprehensive catalogue of genes that drive tumor initiation and progression in cancer is key to advancing diagnostics, therapeutics and treatment. Given the complexity of cancer, the catalogue is far from complete yet. Increasing evidence shows that driver genes exhibit consistent aberration patterns across multiple-omics in tumors. In this study, we aim to leverage complementary information encoded in each of the omics data to identify novel driver genes through an integrative framework. Specifically, we integrated mutations, gene expression, DNA copy numbers, DNA methylation and protein abundance, all available in The Cancer Genome Atlas (TCGA) and developed iDriver, a non-parametric Bayesian framework based on multivariate statistical modeling to identify driver genes in an unsupervised fashion. iDriver captures the inherent clusters of gene aberrations and constructs the background distribution that is used to assess and calibrate the confidence of driver genes identified through multi-dimensional genomic data.",
			"category": 2,
			"name": "Yang Hai,2017"
		},
		{
			"PMID": 27784327,
			"title": "Integrating cancer genomic data into electronic health records.",
			"journal": "Genome medicine",
			"authorList": [
				"Warner Jeremy L",
				"Jain Sandeep K",
				"Levy Mia A"
			],
			"DOI": "",
			"date": "2017-03-17",
			"PMC": "",
			"citation": "",
			"abstract": "The rise of genomically targeted therapies and immunotherapy has revolutionized the practice of oncology in the last 10-15 years. At the same time, new technologies and the electronic health record (EHR) in particular have permeated the oncology clinic. Initially designed as billing and clinical documentation systems, EHR systems have not anticipated the complexity and variety of genomic information that needs to be reviewed, interpreted, and acted upon on a daily basis. Improved integration of cancer genomic data with EHR systems will help guide clinician decision making, support secondary uses, and ultimately improve patient care within oncology clinics. Some of the key factors relating to the challenge of integrating cancer genomic data into EHRs include: the bioinformatics pipelines that translate raw genomic data into meaningful, actionable results; the role of human curation in the interpretation of variant calls; and the need for consistent standards with regard to genomic and clinical data. Several emerging paradigms for integration are discussed in this review, including: non-standardized efforts between individual institutions and genomic testing laboratories; \"middleware\" products that portray genomic information, albeit outside of the clinical workflow; and application programming interfaces that have the potential to work within clinical workflow. The critical need for clinical-genomic knowledge bases, which can be independent or integrated into the aforementioned solutions, is also discussed.",
			"category": 2,
			"name": "Warner Jeremy L,2017"
		},
		{
			"PMID": 27769991,
			"title": "Computational pan-genomics: status, promises and challenges.",
			"journal": "Briefings in bioinformatics",
			"authorList": [
				"Computational Pan-Genomics Consortium"
			],
			"DOI": "10.1093/bib/bbw089",
			"date": "2018-10-22",
			"PMC": "",
			"citation": "",
			"abstract": "Many disciplines, from human genetics and oncology to plant breeding, microbiology and virology, commonly face the challenge of analyzing rapidly increasing numbers of genomes. In case of Homo sapiens, the number of sequenced genomes will approach hundreds of thousands in the next few years. Simply scaling up established bioinformatics pipelines will not be sufficient for leveraging the full potential of such rich genomic data sets. Instead, novel, qualitatively different computational methods and paradigms are needed. We will witness the rapid extension of computational pan-genomics, a new sub-area of research in computational biology. In this article, we generalize existing definitions and understand a pan-genome as any collection of genomic sequences to be analyzed jointly or to be used as a reference. We examine already available approaches to construct and use pan-genomes, discuss the potential benefits of future technologies and methodologies and review open challenges from the vantage point of the above-mentioned biological disciplines. As a prominent example for a computational paradigm shift, we particularly highlight the transition from the representation of reference genomes as strings to representations as graphs. We outline how this and other challenges from different application domains translate into common computational problems, point out relevant bioinformatics techniques and identify open problems in computer science. With this review, we aim to increase awareness that a joint approach to computational pan-genomics can help address many of the problems currently faced in various domains.",
			"category": 2,
			"name": "Computational Pan-Genomics Consortium,2018"
		},
		{
			"PMID": 27760307,
			"title": "Molecular genetics of osteosarcoma.",
			"journal": "Bone",
			"authorList": [
				"Rickel Kirby",
				"Fang Fang",
				"Tao Jianning"
			],
			"DOI": "10.1016/j.bone.2016.10.017",
			"date": "2018-07-27",
			"PMC": "",
			"citation": "",
			"abstract": "Osteosarcoma is the predominant form of bone cancer, affecting mostly adolescents. Recent progress made in molecular genetic studies of osteosarcoma has changed our view on the cause of the disease and ongoing therapeutic approaches for patients. As we draw closer to gaining more complete catalogs of candidate cancer driver genes in common forms of cancer, the landscape of somatic mutations in osteosarcoma is emerging from its first phase. In this review, we summarize recent whole genome and/or whole exome genomic studies, and then put these findings in the context of genetic hallmarks of somatic mutations and mutational processes in human osteosarcoma. One of the lessons learned here is that the extent of somatic mutations and complexity of the osteosarcoma genome are similar to that of common forms of adult cancer. Thus, a much higher number of samples than those currently obtained are needed to complete the catalog of driver mutations in human osteosarcoma. In parallel, genetic studies in other species have revealed candidate driver genes and their roles in the genesis of osteosarcoma. This review also summarizes newly identified drivers in genetically engineered mouse models (GEMMs) and discusses our understanding of the impact of nature and number of drivers on tumor latency, subtypes, and metastatic potentials of osteosarcoma. It is becoming apparent that a synergistic team composed of three drivers (one 'first driver' and two 'synergistic drivers') may be required to generate an animal model that recapitulates aggressive osteosarcoma with a short latency. Finally, new cancer therapies are urgently needed to improve survival rate and quality of life for osteosarcoma patients. Several vulnerabilities in osteosarcoma are illustrated in this review to exemplify the opportunities for next generation molecularly targeted therapies. However, much work remains in order to complete our understanding of the somatic mutation basis of osteosarcoma, to develop reliable animal models of human disease, and to apply this information to guide new therapeutic approaches for reducing morbidity and mortality of this rare disease.",
			"category": 2,
			"name": "Rickel Kirby,2018"
		},
		{
			"PMID": 27739435,
			"title": "Identification of recurrent mutational events in anorectal melanoma.",
			"journal": "Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc",
			"authorList": [
				"Yang Hui Min",
				"Hsiao Susan J",
				"Schaeffer David F",
				"Lai Chi",
				"Remotti Helen E",
				"Horst David",
				"Mansukhani Mahesh M",
				"Horst Basil A"
			],
			"DOI": "10.1038/modpathol.2016.179",
			"date": "2018-02-22",
			"PMC": "",
			"citation": "",
			"abstract": "Anorectal melanoma is a rare disease that carries a poor prognosis. To date, limited genetic analyses confirmed KIT mutations as a recurrent genetic event similar to other mucosal melanomas, occurring in up to 30% of anorectal melanomas. Importantly, a subset of tumors harboring activating KIT mutations have been found to respond to c-Kit inhibitor-based therapy, with improved patient survival at advanced tumor stages. We performed comprehensive targeted exon sequencing analysis of 467 cancer-related genes in a larger series of 15 anorectal melanomas, focusing on potentially actionable variants based on gain- and loss-of-function mutations. We report the identification of oncogenic driver events in the majority (93%) of anorectal melanomas. These included variants in canonical MAPK pathway effectors rarely observed in cutaneous melanomas (including an HRAS mutation, as well as a BRAF mutation resulting in duplication of threonine 599), and recurrent mutations in the tumor suppressor NF1 in 20% of cases, which represented the second-most frequently mutated gene after KIT in our series. Furthermore, we identify SF3B1 mutations as a recurrent genetic event in mucosal melanomas. Our findings provide an insight into the genetic diversity of anorectal melanomas, and suggest significant potential for alternative targeted therapeutics in addition to c-Kit inhibitors for this melanoma subtype.",
			"category": 2,
			"name": "Yang Hui Min,2018"
		},
		{
			"PMID": 27738745,
			"title": "Next-generation molecular diagnosis: single-cell sequencing from bench to bedside.",
			"journal": "Cellular and molecular life sciences : CMLS",
			"authorList": [
				"Zhu Wanjun",
				"Zhang Xiao-Yan",
				"Marjani Sadie L",
				"Zhang Jialing",
				"Zhang Wengeng",
				"Wu Shixiu",
				"Pan Xinghua"
			],
			"DOI": "10.1007/s00018-016-2368-x",
			"date": "2017-08-28",
			"PMC": "",
			"citation": "",
			"abstract": "Single-cell sequencing (SCS) is a fast-growing, exciting field in genomic medicine. It enables the high-resolution study of cellular heterogeneity, and reveals the molecular basis of complicated systems, which facilitates the identification of new biomarkers for diagnosis and for targeting therapies. It also directly promotes the next generation of genomic medicine because of its ultra-high resolution and sensitivity that allows for the non-invasive and early\u00a0detection of abnormalities, such as aneuploidy, chromosomal translocation, and single-gene disorders. This review provides an overview of the current progress and prospects for the diagnostic applications of SCS, specifically in pre-implantation genetic diagnosis/screening, non-invasive prenatal diagnosis, and analysis of circulating tumor cells. These analyses will accelerate the early and precise control of germline- or somatic-mutation-based diseases, particularly single-gene disorders, chromosome abnormalities, and cancers.",
			"category": 2,
			"name": "Zhu Wanjun,2017"
		},
		{
			"PMID": 27738330,
			"title": "Interleukin-6 and C-reactive protein as prognostic biomarkers in metastatic colorectal cancer.",
			"journal": "Oncotarget",
			"authorList": [
				"Thomsen Maria",
				"Kersten Christian",
				"Sorbye Halfdan",
				"Skovlund Eva",
				"Glimelius Bengt",
				"Pfeiffer Per",
				"Johansen Julia S",
				"Kure Elin H",
				"Ikdahl Tone",
				"Tveit Kjell Magne",
				"Christoffersen Thoralf",
				"Guren Tormod Kyrre"
			],
			"DOI": "10.18632/oncotarget.12601",
			"date": "2018-02-26",
			"PMC": "",
			"citation": "",
			"abstract": "The aim was to explore the prognostic significance of IL-6 and markers of systemic inflammatory response (SIR), in particular C-reactive protein (CRP), in metastatic colorectal cancer (mCRC) patients, in the total study population and according to RAS and BRAF mutation status.",
			"category": 2,
			"name": "Thomsen Maria,2018"
		},
		{
			"PMID": 27729614,
			"title": "Genomic profiling of stage II and III colon cancers reveals APC mutations to be associated with survival in stage III colon cancer patients.",
			"journal": "Oncotarget",
			"authorList": [
				"van den Broek Evert",
				"Krijgsman Oscar",
				"Sie Daoud",
				"Tijssen Marianne",
				"Mongera Sandra",
				"van de Wiel Mark A",
				"Belt Eric J Th",
				"den Uil Sjoerd H",
				"Bril Herman",
				"Stockmann Hein B A C",
				"Ylstra Bauke",
				"Carvalho Beatriz",
				"Meijer Gerrit A",
				"Fijneman Remond J A"
			],
			"DOI": "10.18632/oncotarget.12510",
			"date": "2018-03-05",
			"PMC": "",
			"citation": "",
			"abstract": "Tumor profiling of DNA alterations, i.e. gene point mutations, somatic copy number aberrations (CNAs) and structural variants (SVs), improves insight into the molecular pathology of cancer and clinical outcome. Here, associations between genomic aberrations and disease recurrence in stage II and III colon cancers were investigated. A series of 114 stage II and III microsatellite stable colon cancer samples were analyzed by high-resolution array-comparative genomic hybridization (array-CGH) to detect CNAs and CNA-associated chromosomal breakpoints (SVs). For 60 of these samples mutation status of APC, TP53, KRAS, PIK3CA, FBXW7, SMAD4, BRAF and NRAS was determined using targeted massive parallel sequencing. Loss of chromosome 18q12.1-18q12.2 occurred more frequently in tumors that relapsed than in relapse-free tumors (p < 0.001; FDR = 0.13). In total, 267 genes were recurrently affected by SVs (FDR < 0.1). CNAs and SVs were not associated with disease-free survival (DFS). Mutations in APC and TP53 were associated with increased CNAs. APC mutations were associated with poor prognosis in (5-fluorouracil treated) stage III colon cancers (p = 0.005; HR = 4.1), an effect that was further enhanced by mutations in MAPK pathway (KRAS, NRAS, BRAF) genes. We conclude that among multiple genomic alterations in CRC, strongest associations with clinical outcome were observed for common mutations in APC.",
			"category": 2,
			"name": "van den Broek Evert,2018"
		},
		{
			"PMID": 27698416,
			"title": "Tissue-specific mutation accumulation in human adult stem cells during life.",
			"journal": "Nature",
			"authorList": [
				"Blokzijl Francis",
				"de Ligt Joep",
				"Jager Myrthe",
				"Sasselli Valentina",
				"Roerink Sophie",
				"Sasaki Nobuo",
				"Huch Meritxell",
				"Boymans Sander",
				"Kuijk Ewart",
				"Prins Pjotr",
				"Nijman Isaac J",
				"Martincorena Inigo",
				"Mokry Michal",
				"Wiegerinck Caroline L",
				"Middendorp Sabine",
				"Sato Toshiro",
				"Schwank Gerald",
				"Nieuwenhuis Edward E S",
				"Verstegen Monique M A",
				"van der Laan Luc J W",
				"de Jonge Jeroen",
				"IJzermans Jan N M",
				"Vries Robert G",
				"van de Wetering Marc",
				"Stratton Michael R",
				"Clevers Hans",
				"Cuppen Edwin",
				"van Boxtel Ruben"
			],
			"DOI": "10.1038/nature19768",
			"date": "2017-02-28",
			"PMC": "",
			"citation": "",
			"abstract": "The gradual accumulation of genetic mutations in human adult stem cells (ASCs) during life is associated with various age-related diseases, including cancer. Extreme variation in cancer risk across tissues was recently proposed to depend on the lifetime number of ASC divisions, owing to unavoidable random mutations that arise during DNA replication. However, the rates and patterns of mutations in normal ASCs remain unknown. Here we determine genome-wide mutation patterns in ASCs of the small intestine, colon and liver of human donors with ages ranging from 3 to 87 years by sequencing clonal organoid cultures derived from primary multipotent cells. Our results show that mutations accumulate steadily over time in all of the assessed tissue types, at a rate of approximately 40 novel mutations per year, despite the large variation in cancer incidence among these tissues. Liver ASCs, however, have different mutation spectra compared to those of the colon and small intestine. Mutational signature analysis reveals that this difference can be attributed to spontaneous deamination of methylated cytosine residues in the colon and small intestine, probably reflecting their high ASC division rate. In liver, a signature with an as-yet-unknown underlying mechanism is predominant. Mutation spectra of driver genes in cancer show high similarity to the tissue-specific ASC mutation spectra, suggesting that intrinsic mutational processes in ASCs can initiate tumorigenesis. Notably, the inter-individual variation in mutation rate and spectra are low, suggesting tissue-specific activity of common mutational processes throughout life.",
			"category": 2,
			"name": "Blokzijl Francis,2017"
		},
		{
			"PMID": 27688613,
			"title": "Epidermal growth factor receptor mutation in adenocarcinoma lung in a North Indian population: Prevalence and relation with different clinical variables.",
			"journal": "Indian journal of medical and paediatric oncology : official journal of Indian Society of Medical & Paediatric Oncology",
			"authorList": [
				"Kasana Basharat Ahmad",
				"Dar Waseem Raja",
				"Aziz Sheikh Aijaz",
				"Lone Abdul Rashid",
				"Sofi Najeeb Ullah",
				"Dar Imtiyaz Ahmad",
				"Latief Muzamil",
				"Arshad Faheem",
				"Hussain Moomin",
				"Hussain Mir"
			],
			"DOI": "10.4103/0971-5851.190356",
			"date": "2016-10-05",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer is one of the most common causes of cancer deaths worldwide. Adenocarcinoma is taking over squamous cell lung cancer as the predominant histological subtype. Several cytotoxic drugs are available for the treatment of lung cancer, but side effects limit their use. Recently, targeted therapies for cancers have come into clinical practice.",
			"category": 2,
			"name": "Kasana Basharat Ahmad,2016"
		},
		{
			"PMID": 27649156,
			"title": "Targeted Cancer Therapy: Vital Oncogenes and a New Molecular Genetic Paradigm for Cancer Initiation Progression and Treatment.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Willis Rudolph E"
			],
			"DOI": "10.3390/ijms17091552",
			"date": "2017-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis.",
			"category": 2,
			"name": "Willis Rudolph E,2017"
		},
		{
			"PMID": 27631787,
			"title": "Accumulation of Deleterious Passenger Mutations Is Associated with the Progression of Hepatocellular Carcinoma.",
			"journal": "PloS one",
			"authorList": [
				"Budzinska Magdalena A",
				"Tu Thomas",
				"d'Avigdor William M H",
				"McCaughan Geoffrey W",
				"Luciani Fabio",
				"Shackel Nicholas A"
			],
			"DOI": "10.1371/journal.pone.0162586",
			"date": "2017-08-02",
			"PMC": "",
			"citation": "",
			"abstract": "In hepatocellular carcinoma (HCC), somatic genome-wide DNA mutations are numerous, universal and heterogeneous. Some of these somatic mutations are drivers of the malignant process but the vast majority are passenger mutations. These passenger mutations can be deleterious to individual protein function but are tolerated by the cell or are offset by a survival advantage conferred by driver mutations. It is unknown if these somatic deleterious passenger mutations (DPMs) develop in the precancerous state of cirrhosis or if it is confined to HCC. Therefore, we studied four whole-exome sequencing datasets, including patients with non-cirrhotic liver (n = 12), cirrhosis without HCC (n = 6) and paired HCC with surrounding non-HCC liver (n = 74 paired samples), to identify DPMs. After filtering out putative germline mutations, we identified 187\u00b122 DPMs per non-diseased tissue. DPMs number was associated with liver disease progressing to HCC, independent of the number of exonic mutations. Tumours contained significantly more DPMs compared to paired non-tumour tissue (258-293 per HCC exome). Cirrhosis- and HCC-associated DPMs do not occur predominantly in specific genes, chromosomes or biological pathways and the effect on tumour biology is presently unknown. Importantly, for the first time we have shown a significant increase in DPMs with HCC.",
			"category": 2,
			"name": "Budzinska Magdalena A,2017"
		},
		{
			"PMID": 27621418,
			"title": "RAG-induced DNA lesions activate proapoptotic BIM to suppress lymphomagenesis in p53-deficient mice.",
			"journal": "The Journal of experimental medicine",
			"authorList": [
				"Delbridge Alex R D",
				"Pang Swee Heng Milon",
				"Vandenberg Cassandra J",
				"Grabow Stephanie",
				"Aubrey Brandon J",
				"Tai Lin",
				"Herold Marco J",
				"Strasser Andreas"
			],
			"DOI": "10.1084/jem.20150477",
			"date": "2017-07-31",
			"PMC": "",
			"citation": "",
			"abstract": "Neoplastic transformation is driven by oncogenic lesions that facilitate unrestrained cell expansion and resistance to antiproliferative signals. These oncogenic DNA lesions, acquired through errors in DNA replication, gene recombination, or extrinsically imposed damage, are thought to activate multiple tumor suppressive pathways, particularly apoptotic cell death. DNA damage induces apoptosis through well-described p53-mediated induction of PUMA and NOXA. However, loss of both these mediators (even together with defects in p53-mediated induction of cell cycle arrest and cell senescence) does not recapitulate the tumor susceptibility observed in p53(-/-) mice. Thus, potentially oncogenic DNA lesions are likely to also trigger apoptosis through additional, p53-independent processes. We found that loss of the BH3-only protein BIM accelerated lymphoma development in p53-deficient mice. This process was negated by concomitant loss of RAG1/2-mediated antigen receptor gene rearrangement. This demonstrates that BIM is critical for the induction of apoptosis caused by potentially oncogenic DNA lesions elicited by RAG1/2-induced gene rearrangement. Furthermore, this highlights the role of a BIM-mediated tumor suppressor pathway that acts in parallel to the p53 pathway and remains active even in the absence of wild-type p53 function, suggesting this may be exploited in the treatment of p53-deficient cancers.",
			"category": 2,
			"name": "Delbridge Alex R D,2017"
		},
		{
			"PMID": 27596597,
			"title": "Personalized characterization of diseases using sample-specific networks.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Liu Xiaoping",
				"Wang Yuetong",
				"Ji Hongbin",
				"Aihara Kazuyuki",
				"Chen Luonan"
			],
			"DOI": "",
			"date": "2017-06-15",
			"PMC": "",
			"citation": "",
			"abstract": "A complex disease generally results not from malfunction of individual molecules but from dysfunction of the relevant system or network, which dynamically changes with time and conditions. Thus, estimating a condition-specific network from a single sample is crucial to elucidating the molecular mechanisms of complex diseases at the system level. However, there is currently no effective way to construct such an individual-specific network by expression profiling of a single sample because of the requirement of multiple samples for computing correlations. We developed here with a statistical method, i.e. a sample-specific network (SSN) method, which allows us to construct individual-specific networks based on molecular expressions of a single sample. Using this method, we can characterize various human diseases at a network level. In particular, such SSNs can lead to the identification of individual-specific disease modules as well as driver genes, even without gene sequencing information. Extensive analysis by using the Cancer Genome Atlas data not only demonstrated the effectiveness of the method, but also found new individual-specific driver genes and network patterns for various types of cancer. Biological experiments on drug resistance further validated one important advantage of our method over the traditional methods, i.e. we can even identify such drug resistance genes that actually have no clear differential expression between samples with and without the resistance, due to the additional network information.",
			"category": 2,
			"name": "Liu Xiaoping,2017"
		},
		{
			"PMID": 27579614,
			"title": "GBM-associated mutations and altered protein expression are more common in young patients.",
			"journal": "Oncotarget",
			"authorList": [
				"Ferguson Sherise D",
				"Xiu Joanne",
				"Weathers Shiao-Pei",
				"Zhou Shouhao",
				"Kesari Santosh",
				"Weiss Stephanie E",
				"Verhaak Roeland G",
				"Hohl Raymond J",
				"Barger Geoffrey R",
				"Reddy Sandeep K",
				"Heimberger Amy B"
			],
			"DOI": "10.18632/oncotarget.11617",
			"date": "2018-02-12",
			"PMC": "",
			"citation": "",
			"abstract": "Geriatric glioblastoma (GBM) patients have a poorer prognosis than younger patients, but IDH1/2 mutations (more common in younger patients) confer a favorable prognosis. We compared key GBM molecular alterations between an elderly (age \u2265 70) and younger (18 < = age < = 45) cohort to explore potential therapeutic opportunities.",
			"category": 2,
			"name": "Ferguson Sherise D,2018"
		},
		{
			"PMID": 27563651,
			"title": "DNA damage, tumor mutational load and their impact on immune responses against cancer.",
			"journal": "Annals of translational medicine",
			"authorList": [
				"Liontos Michalis",
				"Anastasiou Ioannis",
				"Bamias Aristotelis",
				"Dimopoulos Meletios-Athanasios"
			],
			"DOI": "10.21037/atm.2016.07.11",
			"date": "2016-08-26",
			"PMC": "",
			"citation": "",
			"abstract": "Advances in immunotherapy have changed the therapeutic landscape in many malignancies. Immune checkpoint inhibitors have already received regulatory approval in melanomas, lung, renal and bladder carcinomas. A common feature of these neoplasms is the increased mutational load, related to a possible increase number of tumor neoantigens that are recognized by the immune system. The mechanisms that DNA damage could confer to the mutational load and the formation of neoantigens and how this could be exploited to advance our immunotherapeutic strategies is discussed in this review.",
			"category": 2,
			"name": "Liontos Michalis,2016"
		},
		{
			"PMID": 27556693,
			"title": "Association mining of mutated cancer genes in different clinical stages across 11 cancer types.",
			"journal": "Oncotarget",
			"authorList": [
				"Hu Wangxiong",
				"Li Xiaofen",
				"Wang Tingzhang",
				"Zheng Shu"
			],
			"DOI": "10.18632/oncotarget.11392",
			"date": "2018-02-21",
			"PMC": "",
			"citation": "",
			"abstract": "Many studies have demonstrated that some genes (e.g. APC, BRAF, KRAS, PTEN, TP53) are frequently mutated in cancer, however, underlying mechanism that contributes to their high mutation frequency remains unclear. Here we used Apriori algorithm to find the frequent mutational gene sets (FMGSs) from 4,904 tumors across 11 cancer types as part of the TCGA Pan-Cancer effort and then mined the hidden association rules (ARs) within these FMGSs. Intriguingly, we found that well-known cancer driver genes such as BRAF, KRAS, PTEN, and TP53 were often co-occurred with other driver genes and FMGSs size peaked at an itemset size of 3~4 genes. Besides, the number and constitution of FMGS and ARs differed greatly among different cancers and stages. In addition, FMGS and ARs were rare in endocrine-related cancers such as breast carcinoma, ovarian cystadenocarcinoma, and thyroid carcinoma, but abundant in cancers contact directly with external environments such as skin melanoma and stomach adenocarcinoma. Furthermore, we observed more rules in stage IV than in other stages, indicating that distant metastasis needed more sophisticated gene regulatory network.",
			"category": 2,
			"name": "Hu Wangxiong,2018"
		},
		{
			"PMID": 27554797,
			"title": "Microbiota as a mediator of cancer progression and therapy.",
			"journal": "Translational research : the journal of laboratory and clinical medicine",
			"authorList": [
				"Pope Jillian L",
				"Tomkovich Sarah",
				"Yang Ye",
				"Jobin Christian"
			],
			"DOI": "10.1016/j.trsl.2016.07.021",
			"date": "2017-06-26",
			"PMC": "",
			"citation": "",
			"abstract": "Complex and intricate circuitries regulate cellular proliferation, survival, and growth, and alterations of this network through genetic and epigenetic events result in aberrant cellular behaviors, often leading to carcinogenesis. Although specific germline mutations have been recognized as cancer inducers, the vast majority of neoplastic changes in humans occur through environmental exposure, lifestyle, and diet. An emerging concept in cancer biology implicates the microbiota as a powerful environmental factor modulating the carcinogenic process. For example, the intestinal microbiota influences cancer development or therapeutic responses through specific activities (immune responses, metabolites, microbial structures, and toxins). The numerous effects of microbiota on carcinogenesis, ranging from promoting, preventing, or even influencing therapeutic outcomes, highlight the complex relationship between the biota and the host. In this review, we discuss the latest findings on this complex microbial interaction with the host and highlight potential mechanisms by which the microbiota mediates such a wide impact on carcinogenesis.",
			"category": 2,
			"name": "Pope Jillian L,2017"
		},
		{
			"PMID": 27551064,
			"title": "Overexpression screens identify conserved dosage chromosome instability genes in yeast and human cancer.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Duffy Supipi",
				"Fam Hok Khim",
				"Wang Yi Kan",
				"Styles Erin B",
				"Kim Jung-Hyun",
				"Ang J Sidney",
				"Singh Tejomayee",
				"Larionov Vladimir",
				"Shah Sohrab P",
				"Andrews Brenda",
				"Boerkoel Cornelius F",
				"Hieter Philip"
			],
			"DOI": "10.1073/pnas.1611839113",
			"date": "2018-01-25",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic copy number amplification and gene overexpression are common features of many cancers. To determine the role of gene overexpression on chromosome instability (CIN), we performed genome-wide screens in the budding yeast for yeast genes that cause CIN when overexpressed, a phenotype we refer to as dosage CIN (dCIN), and identified 245 dCIN genes. This catalog of genes reveals human orthologs known to be recurrently overexpressed and/or amplified in tumors. We show that two genes, TDP1, a tyrosyl-DNA-phosphdiesterase, and TAF12, an RNA polymerase II TATA-box binding factor, cause CIN when overexpressed in human cells. Rhabdomyosarcoma lines with elevated human Tdp1 levels also exhibit CIN that can be partially rescued by siRNA-mediated knockdown of TDP1 Overexpression of dCIN genes represents a genetic vulnerability that could be leveraged for selective killing of cancer cells through targeting of an unlinked synthetic dosage lethal (SDL) partner. Using SDL screens in yeast, we identified a set of genes that when deleted specifically kill cells with high levels of Tdp1. One gene was the histone deacetylase RPD3, for which there are known inhibitors. Both HT1080 cells overexpressing hTDP1 and rhabdomyosarcoma cells with elevated levels of hTdp1 were more sensitive to histone deacetylase inhibitors valproic acid (VPA) and trichostatin A (TSA), recapitulating the SDL interaction in human cells and suggesting VPA and TSA as potential therapeutic agents for tumors with elevated levels of hTdp1. The catalog of dCIN genes presented here provides a candidate list to identify genes that cause CIN when overexpressed in cancer, which can then be leveraged through SDL to selectively target tumors.",
			"category": 2,
			"name": "Duffy Supipi,2018"
		},
		{
			"PMID": 27549118,
			"title": "Aggregation and Prion-Like Properties of Misfolded Tumor Suppressors: Is Cancer a Prion Disease?",
			"journal": "Cold Spring Harbor perspectives in biology",
			"authorList": [
				"Costa Danielly C F",
				"de Oliveira Guilherme A P",
				"Cino Elio A",
				"Soares Iaci N",
				"Rangel Luciana P",
				"Silva Jerson L"
			],
			"DOI": "10.1101/cshperspect.a023614",
			"date": "2017-11-24",
			"PMC": "",
			"citation": "",
			"abstract": "Prion diseases are disorders that share several characteristics that are typical of many neurodegenerative diseases. Recently, several studies have extended the prion concept to pathological aggregation in malignant tumors involving misfolded p53, a tumor-suppressor protein. The aggregation of p53 and its coaggregation with p53 family members, p63 and p73, have been shown. Certain p53 mutants exert a dominant-negative regulatory effect on wild-type (WT) p53. The basis for this dominant-negative effect is that amyloid-like mutant p53 converts WT p53 into an aggregated species, leading to a gain-of-function (GoF) phenotype and the loss of its tumor-suppressor function. Recently, it was shown that p53 aggregates can be internalized by cells and can coaggregate with endogenous p53, corroborating the prion-like properties of p53 aggregates. The prion-like behavior of oncogenic p53 mutants provides an explanation for its dominant-negative and GoF properties, including the high metastatic potential of cancer cells carrying p53 mutations. The inhibition of p53 aggregation appears to represent a promising target for therapeutic intervention in patients with malignant tumors.",
			"category": 2,
			"name": "Costa Danielly C F,2017"
		},
		{
			"PMID": 27538789,
			"title": "CloneCNA: detecting subclonal somatic copy number alterations in heterogeneous tumor samples from whole-exome sequencing data.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"Yu Zhenhua",
				"Li Ao",
				"Wang Minghui"
			],
			"DOI": "10.1186/s12859-016-1174-7",
			"date": "2016-12-13",
			"PMC": "",
			"citation": "",
			"abstract": "Copy number alteration is a main genetic structural variation that plays an important role in tumor initialization and progression. Accurate detection of copy number alterations is necessary for discovering cancer-causing genes. Whole-exome sequencing has become a widely used technology in the last decade for detecting various types of genomic aberrations in cancer genomes. However, there are several major issues encountered in these detection problems, including normal cell contamination, tumor aneuploidy, and intra-tumor heterogeneity. Especially, deciphering the intra-tumor heterogeneity is imperative for identifying clonal and subclonal copy number alterations.",
			"category": 2,
			"name": "Yu Zhenhua,2016"
		},
		{
			"PMID": 27537329,
			"title": "Discretization of Gene Expression Data Unmasks Molecular Subgroups Recurring in Different Human Cancer Types.",
			"journal": "PloS one",
			"authorList": [
				"Beleut Manfred",
				"Soeldner Robert",
				"Egorov Mark",
				"Guenther Rolf",
				"Dehler Silvia",
				"Morys-Wortmann Corinna",
				"Moch Holger",
				"Henco Karsten",
				"Schraml Peter"
			],
			"DOI": "10.1371/journal.pone.0161514",
			"date": "2017-07-27",
			"PMC": "",
			"citation": "",
			"abstract": "Despite the individually different molecular alterations in tumors, the malignancy associated biological traits are strikingly similar. Results of a previous study using renal cell carcinoma (RCC) as a model pointed towards cancer-related features, which could be visualized as three groups by microarray based gene expression analysis. In this study, we used a mathematic model to verify the presence of these groups in RCC as well as in other cancer types. We developed an algorithm for gene-expression deviation profiling for analyzing gene expression data of a total of 8397 patients with 13 different cancer types and normal tissues. We revealed three common Cancer Transcriptomic Profiles (CTPs) which recurred in all investigated tumors. Additionally, CTPs remained robust regardless of the functions or numbers of genes analyzed. CTPs may represent common genetic fingerprints, which potentially reflect the closely related biological traits of human cancers.",
			"category": 2,
			"name": "Beleut Manfred,2017"
		},
		{
			"PMID": 27535740,
			"title": "Long noncoding RNA C17orf91 is a potential prognostic marker and functions as an oncogene in ovarian cancer.",
			"journal": "Journal of ovarian research",
			"authorList": [
				"Li Jun",
				"Yu Hailin",
				"Xi Meili",
				"Lu Xin"
			],
			"DOI": "10.1186/s13048-016-0258-3",
			"date": "2017-03-07",
			"PMC": "",
			"citation": "",
			"abstract": "This study was aimed to explore the role of long noncoding RNA C17orf91 and its potential mechanisms in ovarian cancer development.",
			"category": 2,
			"name": "Li Jun,2017"
		},
		{
			"PMID": 27528664,
			"title": "Genome-wide quantification of rare somatic mutations in normal human tissues using massively parallel sequencing.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Hoang Margaret L",
				"Kinde Isaac",
				"Tomasetti Cristian",
				"McMahon K Wyatt",
				"Rosenquist Thomas A",
				"Grollman Arthur P",
				"Kinzler Kenneth W",
				"Vogelstein Bert",
				"Papadopoulos Nickolas"
			],
			"DOI": "10.1073/pnas.1607794113",
			"date": "2018-03-26",
			"PMC": "",
			"citation": "",
			"abstract": "We present the bottleneck sequencing system (BotSeqS), a next-generation sequencing method that simultaneously quantifies rare somatic point mutations across the mitochondrial and nuclear genomes. BotSeqS combines molecular barcoding with a simple dilution step immediately before library amplification. We use BotSeqS to show age- and tissue-dependent accumulations of rare mutations and demonstrate that somatic mutational burden in normal human tissues can vary by several orders of magnitude, depending on biologic and environmental factors. We further show major differences between the mutational patterns of the mitochondrial and nuclear genomes in normal tissues. Lastly, the mutation spectra of normal tissues were different from each other, but similar to those of the cancers that arose in them. This technology can provide insights into the number and nature of genetic alterations in normal tissues and can be used to address a variety of fundamental questions about the genomes of diseased tissues.",
			"category": 2,
			"name": "Hoang Margaret L,2018"
		},
		{
			"PMID": 27513445,
			"title": "The Tumor-Associated Variant RAD51 G151D Induces a Hyper-Recombination Phenotype.",
			"journal": "PLoS genetics",
			"authorList": [
				"Marsden Carolyn G",
				"Jensen Ryan B",
				"Zagelbaum Jennifer",
				"Rothenberg Eli",
				"Morrical Scott W",
				"Wallace Susan S",
				"Sweasy Joann B"
			],
			"DOI": "10.1371/journal.pgen.1006208",
			"date": "2017-05-23",
			"PMC": "",
			"citation": "",
			"abstract": "The RAD51 protein plays a key role in the homology-directed repair of DNA double-strand breaks and is important for maintaining genome stability. Here we report on a novel human RAD51 variant found in an aggressive and therapy-refractive breast carcinoma. Expression of the RAD51 G151D variant in human breast epithelial cells increases the levels of homology-directed repair. Expression of RAD51 G151D in cells also promotes high levels of chromosomal aberrations and sister chromatid exchanges. In vitro, the purified RAD51 G151D protein directly and significantly enhances DNA strand exchange activity in the presence of RPA. In concordance with this result, co-incubation of G151D with BRCA2 resulted in a much higher level of strand-exchange activity compared to WT RAD51. Strikingly, the RAD51 G151D variant confers resistance to multiple DNA damaging agents, including ionizing radiation, mitomycin C, and doxorubicin. Our findings demonstrate that the RAD51 G151D somatic variant has a novel hyper-recombination phenotype and suggest that this property of the protein is important for the repair of DNA damage, leading to drug resistance.",
			"category": 2,
			"name": "Marsden Carolyn G,2017"
		},
		{
			"PMID": 27507050,
			"title": "The truncated somatostatin receptor sst5TMD4 stimulates the angiogenic process and is associated to lymphatic metastasis and disease-free survival in breast cancer patients.",
			"journal": "Oncotarget",
			"authorList": [
				"Gahete Manuel D",
				"Rinc\u00f3n-Fern\u00e1ndez David",
				"Dur\u00e1n-Prado Mario",
				"Hergueta-Redondo Marta",
				"Ib\u00e1\u00f1ez-Costa Alejandro",
				"Rojo-Sebasti\u00e1n Alejandro",
				"Gracia-Navarro Francisco",
				"Culler Michael D",
				"Casanovas Oriol",
				"Moreno-Bueno Gema",
				"Luque Ra\u00fal M",
				"Casta\u00f1o Justo P"
			],
			"DOI": "10.18632/oncotarget.11076",
			"date": "2018-02-05",
			"PMC": "",
			"citation": "",
			"abstract": "The truncated somatostatin receptor sst5TMD4 is associated with poor prognosis in breast cancer and increases breast cancer cell malignancy. Here, we examined the cellular/molecular mechanisms underlying this association, aiming to identify new molecular tools to improve diagnosis, prognosis or therapy. A gene expression array comparing sst5TMD4 stably-transfected MCF-7 cells and their controls (empty-plasmid) revealed the existence of profound alterations in the expression of genes involved in key tumoral processes, such as cell survival or angiogenesis. Moreover, sst5TMD4-overexpressing MCF-7 and MDA-MB-231 cells demonstrated increased expression/production of pro-angiogenic factors and enhanced capacity to form mammospheres. Consistently, sst5TMD4-expressing MCF-7 cells induced xenografted tumors with higher VEGF levels and elevated number of blood vessels. Importantly, sst5TMD4 was expressed in a subset of breast cancers, where it correlated with angiogenic markers, lymphatic metastasis, and reduced disease-free survival. These results, coupled to our previous data, support a relevant role of sst5TMD4 in the angiogenic process and reinforce the role of sst5TMD4 in breast cancer malignancy and metastatic potential, supporting its possible utility to develop new molecular biomarkers and drug therapies for these tumors.",
			"category": 2,
			"name": "Gahete Manuel D,2018"
		},
		{
			"PMID": 27498871,
			"title": "Direct Transcriptional Consequences of Somatic Mutation in Breast Cancer.",
			"journal": "Cell reports",
			"authorList": [
				"Shlien Adam",
				"Raine Keiran",
				"Fuligni Fabio",
				"Arnold Roland",
				"Nik-Zainal Serena",
				"Dronov Serge",
				"Mamanova Lira",
				"Rosic Andrej",
				"Ju Young Seok",
				"Cooke Susanna L",
				"Ramakrishna Manasa",
				"Papaemmanuil Elli",
				"Davies Helen R",
				"Tarpey Patrick S",
				"Van Loo Peter",
				"Wedge David C",
				"Jones David R",
				"Martin Sancha",
				"Marshall John",
				"Anderson Elizabeth",
				"Hardy Claire",
				"ICGC Breast Cancer Working Group, Oslo Breast Cancer Research Consortium",
				"Barbashina Violetta",
				"Aparicio Samuel A J R",
				"Sauer Torill",
				"Garred \u00d8ystein",
				"Vincent-Salomon Anne",
				"Mariani Odette",
				"Boyault Sandrine",
				"Fatima Aquila",
				"Langer\u00f8d Anita",
				"Borg \u00c5ke",
				"Thomas Gilles",
				"Richardson Andrea L",
				"B\u00f8rresen-Dale Anne-Lise",
				"Polyak Kornelia",
				"Stratton Michael R",
				"Campbell Peter J"
			],
			"DOI": "10.1016/j.celrep.2016.07.028",
			"date": "2017-11-13",
			"PMC": "",
			"citation": "",
			"abstract": "Disordered transcriptomes of cancer encompass direct effects of somatic mutation on transcription, coordinated secondary pathway alterations, and increased transcriptional noise. To catalog the rules governing how somatic mutation exerts direct transcriptional effects, we developed an exhaustive pipeline for analyzing RNA sequencing data, which we integrated with whole genomes from 23 breast cancers. Using X-inactivation analyses, we found that cancer cells are more transcriptionally active than intermixed stromal cells. This is especially true in estrogen receptor (ER)-negative tumors. Overall, 59% of substitutions were expressed. Nonsense mutations showed lower expression levels than expected, with patterns characteristic of nonsense-mediated decay. 14% of 4,234 rearrangements caused transcriptional abnormalities, including exon skips, exon reusage, fusions, and premature polyadenylation. We found productive, stable transcription from sense-to-antisense gene fusions and gene-to-intergenic rearrangements, suggesting that these mutation classes drive more transcriptional disruption than previously suspected. Systematic integration of transcriptome with genome data reveals the rules by which transcriptional machinery interprets somatic mutation.",
			"category": 2,
			"name": "Shlien Adam,2017"
		},
		{
			"PMID": 27490693,
			"title": "Mutational Biases Drive Elevated Rates of Substitution at Regulatory Sites across Cancer Types.",
			"journal": "PLoS genetics",
			"authorList": [
				"Kaiser Vera B",
				"Taylor Martin S",
				"Semple Colin A"
			],
			"DOI": "10.1371/journal.pgen.1006207",
			"date": "2017-05-23",
			"PMC": "",
			"citation": "",
			"abstract": "Disruption of gene regulation is known to play major roles in carcinogenesis and tumour progression. Here, we comprehensively characterize the mutational profiles of diverse transcription factor binding sites (TFBSs) across 1,574 completely sequenced cancer genomes encompassing 11 tumour types. We assess the relative rates and impact of the mutational burden at the binding sites of 81 transcription factors (TFs), by comparing the abundance and patterns of single base substitutions within putatively functional binding sites to control sites with matched sequence composition. There is a strong (1.43-fold) and significant excess of mutations at functional binding sites across TFs, and the mutations that accumulate in cancers are typically more disruptive than variants tolerated in extant human populations at the same sites. CTCF binding sites suffer an exceptionally high mutational load in cancer (3.31-fold excess) relative to control sites, and we demonstrate for the first time that this effect is seen in essentially all cancer types with sufficient data. The sub-set of CTCF sites involved in higher order chromatin structures has the highest mutational burden, suggesting a widespread breakdown of chromatin organization. However, we find no evidence for selection driving these distinctive patterns of mutation. The mutational load at CTCF-binding sites is substantially determined by replication timing and the mutational signature of the tumor in question, suggesting that selectively neutral processes underlie the unusual mutation patterns. Pervasive hyper-mutation within transcription factor binding sites rewires the regulatory landscape of the cancer genome, but it is dominated by mutational processes rather than selection.",
			"category": 2,
			"name": "Kaiser Vera B,2017"
		},
		{
			"PMID": 27483324,
			"title": "Telomerase: The Devil Inside.",
			"journal": "Genes",
			"authorList": [
				"Kumar Mukesh",
				"Lechel Andre",
				"G\u00fcne\u015f \u00c7agatay"
			],
			"DOI": "10.3390/genes7080043",
			"date": "2016-08-03",
			"PMC": "",
			"citation": "",
			"abstract": "High telomerase activity is detected in nearly all human cancers but most human cells are devoid of telomerase activity. There is well-documented evidence that reactivation of telomerase occurs during cellular transformation. In humans, tumors can rely in reactivation of telomerase or originate in a telomerase positive stem/progenitor cell, or rely in alternative lengthening of telomeres, a telomerase-independent telomere-length maintenance mechanism. In this review, we will focus on the telomerase positive tumors. In this context, the recent findings that telomerase reverse transcriptase (TERT) promoter mutations represent the most common non-coding mutations in human cancer have flared up the long-standing discussion whether cancer originates from telomerase positive stem cells or telomerase reactivation is a final step in cellular transformation. Here, we will discuss the pros and cons of both concepts in the context of telomere length-dependent and telomere length-independent functions of telomerase. Together, these observations may provoke a re-evaluation of telomere and telomerase based therapies, both in telomerase inhibition for cancer therapy and telomerase activation for tissue regeneration and anti-ageing strategies.",
			"category": 2,
			"name": "Kumar Mukesh,2016"
		},
		{
			"PMID": 27478040,
			"title": "High-throughput Phenotyping of Lung Cancer Somatic Mutations.",
			"journal": "Cancer cell",
			"authorList": [
				"Berger Alice H",
				"Brooks Angela N",
				"Wu Xiaoyun",
				"Shrestha Yashaswi",
				"Chouinard Candace",
				"Piccioni Federica",
				"Bagul Mukta",
				"Kamburov Atanas",
				"Imielinski Marcin",
				"Hogstrom Larson",
				"Zhu Cong",
				"Yang Xiaoping",
				"Pantel Sasha",
				"Sakai Ryo",
				"Watson Jacqueline",
				"Kaplan Nathan",
				"Campbell Joshua D",
				"Singh Shantanu",
				"Root David E",
				"Narayan Rajiv",
				"Natoli Ted",
				"Lahr David L",
				"Tirosh Itay",
				"Tamayo Pablo",
				"Getz Gad",
				"Wong Bang",
				"Doench John",
				"Subramanian Aravind",
				"Golub Todd R",
				"Meyerson Matthew",
				"Boehm Jesse S"
			],
			"DOI": "10.1016/j.ccell.2016.06.022",
			"date": "2017-08-21",
			"PMC": "",
			"citation": "",
			"abstract": "Recent genome sequencing efforts have identified millions of somatic mutations in cancer. However, the functional impact of most variants is poorly understood. Here we characterize 194 somatic mutations identified in primary lung adenocarcinomas. We present an expression-based variant-impact phenotyping (eVIP) method that uses gene expression changes to distinguish impactful from neutral somatic mutations. eVIP identified 69% of mutations analyzed as impactful and 31% as functionally neutral. A subset of the impactful mutations induces xenograft tumor formation in mice and/or confers resistance to cellular EGFR inhibition. Among these impactful variants are rare somatic, clinically actionable variants including EGFR S645C, ARAF S214C and S214F, ERBB2 S418T, and multiple BRAF variants, demonstrating that rare mutations can be functionally important in cancer.",
			"category": 2,
			"name": "Berger Alice H,2017"
		},
		{
			"PMID": 27474172,
			"title": "Clonal evolution of acute myeloid leukemia highlighted by latest genome sequencing studies.",
			"journal": "Oncotarget",
			"authorList": [
				"Zhang Xuehong",
				"Lv Dekang",
				"Zhang Yu",
				"Liu Quentin",
				"Li Zhiguang"
			],
			"DOI": "10.18632/oncotarget.10850",
			"date": "2018-02-22",
			"PMC": "",
			"citation": "",
			"abstract": "Decades of years might be required for an initiated cell to become a fully-pledged, metastasized tumor. DNA mutations are accumulated during this process including background mutations that emerge scholastically, as well as driver mutations that selectively occur in a handful of cancer genes and confer the cell a growth advantage over its neighbors. A clone of tumor cells could be superseded by another clone that acquires new mutations and grows more aggressively. Tumor evolutional patterns have been studied for years using conventional approaches that focus on the investigation of a single or a couple of genes. Latest deep sequencing technology enables a global view of tumor evolution by deciphering almost all genome aberrations in a tumor. Tumor clones and the fate of each clone during tumor evolution can be depicted with the help of the concept of variant allele frequency. Here, we summarize the new insights of cancer evolutional progression in acute myeloid leukemia. Cancer evolution is currently thought to start from a clone that has accumulated the requisite somatically-acquired genetic aberrations through a series of increasingly disordered clinical and pathological phases, eventually leading to malignant transformation [1-3]. The observations in invasive colorectal cancer that usually emerges from an antecedent benign adenomatous polyp and in cervical cancer that proceeds through intraepithelial neoplasia support the idea of stepwise or linear cancerous progression [3-5]. Genetically, such progression is achieved by successive waves of clonal expansion during which cells acquire novel genomic alterations including single nucleotide variants (SNVs), small insertions and deletions (indels), and/or copy number variations (CNVs) [6]. The latest improvement in sequencing technology has allowed the deciphering of the whole exome or genome in different types of tumor and normal tissue pairs, providing detailed catalogue about genome aberrations during tumor initiation and progression, which have been reviewed in several papers [7-10]. Here, we focus on demonstrating the cancer clonal evolution pattern revealed by recent deep sequencing studies of samples from acute myeloid leukemia (AML) patients.",
			"category": 2,
			"name": "Zhang Xuehong,2018"
		},
		{
			"PMID": 27471406,
			"title": "Cancer pharmacogenomics, challenges in implementation, and patient-focused perspectives.",
			"journal": "Pharmacogenomics and personalized medicine",
			"authorList": [
				"Patel Jai N"
			],
			"DOI": "10.2147/PGPM.S62918",
			"date": "2016-07-29",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer pharmacogenomics is an evolving landscape and has the potential to significantly impact cancer care and precision medicine. Harnessing and understanding the genetic code of both the patient (germline) and the tumor (somatic) provides the opportunity for personalized dose and therapy selection for cancer patients. While germline DNA is useful in understanding the pharmacokinetic and pharmacodynamic disposition of a drug, somatic DNA is particularly useful in identifying drug targets and predicting drug response. Molecular profiling of somatic DNA has resulted in the current breadth of targeted therapies available, expanding the armamentarium to battle cancer. This review provides an update on cancer pharmacogenomics and genomics-based medicine, challenges in applying pharmacogenomics to the clinical setting, and patient perspectives on the use of pharmacogenomics to personalize cancer therapy.",
			"category": 2,
			"name": "Patel Jai N,2016"
		},
		{
			"PMID": 27436342,
			"title": "Loss of mutL homolog-1 (MLH1) expression promotes acquisition of oncogenic and inhibitor-resistant point mutations in tyrosine kinases.",
			"journal": "Cellular and molecular life sciences : CMLS",
			"authorList": [
				"Springuel Lorraine",
				"Losdyck Elisabeth",
				"Saussoy Pascale",
				"Turcq B\u00e9atrice",
				"Mahon Fran\u00e7ois-Xavier",
				"Knoops Laurent",
				"Renauld Jean-Christophe"
			],
			"DOI": "",
			"date": "2017-08-04",
			"PMC": "",
			"citation": "",
			"abstract": "Genomic instability drives cancer progression by promoting genetic abnormalities that allow for the multi-step clonal selection of cells with growth advantages. We previously reported that the IL-9-dependent TS1 cell line sequentially acquired activating substitutions in JAK1 and JAK3 upon successive selections for growth factor independent and JAK inhibitor-resistant cells, suggestive of a defect in mutation avoidance mechanisms. In the first part of this paper, we discovered that the gene encoding mutL homolog-1 (MLH1), a key component of the DNA mismatch repair system, is silenced by promoter methylation in TS1 cells. By means of stable ectopic expression and RNA interference methods, we showed that the high frequencies of growth factor-independent and inhibitor-resistant cells with activating JAK mutations can be attributed to the absence of MLH1 expression. In the second part of this paper, we confirm the clinical relevance of our findings by showing that chronic myeloid leukemia relapses upon ABL-targeted therapy correlated with a lower expression of MLH1 messenger RNA. Interestingly, the mutational profile observed in our TS1 model, characterized by a strong predominance of T:A>C:G transitions, was identical to the one described in the literature for primitive cells derived from chronic myeloid leukemia patients. Taken together, our observations demonstrate for the first time a causal relationship between MLH1-deficiency and incidence of oncogenic point mutations in tyrosine kinases driving cell transformation and acquired resistance to kinase-targeted cancer therapies.",
			"category": 2,
			"name": "Springuel Lorraine,2017"
		},
		{
			"PMID": 27427556,
			"title": "Intrinsically disordered proteins and prostate cancer: pouring new wine in an old bottle.",
			"journal": "Asian journal of andrology",
			"authorList": [
				"Kulkarni Prakash"
			],
			"DOI": "10.4103/1008-682X.184272",
			"date": "2017-03-13",
			"PMC": "",
			"citation": "",
			"abstract": "An inconvenient truth in urology is that despite decades of intense research, prostate cancer (PCa) has remained one of the most prevalent cancers and leading cause of cancer-related deaths in men, particularly in the industrialized world. It is rather sobering to acknowledge that even with early diagnosis and treatment, the incidence and death due to the disease are almost paradoxically projected to increase in the coming decades.",
			"category": 2,
			"name": "Kulkarni Prakash,2017"
		},
		{
			"PMID": 27424552,
			"title": "Genomics era and complex disorders: Implications of GWAS with special reference to coronary artery disease, type 2 diabetes mellitus, and cancers.",
			"journal": "Journal of postgraduate medicine",
			"authorList": [
				"Pranavchand R",
				"Reddy B M"
			],
			"DOI": "10.4103/0022-3859.186390",
			"date": "2016-12-14",
			"PMC": "",
			"citation": "",
			"abstract": "The Human Genome Project (HGP) has identified millions of single nucleotide polymorphisms (SNPs) and their association with several diseases, apart from successfully characterizing the Mendelian/monogenic diseases. However, the dissection of precise etiology of complex genetic disorders still poses a challenge for human geneticists. This review outlines the landmark results of genome-wide association studies (GWAS) with respect to major complex diseases - Coronary artery disease (CAD), type 2 diabetes mellitus (T2DM), and predominant cancers. A brief account on the current Indian scenario is also given. All the relevant publications till mid-2015 were accessed through web databases such as PubMed and Google. Several databases providing genetic information related to these diseases were tabulated and in particular, the list of the most significant SNPs identified through GWAS was made, which may be useful for designing studies in functional validation. Post-GWAS implications and emerging concepts such as epigenomics and pharmacogenomics were also discussed.",
			"category": 2,
			"name": "Pranavchand R,2016"
		},
		{
			"PMID": 27417679,
			"title": "Challenges in identifying cancer genes by analysis of exome sequencing data.",
			"journal": "Nature communications",
			"authorList": [
				"Hofree Matan",
				"Carter Hannah",
				"Kreisberg Jason F",
				"Bandyopadhyay Sourav",
				"Mischel Paul S",
				"Friend Stephen",
				"Ideker Trey"
			],
			"DOI": "10.1038/ncomms12096",
			"date": "2018-09-11",
			"PMC": "",
			"citation": "",
			"abstract": "Massively parallel sequencing has permitted an unprecedented examination of the cancer exome, leading to predictions that all genes important to cancer will soon be identified by genetic analysis of tumours. To examine this potential, here we evaluate the ability of state-of-the-art sequence analysis methods to specifically recover known cancer genes. While some cancer genes are identified by analysis of recurrence, spatial clustering or predicted impact of somatic mutations, many remain undetected due to lack of power to discriminate driver mutations from the background mutational load (13-60% recall of cancer genes impacted by somatic single-nucleotide variants, depending on the method). Cancer genes not detected by mutation recurrence also tend to be missed by all types of exome analysis. Nonetheless, these genes are implicated by other experiments such as functional genetic screens and expression profiling. These challenges are only partially addressed by increasing sample size and will likely hold even as greater numbers of tumours are analysed.",
			"category": 2,
			"name": "Hofree Matan,2018"
		},
		{
			"PMID": 27402678,
			"title": "TMC-SNPdb: an Indian germline variant database derived from whole exome sequences.",
			"journal": "Database : the journal of biological databases and curation",
			"authorList": [
				"Upadhyay Pawan",
				"Gardi Nilesh",
				"Desai Sanket",
				"Sahoo Bikram",
				"Singh Ankita",
				"Togar Trupti",
				"Iyer Prajish",
				"Prasad Ratnam",
				"Chandrani Pratik",
				"Gupta Sudeep",
				"Dutt Amit"
			],
			"DOI": "10.1093/database/baw104",
			"date": "2017-11-20",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is predominantly a somatic disease. A mutant allele present in a cancer cell genome is considered somatic when it's absent in the paired normal genome along with public SNP databases. The current build of dbSNP, the most comprehensive public SNP database, however inadequately represents several non-European Caucasian populations, posing a limitation in cancer genomic analyses of data from these populations. We present the T: ata M: emorial C: entre-SNP D: ata B: ase (TMC-SNPdb), as the first open source, flexible, upgradable, and freely available SNP database (accessible through dbSNP build 149 and ANNOVAR)-representing 114 309 unique germline variants-generated from whole exome data of 62 normal samples derived from cancer patients of Indian origin. The TMC-SNPdb is presented with a companion subtraction tool that can be executed with command line option or using an easy-to-use graphical user interface with the ability to deplete additional Indian population specific SNPs over and above dbSNP and 1000 Genomes databases. Using an institutional generated whole exome data set of 132 samples of Indian origin, we demonstrate that TMC-SNPdb could deplete 42, 33 and 28% false positive somatic events post dbSNP depletion in Indian origin tongue, gallbladder, and cervical cancer samples, respectively. Beyond cancer somatic analyses, we anticipate utility of the TMC-SNPdb in several Mendelian germline diseases. In addition to dbSNP build 149 and ANNOVAR, the TMC-SNPdb along with the subtraction tool is available for download in the public domain at the following:Database URL: http://www.actrec.gov.in/pi-webpages/AmitDutt/TMCSNP/TMCSNPdp.html.",
			"category": 2,
			"name": "Upadhyay Pawan,2017"
		},
		{
			"PMID": 27399778,
			"title": "Cells Deficient in the Fanconi Anemia Protein FANCD2 are Hypersensitive to the Cytotoxicity and DNA Damage Induced by Coffee and Caffeic Acid.",
			"journal": "Toxins",
			"authorList": [
				"Burgos-Mor\u00f3n Estefan\u00eda",
				"Calder\u00f3n-Monta\u00f1o Jos\u00e9 Manuel",
				"Orta Manuel Luis",
				"Guill\u00e9n-Mancina Emilio",
				"Mateos Santiago",
				"L\u00f3pez-L\u00e1zaro Miguel"
			],
			"DOI": "10.3390/toxins8070211",
			"date": "2017-11-22",
			"PMC": "",
			"citation": "",
			"abstract": "Epidemiological studies have found a positive association between coffee consumption and a lower risk of cardiovascular disorders, some cancers, diabetes, Parkinson and Alzheimer disease. Coffee consumption, however, has also been linked to an increased risk of developing some types of cancer, including bladder cancer in adults and leukemia in children of mothers who drink coffee during pregnancy. Since cancer is driven by the accumulation of DNA alterations, the ability of the coffee constituent caffeic acid to induce DNA damage in cells may play a role in the carcinogenic potential of this beverage. This carcinogenic potential may be exacerbated in cells with DNA repair defects. People with the genetic disease Fanconi Anemia have DNA repair deficiencies and are predisposed to several cancers, particularly acute myeloid leukemia. Defects in the DNA repair protein Fanconi Anemia D2 (FANCD2) also play an important role in the development of a variety of cancers (e.g., bladder cancer) in people without this genetic disease. This communication shows that cells deficient in FANCD2 are hypersensitive to the cytotoxicity (clonogenic assay) and DNA damage (\u03b3-H2AX and 53BP1 focus assay) induced by caffeic acid and by a commercial lyophilized coffee extract. These data suggest that people with Fanconi Anemia, or healthy people who develop sporadic mutations in FANCD2, may be hypersensitive to the carcinogenic activity of coffee.",
			"category": 2,
			"name": "Burgos-Mor\u00f3n Estefan\u00eda,2017"
		},
		{
			"PMID": 27397505,
			"title": "A Landscape of Pharmacogenomic Interactions in Cancer.",
			"journal": "Cell",
			"authorList": [
				"Iorio Francesco",
				"Knijnenburg Theo A",
				"Vis Daniel J",
				"Bignell Graham R",
				"Menden Michael P",
				"Schubert Michael",
				"Aben Nanne",
				"Gon\u00e7alves Emanuel",
				"Barthorpe Syd",
				"Lightfoot Howard",
				"Cokelaer Thomas",
				"Greninger Patricia",
				"van Dyk Ewald",
				"Chang Han",
				"de Silva Heshani",
				"Heyn Holger",
				"Deng Xianming",
				"Egan Regina K",
				"Liu Qingsong",
				"Mironenko Tatiana",
				"Mitropoulos Xeni",
				"Richardson Laura",
				"Wang Jinhua",
				"Zhang Tinghu",
				"Moran Sebastian",
				"Sayols Sergi",
				"Soleimani Maryam",
				"Tamborero David",
				"Lopez-Bigas Nuria",
				"Ross-Macdonald Petra",
				"Esteller Manel",
				"Gray Nathanael S",
				"Haber Daniel A",
				"Stratton Michael R",
				"Benes Cyril H",
				"Wessels Lodewyk F A",
				"Saez-Rodriguez Julio",
				"McDermott Ultan",
				"Garnett Mathew J"
			],
			"DOI": "10.1016/j.cell.2016.06.017",
			"date": "2016-12-13",
			"PMC": "",
			"citation": "",
			"abstract": "Systematic studies of cancer genomes have provided unprecedented insights into the molecular nature of cancer. Using this information to guide the development and application of therapies in the clinic is challenging. Here, we report how cancer-driven alterations identified in 11,289 tumors from 29 tissues (integrating somatic mutations, copy number alterations, DNA methylation, and gene expression) can be mapped onto 1,001 molecularly annotated human cancer cell lines and correlated with sensitivity to 265 drugs. We find that cell lines faithfully recapitulate oncogenic alterations identified in tumors, find that many of these associate with drug sensitivity/resistance, and highlight the importance of tissue lineage in mediating drug response. Logic-based modeling uncovers combinations of alterations that sensitize to drugs, while machine learning demonstrates the relative importance of different data types in predicting drug response. Our analysis and datasets are rich resources to link genotypes with cellular phenotypes and to identify therapeutic options for selected cancer sub-populations.",
			"category": 2,
			"name": "Iorio Francesco,2016"
		},
		{
			"PMID": 27357839,
			"title": "KinMutRF: a random forest classifier of sequence variants in the human protein kinase superfamily.",
			"journal": "BMC genomics",
			"authorList": [
				"Pons Tirso",
				"Vazquez Miguel",
				"Matey-Hernandez Mar\u00eda Luisa",
				"Brunak S\u00f8ren",
				"Valencia Alfonso",
				"Izarzugaza Jose Mg"
			],
			"DOI": "10.1186/s12864-016-2723-1",
			"date": "2017-09-05",
			"PMC": "",
			"citation": "",
			"abstract": "The association between aberrant signal processing by protein kinases and human diseases such as cancer was established long time ago. However, understanding the link between sequence variants in the protein kinase superfamily and the mechanistic complex traits at the molecular level remains challenging: cells tolerate most genomic alterations and only a minor fraction disrupt molecular function sufficiently and drive disease.",
			"category": 2,
			"name": "Pons Tirso,2017"
		},
		{
			"PMID": 27338107,
			"title": "Genomic and Epigenomic Alterations in Cancer.",
			"journal": "The American journal of pathology",
			"authorList": [
				"Chakravarthi Balabhadrapatruni V S K",
				"Nepal Saroj",
				"Varambally Sooryanarayana"
			],
			"DOI": "10.1016/j.ajpath.2016.02.023",
			"date": "2017-05-12",
			"PMC": "",
			"citation": "",
			"abstract": "Multiple genetic and epigenetic events characterize tumor progression and define the identity of the tumors. Advances in high-throughput technologies, like gene expression profiling, next-generation sequencing, proteomics, and metabolomics, have enabled detailed molecular characterization of various tumors. The integration and analyses of these high-throughput data have unraveled many novel molecular aberrations and network alterations in tumors. These molecular alterations include multiple cancer-driving mutations, gene fusions, amplification, deletion, and post-translational modifications, among others. Many of these genomic events are being used in cancer diagnosis, whereas others are therapeutically targeted with small-molecule inhibitors. Multiple genes/enzymes that play a role in DNA and histone modifications are also altered in various cancers, changing the epigenomic landscape during cancer initiation and progression. Apart from protein-coding genes, studies are uncovering the critical regulatory roles played by noncoding RNAs and noncoding regions of the genome during cancer progression. Many of these genomic and epigenetic events function in tandem to drive tumor development and metastasis. Concurrent advances in genome-modulating technologies, like gene silencing and genome editing, are providing ability to understand in detail\u00a0the process of cancer initiation, progression, and signaling as well as opening up avenues for\u00a0therapeutic targeting. In this review, we discuss some of the recent advances in cancer genomic\u00a0and epigenomic research.",
			"category": 2,
			"name": "Chakravarthi Balabhadrapatruni V S K,2017"
		},
		{
			"PMID": 27333808,
			"title": "MUFFINN: cancer gene discovery via network analysis of somatic mutation data.",
			"journal": "Genome biology",
			"authorList": [
				"Cho Ara",
				"Shim Jung Eun",
				"Kim Eiru",
				"Supek Fran",
				"Lehner Ben",
				"Lee Insuk"
			],
			"DOI": "10.1186/s13059-016-0989-x",
			"date": "2017-06-23",
			"PMC": "",
			"citation": "",
			"abstract": "A major challenge for distinguishing cancer-causing driver mutations from inconsequential passenger mutations is the long-tail of infrequently mutated genes in cancer genomes. Here, we present and evaluate a method for prioritizing cancer genes accounting not only for mutations in individual genes but also in their neighbors in functional networks, MUFFINN (MUtations For Functional Impact on Network Neighbors). This pathway-centric method shows high sensitivity compared with gene-centric analyses of mutation data. Notably, only a marginal decrease in performance is observed when using 10\u00a0% of TCGA patient samples, suggesting the method may potentiate cancer genome projects with small patient populations.",
			"category": 2,
			"name": "Cho Ara,2017"
		},
		{
			"PMID": 27294782,
			"title": "Functional interdependence of BRD4 and DOT1L in MLL leukemia.",
			"journal": "Nature structural & molecular biology",
			"authorList": [
				"Gilan Omer",
				"Lam Enid Y N",
				"Becher Isabelle",
				"Lugo Dave",
				"Cannizzaro Ester",
				"Joberty Gerard",
				"Ward Aoife",
				"Wiese Meike",
				"Fong Chun Yew",
				"Ftouni Sarah",
				"Tyler Dean",
				"Stanley Kym",
				"MacPherson Laura",
				"Weng Chen-Fang",
				"Chan Yih-Chih",
				"Ghisi Margherita",
				"Smil David",
				"Carpenter Christopher",
				"Brown Peter",
				"Garton Neil",
				"Blewitt Marnie E",
				"Bannister Andrew J",
				"Kouzarides Tony",
				"Huntly Brian J P",
				"Johnstone Ricky W",
				"Drewes Gerard",
				"Dawson Sarah-Jane",
				"Arrowsmith Cheryl H",
				"Grandi Paola",
				"Prinjha Rab K",
				"Dawson Mark A"
			],
			"DOI": "10.1038/nsmb.3249",
			"date": "2017-06-06",
			"PMC": "",
			"citation": "",
			"abstract": "Targeted therapies against disruptor of telomeric silencing 1-like (DOT1L) and bromodomain-containing protein 4 (BRD4) are currently being evaluated in clinical trials. However, the mechanisms by which BRD4 and DOT1L regulate leukemogenic transcription programs remain unclear. Using quantitative proteomics, chemoproteomics and biochemical fractionation, we found that native BRD4 and DOT1L exist in separate protein complexes. Genetic disruption or small-molecule inhibition of BRD4 and DOT1L showed marked synergistic activity against MLL leukemia cell lines, primary human leukemia cells and mouse leukemia models. Mechanistically, we found a previously unrecognized functional collaboration between DOT1L and BRD4 that is especially important at highly transcribed genes in proximity to superenhancers. DOT1L, via dimethylated histone H3 K79, facilitates histone H4 acetylation, which in turn regulates the binding of BRD4 to chromatin. These data provide new insights into the regulation of transcription and specify a molecular framework for therapeutic intervention in this disease with poor prognosis.",
			"category": 2,
			"name": "Gilan Omer,2017"
		},
		{
			"PMID": 27270430,
			"title": "Base changes in tumour DNA have the power to reveal the causes and evolution of cancer.",
			"journal": "Oncogene",
			"authorList": [
				"Hollstein M",
				"Alexandrov L B",
				"Wild C P",
				"Ardin M",
				"Zavadil J"
			],
			"DOI": "10.1038/onc.2016.192",
			"date": "2017-08-31",
			"PMC": "",
			"citation": "",
			"abstract": "Next-generation sequencing (NGS) technology has demonstrated that the cancer genomes are peppered with mutations. Although most somatic tumour mutations are unlikely to have any role in the cancer process per se, the spectra of DNA sequence changes in tumour mutation catalogues have the potential to identify the mutagens, and to reveal the mutagenic processes responsible for human cancer. Very recently, a novel approach for data mining of the vast compilations of tumour NGS data succeeded in separating and precisely defining at least 30 distinct patterns of sequence change hidden in mutation databases. At least half of these mutational signatures can be readily assigned to known human carcinogenic exposures or endogenous mechanisms of mutagenesis. A quantum leap in our knowledge of mutagenesis in human cancers has resulted, stimulating a flurry of research activity. We trace here the major findings leading first to the hypothesis that carcinogenic insults leave characteristic imprints on the DNA sequence of tumours, and culminating in empirical evidence from NGS data that well-defined carcinogen mutational signatures are indeed present in tumour genomic DNA from a variety of cancer types. The notion that tumour DNAs can divulge environmental sources of mutation is now a well-accepted fact. This approach to cancer aetiology has also incriminated various endogenous, enzyme-driven processes that increase the somatic mutation load in sporadic cancers. The tasks now confronting the field of molecular epidemiology are to assign mutagenic processes to orphan and newly discovered tumour mutation patterns, and to determine whether avoidable cancer risk factors influence signatures produced by endogenous enzymatic mechanisms. Innovative research with experimental models and exploitation of the geographical heterogeneity in cancer incidence can address these challenges.",
			"category": 2,
			"name": "Hollstein M,2017"
		},
		{
			"PMID": 27260798,
			"title": "Copy number analysis of whole-genome data using BIC-seq2 and its application to detection of cancer susceptibility variants.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Xi Ruibin",
				"Lee Semin",
				"Xia Yuchao",
				"Kim Tae-Min",
				"Park Peter J"
			],
			"DOI": "10.1093/nar/gkw491",
			"date": "2017-06-13",
			"PMC": "",
			"citation": "",
			"abstract": "Whole-genome sequencing data allow detection of copy number variation (CNV) at high resolution. However, estimation based on read coverage along the genome suffers from bias due to GC content and other factors. Here, we develop an algorithm called BIC-seq2 that combines normalization of the data at the nucleotide level and Bayesian information criterion-based segmentation to detect both somatic and germline CNVs accurately. Analysis of simulation data showed that this method outperforms existing methods. We apply this algorithm to low coverage whole-genome sequencing data from peripheral blood of nearly a thousand patients across eleven cancer types in The Cancer Genome Atlas (TCGA) to identify cancer-predisposing CNV regions. We confirm known regions and discover new ones including those covering KMT2C, GOLPH3, ERBB2 and PLAG1 Analysis of colorectal cancer genomes in particular reveals novel recurrent CNVs including deletions at two chromatin-remodeling genes RERE and NPM2 This method will be useful to many researchers interested in profiling CNVs from whole-genome sequencing data.",
			"category": 2,
			"name": "Xi Ruibin,2017"
		},
		{
			"PMID": 27258260,
			"title": "DNA Damage and Repair in Schizophrenia and Autism: Implications for Cancer Comorbidity and Beyond.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Markkanen Enni",
				"Meyer Urs",
				"Dianov Grigory L"
			],
			"DOI": "10.3390/ijms17060856",
			"date": "2017-03-23",
			"PMC": "",
			"citation": "",
			"abstract": "Schizophrenia and autism spectrum disorder (ASD) are multi-factorial and multi-symptomatic psychiatric disorders, each affecting 0.5%-1% of the population worldwide. Both are characterized by impairments in cognitive functions, emotions and behaviour, and they undermine basic human processes of perception and judgment. Despite decades of extensive research, the aetiologies of schizophrenia and ASD are still poorly understood and remain a significant challenge to clinicians and scientists alike. Adding to this unsatisfactory situation, patients with schizophrenia or ASD often develop a variety of peripheral and systemic disturbances, one prominent example of which is cancer, which shows a direct (but sometimes inverse) comorbidity in people affected with schizophrenia and ASD. Cancer is a disease characterized by uncontrolled proliferation of cells, the molecular origin of which derives from mutations of a cell's DNA sequence. To counteract such mutations and repair damaged DNA, cells are equipped with intricate DNA repair pathways. Oxidative stress, oxidative DNA damage, and deficient repair of oxidative DNA lesions repair have been proposed to contribute to the development of schizophrenia and ASD. In this article, we summarize the current evidence of cancer comorbidity in these brain disorders and discuss the putative roles of oxidative stress, DNA damage and DNA repair in the aetiopathology of schizophrenia and ASD.",
			"category": 2,
			"name": "Markkanen Enni,2017"
		},
		{
			"PMID": 27247954,
			"title": "Capture-based next-generation sequencing reveals multiple actionable mutations in cancer patients failed in traditional testing.",
			"journal": "Molecular genetics & genomic medicine",
			"authorList": [
				"Xie Jing",
				"Lu Xiongxiong",
				"Wu Xue",
				"Lin Xiaoyi",
				"Zhang Chao",
				"Huang Xiaofang",
				"Chang Zhili",
				"Wang Xinjing",
				"Wen Chenlei",
				"Tang Xiaomei",
				"Shi Minmin",
				"Zhan Qian",
				"Chen Hao",
				"Deng Xiaxing",
				"Peng Chenghong",
				"Li Hongwei",
				"Fang Yuan",
				"Shao Yang",
				"Shen Baiyong"
			],
			"DOI": "10.1002/mgg3.201",
			"date": "2016-06-01",
			"PMC": "",
			"citation": "",
			"abstract": "Targeted therapies including monoclonal antibodies and small molecule inhibitors have dramatically changed the treatment of cancer over past 10\u00a0years. Their therapeutic advantages are more tumor specific and with less side effects. For precisely tailoring available targeted therapies to each individual or a subset of cancer patients, next-generation sequencing (NGS) has been utilized as a promising diagnosis tool with its advantages of accuracy, sensitivity, and high throughput.",
			"category": 2,
			"name": "Xie Jing,2016"
		},
		{
			"PMID": 27240214,
			"title": "Systems medicine in colorectal cancer: from a mathematical model toward a new type of clinical trial.",
			"journal": "Wiley interdisciplinary reviews. Systems biology and medicine",
			"authorList": [
				"Castagnino Nicoletta",
				"Maffei Massimo",
				"Tortolina Lorenzo",
				"Zoppoli Gabriele",
				"Piras Daniela",
				"Nencioni Alessio",
				"Moran Eva",
				"Ballestrero Alberto",
				"Patrone Franco",
				"Parodi Silvio"
			],
			"DOI": "10.1002/wsbm.1342",
			"date": "2017-11-13",
			"PMC": "",
			"citation": "",
			"abstract": "Current colorectal cancer (CRC) treatment guidelines are primarily based on clinical features, such as cancer stage and grade. However, outcomes may be improved using molecular treatment guidelines. Potentially useful biomarkers include driver mutations and somatically inherited alterations, signaling proteins (their expression levels and (post) translational modifications), mRNAs, micro-RNAs and long noncoding RNAs. Moving to an integrated system is potentially very relevant. To implement such an integrated system: we focus on an important region of the signaling network, immediately above the G1-S restriction point, and discuss the reconstruction of a Molecular Interaction Map and interrogating it with a dynamic mathematical model. Extensive model pretraining achieved satisfactory, validated, performance. The model helps to propose future target combination priorities, and restricts drastically the number of drugs to be finally tested at a cellular, in vivo, and clinical-trial level. Our model allows for the inclusion of the unique molecular profiles of each individual patient's tumor. While existing clinical guidelines are well established, dynamic modeling may be used for future targeted combination therapies, which may progressively become part of clinical practice within the near future. WIREs Syst Biol Med 2016, 8:314-336. doi: 10.1002/wsbm.1342 For further resources related to this article, please visit the WIREs website.",
			"category": 2,
			"name": "Castagnino Nicoletta,2017"
		},
		{
			"PMID": 27235476,
			"title": "Oncogenic Mutant p53 Gain of Function Nourishes the Vicious Cycle of Tumor Development and Cancer Stem-Cell Formation.",
			"journal": "Cold Spring Harbor perspectives in medicine",
			"authorList": [
				"Shetzer Yoav",
				"Molchadsky Alina",
				"Rotter Varda"
			],
			"DOI": "10.1101/cshperspect.a026203",
			"date": "2017-12-26",
			"PMC": "",
			"citation": "",
			"abstract": "More than half of human tumors harbor an inactivated p53 tumor-suppressor gene. It is well accepted that mutant p53 shows an oncogenic gain-of-function (GOF) activity that facilitates the transformed phenotype of cancer cells. In addition, a growing body of evidence supports the notion that cancer stem cells comprise a seminal constituent in the initiation and progression of cancer development. Here, we elaborate on the mutant p53 oncogenic GOF leading toward the acquisition of a transformed phenotype, as well as placing mutant p53 as a major component in the establishment of cancer stem cell entity. Therefore, therapy targeted toward cancer stem cells harboring mutant p53 is expected to pave the way to eradicate tumor growth and recurrence.",
			"category": 2,
			"name": "Shetzer Yoav,2017"
		},
		{
			"PMID": 27234388,
			"title": "Oncogenic driver mutations in lung cancer.",
			"journal": "Translational respiratory medicine",
			"authorList": [
				"Luo Susan Y",
				"Lam David Cl"
			],
			"DOI": "10.1186/2213-0802-1-6",
			"date": "2016-05-28",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer is a heterogeneous and complex disease. Genomic and transcriptomic profiling of lung cancer not only further our knowledge about cancer initiation and progression, but could also provide guidance on treatment decisions. The fact that targeted treatment is most successful in a subset of tumors indicates the need for better classification of clinically related molecular tumor phenotypes based on better understanding of the mutations in relevant genes, especially in those oncogenic driver mutations. EGFR gene mutations, KRAS gene mutations, EML4-ALK rearrangements and altered MET signaling are widely recognized alterations that play important roles in both the biological mechanisms and the clinical sensitivity to treatment in lung cancer. In this article, we reviewed the discovery of the clinical values of these oncogenic driver mutations and the clinical studies revealing the prognostic and predictive values of these biomarkers for clinical sensitivity and resistance to anti-EGFR therapy or other targeted therapies. These form the basis of personalized treatment in lung cancer based on biomarker profiles of individual tumor, leading to therapeutic advancement and betterment.",
			"category": 2,
			"name": "Luo Susan Y,2016"
		},
		{
			"PMID": 27224236,
			"title": "Randomness in Sequence Evolution Increases over Time.",
			"journal": "PloS one",
			"authorList": [
				"Wang Guangyu",
				"Sun Shixiang",
				"Zhang Zhang"
			],
			"DOI": "10.1371/journal.pone.0155935",
			"date": "2017-07-06",
			"PMC": "",
			"citation": "",
			"abstract": "The second law of thermodynamics states that entropy, as a measure of randomness in a system, increases over time. Although studies have investigated biological sequence randomness from different aspects, it remains unknown whether sequence randomness changes over time and whether this change consists with the second law of thermodynamics. To capture the dynamics of randomness in molecular sequence evolution, here we detect sequence randomness based on a collection of eight statistical random tests and investigate the randomness variation of coding sequences with an application to Escherichia coli. Given that core/essential genes are more ancient than specific/non-essential genes, our results clearly show that core/essential genes are more random than specific/non-essential genes and accordingly indicate that sequence randomness indeed increases over time, consistent well with the second law of thermodynamics. We further find that an increase in sequence randomness leads to increasing randomness of GC content and longer sequence length. Taken together, our study presents an important finding, for the first time, that sequence randomness increases over time, which may provide profound insights for unveiling the underlying mechanisms of molecular sequence evolution.",
			"category": 2,
			"name": "Wang Guangyu,2017"
		},
		{
			"PMID": 27220640,
			"title": "Introducing STRaNDs: shuttling transcriptional regulators that are non-DNA binding.",
			"journal": "Nature reviews. Molecular cell biology",
			"authorList": [
				"Lu Min",
				"Muers Mary R",
				"Lu Xin"
			],
			"DOI": "10.1038/nrm.2016.41",
			"date": "2017-05-23",
			"PMC": "",
			"citation": "",
			"abstract": "Many proteins originally identified as cytoplasmic - including many associated with the cytoskeleton or cell junctions - are increasingly being found in the nucleus, where they have specific functions. Here, we focus on proteins that translocate from the cytoplasm to the nucleus in response to external signals and regulate transcription without binding to DNA directly (for example, through interaction with transcription factors). We propose that proteins with such characteristics are classified as a distinct group of extracellular signalling effectors, and we suggest the term STRaND (shuttling transcriptional regulators and non-DNA binding) to refer to this group. Crucial roles of STRaNDs include linking cell morphology and adhesion with changes in transcriptional programmes in response to signals such as mechanical stresses.",
			"category": 2,
			"name": "Lu Min,2017"
		},
		{
			"PMID": 27198694,
			"title": "Reconstruction of gene regulatory networks reveals chromatin remodelers and key transcription factors in tumorigenesis.",
			"journal": "Genome medicine",
			"authorList": [
				"Malysheva Valeriya",
				"Mendoza-Parra Marco Antonio",
				"Saleem Mohamed-Ashick M",
				"Gronemeyer Hinrich"
			],
			"DOI": "10.1186/s13073-016-0310-3",
			"date": "2017-02-24",
			"PMC": "",
			"citation": "",
			"abstract": "Alterations in genetic and epigenetic landscapes are known to contribute to the development of different types of cancer. However, the mechanistic links between transcription factors and the epigenome which coordinate the deregulation of gene networks during cell transformation are largely unknown.",
			"category": 2,
			"name": "Malysheva Valeriya,2017"
		},
		{
			"PMID": 27185408,
			"title": "Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer.",
			"journal": "eLife",
			"authorList": [
				"Strakova Andrea",
				"N\u00ed Leathlobhair M\u00e1ire",
				"Wang Guo-Dong",
				"Yin Ting-Ting",
				"Airikkala-Otter Ilona",
				"Allen Janice L",
				"Allum Karen M",
				"Bansse-Issa Leontine",
				"Bisson Jocelyn L",
				"Castillo Domracheva Artemio",
				"de Castro Karina F",
				"Corrigan Anne M",
				"Cran Hugh R",
				"Crawford Jane T",
				"Cutter Stephen M",
				"Delgadillo Keenan Laura",
				"Donelan Edward M",
				"Faramade Ibikunle A",
				"Flores Reynoso Erika",
				"Fotopoulou Eleni",
				"Fruean Skye N",
				"Gallardo-Arrieta Fanny",
				"Glebova Olga",
				"H\u00e4felin Manrique Rodrigo F",
				"Henriques Joaquim Jgp",
				"Ignatenko Natalia",
				"Koenig Debbie",
				"Lanza-Perea Marta",
				"Lobetti Remo",
				"Lopez Quintana Adriana M",
				"Losfelt Thibault",
				"Marino Gabriele",
				"Martincorena Inigo",
				"Mart\u00ednez Casta\u00f1eda Sim\u00f3n",
				"Mart\u00ednez-L\u00f3pez Mayra F",
				"Meyer Michael",
				"Nakanwagi Berna",
				"De Nardi Andrigo B",
				"Neunzig Winifred",
				"Nixon Sally J",
				"Onsare Marsden M",
				"Ortega-Pacheco Antonio",
				"Peleteiro Maria C",
				"Pye Ruth J",
				"Reece John F",
				"Rojas Gutierrez Jose",
				"Sadia Haleema",
				"Schmeling Sheila K",
				"Shamanova Olga",
				"Ssuna Richard K",
				"Steenland-Smit Audrey E",
				"Svitich Alla",
				"Thoya Ngoka Ismail",
				"Vi\u021b\u0103laru Bogdan A",
				"de Vos Anna P",
				"de Vos Johan P",
				"Walkinton Oliver",
				"Wedge David C",
				"Wehrle-Martinez Alvaro S",
				"van der Wel Mirjam G",
				"Widdowson Sophie Ae",
				"Murchison Elizabeth P"
			],
			"DOI": "10.7554/eLife.14552",
			"date": "2017-11-13",
			"PMC": "",
			"citation": "",
			"abstract": "Canine transmissible venereal tumour (CTVT) is a clonally transmissible cancer that originated approximately 11,000 years ago and affects dogs worldwide. Despite the clonal origin of the CTVT nuclear genome, CTVT mitochondrial genomes (mtDNAs) have been acquired by periodic capture from transient hosts. We sequenced 449 complete mtDNAs from a global population of CTVTs, and show that mtDNA horizontal transfer has occurred at least five times, delineating five tumour clades whose distributions track two millennia of dog global migration. Negative selection has operated to prevent accumulation of deleterious mutations in captured mtDNA, and recombination has caused occasional mtDNA re-assortment. These findings implicate functional mtDNA as a driver of CTVT global metastatic spread, further highlighting the important role of mtDNA in cancer evolution.",
			"category": 2,
			"name": "Strakova Andrea,2017"
		},
		{
			"PMID": 27150584,
			"title": "Systematic analysis of somatic mutations driving cancer: uncovering functional protein regions in disease development.",
			"journal": "Biology direct",
			"authorList": [
				"M\u00e9sz\u00e1ros B\u00e1lint",
				"Zeke Andr\u00e1s",
				"Rem\u00e9nyi Attila",
				"Simon Istv\u00e1n",
				"Doszt\u00e1nyi Zsuzsanna"
			],
			"DOI": "10.1186/s13062-016-0125-6",
			"date": "2017-12-13",
			"PMC": "",
			"citation": "",
			"abstract": "Recent advances in sequencing technologies enable the large-scale identification of genes that are affected by various genetic alterations in cancer. However, understanding tumor development requires insights into how these changes cause altered protein function and impaired network regulation in general and/or in specific cancer types.",
			"category": 2,
			"name": "M\u00e9sz\u00e1ros B\u00e1lint,2017"
		},
		{
			"PMID": 27147599,
			"title": "Systematic Functional Interrogation of Rare Cancer Variants Identifies Oncogenic Alleles.",
			"journal": "Cancer discovery",
			"authorList": [
				"Kim Eejung",
				"Ilic Nina",
				"Shrestha Yashaswi",
				"Zou Lihua",
				"Kamburov Atanas",
				"Zhu Cong",
				"Yang Xiaoping",
				"Lubonja Rakela",
				"Tran Nancy",
				"Nguyen Cindy",
				"Lawrence Michael S",
				"Piccioni Federica",
				"Bagul Mukta",
				"Doench John G",
				"Chouinard Candace R",
				"Wu Xiaoyun",
				"Hogstrom Larson",
				"Natoli Ted",
				"Tamayo Pablo",
				"Horn Heiko",
				"Corsello Steven M",
				"Lage Kasper",
				"Root David E",
				"Subramanian Aravind",
				"Golub Todd R",
				"Getz Gad",
				"Boehm Jesse S",
				"Hahn William C"
			],
			"DOI": "10.1158/2159-8290.CD-16-0160",
			"date": "2017-11-03",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer genome characterization efforts now provide an initial view of the somatic alterations in primary tumors. However, most point mutations occur at low frequency, and the function of these alleles remains undefined. We have developed a scalable systematic approach to interrogate the function of cancer-associated gene variants. We subjected 474 mutant alleles curated from 5,338 tumors to pooled in vivo tumor formation assays and gene expression profiling. We identified 12 transforming alleles, including two in genes (PIK3CB, POT1) that have not been shown to be tumorigenic. One rare KRAS allele, D33E, displayed tumorigenicity and constitutive activation of known RAS effector pathways. By comparing gene expression changes induced upon expression of wild-type and mutant alleles, we inferred the activity of specific alleles. Because alleles found to be mutated only once in 5,338 tumors rendered cells tumorigenic, these observations underscore the value of integrating genomic information with functional studies.",
			"category": 2,
			"name": "Kim Eejung,2017"
		},
		{
			"PMID": 27138791,
			"title": "Surrogate Markers: Lessons from the Next Gen?",
			"journal": "Cancer prevention research (Philadelphia, Pa.)",
			"authorList": [
				"Reid Brian J"
			],
			"DOI": "10.1158/1940-6207.CAPR-16-0059",
			"date": "2019-05-30",
			"PMC": "",
			"citation": "",
			"abstract": "The article by Banerjee and colleagues published in this issue of the journal involving a randomized control prevention trial of ursodeoxycholic acid (UDCA) in Barrett esophagus reported a null outcome despite being well designed and executed. Possible reasons for this null outcome are discussed focusing on use of surrogate endpoints in the trial. The trial is especially topical because it comes at a time when there are calls for a Pre-Cancer Genome Atlas (PCGA) for \"understanding the earliest molecular and cellular events associated with cancer initiation\u2026\" This commentary discusses current concepts in prevention research including branched evolution that leads to therapeutic resistance. Length bias sampling postulates underdiagnosis is due to rapidly progressing disease that is difficult to detect by screening because it progresses to cancer too rapidly and that overdiagnosis is the result of very slowly or nonprogressing disease that is easy to detect by screening because it persists for a lifetime and the patient dies of unrelated causes. Finally, it also explores study designs, including surrogate endpoints in Barrett esophagus trials, and opportunities and pitfalls for a PCGA in the context of high levels of over and underdiagnosis of Barrett esophagus as well as many other cancers and their precursors. Cancer Prev Res; 9(7); 512-7. \u00a92016 AACRSee related article by Banerjee, et al., p. 528.",
			"category": 2,
			"name": "Reid Brian J,2019"
		},
		{
			"PMID": 27135926,
			"title": "Landscape of somatic mutations in 560 breast cancer whole-genome sequences.",
			"journal": "Nature",
			"authorList": [
				"Nik-Zainal Serena",
				"Davies Helen",
				"Staaf Johan",
				"Ramakrishna Manasa",
				"Glodzik Dominik",
				"Zou Xueqing",
				"Martincorena Inigo",
				"Alexandrov Ludmil B",
				"Martin Sancha",
				"Wedge David C",
				"Van Loo Peter",
				"Ju Young Seok",
				"Smid Marcel",
				"Brinkman Arie B",
				"Morganella Sandro",
				"Aure Miriam R",
				"Lingj\u00e6rde Ole Christian",
				"Langer\u00f8d Anita",
				"Ringn\u00e9r Markus",
				"Ahn Sung-Min",
				"Boyault Sandrine",
				"Brock Jane E",
				"Broeks Annegien",
				"Butler Adam",
				"Desmedt Christine",
				"Dirix Luc",
				"Dronov Serge",
				"Fatima Aquila",
				"Foekens John A",
				"Gerstung Moritz",
				"Hooijer Gerrit K J",
				"Jang Se Jin",
				"Jones David R",
				"Kim Hyung-Yong",
				"King Tari A",
				"Krishnamurthy Savitri",
				"Lee Hee Jin",
				"Lee Jeong-Yeon",
				"Li Yilong",
				"McLaren Stuart",
				"Menzies Andrew",
				"Mustonen Ville",
				"O'Meara Sarah",
				"Pauport\u00e9 Iris",
				"Pivot Xavier",
				"Purdie Colin A",
				"Raine Keiran",
				"Ramakrishnan Kamna",
				"Rodr\u00edguez-Gonz\u00e1lez F Germ\u00e1n",
				"Romieu Gilles",
				"Sieuwerts Anieta M",
				"Simpson Peter T",
				"Shepherd Rebecca",
				"Stebbings Lucy",
				"Stefansson Olafur A",
				"Teague Jon",
				"Tommasi Stefania",
				"Treilleux Isabelle",
				"Van den Eynden Gert G",
				"Vermeulen Peter",
				"Vincent-Salomon Anne",
				"Yates Lucy",
				"Caldas Carlos",
				"van't Veer Laura",
				"Tutt Andrew",
				"Knappskog Stian",
				"Tan Benita Kiat Tee",
				"Jonkers Jos",
				"Borg \u00c5ke",
				"Ueno Naoto T",
				"Sotiriou Christos",
				"Viari Alain",
				"Futreal P Andrew",
				"Campbell Peter J",
				"Span Paul N",
				"Van Laere Steven",
				"Lakhani Sunil R",
				"Eyfjord Jorunn E",
				"Thompson Alastair M",
				"Birney Ewan",
				"Stunnenberg Hendrik G",
				"van de Vijver Marc J",
				"Martens John W M",
				"B\u00f8rresen-Dale Anne-Lise",
				"Richardson Andrea L",
				"Kong Gu",
				"Thomas Gilles",
				"Stratton Michael R"
			],
			"DOI": "10.1038/nature17676",
			"date": "2016-06-28",
			"PMC": "",
			"citation": "",
			"abstract": "We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.",
			"category": 2,
			"name": "Nik-Zainal Serena,2016"
		},
		{
			"PMID": 27131784,
			"title": "ICM: a web server for integrated clustering of multi-dimensional biomedical data.",
			"journal": "Nucleic acids research",
			"authorList": [
				"He Song",
				"He Haochen",
				"Xu Wenjian",
				"Huang Xin",
				"Jiang Shuai",
				"Li Fei",
				"He Fuchu",
				"Bo Xiaochen"
			],
			"DOI": "10.1093/nar/gkw378",
			"date": "2017-06-07",
			"PMC": "",
			"citation": "",
			"abstract": "Large-scale efforts for parallel acquisition of multi-omics profiling continue to generate extensive amounts of multi-dimensional biomedical data. Thus, integrated clustering of multiple types of omics data is essential for developing individual-based treatments and precision medicine. However, while rapid progress has been made, methods for integrated clustering are lacking an intuitive web interface that facilitates the biomedical researchers without sufficient programming skills. Here, we present a web tool, named Integrated Clustering of Multi-dimensional biomedical data (ICM), that provides an interface from which to fuse, cluster and visualize multi-dimensional biomedical data and knowledge. With ICM, users can explore the heterogeneity of a disease or a biological process by identifying subgroups of patients. The results obtained can then be interactively modified by using an intuitive user interface. Researchers can also exchange the results from ICM with collaborators via a web link containing a Project ID number that will directly pull up the analysis results being shared. ICM also support incremental clustering that allows users to add new sample data into the data of a previous study to obtain a clustering result. Currently, the ICM web server is available with no login requirement and at no cost at http://biotech.bmi.ac.cn/icm/.",
			"category": 2,
			"name": "He Song,2017"
		},
		{
			"PMID": 27129147,
			"title": "Synonymous mutations in oncogenesis and apoptosis versus survival unveiled by network modeling.",
			"journal": "Oncotarget",
			"authorList": [
				"Li Xiang",
				"Chen Yuan",
				"Qi Hong",
				"Liu Liyu",
				"Shuai Jianwei"
			],
			"DOI": "10.18632/oncotarget.8963",
			"date": "2017-12-29",
			"PMC": "",
			"citation": "",
			"abstract": "Synonymous mutations, which do not alter the encoded amino acid, have been routinely assumed to be 'neutral' and would have no effect on phenotype or fitness. Yet increasing observations have emerged to overturn this conventional concept. However, convicted elucidation of how synonymous mutations exert biological consequences in oncogenesis is still lacking. By performing systematic analysis of the TNF-\u03b1 signaling network model, we identify the critical dose which separates the cell survival and apoptosis regions and define the sensitive parameters with single-parameter sensitivity analysis. Combining with the cancer-related mutation spectra obtained from 9 cancers, our results hint that, similar as missense and nonsense mutations, synonymous mutations are also strongly correlated with the parameter sensitivity of the critical dose, providing possible causal mechanism of the mutations in cancer development. Based on such a correlation, we furthermore dissect that members of caspases family proteases (caspase3, 6, 8) could jointly inhibit NF\u03baB activation, providing efficient pro-apoptotic behavior. Thus, we argue that apoptosis module could suppress survival module through negative feedback of caspases family on NF\u03baB.",
			"category": 2,
			"name": "Li Xiang,2017"
		},
		{
			"PMID": 27114748,
			"title": "Retinoblastoma tumor suppressor functions shared by stem cell and cancer cell strategies.",
			"journal": "World journal of stem cells",
			"authorList": [
				"Kohno Susumu",
				"Kitajima Shunsuke",
				"Sasaki Nobunari",
				"Takahashi Chiaki"
			],
			"DOI": "10.4252/wjsc.v8.i4.170",
			"date": "2016-04-26",
			"PMC": "",
			"citation": "",
			"abstract": "Carcinogenic transformation of somatic cells resembles nuclear reprogramming toward the generation of pluripotent stem cells. These events share eternal escape from cellular senescence, continuous self-renewal in limited but certain population of cells, and refractoriness to terminal differentiation while maintaining the potential to differentiate into cells of one or multiple lineages. As represented by several oncogenes those appeared to be first keys to pluripotency, carcinogenesis and nuclear reprogramming seem to share a number of core mechanisms. The retinoblastoma tumor suppressor product retinoblastoma (RB) seems to be critically involved in both events in highly complicated manners. However, disentangling such complicated interactions has enabled us to better understand how stem cell strategies are shared by cancer cells. This review covers recent findings on RB functions related to stem cells and stem cell-like behaviors of cancer cells.",
			"category": 2,
			"name": "Kohno Susumu,2016"
		},
		{
			"PMID": 27112209,
			"title": "Defining actionable mutations for oncology therapeutic development.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Carr T Hedley",
				"McEwen Robert",
				"Dougherty Brian",
				"Johnson Justin H",
				"Dry Jonathan R",
				"Lai Zhongwu",
				"Ghazoui Zara",
				"Laing Naomi M",
				"Hodgson Darren R",
				"Cruzalegui Francisco",
				"Hollingsworth Simon J",
				"Barrett J Carl"
			],
			"DOI": "10.1038/nrc.2016.35",
			"date": "2017-05-31",
			"PMC": "",
			"citation": "",
			"abstract": "Genomic profiling of tumours in patients in clinical trials enables rapid testing of multiple hypotheses to confirm which genomic events determine likely responder groups for targeted agents. A key challenge of this new capability is defining which specific genomic events should be classified as 'actionable' (that is, potentially responsive to a targeted therapy), especially when looking for early indications of patient subgroups likely to be responsive to new drugs. This Opinion article discusses some of the different approaches being taken in early clinical development to define actionable mutations, and describes our strategy to address this challenge in early-stage exploratory clinical trials.",
			"category": 2,
			"name": "Carr T Hedley,2017"
		},
		{
			"PMID": 27100181,
			"title": "Mutational Profiles Reveal an Aberrant TGF-\u03b2-CEA Regulated Pathway in Colon Adenomas.",
			"journal": "PloS one",
			"authorList": [
				"Chen Jian",
				"Raju Gottumukkala S",
				"Jogunoori Wilma",
				"Menon Vipin",
				"Majumdar Avijit",
				"Chen Jiun-Sheng",
				"Gi Young Jin",
				"Jeong Yun Seong",
				"Phan Liem",
				"Belkin Mitchell",
				"Gu Shoujun",
				"Kundra Suchin",
				"Mistry Nipun A",
				"Zhang Jianping",
				"Su Xiaoping",
				"Li Shulin",
				"Lin Sue-Hwa",
				"Javle Milind",
				"McMurray John S",
				"Rahlfs Thomas F",
				"Mishra Bibhuti",
				"White Jon",
				"Rashid Asif",
				"Beauchemin Nicole",
				"Weston Brian R",
				"Shafi Mehnaz A",
				"Stroehlein John R",
				"Davila Marta",
				"Akbani Rehan",
				"Weinstein John N",
				"Wu Xifeng",
				"Mishra Lopa"
			],
			"DOI": "10.1371/journal.pone.0153933",
			"date": "2016-09-13",
			"PMC": "",
			"citation": "",
			"abstract": "Mutational processes and signatures that drive early tumorigenesis are centrally important for early cancer prevention. Yet, to date, biomarkers and risk factors for polyps (adenomas) that inordinately and rapidly develop into colon cancer remain poorly defined. Here, we describe surprisingly high mutational profiles through whole-genome sequence (WGS) analysis in 2 of 4 pairs of benign colorectal adenoma tissue samples. Unsupervised hierarchical clustered transcriptomic analysis of a further 7 pairs of adenomas reveals distinct mutational signatures regardless of adenoma size. Transitional single nucleotide substitutions of C:G>T:A predominate in the adenoma mutational spectrum. Strikingly, we observe mutations in the TGF-\u03b2 pathway and CEA-associated genes in 4 out of 11 adenomas, overlapping with the Wnt pathway. Immunohistochemical labeling reveals a nearly 5-fold increase in CEA levels in 23% of adenoma samples with a concomitant loss of TGF-\u03b2 signaling. We also define a functional role by which the CEA B3 domain interacts with TGFBR1, potentially inactivating the tumor suppressor function of TGF-\u03b2 signaling. Our study uncovers diverse mutational processes underlying the transition from early adenoma to cancer. This has broad implications for biomarker-driven targeting of CEA/TGF-\u03b2 in high-risk adenomas and may lead to early detection of aggressive adenoma to CRC progression.",
			"category": 2,
			"name": "Chen Jian,2016"
		},
		{
			"PMID": 27088132,
			"title": "Glioblastoma: Defining Tumor Niches.",
			"journal": "Trends in cancer",
			"authorList": [
				"Hambardzumyan Dolores",
				"Bergers Gabriele"
			],
			"DOI": "",
			"date": "2019-11-20",
			"PMC": "",
			"citation": "",
			"abstract": "Glioblastomas (GBM) are one of the most recalcitrant brain tumors because of their aggressive invasive growth and resistance to therapy. They are highly heterogeneous malignancies at both the molecular and histological levels. Specific histological hallmarks including pseudopalisading necrosis and microvascular proliferation distinguish GBM from lower-grade gliomas, and make GBM one of the most hypoxic as well as angiogenic tumors. These microanatomical compartments present specific niches within the tumor microenvironment that regulate metabolic needs, immune surveillance, survival, invasion as well as cancer stem cell maintenance. Here we review features and functions of the distinct GBM niches, detail the different cell constituents and the functional status of the vasculature, and discuss prospects of therapeutically targeting GBM niche constituents.",
			"category": 2,
			"name": "Hambardzumyan Dolores,2019"
		},
		{
			"PMID": 27081639,
			"title": "Estrogen receptor alpha gene amplification in breast cancer: 25 years of debate.",
			"journal": "World journal of clinical oncology",
			"authorList": [
				"Holst Frederik"
			],
			"DOI": "10.5306/wjco.v7.i2.160",
			"date": "2016-04-15",
			"PMC": "",
			"citation": "",
			"abstract": "Twenty-five years ago, Nembrot and colleagues reported amplification of the estrogen receptor alpha gene (ESR1) in breast cancer, initiating a broad and still ongoing scientific debate on the prevalence and clinical significance of this genetic aberration, which affects one of the most important genes in breast cancer. Since then, a multitude of studies on this topic has been published, covering a wide range of divergent results and arguments. The reported prevalence of this alteration in breast cancer ranges from 0% to 75%, suggesting that ESR1 copy number analysis is hampered by technical and interpreter issues. To date, two major issues related to ESR1 amplification remain to be conclusively addressed: (1) The extent to which abundant amounts of messenger RNA can mimic amplification in standard fluorescence in situ hybridization assays in the analysis of strongly expressed genes like ESR1, and (2) the clinical relevance of ESR1 amplification: Such relevance is strongly disputed, with data showing predictive value for response as well as for resistance of the cancer to anti-estrogen therapies, or for subsequent development of cancers in the case of precursor lesions that display amplification of ESR1. This review provides a comprehensive summary of the various views on ESR1 amplification, and highlights explanations for the contradictions and conflicting data that could inform future ESR1 research.",
			"category": 2,
			"name": "Holst Frederik,2016"
		},
		{
			"PMID": 27066794,
			"title": "Review: the Contribution of both Nature and Nurture to Carcinogenesis and Progression in Solid Tumours.",
			"journal": "Cancer microenvironment : official journal of the International Cancer Microenvironment Society",
			"authorList": [
				"Hyndman Iain Joseph"
			],
			"DOI": "10.1007/s12307-016-0183-4",
			"date": "2016-04-25",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a leading cause of mortality worldwide. Cancer arises due to a series of somatic mutations that accumulate within the nucleus of a cell which enable the cell to proliferate in an unregulated manner. These mutations arise as a result of both endogenous and exogenous factors. Genes that are commonly mutated in cancer cells are involved in cell cycle regulation, growth and proliferation. It is known that both nature and nurture play important roles in cancer development through complex gene-environment interactions; however, the exact mechanism of these interactions in carcinogenesis is presently unclear. Key environmental factors that play a role in carcinogenesis include smoking, UV light and oncoviruses. Angiogenesis, inflammation and altered cell metabolism are important factors in carcinogenesis and are influenced by both genetic and environmental factors. Although the exact mechanism of nature-nurture interactions in solid tumour formation are not yet fully understood, it is evident that neither nature nor nurture can be considered in isolation. By understanding more about gene-environment interactions, it is possible that cancer mortality could be reduced.",
			"category": 2,
			"name": "Hyndman Iain Joseph,2016"
		},
		{
			"PMID": 27059373,
			"title": "The Conundrum of Genetic \"Drivers\" in Benign Conditions.",
			"journal": "Journal of the National Cancer Institute",
			"authorList": [
				"Kato Shumei",
				"Lippman Scott M",
				"Flaherty Keith T",
				"Kurzrock Razelle"
			],
			"DOI": "10.1093/jnci/djw036",
			"date": "2017-07-07",
			"PMC": "",
			"citation": "",
			"abstract": "Advances in deep genomic sequencing have identified a spectrum of cancer-specific passenger and driver aberrations. Clones with driver anomalies are believed to be positively selected during carcinogenesis. Accumulating evidence, however, shows that genomic alterations, such as those inBRAF,RAS,EGFR,HER2,FGFR3,PIK3CA,TP53,CDKN2A, andNF1/2, all of which are considered hallmark drivers of specific cancers, can also be identified in benign and premalignant conditions, occasionally at frequencies higher than in their malignant counterparts. Targeting these genomic drivers can produce dramatic responses in advanced cancer, but the effects on their benign counterparts are less clear. This benign-malignant phenomenon is well illustrated in studies ofBRAFV600E mutations, which are paradoxically more frequent in benign nevi (\u223c80%) than in dysplastic nevi (\u223c60%) or melanoma (\u223c40%-45%). Similarly, human epidermal growth factor receptor 2 is more commonly overexpressed in ductal carcinoma in situ (\u223c27%-56%) when compared with invasive breast cancer (\u223c11%-20%).FGFR3mutations in bladder cancer also decrease with tumor grade (low-grade tumors, \u223c61%; high-grade, \u223c11%). \"Driver\" mutations also occur in nonmalignant settings:TP53mutations in synovial tissue from rheumatoid arthritis andFGFR3mutations in seborrheic keratosis. The latter observations suggest that the oncogenicity of these alterations may be tissue context-dependent. The conversion of benign conditions to premalignant disease may involve other genetic events and/or epigenetic reprogramming. Putative driver mutations can also be germline and associated with increased cancer risk (eg, germlineRASorTP53alterations), but germlineFGFR3orNF2abnormalities do not predispose to malignancy. We discuss the enigma of genetic \"drivers\" in benign and premalignant conditions and the implications for prevention strategies and theories of tumorigenesis.",
			"category": 2,
			"name": "Kato Shumei,2017"
		},
		{
			"PMID": 27054363,
			"title": "Mutational History of a Human Cell Lineage from Somatic to Induced Pluripotent Stem Cells.",
			"journal": "PLoS genetics",
			"authorList": [
				"Rouhani Foad J",
				"Nik-Zainal Serena",
				"Wuster Arthur",
				"Li Yilong",
				"Conte Nathalie",
				"Koike-Yusa Hiroko",
				"Kumasaka Natsuhiko",
				"Vallier Ludovic",
				"Yusa Kosuke",
				"Bradley Allan"
			],
			"DOI": "10.1371/journal.pgen.1005932",
			"date": "2016-08-26",
			"PMC": "",
			"citation": "",
			"abstract": "The accuracy of replicating the genetic code is fundamental. DNA repair mechanisms protect the fidelity of the genome ensuring a low error rate between generations. This sustains the similarity of individuals whilst providing a repertoire of variants for evolution. The mutation rate in the human genome has recently been measured to be 50-70 de novo single nucleotide variants (SNVs) between generations. During development mutations accumulate in somatic cells so that an organism is a mosaic. However, variation within a tissue and between tissues has not been analysed. By reprogramming somatic cells into induced pluripotent stem cells (iPSCs), their genomes and the associated mutational history are captured. By sequencing the genomes of polyclonal and monoclonal somatic cells and derived iPSCs we have determined the mutation rates and show how the patterns change from a somatic lineage in vivo through to iPSCs. Somatic cells have a mutation rate of 14 SNVs per cell per generation while iPSCs exhibited a ten-fold lower rate. Analyses of mutational signatures suggested that deamination of methylated cytosine may be the major mutagenic source in vivo, whilst oxidative DNA damage becomes dominant in vitro. Our results provide insights for better understanding of mutational processes and lineage relationships between human somatic cells. Furthermore it provides a foundation for interpretation of elevated mutation rates and patterns in cancer.",
			"category": 2,
			"name": "Rouhani Foad J,2016"
		},
		{
			"PMID": 27028857,
			"title": "Chronic inflammation-associated genomic instability paves the way for human esophageal carcinogenesis.",
			"journal": "Oncotarget",
			"authorList": [
				"Lin Runhua",
				"Zhang Chong",
				"Zheng Jiaxuan",
				"Tian Dongping",
				"Lei Zhijin",
				"Chen Donglin",
				"Xu Zexin",
				"Su Min"
			],
			"DOI": "10.18632/oncotarget.8356",
			"date": "2017-12-04",
			"PMC": "",
			"citation": "",
			"abstract": "Chronic inflammation is associated with increased risk of cancer development, whereas the link between chronic inflammation and esophageal carcinogenesis is still obscure heretofore. This study aimed to investigate the relationship between chronic inflammation and DNA damage, as well as the possible role of DNA damage in esophageal carcinogenic process. Endoscopic esophageal biopsies from 109 individuals from Chaoshan littoral, a high-risk region for esophageal squamous cell carcinoma (ESCC), were examined to evaluate the association between chronic inflammation and histological severity, while additional 204 esophageal non-tumor samples from patients with ESCC were collected. Immunohistochemistry was performed to detect the oxidative DNA damage and DNA double-strand breaks (DSBs). Significantly positive correlation was observed between degree of chronic inflammation and esophageal precursor lesions (rs = 0.37, P < 0.01). Immunohistochemical analysis showed that oxidative DNA damage level was positively correlated with the degree of chronic inflammation (rs = 0.21, P < 0.05). Moreover, the level of oxidative DNA damage positively correlated with histological severity (rs = 0.49, P < 0.01). We found that the extent of DSBs was progressively increased with inflammation degree (P < 0.01) and the progression of precancerous lesions (P < 0.001). Collectively, these findings provide evidence linking chronic inflammation-associated genomic instability with esophageal carcinogenesis and suggest possibilities for early detection and intervention of esophageal carcinogenesis.",
			"category": 2,
			"name": "Lin Runhua,2017"
		},
		{
			"PMID": 27009843,
			"title": "Analysis of ultra-deep targeted sequencing reveals mutation burden is associated with gender and clinical outcome in lung adenocarcinoma.",
			"journal": "Oncotarget",
			"authorList": [
				"Xiao Dakai",
				"Pan Hui",
				"Li Fuqiang",
				"Wu Kui",
				"Zhang Xin",
				"He Jianxing"
			],
			"DOI": "10.18632/oncotarget.8213",
			"date": "2017-12-12",
			"PMC": "",
			"citation": "",
			"abstract": "Gender-associated difference in incidence and clinical outcomes of lung cancer have been established, but the biological mechanisms underlying these gender-associated differences are less studied. Recently we have characterized the genomic landscape of lung adenocarcinoma derived from Chinese population (Reference [1]). In this study we evaluated the clinical significance of mutation burden in lung adenocarcinoma and found that the male tumors harbored statistically greater burden of genetic alterations than female counterparts (Male median 3 (range 0-34) vs female median = 2 (0-24), male to female ratio = 1.636, 95% CI = 1.343-1.992) after adjustment of age at surgery, stage, smoking status. Kaplan-Meier survival analysis revealed that greater burden of genetic alterations was associated with worse overall survival. Moreover, multivariable analysis demonstrated mutation burden was an independent prognostic factor for the patients. Taken together, our analysis demonstrated gender disparity of mutation burden and their prognostic value in lung adenocarcinoma. This gender difference in mutation burden might provide an explanation for the distinct difference in the clinical outcomes between sexes in lung adenocarcinoma.",
			"category": 2,
			"name": "Xiao Dakai,2017"
		},
		{
			"PMID": 27008846,
			"title": "CUSTOM-SEQ: a prototype for oncology rapid learning in a comprehensive EHR environment.",
			"journal": "Journal of the American Medical Informatics Association : JAMIA",
			"authorList": [
				"Warner Jeremy L",
				"Wang Lucy",
				"Pao William",
				"Sosman Jeffrey A",
				"Atreya Ravi V",
				"Carney Pam",
				"Levy Mia A"
			],
			"DOI": "10.1093/jamia/ocw008",
			"date": "2017-11-30",
			"PMC": "",
			"citation": "",
			"abstract": "As targeted cancer therapies and molecular profiling become widespread, the era of \"precision oncology\" is at hand. However, cancer genomes are complex, making mutation-specific outcomes difficult to track. We created a proof-of-principle, CUSTOM-SEQ: Continuously Updating System for Tracking Outcome by Mutation, to Support Evidence-based Querying, to automatically calculate and display mutation-specific survival statistics from electronic health record data.",
			"category": 2,
			"name": "Warner Jeremy L,2017"
		},
		{
			"PMID": 26992833,
			"title": "The dark matter of the cancer genome: aberrations in regulatory elements, untranslated regions, splice sites, non-coding RNA and synonymous mutations.",
			"journal": "EMBO molecular medicine",
			"authorList": [
				"Diederichs Sven",
				"Bartsch Lorenz",
				"Berkmann Julia C",
				"Fr\u00f6se Karin",
				"Heitmann Jana",
				"Hoppe Caroline",
				"Iggena Deetje",
				"Jazmati Danny",
				"Karschnia Philipp",
				"Linsenmeier Miriam",
				"Maulhardt Thomas",
				"M\u00f6hrmann Lino",
				"Morstein Johannes",
				"Paffenholz Stella V",
				"R\u00f6penack Paula",
				"R\u00fcckert Timo",
				"Sandig Ludger",
				"Schell Maximilian",
				"Steinmann Anna",
				"Voss Gjendine",
				"Wasmuth Jacqueline",
				"Weinberger Maria E",
				"Wullenkord Ramona"
			],
			"DOI": "10.15252/emmm.201506055",
			"date": "2017-09-13",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a disease of the genome caused by oncogene activation and tumor suppressor gene inhibition. Deep sequencing studies including large consortia such as TCGA and ICGC identified numerous tumor-specific mutations not only in protein-coding sequences but also in non-coding sequences. Although 98% of the genome is not translated into proteins, most studies have neglected the information hidden in this \"dark matter\" of the genome. Malignancy-driving mutations can occur in all genetic elements outside the coding region, namely in enhancer, silencer, insulator, and promoter as well as in 5'-UTR and 3'-UTR Intron or splice site mutations can alter the splicing pattern. Moreover, cancer genomes contain mutations within non-coding RNA, such as microRNA, lncRNA, and lincRNA A synonymous mutation changes the coding region in the DNA and RNA but not the protein sequence. Importantly, oncogenes such as TERT or miR-21 as well as tumor suppressor genes such as TP53/p53, APC, BRCA1, or RB1 can be affected by these alterations. In summary, coding-independent mutations can affect gene regulation from transcription, splicing, mRNA stability to translation, and hence, this largely neglected area needs functional studies to elucidate the mechanisms underlying tumorigenesis. This review will focus on the important role and novel mechanisms of these non-coding or allegedly silent mutations in tumorigenesis.",
			"category": 2,
			"name": "Diederichs Sven,2017"
		},
		{
			"PMID": 26992457,
			"title": "Dynamic changes of driver genes' mutations across clinical stages in nine cancer types.",
			"journal": "Cancer medicine",
			"authorList": [
				"Li Xia"
			],
			"DOI": "10.1002/cam4.704",
			"date": "2017-11-16",
			"PMC": "",
			"citation": "",
			"abstract": "The driver genes play critical roles for tumorigenesis, and the number of identified driver genes reached plateau. But how they act during different cancer development stages is lack of knowledge. We investigated 138 driver genes' mutation changes across clinical stages using 3,477 cases in nine cancer types from the Cancer Genome Atlas (TCGA) and constructed their temporal order relationships. We also examined the codon changes for the widely mutated TP53 and PIK3CA in tumor stages. Combinations of one to three driver genes specifically dominated in each cancer. Across the clinical stages, we categorized three patterns for the behaviors of driver genes' mutation changes in the nine cancer types: recurrently mutated in all the stages and triggering other mutations; certain mutations lost meanwhile other mutations emerged; mutations dominated across entire stages, while other mutations gradually appeared or disappeared. We observed different codon changes dominated in different stages and revealed mutations recurrently occurring on the hotspot regions of the coding sequence may be the core factor for driver genes' tumorigenesis. Our results highlighted the dynamic changes of oncogenesis roles in different clinical stages and suggested different diagnostic decision making according to the clinical stages of patients.",
			"category": 2,
			"name": "Li Xia,2017"
		},
		{
			"PMID": 26972558,
			"title": "Update on rational targeted therapy in AML.",
			"journal": "Blood reviews",
			"authorList": [
				"Shafer Danielle",
				"Grant Steven"
			],
			"DOI": "10.1016/j.blre.2016.02.001",
			"date": "2017-12-11",
			"PMC": "",
			"citation": "",
			"abstract": "Acute myeloid leukemia (AML) remains a challenge to both patients and clinicians. Despite improvements in our understanding of the disease, treatment has changed minimally and outcomes remain poor for the majority of patients. Within the last decade, there have been an increasing number of potential targets and pathways identified for development in AML. The classes of agents described in this review include but are not limited to epigenetic modifiers such as IDH inhibitors, BET inhibitors, and HDAC inhibitors as well as cell cycle and signaling inhibitors such as Aurora kinase inhibitors and CDK inhibitors. While the developments are encouraging, it is unlikely that targeting a single pathway will result in long-term disease control. Accordingly, we will also highlight potential rational partners for the novel agents described herein.",
			"category": 2,
			"name": "Shafer Danielle,2017"
		},
		{
			"PMID": 26949746,
			"title": "Cancer Evolution and the Limits of Predictability in Precision Cancer Medicine.",
			"journal": "Trends in cancer",
			"authorList": [
				"Lipinski Kamil A",
				"Barber Louise J",
				"Davies Matthew N",
				"Ashenden Matthew",
				"Sottoriva Andrea",
				"Gerlinger Marco"
			],
			"DOI": "10.1016/j.trecan.2015.11.003",
			"date": "2024-02-10",
			"PMC": "",
			"citation": "",
			"abstract": "The ability to predict the future behavior of an individual cancer is crucial for precision cancer medicine. The discovery of extensive intratumor heterogeneity and ongoing clonal adaptation in human tumors substantiated the notion of cancer as an evolutionary process. Random events are inherent in evolution and tumor spatial structures hinder the efficacy of selection, which is the only deterministic evolutionary force. This review outlines how the interaction of these stochastic and deterministic processes, which have been extensively studied in evolutionary biology, limits cancer predictability and develops evolutionary strategies to improve predictions. Understanding and advancing the cancer predictability horizon is crucial to improve precision medicine outcomes.",
			"category": 2,
			"name": "Lipinski Kamil A,2024"
		},
		{
			"PMID": 26942671,
			"title": "Mitochondria and Cancer.",
			"journal": "Molecular cell",
			"authorList": [
				"Zong Wei-Xing",
				"Rabinowitz Joshua D",
				"White Eileen"
			],
			"DOI": "10.1016/j.molcel.2016.02.011",
			"date": "2016-07-25",
			"PMC": "",
			"citation": "",
			"abstract": "Decades ago, Otto Warburg observed that cancers ferment glucose in the presence of oxygen, suggesting that defects in mitochondrial respiration may be the underlying cause of cancer. We now know that the genetic events that drive aberrant cancer cell proliferation also alter biochemical metabolism, including promoting aerobic glycolysis, but do not typically impair mitochondrial function. Mitochondria supply energy; provide building blocks for new cells; and control redox homeostasis, oncogenic signaling, innate immunity, and apoptosis. Indeed, mitochondrial biogenesis and quality control are often upregulated in cancers. While some cancers have mutations in nuclear-encoded mitochondrial tricarboxylic acid (TCA) cycle enzymes that produce oncogenic metabolites, there is negative selection for pathogenic mitochondrial genome mutations. Eliminating mtDNA limits tumorigenesis, and rare human tumors with mutant mitochondrial genomes are relatively benign. Thus, mitochondria play a central and multifunctional role in malignant tumor progression, and targeting mitochondria provides therapeutic opportunities.",
			"category": 2,
			"name": "Zong Wei-Xing,2016"
		},
		{
			"PMID": 26932841,
			"title": "Limitations of the Driver/Passenger Model in Cancer Prevention.",
			"journal": "Cancer prevention research (Philadelphia, Pa.)",
			"authorList": [
				"Kuhner Mary K",
				"Kostadinov Rumen",
				"Reid Brian J"
			],
			"DOI": "10.1158/1940-6207.CAPR-15-0343",
			"date": "2017-04-27",
			"PMC": "",
			"citation": "",
			"abstract": "Mutations detected in cancers are often divided into \"drivers\" and \"passengers.\" We suggest that this classification is potentially misleading for purposes of early detection and prevention. Specifically, some mutations are frequent in tumors and thus appear to be drivers, but are poor predictors of cancer; other mutations are individually rare and thus appear to be passengers, but may collectively explain a large proportion of risk. The assumptions bundled into the terms \"driver\" and \"passenger\" can lead to misunderstandings of neoplastic progression, with unintended consequences including overdiagnosis, overtreatment, and failure to identify the true sources of risk. We argue that samples from healthy, benign, or neoplastic tissues are critical for evaluating the risk of future cancer posed by mutations in a given gene. Cancer Prev Res; 9(5); 335-8. \u00a92016 AACR.",
			"category": 2,
			"name": "Kuhner Mary K,2017"
		},
		{
			"PMID": 26925973,
			"title": "Clinical application of genomic profiling to find druggable targets for adolescent and young adult (AYA) cancer patients with metastasis.",
			"journal": "BMC cancer",
			"authorList": [
				"Cha Soojin",
				"Lee Jeongeun",
				"Shin Jong-Yeon",
				"Kim Ji-Yeon",
				"Sim Sung Hoon",
				"Keam Bhumsuk",
				"Kim Tae Min",
				"Kim Dong-Wan",
				"Heo Dae Seog",
				"Lee Se-Hoon",
				"Kim Jong-Il"
			],
			"DOI": "10.1186/s12885-016-2209-1",
			"date": "2016-12-13",
			"PMC": "",
			"citation": "",
			"abstract": "Although adolescent and young adult (AYA) cancers are characterized by biological features and clinical outcomes distinct from those of other age groups, the molecular profile of AYA cancers has not been well defined. In this study, we analyzed cancer genomes from rare types of metastatic AYA cancers to identify driving and/or druggable genetic alterations.",
			"category": 2,
			"name": "Cha Soojin,2016"
		},
		{
			"PMID": 26920143,
			"title": "Analysis of functional germline variants in APOBEC3 and driver genes on breast cancer risk in Moroccan study population.",
			"journal": "BMC cancer",
			"authorList": [
				"Marouf Chaymaa",
				"G\u00f6hler Stella",
				"Filho Miguel Inacio Da Silva",
				"Hajji Omar",
				"Hemminki Kari",
				"Nadifi Sellama",
				"F\u00f6rsti Asta"
			],
			"DOI": "10.1186/s12885-016-2210-8",
			"date": "2016-12-13",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer (BC) is the most prevalent cancer in women and a major public health problem in Morocco. Several Moroccan studies have focused on studying this disease, but more are needed, especially at the genetic and molecular levels. Therefore, we investigated the potential association of several functional germline variants in the genes commonly mutated in sporadic breast cancer.",
			"category": 2,
			"name": "Marouf Chaymaa,2016"
		},
		{
			"PMID": 26912831,
			"title": "More than 10% of yeast genes are related to genome stability and influence cellular senescence via rDNA maintenance.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Saka Kimiko",
				"Takahashi Akihiro",
				"Sasaki Mariko",
				"Kobayashi Takehiko"
			],
			"DOI": "10.1093/nar/gkw110",
			"date": "2017-07-04",
			"PMC": "",
			"citation": "",
			"abstract": "Genome instability triggers cellular senescence and is a common cause of cancer. The ribosomal RNA genes (rDNA), due to their repetitive structure, form a fragile site with frequent rearrangements. To identify eukaryotic factors that connect reduced genome stability to senescence we screened 4,876 strains of a Saccharomyces cerevisiae deletion library for aberrant rDNA and found 708 genes that contribute to its upkeep. 28 mutants caused abnormalities in non-rDNA chromosomes and among them 12 mutants have abnormalities both in rDNA and in non-rDNA chromosomes. Many mutated genes have not previously been implicated with genome maintenance nor their homologues with tumorigenesis in mammals. The link between rDNA state and senescence was broken after deletion of factors related with DNA polymerase \u03f5. These mutations also suppressed the short lifespan phenotype of a sir2 mutant, suggesting a model in which molecular events at the heart of the replication fork induce abnormal rDNA recombination and are responsible for the emergence of an aging signal.",
			"category": 2,
			"name": "Saka Kimiko,2017"
		},
		{
			"PMID": 26912005,
			"title": "Fine-tuning patient-derived xenograft models for precision medicine approaches in leukemia.",
			"journal": "Journal of investigative medicine : the official publication of the American Federation for Clinical Research",
			"authorList": [
				"Francis Olivia L",
				"Milford Terry-Ann M",
				"Beldiman Cornelia",
				"Payne Kimberly J"
			],
			"DOI": "10.1136/jim-2016-000076",
			"date": "2017-01-09",
			"PMC": "",
			"citation": "",
			"abstract": "Many leukemias are characterized by well-known mutations that drive oncogenesis. Mice engineered with these mutations provide a foundation for understanding leukemogenesis and identifying therapies. However, data from whole genome studies provide evidence that malignancies are characterized by multiple genetic alterations that vary between patients, as well as inherited genetic variation that can also contribute to oncogenesis. Improved outcomes will require precision medicine approaches-targeted therapies tailored to malignancies in each patient. Preclinical models that reflect the range of mutations and the genetic background present in patient populations are required to develop and test the combinations of therapies that will be used to provide precision medicine therapeutic strategies. Patient-derived xenografts (PDX) produced by transplanting leukemia cells from patients into immune deficient mice provide preclinical models where disease mechanisms and therapeutic efficacy can be studied in vivo in context of the genetic variability present in patient tumors. PDX models are possible because many elements in the bone marrow microenvironment show cross-species activity between mice and humans. However, several cytokines likely to impact leukemia cells are species-specific with limited activity on transplanted human leukemia cells. In this review we discuss the importance of PDX models for developing precision medicine approaches to leukemia treatment. We illustrate how PDX models can be optimized to overcome a lack of cross-species cytokine activity by reviewing a recent strategy developed for use with a high-risk form of B-cell acute lymphoblastic leukemia (B-ALL) that is characterized by overexpression of CRLF2, a receptor component for the cytokine, TSLP.",
			"category": 2,
			"name": "Francis Olivia L,2017"
		},
		{
			"PMID": 26894955,
			"title": "Registered report: Diverse somatic mutation patterns and pathway alterations in human cancers.",
			"journal": "eLife",
			"authorList": [
				"Sharma Vidhu",
				"Young Lisa",
				"Allison Anne B",
				"Owen Kate",
				"Reproducibility Project: Cancer Biology",
				"Reproducibility Project Cancer Biology"
			],
			"DOI": "10.7554/eLife.11566",
			"date": "2017-01-10",
			"PMC": "",
			"citation": "",
			"abstract": "The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered Report describes the proposed replication plan of key experiments from \"Diverse somatic mutation patterns and pathway alterations in human cancers\" by Kan and colleagues published in Nature in 2010 (Kan et al., 2010). The experiments to be replicated are those reported in Figures 3D-F and 4C-F. Kan and colleagues utilized mismatch repair detection (MRD) technology to identify somatic mutations in primary human tumor samples and identified a previously uncharacterized arginine 243 to histidine (R243H) mutation in the G-protein \u03b1 subunit GNAO1 in breast carcinoma tissue. In Figures 3D-F, Kan and colleagues demonstrated that stable expression of mutant GNAO1(R243D) conferred a significant growth advantage in human mammary epithelial cells, confirming the oncogenic potential of this mutation. Similarly, expression of variants with somatic mutations in MAP2K4, a JNK pathway kinase (shown in Figures 4C-E) resulted in a significant increase in anchorage-independent growth. Interestingly, these mutants exhibited reduced kinase activity compared to wild type MAP2K4, indicating these mutations impose a dominant-negative influence to promote growth (Figure 4F). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published in eLife.",
			"category": 2,
			"name": "Sharma Vidhu,2017"
		},
		{
			"PMID": 26886957,
			"title": "Genetic Testing in Differentiated Thyroid Carcinoma: Indications and Clinical Implications.",
			"journal": "Rambam Maimonides medical journal",
			"authorList": [
				"Zolotov Sagit"
			],
			"DOI": "10.5041/RMMJ.10236",
			"date": "2016-02-18",
			"PMC": "",
			"citation": "",
			"abstract": "Differentiated thyroid cancer (DTC) is a common and diverse endocrine malignancy. In most patients DTC results in an indolent and curable disease. Nevertheless, disease recurrence rates are relatively high (10%-30%), while 5% of the patients are resistant to conventional treatment and some of these patients are incurable. Over the past 20 years much progress has been made in identifying genetic changes that occur in DTC. In addition, studies aimed to understand the role of these genetic changes in tumorigenesis and their effects on the clinical characteristics of the disease have been conducted. The accrued knowledge has set the stage for development of genetic tests aimed to identify these changes in samples obtained from DTC patients and use this information in the clinical decision process. This paper reviews genetic changes that were identified in DTC, and how the emerging data obtained by genetic testing are currently used to gain key information on the diagnosis, risk stratification, and personalized care of DTC patients.",
			"category": 2,
			"name": "Zolotov Sagit,2016"
		},
		{
			"PMID": 26862731,
			"title": "Chromothripsis-like chromosomal rearrangements induced by ionizing radiation using proton microbeam irradiation system.",
			"journal": "Oncotarget",
			"authorList": [
				"Morishita Maki",
				"Muramatsu Tomoki",
				"Suto Yumiko",
				"Hirai Momoki",
				"Konishi Teruaki",
				"Hayashi Shin",
				"Shigemizu Daichi",
				"Tsunoda Tatsuhiko",
				"Moriyama Keiji",
				"Inazawa Johji"
			],
			"DOI": "10.18632/oncotarget.7186",
			"date": "2016-12-30",
			"PMC": "",
			"citation": "",
			"abstract": "Chromothripsis is the massive but highly localized chromosomal rearrangement in response to a one-step catastrophic event, rather than an accumulation of a series of subsequent and random alterations. Chromothripsis occurs commonly in various human cancers and is thought to be associated with increased malignancy and carcinogenesis. However, the causes and consequences of chromothripsis remain unclear. Therefore, to identify the mechanism underlying the generation of chromothripsis, we investigated whether chromothripsis could be artificially induced by ionizing radiation. We first elicited DNA double-strand breaks in an oral squamous cell carcinoma cell line HOC313-P and its highly metastatic subline HOC313-LM, using Single Particle Irradiation system to Cell (SPICE), a focused vertical microbeam system designed to irradiate a spot within the nuclei of adhesive cells, and then established irradiated monoclonal sublines from them, respectively. SNP array analysis detected a number of chromosomal copy number alterations (CNAs) in these sublines, and one HOC313-LM-derived monoclonal subline irradiated with 200 protons by the microbeam displayed multiple CNAs involved locally in chromosome 7. Multi-color FISH showed a complex translocation of chromosome 7 involving chromosomes 11 and 12. Furthermore, whole genome sequencing analysis revealed multiple de novo complex chromosomal rearrangements localized in chromosomes 2, 5, 7, and 20, resembling chromothripsis. These findings suggested that localized ionizing irradiation within the nucleus may induce chromothripsis-like complex chromosomal alterations via local DNA damage in the nucleus.",
			"category": 2,
			"name": "Morishita Maki,2016"
		},
		{
			"PMID": 26851938,
			"title": "Scenario drafting for early technology assessment of next generation sequencing in clinical oncology.",
			"journal": "BMC cancer",
			"authorList": [
				"Joosten S E P",
				"Ret\u00e8l V P",
				"Coup\u00e9 V M H",
				"van den Heuvel M M",
				"van Harten W H"
			],
			"DOI": "10.1186/s12885-016-2100-0",
			"date": "2016-09-29",
			"PMC": "",
			"citation": "",
			"abstract": "Next Generation Sequencing (NGS) is expected to lift molecular diagnostics in clinical oncology to the next level. It enables simultaneous identification of mutations in a patient tumor, after which targeted therapy may be assigned. This approach could improve patient survival and/or assist in controlling healthcare costs by offering expensive treatment to only those likely to benefit. However, NGS has yet to make its way into the clinic. Health Technology Assessment can support the adoption and implementation of a novel technology, but at this early stage many of the required variables are still unknown.",
			"category": 2,
			"name": "Joosten S E P,2016"
		},
		{
			"PMID": 26843812,
			"title": "Big Data Application in Biomedical Research and Health Care: A Literature Review.",
			"journal": "Biomedical informatics insights",
			"authorList": [
				"Luo Jake",
				"Wu Min",
				"Gopukumar Deepika",
				"Zhao Yiqing"
			],
			"DOI": "10.4137/BII.S31559",
			"date": "2016-02-04",
			"PMC": "",
			"citation": "",
			"abstract": "Big data technologies are increasingly used for biomedical and health-care informatics research. Large amounts of biological and clinical data have been generated and collected at an unprecedented speed and scale. For example, the new generation of sequencing technologies enables the processing of billions of DNA sequence data per day, and the application of electronic health records (EHRs) is documenting large amounts of patient data. The cost of acquiring and analyzing biomedical data is expected to decrease dramatically with the help of technology upgrades, such as the emergence of new sequencing machines, the development of novel hardware and software for parallel computing, and the extensive expansion of EHRs. Big data applications present new opportunities to discover new knowledge and create novel methods to improve the quality of health care. The application of big data in health care is a fast-growing field, with many new discoveries and methodologies published in the last five years. In this paper, we review and discuss big data application in four major biomedical subdisciplines: (1) bioinformatics, (2) clinical informatics, (3) imaging informatics, and (4) public health informatics. Specifically, in bioinformatics, high-throughput experiments facilitate the research of new genome-wide association studies of diseases, and with clinical informatics, the clinical field benefits from the vast amount of collected patient data for making intelligent decisions. Imaging informatics is now more rapidly integrated with cloud platforms to share medical image data and workflows, and public health informatics leverages big data techniques for predicting and monitoring infectious disease outbreaks, such as Ebola. In this paper, we review the recent progress and breakthroughs of big data applications in these health-care domains and summarize the challenges, gaps, and opportunities to improve and advance big data applications in health care.",
			"category": 2,
			"name": "Luo Jake,2016"
		},
		{
			"PMID": 26819545,
			"title": "Correlation between Gene Variants, Signaling Pathways, and Efficacy of Chemotherapy Drugs against Colon Cancers.",
			"journal": "Cancer informatics",
			"authorList": [
				"Tripathi Swarnendu",
				"Belkacemi Louiza",
				"Cheung Margaret S",
				"Bose Rathindra N"
			],
			"DOI": "10.4137/CIN.S34506",
			"date": "2016-01-28",
			"PMC": "",
			"citation": "",
			"abstract": "Efficacies, toxicities, and resistance mechanisms of chemotherapy drugs, such as oxaliplatin and 5-fluorouracil (5-FU), vary widely among various categories and subcategories of colon cancers. By understanding the differences in the drug efficacy and resistance at the level of protein-protein networks, we identified the correlation between the drug activity of oxaliplatin/5-FU and gene variations from the US National Cancer Institute-60 human cancer cell lines. The activity of either of these drugs is correlated with specific amino acid variant(s) of KRAS and other genes from the signaling pathways of colon cancer progression. We also discovered that the activity of a non-DNA-binding novel platinum drug, phosphaplatin, is comparable with oxaliplatin and 5-FU when it was tested against colon cancer cell lines. Our strategy that combines the knowledge from pharmacogenomics across cell lines with the molecular information from specific cancer cells is beneficial for predicting the outcome of a possible combination therapy for personalized treatment.",
			"category": 2,
			"name": "Tripathi Swarnendu,2016"
		},
		{
			"PMID": 26805845,
			"title": "Graphene: The Missing Piece for Cancer Diagnosis?",
			"journal": "Sensors (Basel, Switzerland)",
			"authorList": [
				"Cruz Sandra M A",
				"Gir\u00e3o Andr\u00e9 F",
				"Gon\u00e7alves Gil",
				"Marques Paula A A P"
			],
			"DOI": "10.3390/s16010137",
			"date": "2016-09-01",
			"PMC": "",
			"citation": "",
			"abstract": "This paper reviews recent advances in graphene-based biosensors development in order to obtain smaller and more portable devices with better performance for earlier cancer detection. In fact, the potential of Graphene for sensitive detection and chemical/biological free-label applications results from its exceptional physicochemical properties such as high electrical and thermal conductivity, aspect-ratio, optical transparency and remarkable mechanical and chemical stability. Herein we start by providing a general overview of the types of graphene and its derivatives, briefly describing the synthesis procedure and main properties. It follows the reference to different routes to engineer the graphene surface for sensing applications with organic biomolecules and nanoparticles for the development of advanced biosensing platforms able to detect/quantify the characteristic cancer biomolecules in biological fluids or overexpressed on cancerous cells surface with elevated sensitivity, selectivity and stability. We then describe the application of graphene in optical imaging methods such as photoluminescence and Raman imaging, electrochemical sensors for enzymatic biosensing, DNA sensing, and immunosensing. The bioquantification of cancer biomarkers and cells is finally discussed, particularly electrochemical methods such as voltammetry and amperometry which are generally adopted transducing techniques for the development of graphene based sensors for biosensing due to their simplicity, high sensitivity and low-cost. To close, we discuss the major challenges that graphene based biosensors must overcome in order to reach the necessary standards for the early detection of cancer biomarkers by providing reliable information about the patient disease stage.",
			"category": 2,
			"name": "Cruz Sandra M A,2016"
		},
		{
			"PMID": 26796710,
			"title": "Same strategy for pitfalls of radiotherapy in different anatomical districts.",
			"journal": "Lasers in medical science",
			"authorList": [
				"Gobbo Margherita",
				"Ottaviani Giulia",
				"Rupel Katia",
				"Ciriello Francesca",
				"Beorchia Aulo",
				"Di Lenarda Roberto",
				"Zacchigna Serena",
				"Biasotto Matteo"
			],
			"DOI": "10.1007/s10103-015-1857-8",
			"date": "2016-11-02",
			"PMC": "",
			"citation": "",
			"abstract": "Oral mucositis (OM) and radiodermatitis (RD) are serious side effects of radiotherapy (RT), often leading to its suspension, need for analgesics, and enteral/parenteral nutrition. Laser therapy is becoming a recommended treatment option. This prospective study aimed at demonstrating the beneficial effect of class IV laser therapy (HPLT) on RT-induced OM, an off-label use of HPLT to treat RD in breast cancer patients. Fifty-three cancer patients, during/after RT and/or chemotherapy (CT), affected by OM, were treated with HPLT during four consecutive days (970\u2009\u00b1\u200915 nm, 5 W (50 %), 35-6000 Hz, 240 s). Assessment of OM (Grading Objective Scale, WHO-SCALE), pain (visual analogue scale, VAS), functional ability, subjective parameters, and site/severity of OM were recorded over time. Similarly, 27 breast cancer patients affected by RD were treated by HPLT and monitored over time for grade, discomfort, itching, and bleeding. Progressive improvement of WHO-SCALE from day 7 on, and of VAS from day 2 on (p\u2009<\u20090.000) was registered. All patients' functional capacity improved on day 4 (p\u2009<\u20090.05). All subjective parameters improved on day 14 (p\u2009<\u20090.001) except for voice, which improved on day 21 (p\u2009<\u20090.000). Ulcerations' dimension and erythema's severity significantly decreased in all sites examined (p\u2009<\u20090.05). Similarly, HPLT proved to be beneficial in managing RD for all the parameters considered (p\u2009<\u20090.002). Regardless of OM grade/site and of kind/site of tumor, HPLT proved to be effective in healing OM as well as RD. In both cases, effective treatment can improve life quality through a safe, easy, innovative approach. Therefore, HPLT may become an integral part of everyday practice in the management of RT adverse effects.",
			"category": 2,
			"name": "Gobbo Margherita,2016"
		},
		{
			"PMID": 26778171,
			"title": "Non-invasive detection of genome-wide somatic copy number alterations by liquid biopsies.",
			"journal": "Molecular oncology",
			"authorList": [
				"Heitzer Ellen",
				"Ulz Peter",
				"Geigl Jochen B",
				"Speicher Michael R"
			],
			"DOI": "10.1016/j.molonc.2015.12.004",
			"date": "2016-12-13",
			"PMC": "",
			"citation": "",
			"abstract": "Liquid biopsies, i.e. the analysis of circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA), are evolving into promising clinical tools. Indeed, a plethora of liquid biopsy technologies to deduce non-invasively characteristics of the tumor genome from the peripheral blood have been developed over the last few years. For example, liquid biopsies have been used to assess the tumor burden, to monitor the evolution of tumor genomes, to unravel mechanisms of resistance, to establish the tumor heterogeneity, and for the identification of prognostic and predictive markers. In this review we focus on methods to establish genome-wide profiles of somatic copy number alterations (SCNAs) from plasma DNA and show how they provide novel insights into the biology of cancer and their impact on the management of patients.",
			"category": 2,
			"name": "Heitzer Ellen,2016"
		},
		{
			"PMID": 26777304,
			"title": "dbEM: A database of epigenetic modifiers curated from cancerous and normal genomes.",
			"journal": "Scientific reports",
			"authorList": [
				"Singh Nanda Jagpreet",
				"Kumar Rahul",
				"Raghava Gajendra P S"
			],
			"DOI": "10.1038/srep19340",
			"date": "2016-12-26",
			"PMC": "",
			"citation": "",
			"abstract": "We have developed a database called dbEM (database of Epigenetic Modifiers) to maintain the genomic information of about 167 epigenetic modifiers/proteins, which are considered as potential cancer targets. In dbEM, modifiers are classified on functional basis and comprise of 48 histone methyl transferases, 33 chromatin remodelers and 31 histone demethylases. dbEM maintains the genomic information like mutations, copy number variation and gene expression in thousands of tumor samples, cancer cell lines and healthy samples. This information is obtained from public resources viz. COSMIC, CCLE and 1000-genome project. Gene essentiality data retrieved from COLT database further highlights the importance of various epigenetic proteins for cancer survival. We have also reported the sequence profiles, tertiary structures and post-translational modifications of these epigenetic proteins in cancer. It also contains information of 54 drug molecules against different epigenetic proteins. A wide range of tools have been integrated in dbEM e.g. Search, BLAST, Alignment and Profile based prediction. In our analysis, we found that epigenetic proteins DNMT3A, HDAC2, KDM6A, and TET2 are highly mutated in variety of cancers. We are confident that dbEM will be very useful in cancer research particularly in the field of epigenetic proteins based cancer therapeutics. This database is available for public at URL: http://crdd.osdd.net/raghava/dbem.",
			"category": 2,
			"name": "Singh Nanda Jagpreet,2016"
		},
		{
			"PMID": 26753012,
			"title": "Clinical features and outcomes of germline mutation BRCA1-linked versus sporadic ovarian cancer patients.",
			"journal": "Hereditary cancer in clinical practice",
			"authorList": [
				"Synowiec Agnieszka",
				"Wcis\u0142o Gabriel",
				"Bodnar Lubomir",
				"G\u00f3rski Bohdan",
				"Szenajch Jolanta",
				"Szarlej-Wcis\u0142o Katarzyna",
				"Szczylik Cezary"
			],
			"DOI": "10.1186/s13053-015-0044-z",
			"date": "2016-01-12",
			"PMC": "",
			"citation": "",
			"abstract": "The role of germline mutations in BRCA1 and BRCA2 genes in the risk of the development of ovarian cancer is clinically well established. BRCA1/2 testing seems to have increasing role in clinical management in patients with advanced ovarian cancer who require treatment with poly(ADP-ribose) polymerase inhibitors.",
			"category": 2,
			"name": "Synowiec Agnieszka,2016"
		},
		{
			"PMID": 26716650,
			"title": "Enhanced expression of LINE-1-encoded ORF2 protein in early stages of colon and prostate transformation.",
			"journal": "Oncotarget",
			"authorList": [
				"De Luca Chiara",
				"Guadagni Fiorella",
				"Sinibaldi-Vallebona Paola",
				"Sentinelli Steno",
				"Gallucci Michele",
				"Hoffmann Andreas",
				"Schumann Gerald G",
				"Spadafora Corrado",
				"Sciamanna Ilaria"
			],
			"DOI": "10.18632/oncotarget.6767",
			"date": "2016-11-01",
			"PMC": "",
			"citation": "",
			"abstract": "LINE-1 (L1) retrotransposons are a source of endogenous reverse transcriptase (RT) activity, which is expressed as part of the L1-encoded ORF2 protein (L1-ORF2p). L1 elements are highly expressed in many cancer types, while being silenced in most differentiated somatic tissues. We previously found that RT inhibition reduces cell proliferation and promotes differentiation in neoplastic cells, indicating that high endogenous RT activity promotes cancer growth. Here we investigate the expression of L1-ORF2p in several human types of cancer.We have developed a highly specific monoclonal antibody (mAb chA1-L1) to study ORF2p expression and localization in human cancer cells and tissues.We uncover new evidence for high levels of L1-ORF2p in transformed cell lines and staged epithelial cancer tissues (colon, prostate, lung and breast) while no or only basal ORF2p expression was detected in non-transformed cells. An in-depth analysis of colon and prostate tissues shows ORF2p expression in preneoplastic stages, namely transitional mucosa and prostate intraepithelial neoplasia (PIN), respectively.Our results show that L1-ORF2p is overexpressed in tumor and in preneoplastic colon and prostate tissues; this latter finding suggests that ORF2p could be considered as a potential early diagnostic biomarker.",
			"category": 2,
			"name": "De Luca Chiara,2016"
		},
		{
			"PMID": 26699486,
			"title": "Deep sequencing as a probe of normal stem cell fate and preneoplasia in human epidermis.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Simons Benjamin D"
			],
			"DOI": "10.1073/pnas.1516123113",
			"date": "2016-05-13",
			"PMC": "",
			"citation": "",
			"abstract": "Using deep sequencing technology, methods based on the sporadic acquisition of somatic DNA mutations in human tissues have been used to trace the clonal evolution of progenitor cells in diseased states. However, the potential of these approaches to explore cell fate behavior of normal tissues and the initiation of preneoplasia remain underexploited. Focusing on the results of a recent deep sequencing study of eyelid epidermis, we show that the quantitative analysis of mutant clone size provides a general method to resolve the pattern of normal stem cell fate and to detect and characterize the mutational signature of rare field transformations in human tissues, with implications for the early detection of preneoplasia.",
			"category": 2,
			"name": "Simons Benjamin D,2016"
		},
		{
			"PMID": 26656844,
			"title": "Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers.",
			"journal": "Nature genetics",
			"authorList": [
				"Zhang Xiaoyang",
				"Choi Peter S",
				"Francis Joshua M",
				"Imielinski Marcin",
				"Watanabe Hideo",
				"Cherniack Andrew D",
				"Meyerson Matthew"
			],
			"DOI": "10.1038/ng.3470",
			"date": "2016-06-03",
			"PMC": "",
			"citation": "",
			"abstract": "Whole-genome analysis approaches are identifying recurrent cancer-associated somatic alterations in noncoding DNA regions. We combined somatic copy number analysis of 12 tumor types with tissue-specific epigenetic profiling to identify significant regions of focal amplification harboring super-enhancers. Copy number gains of noncoding regions harboring super-enhancers near KLF5, USP12, PARD6B and MYC are associated with overexpression of these cancer-related genes. We show that two distinct focal amplifications of super-enhancers 3' to MYC in lung adenocarcinoma (MYC-LASE) and endometrial carcinoma (MYC-ECSE) are physically associated with the MYC promoter and correlate with MYC overexpression. CRISPR/Cas9-mediated repression or deletion of a constituent enhancer within the MYC-LASE region led to significant reductions in the expression of MYC and its target genes and to the impairment of anchorage-independent and clonogenic growth, consistent with an oncogenic function. Our results suggest that genomic amplification of super-enhancers represents a common mechanism to activate cancer driver genes in multiple cancer types.",
			"category": 2,
			"name": "Zhang Xiaoyang,2016"
		},
		{
			"PMID": 26630308,
			"title": "A Simple Model-Based Approach to Inferring and Visualizing Cancer Mutation Signatures.",
			"journal": "PLoS genetics",
			"authorList": [
				"Shiraishi Yuichi",
				"Tremmel Georg",
				"Miyano Satoru",
				"Stephens Matthew"
			],
			"DOI": "10.1371/journal.pgen.1005657",
			"date": "2016-06-07",
			"PMC": "",
			"citation": "",
			"abstract": "Recent advances in sequencing technologies have enabled the production of massive amounts of data on somatic mutations from cancer genomes. These data have led to the detection of characteristic patterns of somatic mutations or \"mutation signatures\" at an unprecedented resolution, with the potential for new insights into the causes and mechanisms of tumorigenesis. Here we present new methods for modelling, identifying and visualizing such mutation signatures. Our methods greatly simplify mutation signature models compared with existing approaches, reducing the number of parameters by orders of magnitude even while increasing the contextual factors (e.g. the number of flanking bases) that are accounted for. This improves both sensitivity and robustness of inferred signatures. We also provide a new intuitive way to visualize the signatures, analogous to the use of sequence logos to visualize transcription factor binding sites. We illustrate our new method on somatic mutation data from urothelial carcinoma of the upper urinary tract, and a larger dataset from 30 diverse cancer types. The results illustrate several important features of our methods, including the ability of our new visualization tool to clearly highlight the key features of each signature, the improved robustness of signature inferences from small sample sizes, and more detailed inference of signature characteristics such as strand biases and sequence context effects at the base two positions 5' to the mutated site. The overall framework of our work is based on probabilistic models that are closely connected with \"mixed-membership models\" which are widely used in population genetic admixture analysis, and in machine learning for document clustering. We argue that recognizing these relationships should help improve understanding of mutation signature extraction problems, and suggests ways to further improve the statistical methods. Our methods are implemented in an R package pmsignature (https://github.com/friend1ws/pmsignature) and a web application available at https://friend1ws.shinyapps.io/pmsignature_shiny/.",
			"category": 2,
			"name": "Shiraishi Yuichi,2016"
		},
		{
			"PMID": 26617477,
			"title": "Treatment Individualization in Colorectal Cancer.",
			"journal": "Current colorectal cancer reports",
			"authorList": [
				"van Geel Robin M J M",
				"Beijnen Jos H",
				"Bernards Ren\u00e9",
				"Schellens Jan H M"
			],
			"DOI": "",
			"date": "2020-09-29",
			"PMC": "",
			"citation": "",
			"abstract": "Colorectal cancer has been characterized as a genetically heterogeneous disease, with a large diversity in molecular pathogenesis resulting in differential responses to therapy. However, the currently available validated biomarkers KRAS, BRAF, and microsatellite instability do not sufficiently cover this extensive heterogeneity and are therefore not suitable to successfully guide personalized treatment. Recent studies have focused on novel targets and rationally designed combination strategies. Furthermore, a more comprehensive analysis of the underlying biology of the disease revealed distinct phenotypic differences within subgroups of patients harboring the same genetic driver mutation with both prognostic and predictive relevance. Accordingly, patient stratification based on molecular intrinsic subtypes rather than on single gene aberrations holds promise to improve the clinical outcome of patients with colorectal cancer.",
			"category": 2,
			"name": "van Geel Robin M J M,2020"
		},
		{
			"PMID": 26609214,
			"title": "Precision Medicine for Molecularly Targeted Agents and Immunotherapies in Early-Phase Clinical Trials.",
			"journal": "Translational oncogenomics",
			"authorList": [
				"Lopez Juanita",
				"Harris Sam",
				"Roda Desam",
				"Yap Timothy A"
			],
			"DOI": "10.4137/TOG.S30533",
			"date": "2015-11-26",
			"PMC": "",
			"citation": "",
			"abstract": "Precision medicine in oncology promises the matching of genomic, molecular, and clinical data with underlying mechanisms of a range of novel anticancer therapeutics to develop more rational and effective antitumor strategies in a timely manner. However, despite the remarkable progress made in the understanding of novel drivers of different oncogenic processes, success rates for the approval of oncology drugs remain low with substantial fiscal consequences. In this article, we focus on how recent rapid innovations in technology have brought greater clarity to the biological and clinical complexities of different cancers and advanced the development of molecularly targeted agents and immunotherapies in clinical trials. We discuss the key challenges of identifying and validating predictive biomarkers of response and resistance using both tumor and surrogate tissues, as well as the hurdles associated with intratumor heterogeneity. Finally, we outline evolving strategies employed in early-phase trial designs that incorporate omics-based technologies.",
			"category": 2,
			"name": "Lopez Juanita,2015"
		},
		{
			"PMID": 26603430,
			"title": "Clinical potential of gene mutations in lung cancer.",
			"journal": "Clinical and translational medicine",
			"authorList": [
				"Carper Miranda B",
				"Claudio Pier Paolo"
			],
			"DOI": "10.1186/s40169-015-0074-1",
			"date": "2015-11-25",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer is the most common cancer type worldwide and the leading cause of cancer related deaths in the United States. The majority of newly diagnosed patients present with late stage metastatic lung cancer that is inoperable and resistant to therapies. High-throughput genomic technologies have made the identification of genetic mutations that promote lung cancer progression possible. Identification of the mutations that drive lung cancer provided new targets for non-small cell lung cancer (NSCLC) treatment and led to the development of targeted therapies such as tyrosine kinase inhibitors that can be used to combat the molecular changes that promote cancer progression. Development of targeted therapies is not the only clinical benefit of gene analysis studies. Biomarkers identified from gene analysis can be used for early lung cancer detection, determine patient's prognosis and response to therapy, and monitor disease progression. Biomarkers can be used to identify the NSCLC patient population that would most benefit from treatment (targeted therapies or chemotherapies), providing clinicians tools that can be used to develop a personalized treatment plan. This review explores the clinical potential of NSCLC genetic studies on diagnosing and treating NSCLC.",
			"category": 2,
			"name": "Carper Miranda B,2015"
		},
		{
			"PMID": 26597528,
			"title": "The mathematics of cancer: integrating quantitative models.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Altrock Philipp M",
				"Liu Lin L",
				"Michor Franziska"
			],
			"DOI": "10.1038/nrc4029",
			"date": "2016-03-08",
			"PMC": "",
			"citation": "",
			"abstract": "Mathematical modelling approaches have become increasingly abundant in cancer research. The complexity of cancer is well suited to quantitative approaches as it provides challenges and opportunities for new developments. In turn, mathematical modelling contributes to cancer research by helping to elucidate mechanisms and by providing quantitative predictions that can be validated. The recent expansion of quantitative models addresses many questions regarding tumour initiation, progression and metastases as well as intra-tumour heterogeneity, treatment responses and resistance. Mathematical models can complement experimental and clinical studies, but also challenge current paradigms, redefine our understanding of mechanisms driving tumorigenesis and shape future research in cancer biology.",
			"category": 2,
			"name": "Altrock Philipp M,2016"
		},
		{
			"PMID": 26590477,
			"title": "Designing a broad-spectrum integrative approach for cancer prevention and treatment.",
			"journal": "Seminars in cancer biology",
			"authorList": [
				"Block Keith I",
				"Gyllenhaal Charlotte",
				"Lowe Leroy",
				"Amedei Amedeo",
				"Amin A R M Ruhul",
				"Amin Amr",
				"Aquilano Katia",
				"Arbiser Jack",
				"Arreola Alexandra",
				"Arzumanyan Alla",
				"Ashraf S Salman",
				"Azmi Asfar S",
				"Benencia Fabian",
				"Bhakta Dipita",
				"Bilsland Alan",
				"Bishayee Anupam",
				"Blain Stacy W",
				"Block Penny B",
				"Boosani Chandra S",
				"Carey Thomas E",
				"Carnero Amancio",
				"Carotenuto Marianeve",
				"Casey Stephanie C",
				"Chakrabarti Mrinmay",
				"Chaturvedi Rupesh",
				"Chen Georgia Zhuo",
				"Chen Helen",
				"Chen Sophie",
				"Chen Yi Charlie",
				"Choi Beom K",
				"Ciriolo Maria Rosa",
				"Coley Helen M",
				"Collins Andrew R",
				"Connell Marisa",
				"Crawford Sarah",
				"Curran Colleen S",
				"Dabrosin Charlotta",
				"Damia Giovanna",
				"Dasgupta Santanu",
				"DeBerardinis Ralph J",
				"Decker William K",
				"Dhawan Punita",
				"Diehl Anna Mae E",
				"Dong Jin-Tang",
				"Dou Q Ping",
				"Drew Janice E",
				"Elkord Eyad",
				"El-Rayes Bassel",
				"Feitelson Mark A",
				"Felsher Dean W",
				"Ferguson Lynnette R",
				"Fimognari Carmela",
				"Firestone Gary L",
				"Frezza Christian",
				"Fujii Hiromasa",
				"Fuster Mark M",
				"Generali Daniele",
				"Georgakilas Alexandros G",
				"Gieseler Frank",
				"Gilbertson Michael",
				"Green Michelle F",
				"Grue Brendan",
				"Guha Gunjan",
				"Halicka Dorota",
				"Helferich William G",
				"Heneberg Petr",
				"Hentosh Patricia",
				"Hirschey Matthew D",
				"Hofseth Lorne J",
				"Holcombe Randall F",
				"Honoki Kanya",
				"Hsu Hsue-Yin",
				"Huang Gloria S",
				"Jensen Lasse D",
				"Jiang Wen G",
				"Jones Lee W",
				"Karpowicz Phillip A",
				"Keith W Nicol",
				"Kerkar Sid P",
				"Khan Gazala N",
				"Khatami Mahin",
				"Ko Young H",
				"Kucuk Omer",
				"Kulathinal Rob J",
				"Kumar Nagi B",
				"Kwon Byoung S",
				"Le Anne",
				"Lea Michael A",
				"Lee Ho-Young",
				"Lichtor Terry",
				"Lin Liang-Tzung",
				"Locasale Jason W",
				"Lokeshwar Bal L",
				"Longo Valter D",
				"Lyssiotis Costas A",
				"MacKenzie Karen L",
				"Malhotra Meenakshi",
				"Marino Maria",
				"Martinez-Chantar Maria L",
				"Matheu Ander",
				"Maxwell Christopher",
				"McDonnell Eoin",
				"Meeker Alan K",
				"Mehrmohamadi Mahya",
				"Mehta Kapil",
				"Michelotti Gregory A",
				"Mohammad Ramzi M",
				"Mohammed Sulma I",
				"Morre D James",
				"Muralidhar Vinayak",
				"Muqbil Irfana",
				"Murphy Michael P",
				"Nagaraju Ganji Purnachandra",
				"Nahta Rita",
				"Niccolai Elena",
				"Nowsheen Somaira",
				"Panis Carolina",
				"Pantano Francesco",
				"Parslow Virginia R",
				"Pawelec Graham",
				"Pedersen Peter L",
				"Poore Brad",
				"Poudyal Deepak",
				"Prakash Satya",
				"Prince Mark",
				"Raffaghello Lizzia",
				"Rathmell Jeffrey C",
				"Rathmell W Kimryn",
				"Ray Swapan K",
				"Reichrath J\u00f6rg",
				"Rezazadeh Sarallah",
				"Ribatti Domenico",
				"Ricciardiello Luigi",
				"Robey R Brooks",
				"Rodier Francis",
				"Rupasinghe H P Vasantha",
				"Russo Gian Luigi",
				"Ryan Elizabeth P",
				"Samadi Abbas K",
				"Sanchez-Garcia Isidro",
				"Sanders Andrew J",
				"Santini Daniele",
				"Sarkar Malancha",
				"Sasada Tetsuro",
				"Saxena Neeraj K",
				"Shackelford Rodney E",
				"Shantha Kumara H M C",
				"Sharma Dipali",
				"Shin Dong M",
				"Sidransky David",
				"Siegelin Markus David",
				"Signori Emanuela",
				"Singh Neetu",
				"Sivanand Sharanya",
				"Sliva Daniel",
				"Smythe Carl",
				"Spagnuolo Carmela",
				"Stafforini Diana M",
				"Stagg John",
				"Subbarayan Pochi R",
				"Sundin Tabetha",
				"Talib Wamidh H",
				"Thompson Sarah K",
				"Tran Phuoc T",
				"Ungefroren Hendrik",
				"Vander Heiden Matthew G",
				"Venkateswaran Vasundara",
				"Vinay Dass S",
				"Vlachostergios Panagiotis J",
				"Wang Zongwei",
				"Wellen Kathryn E",
				"Whelan Richard L",
				"Yang Eddy S",
				"Yang Huanjie",
				"Yang Xujuan",
				"Yaswen Paul",
				"Yedjou Clement",
				"Yin Xin",
				"Zhu Jiyue",
				"Zollo Massimo"
			],
			"DOI": "10.1016/j.semcancer.2015.09.007",
			"date": "2016-09-07",
			"PMC": "",
			"citation": "",
			"abstract": "Targeted therapies and the consequent adoption of \"personalized\" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity \"broad-spectrum\" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered.",
			"category": 2,
			"name": "Block Keith I,2016"
		},
		{
			"PMID": 26579543,
			"title": "Mechanisms and Clinical Applications of Genome Instability in Multiple Myeloma.",
			"journal": "BioMed research international",
			"authorList": [
				"Cagnetta Antonia",
				"Lovera Davide",
				"Grasso Raffaella",
				"Colombo Nicoletta",
				"Canepa Letizia",
				"Ballerini Filippo",
				"Calvio Marino",
				"Miglino Maurizio",
				"Gobbi Marco",
				"Lemoli Roberto",
				"Cea Michele"
			],
			"DOI": "10.1155/2015/943096",
			"date": "2016-08-29",
			"PMC": "",
			"citation": "",
			"abstract": "Ongoing genomic instability represents a hallmark of multiple myeloma (MM) cells, which manifests largely as whole chromosome- or translocation-based aneuploidy. Importantly, although it supports tumorigenesis, progression and, response to treatment in MM patients, it remains one of the least understood components of malignant transformation in terms of molecular basis. Therefore these aspects make the comprehension of genomic instability a pioneering strategy for novel therapeutic and clinical speculations to use in the management of MM patients. Here we will review mechanisms mediating genomic instability in MM cells with an emphasis placed on pathogenic mutations affecting DNA recombination, replication and repair, telomere function and mitotic regulation of spindle attachment, centrosome function, and chromosomal segregation. We will discuss the mechanisms by which genetic aberrations give rise to multiple pathogenic events required for myelomagenesis and conclude with a discussion of the clinical applications of these findings in MM patients.",
			"category": 2,
			"name": "Cagnetta Antonia,2016"
		},
		{
			"PMID": 26579496,
			"title": "Putative Breast Cancer Driver Mutations in TBX3 Cause Impaired Transcriptional Repression.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Fischer Kathrin",
				"Pflugfelder Gert O"
			],
			"DOI": "10.3389/fonc.2015.00244",
			"date": "2015-11-20",
			"PMC": "",
			"citation": "",
			"abstract": "The closely related T-box transcription factors TBX2 and TBX3 are frequently overexpressed in melanoma and various types of human cancers, in particular, breast cancer. The overexpression of TBX2 and TBX3 can have several cellular effects, among them suppression of senescence, promotion of epithelial-mesenchymal transition, and invasive cell motility. In contrast, loss of function of TBX3 and most other human T-box genes causes developmental haploinsufficiency syndromes. Stephens and colleagues (1), by exome sequencing of breast tumor samples, identified five different mutations in TBX3, all affecting the DNA-binding T-domain. One in-frame deletion of a single amino acid, p.N212delN, was observed twice. Due to the clustering of these mutations to the T-domain and for statistical reasons, TBX3 was inferred to be a driver gene in breast cancer. Since mutations in the T-domain generally cause loss of function and because the tumorigenic action of TBX3 has generally been attributed to overexpression, we determined whether the putative driver mutations had loss- or gain-of-function properties. We tested two in-frame deletions, one missense, and one frameshift mutant protein for DNA-binding in vitro, and for target gene repression in cell culture. In addition, we performed an in silico analysis of somatic TBX mutations in breast cancer, collected in The Cancer Genome Atlas (TCGA). Both the experimental and the in silico analysis indicate that the observed mutations predominantly cause loss of TBX3 function.",
			"category": 2,
			"name": "Fischer Kathrin,2015"
		},
		{
			"PMID": 26576947,
			"title": "Reference-free inference of tumor phylogenies from single-cell sequencing data.",
			"journal": "BMC genomics",
			"authorList": [
				"Subramanian Ayshwarya",
				"Schwartz Russell"
			],
			"DOI": "10.1186/1471-2164-16-S11-S7",
			"date": "2016-09-02",
			"PMC": "",
			"citation": "",
			"abstract": "Effective management and treatment of cancer continues to be complicated by the rapid evolution and resulting heterogeneity of tumors. Phylogenetic study of cell populations in single tumors provides a way to delineate intra-tumoral heterogeneity and identify robust features of evolutionary processes. The introduction of single-cell sequencing has shown great promise for advancing single-tumor phylogenetics; however, the volume and high noise in these data present challenges for inference, especially with regard to chromosome abnormalities that typically dominate tumor evolution. Here, we investigate a strategy to use such data to track differences in tumor cell genomic content during progression.",
			"category": 2,
			"name": "Subramanian Ayshwarya,2016"
		},
		{
			"PMID": 26562020,
			"title": "SNPase-ARMS qPCR: Ultrasensitive Mutation-Based Detection of Cell-Free Tumor DNA in Melanoma Patients.",
			"journal": "PloS one",
			"authorList": [
				"Stadler Julia",
				"Eder Johanna",
				"Pratscher Barbara",
				"Brandt Sabine",
				"Schneller Doris",
				"M\u00fcllegger Robert",
				"Vogl Claus",
				"Trautinger Franz",
				"Brem Gottfried",
				"Burgstaller Joerg P"
			],
			"DOI": "10.1371/journal.pone.0142273",
			"date": "2016-06-20",
			"PMC": "",
			"citation": "",
			"abstract": "Cell-free circulating tumor DNA in the plasma of cancer patients has become a common point of interest as indicator of therapy options and treatment response in clinical cancer research. Especially patient- and tumor-specific single nucleotide variants that accurately distinguish tumor DNA from wild type DNA are promising targets. The reliable detection and quantification of these single-base DNA variants is technically challenging. Currently, a variety of techniques is applied, with no apparent \"gold standard\". Here we present a novel qPCR protocol that meets the conditions of extreme sensitivity and specificity that are required for detection and quantification of tumor DNA. By consecutive application of two polymerases, one of them designed for extreme base-specificity, the method reaches unprecedented sensitivity and specificity. Three qPCR assays were tested with spike-in experiments, specific for point mutations BRAF V600E, PTEN T167A and NRAS Q61L of melanoma cell lines. It was possible to detect down to one copy of tumor DNA per reaction (Poisson distribution), at a background of up to 200 000 wild type DNAs. To prove its clinical applicability, the method was successfully tested on a small cohort of BRAF V600E positive melanoma patients.",
			"category": 2,
			"name": "Stadler Julia,2016"
		},
		{
			"PMID": 26556407,
			"title": "Advances in Proteomic Technologies and Its Contribution to the Field of Cancer.",
			"journal": "Advances in medicine",
			"authorList": [
				"Mesri Mehdi"
			],
			"DOI": "10.1155/2014/238045",
			"date": "2015-11-11",
			"PMC": "",
			"citation": "",
			"abstract": "Systematic studies of the cancer genome have generated a wealth of knowledge in recent years. These studies have uncovered a number of new cancer genes not previously known to be causal targets in cancer. Genetic markers can be used to determine predisposition to tumor development, but molecularly targeted treatment strategies are not widely available for most cancers. Precision care plans still must be developed by understanding and implementing basic science research into clinical treatment. Proteomics is continuing to make major strides in the discovery of fundamental biological processes as well as more recent transition into an assay platform capable of measuring hundreds of proteins in any biological system. As such, proteomics can translate basic science discoveries into the clinical practice of precision medicine. The proteomic field has progressed at a fast rate over the past five years in technology, breadth and depth of applications in all areas of the bioscience. Some of the previously experimental technical approaches are considered the gold standard today, and the community is now trying to come to terms with the volume and complexity of the data generated. Here I describe contribution of proteomics in general and biological mass spectrometry in particular to cancer research, as well as related major technical and conceptual developments in the field.",
			"category": 2,
			"name": "Mesri Mehdi,2015"
		},
		{
			"PMID": 26551669,
			"title": "Clock-like mutational processes in human somatic cells.",
			"journal": "Nature genetics",
			"authorList": [
				"Alexandrov Ludmil B",
				"Jones Philip H",
				"Wedge David C",
				"Sale Julian E",
				"Campbell Peter J",
				"Nik-Zainal Serena",
				"Stratton Michael R"
			],
			"DOI": "10.1038/ng.3441",
			"date": "2016-06-21",
			"PMC": "",
			"citation": "",
			"abstract": "During the course of a lifetime, somatic cells acquire mutations. Different mutational processes may contribute to the mutations accumulated in a cell, with each imprinting a mutational signature on the cell's genome. Some processes generate mutations throughout life at a constant rate in all individuals, and the number of mutations in a cell attributable to these processes will be proportional to the chronological age of the person. Using mutations from 10,250 cancer genomes across 36 cancer types, we investigated clock-like mutational processes that have been operating in normal human cells. Two mutational signatures show clock-like properties. Both exhibit different mutation rates in different tissues. However, their mutation rates are not correlated, indicating that the underlying processes are subject to different biological influences. For one signature, the rate of cell division may influence its mutation rate. This study provides the first survey of clock-like mutational processes operating in human somatic cells.",
			"category": 2,
			"name": "Alexandrov Ludmil B,2016"
		},
		{
			"PMID": 26539838,
			"title": "Breast Cancer beyond the Age of Mutation.",
			"journal": "Gerontology",
			"authorList": [
				"LaBarge Mark A",
				"Mora-Blanco E Lorena",
				"Samson Susan",
				"Miyano Masaru"
			],
			"DOI": "10.1159/000441030",
			"date": "2018-01-05",
			"PMC": "",
			"citation": "",
			"abstract": "Age is the greatest risk factor for breast cancer, but the reasons underlying this association are unclear. While there is undeniably a genetic component to all cancers, the accumulation of mutations with age is insufficient to explain the age-dependent increase in breast cancer incidence. In this viewpoint, we propose a multilevel framework to better understand the respective roles played by somatic mutation, microenvironment, and epigenetics making women more susceptible to breast cancer with age. The process of aging is associated with gradual breast tissue changes that not only corrupt the tumor-suppressive activity of normal tissue but also impose age-specific epigenetic changes that alter gene expression, thus reinforcing cellular phenotypes that are associated with a continuum of age-related tissue microenvironments. The evidence discussed here suggests that while the riddle of whether epigenetics drives microenvironmental changes, or whether changes in the microenvironment alter heritable cellular memory has not been solved, a path has been cleared enabling functional analysis leading to the prediction of key nodes in the network that link the microenvironment with the epigenome. The hypothesis that the accumulation of somatic mutations with age drives the age-related increase in breast cancer incidence, if correct, has a somewhat nihilistic conclusion, namely that cancers will be impossible to avoid. Alternatively, if microenvironment-driven epigenetic changes are the key to explaining susceptibility to age-related breast cancers, then there is hope that primary prevention is possible because epigenomes are relatively malleable.",
			"category": 2,
			"name": "LaBarge Mark A,2018"
		},
		{
			"PMID": 26528329,
			"title": "Defining order and timing of mutations during cancer progression: the TO-DAG probabilistic graphical model.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Lecca Paola",
				"Casiraghi Nicola",
				"Demichelis Francesca"
			],
			"DOI": "10.3389/fgene.2015.00309",
			"date": "2015-11-03",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic mutations arise and accumulate both during tumor genesis and progression. However, the order in which mutations occur is an open question and the inference of the temporal ordering at the gene level could potentially impact on patient treatment. Thus, exploiting recent observations suggesting that the occurrence of mutations is a non-memoryless process, we developed a computational approach to infer timed oncogenetic directed acyclic graphs (TO-DAGs) from human tumor mutation data. Such graphs represent the path and the waiting times of alterations during tumor evolution. The probability of occurrence of each alteration in a path is the probability that the alteration occurs when all alterations prior to it have occurred. The waiting time between an alteration and the subsequent is modeled as a stochastic function of the conditional probability of the event given the occurrence of the previous one. TO-DAG performances have been evaluated both on synthetic data and on somatic non-silent mutations from prostate cancer and melanoma patients and then compared with those of current well-established approaches. TO-DAG shows high performance scores on synthetic data and recognizes mutations in gatekeeper tumor suppressor genes as trigger for several downstream mutational events in the human tumor data.",
			"category": 2,
			"name": "Lecca Paola,2015"
		},
		{
			"PMID": 26516186,
			"title": "NCG 5.0: updates of a manually curated repository of cancer genes and associated properties from cancer mutational screenings.",
			"journal": "Nucleic acids research",
			"authorList": [
				"An Omer",
				"Dall'Olio Giovanni M",
				"Mourikis Thanos P",
				"Ciccarelli Francesca D"
			],
			"DOI": "10.1093/nar/gkv1123",
			"date": "2016-06-13",
			"PMC": "",
			"citation": "",
			"abstract": "The Network of Cancer Genes (NCG, http://ncg.kcl.ac.uk/) is a manually curated repository of cancer genes derived from the scientific literature. Due to the increasing amount of cancer genomic data, we have introduced a more robust procedure to extract cancer genes from published cancer mutational screenings and two curators independently reviewed each publication. NCG release 5.0 (August 2015) collects 1571 cancer genes from 175 published studies that describe 188 mutational screenings of 13 315 cancer samples from 49 cancer types and 24 primary sites. In addition to collecting cancer genes, NCG also provides information on the experimental validation that supports the role of these genes in cancer and annotates their properties (duplicability, evolutionary origin, expression profile, function and interactions with proteins and miRNAs).",
			"category": 2,
			"name": "An Omer,2016"
		},
		{
			"PMID": 26514359,
			"title": "Somatic gain-of-function HIF2A mutations in sporadic central nervous system hemangioblastomas.",
			"journal": "Journal of neuro-oncology",
			"authorList": [
				"Ta\u00efeb David",
				"Barlier Anne",
				"Yang Chunzhang",
				"Pertuit Morgane",
				"Tchoghandjian Aur\u00e9lie",
				"Rochette Claire",
				"Zattara-Canoni H\u00e9l\u00e8ne",
				"Figarella-Branger Dominique",
				"Zhuang Zhengping",
				"Pacak Karel",
				"Metellus Philippe"
			],
			"DOI": "10.1007/s11060-015-1983-y",
			"date": "2016-11-01",
			"PMC": "",
			"citation": "",
			"abstract": "Central nervous system hemangioblastomas (CNS-HBs) occur sporadically or as a component of von Hippel-Lindau-VHL syndrome. CNS-HBs share some molecular similarities with pheochromocytomas/paragangliomas (PPGLs) and renal cell carcinomas (RCCs). Recently, hypoxia-inducible factors, particularly somatic HIF2A mutations, have been found to play an important role in the pathogenesis of PPGLs. Somatic mutations in HIF2A have been reported in PPGLs associated with polycythemia, which have been reported to also be present in patients with RCCs and HBs. However, whether CNS-HBs is associated with the presence of a HIF2A mutation is currently uknown. We analyzed somatic HIF2A and VHL mutations in a series of 28 sporadic CNS-HBs. We also investigated the expression of HIF target proteins and hypoxia-associated factor (HAF). Two sporadic CNS-HBs were found to have somatic HIF2A mutations. One tumor had 2 HIF2A missense mutations, one of which was previously described in a PPGL (c.1121 T>A, F374Y). The second patient had coexistence of somatic truncated mutations (c.1669 C>T, Q557*) in HIF2A together with a VHL mutation. Neither of the two patients had polycythemia at the time of diagnosis. We demonstrate that the novel truncated mutation in HIF2A (Q557*) affects HIF-2\u03b1 prolyl hydroxylation with its reduced ubiquitination but intact transcriptional activity, resulting in an activating effect. Both CNS-HB samples showed positive expression of VEGFR2/CA9/Glut1 and HAF. Our data support the unique central role of the VHL/HIF-2\u03b1 signaling pathway in the molecular pathogenesis of CNS-HBs and show for the first time the presence of HIF2A mutations in sporadic HB.",
			"category": 2,
			"name": "Ta\u00efeb David,2016"
		},
		{
			"PMID": 26506596,
			"title": "A novel gammaretroviral shuttle vector insertional mutagenesis screen identifies SHARPIN as a breast cancer metastasis gene and prognostic biomarker.",
			"journal": "Oncotarget",
			"authorList": [
				"Bii Victor M",
				"Rae Dustin T",
				"Trobridge Grant D"
			],
			"DOI": "10.18632/oncotarget.6232",
			"date": "2016-09-20",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer (BC) is the second leading cause of malignancy among U.S. women. Metastasis results in a poor prognosis and increased mortality, but the molecular mechanisms by which metastatic tumors occur are not well understood. Identifying the genes that drive the metastatic process could provide targets for improved therapy and biomarkers to improve BC patient outcomes. Using a forward mutagenesis screen, BC cells mutagenized with a replication-incompetent gammaretroviral vector (\u03b3RV) were xenotransplanted into the mammary fat pad of immunodeficient mice. In this approach the vector provirus dysregulates nearby genes, providing a selective advantage to transduced cells to form metastases. Metastatic tumors were analyzed for proviral integration sites to identify nearby candidate metastasis genes. The \u03b3RV has a transgene cassette that allows for rescue in bacteria and rapid identification of vector integration sites. Using this approach, we identified the previously described metastasis gene WWTR1 (TAZ), and three other novel candidate metastasis genes including SHARPIN. SHARPIN was independently validated in vivo as a BC metastasis gene. Analysis of patient data showed that SHARPIN expression predicts metastasis-free survival after adjuvant therapy. Our approach has broad potential to identify genes involved in oncogenic processes for BC and other cancers. We show here it can identify both known (WWTR1) and novel (SHARPIN) BC metastasis genes.",
			"category": 2,
			"name": "Bii Victor M,2016"
		},
		{
			"PMID": 26500804,
			"title": "mBLAST: Keeping up with the sequencing explosion for (meta)genome analysis.",
			"journal": "Journal of data mining in genomics & proteomics",
			"authorList": [
				"Davis Curtis",
				"Kota Karthik",
				"Baldhandapani Venkat",
				"Gong Wei",
				"Abubucker Sahar",
				"Becker Eric",
				"Martin John",
				"Wylie Kristine M",
				"Khetani Radhika",
				"Hudson Matthew E",
				"Weinstock George M",
				"Mitreva Makedonka"
			],
			"DOI": "",
			"date": "2020-10-01",
			"PMC": "",
			"citation": "",
			"abstract": "Recent advances in next-generation sequencing technologies require alignment algorithms and software that can keep pace with the heightened data production. Standard algorithms, especially protein similarity searches, represent significant bottlenecks in analysis pipelines. For metagenomic approaches in particular, it is now often necessary to search hundreds of millions of sequence reads against large databases. Here we describe mBLAST, an accelerated search algorithm for translated and/or protein alignments to large datasets based on the Basic Local Alignment Search Tool (BLAST) and retaining the high sensitivity of BLAST. The mBLAST algorithms achieve substantial speed up over the National Center for Biotechnology Information (NCBI) programs BLASTX, TBLASTX and BLASTP for large datasets, allowing analysis within reasonable timeframes on standard computer architectures. In this article, the impact of mBLAST is demonstrated with sequences originating from the microbiota of healthy humans from the Human Microbiome Project. mBLAST is designed as a plug-in replacement for BLAST for any study that involves short-read sequences and includes high-throughput analysis. The mBLAST software is freely available to academic users at www.multicorewareinc.com.",
			"category": 2,
			"name": "Davis Curtis,2020"
		},
		{
			"PMID": 26500031,
			"title": "Detection of Clonal and Subclonal Copy-Number Variants in Cell-Free DNA from Patients with Breast Cancer Using a Massively Multiplexed PCR Methodology.",
			"journal": "Translational oncology",
			"authorList": [
				"Kirkizlar Eser",
				"Zimmermann Bernhard",
				"Constantin Tudor",
				"Swenerton Ryan",
				"Hoang Bin",
				"Wayham Nicholas",
				"Babiarz Joshua E",
				"Demko Zachary",
				"Pelham Robert J",
				"Kareht Stephanie",
				"Simon Alexander L",
				"Jinnett Kristine N",
				"Rabinowitz Matthew",
				"Sigurjonsson Styrmir",
				"Hill Matthew"
			],
			"DOI": "10.1016/j.tranon.2015.08.004",
			"date": "2015-10-27",
			"PMC": "",
			"citation": "",
			"abstract": "We demonstrate proof-of-concept for the use of massively multiplexed PCR and next-generation sequencing (mmPCR-NGS) to identify both clonal and subclonal copy-number variants (CNVs) in circulating tumor DNA. This is the first report of a targeted methodology for detection of CNVs in plasma. Using an in vitro model of cell-free DNA, we show that mmPCR-NGS can accurately detect CNVs with average allelic imbalances as low as 0.5%, an improvement over previously reported whole-genome sequencing approaches. Our method revealed differences in the spectrum of CNVs detected in tumor tissue subsections and matching plasma samples from 11 patients with stage II breast cancer. Moreover, we showed that liquid biopsies are able to detect subclonal mutations that may be missed in tumor tissue biopsies. We anticipate that this mmPCR-NGS methodology will have broad applicability for the characterization, diagnosis, and therapeutic monitoring of CNV-enriched cancers, such as breast, ovarian, and lung cancer.",
			"category": 2,
			"name": "Kirkizlar Eser,2015"
		},
		{
			"PMID": 26484415,
			"title": "Oncogenomic portals for the visualization and analysis of genome-wide cancer data.",
			"journal": "Oncotarget",
			"authorList": [
				"Klonowska Katarzyna",
				"Czubak Karol",
				"Wojciechowska Marzena",
				"Handschuh Luiza",
				"Zmienko Agnieszka",
				"Figlerowicz Marek",
				"Dams-Kozlowska Hanna",
				"Kozlowski Piotr"
			],
			"DOI": "10.18632/oncotarget.6128",
			"date": "2016-11-02",
			"PMC": "",
			"citation": "",
			"abstract": "Somatically acquired genomic alterations that drive oncogenic cellular processes are of great scientific and clinical interest. Since the initiation of large-scale cancer genomic projects (e.g., the Cancer Genome Project, The Cancer Genome Atlas, and the International Cancer Genome Consortium cancer genome projects), a number of web-based portals have been created to facilitate access to multidimensional oncogenomic data and assist with the interpretation of the data. The portals provide the visualization of small-size mutations, copy number variations, methylation, and gene/protein expression data that can be correlated with the available clinical, epidemiological, and molecular features. Additionally, the portals enable to analyze the gathered data with the use of various user-friendly statistical tools. Herein, we present a highly illustrated review of seven portals, i.e., Tumorscape, UCSC Cancer Genomics Browser, ICGC Data Portal, COSMIC, cBioPortal, IntOGen, and BioProfiling.de. All of the selected portals are user-friendly and can be exploited by scientists from different cancer-associated fields, including those without bioinformatics background. It is expected that the use of the portals will contribute to a better understanding of cancer molecular etiology and will ultimately accelerate the translation of genomic knowledge into clinical practice.",
			"category": 2,
			"name": "Klonowska Katarzyna,2016"
		},
		{
			"PMID": 26473189,
			"title": "Next-Generation Sequencing to Guide Clinical Trials.",
			"journal": "Clinical cancer research : an official journal of the American Association for Cancer Research",
			"authorList": [
				"Siu Lillian L",
				"Conley Barbara A",
				"Boerner Scott",
				"LoRusso Patricia M"
			],
			"DOI": "10.1158/1078-0432.CCR-14-3215",
			"date": "2016-08-01",
			"PMC": "",
			"citation": "",
			"abstract": "Rapidly accruing knowledge of the mutational landscape of malignant neoplasms, the increasing facility of massively parallel genomic sequencing, and the availability of drugs targeting many \"driver\" molecular abnormalities have spurred the oncologic community to consider how to use these new tools to improve cancer treatment. In order to assure that assignment of patients to a particular targeted treatment is likely to be beneficial to the patient, it will be necessary to conduct appropriate clinical research. It is clear that clinical (histology and stage) eligibility criteria are not sufficient for most clinical trials using agents that target mutations that are present in only a minority of patients. Recently, several clinical trial designs have been suggested to test the benefit of targeted treatment in molecular and/or clinical subgroups of patients. However, challenges remain in the implementation of such trials, including choice of assay, levels of evidence regarding gene variants, tumor heterogeneity, identifying resistance mechanisms, the necessity of screening large numbers of patients, infrastructure needs, and collaboration of investigators and industry. This article reviews current trial designs and discusses some of the considerations, advantages, and drawbacks of designing clinical trials that depend on particular molecular variants as eligibility criteria.",
			"category": 2,
			"name": "Siu Lillian L,2016"
		},
		{
			"PMID": 26456849,
			"title": "The mini-driver model of polygenic cancer evolution.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Castro-Giner Francesc",
				"Ratcliffe Peter",
				"Tomlinson Ian"
			],
			"DOI": "10.1038/nrc3999",
			"date": "2016-01-28",
			"PMC": "",
			"citation": "",
			"abstract": "Much of cancer genetics research has focused on the identification of the most-important somatic mutations ('major drivers') that cause tumour growth. However, many mutations found in cancer might not be major drivers or 'passenger' mutations, but instead might have relatively weak tumour-promoting effects. Our aim is to highlight the existence of these mutations (termed 'mini drivers' herein), as multiple mini-driver mutations might substitute for a major-driver change, especially in the presence of genomic instability or high mutagen exposure. The mini-driver model has clinical implications: for example, the effects of therapeutically targeting such genes may be limited. However, the main importance of the model lies in helping to provide a complete understanding of tumorigenesis, especially as we anticipate that an increasing number of mini-driver mutations will be found by cancer genome sequencing.",
			"category": 2,
			"name": "Castro-Giner Francesc,2016"
		},
		{
			"PMID": 26443852,
			"title": "The genome as a record of environmental exposure.",
			"journal": "Mutagenesis",
			"authorList": [
				"Nik-Zainal Serena",
				"Kucab Jill E",
				"Morganella Sandro",
				"Glodzik Dominik",
				"Alexandrov Ludmil B",
				"Arlt Volker M",
				"Weninger Annette",
				"Hollstein Monica",
				"Stratton Michael R",
				"Phillips David H"
			],
			"DOI": "10.1093/mutage/gev073",
			"date": "2016-08-19",
			"PMC": "",
			"citation": "",
			"abstract": "Whole genome sequencing of human tumours has revealed distinct patterns of mutation that hint at the causative origins of cancer. Experimental investigations of the mutations and mutation spectra induced by environmental mutagens have traditionally focused on single genes. With the advent of faster cheaper sequencing platforms, it is now possible to assess mutation spectra in experimental models across the whole genome. As a proof of principle, we have examined the whole genome mutation profiles of mouse embryo fibroblasts immortalised following exposure to benzo[a]pyrene (BaP), ultraviolet light (UV) and aristolochic acid (AA). The results reveal that each mutagen induces a characteristic mutation signature: predominantly G\u2192T mutations for BaP, C\u2192T and CC\u2192TT for UV and A\u2192T for AA. The data are not only consistent with existing knowledge but also provide additional information at higher levels of genomic organisation. The approach holds promise for identifying agents responsible for mutations in human tumours and for shedding light on the aetiology of human cancer.",
			"category": 2,
			"name": "Nik-Zainal Serena,2016"
		},
		{
			"PMID": 26415501,
			"title": "A cell-based model system links chromothripsis with hyperploidy.",
			"journal": "Molecular systems biology",
			"authorList": [
				"Mardin Balca R",
				"Drainas Alexandros P",
				"Waszak Sebastian M",
				"Weischenfeldt Joachim",
				"Isokane Mayumi",
				"St\u00fctz Adrian M",
				"Raeder Benjamin",
				"Efthymiopoulos Theocharis",
				"Buccitelli Christopher",
				"Segura-Wang Maia",
				"Northcott Paul",
				"Pfister Stefan M",
				"Lichter Peter",
				"Ellenberg Jan",
				"Korbel Jan O"
			],
			"DOI": "10.15252/msb.20156505",
			"date": "2016-06-28",
			"PMC": "",
			"citation": "",
			"abstract": "A remarkable observation emerging from recent cancer genome analyses is the identification of chromothripsis as a one-off genomic catastrophe, resulting in massive somatic DNA structural rearrangements (SRs). Largely due to lack of suitable model systems, the mechanistic basis of chromothripsis has remained elusive. We developed an integrative method termed \"complex alterations after selection and transformation (CAST),\" enabling efficient in vitro generation of complex DNA rearrangements including chromothripsis, using cell perturbations coupled with a strong selection barrier followed by massively parallel sequencing. We employed this methodology to characterize catastrophic SR formation processes, their temporal sequence, and their impact on gene expression and cell division. Our in vitro system uncovered a propensity of chromothripsis to occur in cells with damaged telomeres, and in particular in hyperploid cells. Analysis of primary medulloblastoma cancer genomes verified the link between hyperploidy and chromothripsis in vivo. CAST provides the foundation for mechanistic dissection of complex DNA rearrangement processes.",
			"category": 2,
			"name": "Mardin Balca R,2016"
		},
		{
			"PMID": 26396686,
			"title": "Structural Optimization of Indole Derivatives Acting at Colchicine Binding Site as Potential Anticancer Agents.",
			"journal": "ACS medicinal chemistry letters",
			"authorList": [
				"Hwang Dong-Jin",
				"Wang Jin",
				"Li Wei",
				"Miller Duane D"
			],
			"DOI": "10.1021/acsmedchemlett.5b00208",
			"date": "2015-09-23",
			"PMC": "",
			"citation": "",
			"abstract": "A new series of indole analogues based on our earlier lead compound, 2-(1H-indol-5-yl)-4-(3,4,5-trimethoxyphenyl)-1H-imidazo[4,5-c]pyridine (42), was prepared as tubulin inhibitors in an effort to find a molecule with improved cytotoxic potency and metabolic stability. A series of indolyl-imidazopyridines (IIP) were synthesized and exhibited potent tubulin polymerization inhibitory activity with potent IC50 values ranging from 3 to 175 nM against a panel of human melanoma and prostate cancer cell lines. Among these compounds, the 6-indolyl compound 43 showed improved cytotoxic potency (average IC50 of 9.75 nM vs 55.75 nM) and metabolic stability in human liver microsomes (half-life time was 56.3 min vs. 45.4 min) as compared to previously reported 42. It was also shown to be effective against P-glycoprotein (P-gp) mediated multiple drug resistance (MDR) and taxol resistance.",
			"category": 2,
			"name": "Hwang Dong-Jin,2015"
		},
		{
			"PMID": 26389881,
			"title": "CRISPR-Cas9: A Revolutionary Tool for Cancer Modelling.",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Torres-Ruiz Raul",
				"Rodriguez-Perales Sandra"
			],
			"DOI": "10.3390/ijms160922151",
			"date": "2016-06-17",
			"PMC": "",
			"citation": "",
			"abstract": "The cancer-modelling field is now experiencing a conversion with the recent emergence of the RNA-programmable CRISPR-Cas9 system, a flexible methodology to produce essentially any desired modification in the genome. Cancer is a multistep process that involves many genetic mutations and other genome rearrangements. Despite their importance, it is difficult to recapitulate the degree of genetic complexity found in patient tumors. The CRISPR-Cas9 system for genome editing has been proven as a robust technology that makes it possible to generate cellular and animal models that recapitulate those cooperative alterations rapidly and at low cost. In this review, we will discuss the innovative applications of the CRISPR-Cas9 system to generate new models, providing a new way to interrogate the development and progression of cancers.",
			"category": 2,
			"name": "Torres-Ruiz Raul,2016"
		},
		{
			"PMID": 26380552,
			"title": "Targeting Breast Cancer Metastasis.",
			"journal": "Breast cancer : basic and clinical research",
			"authorList": [
				"Jin Xin",
				"Mu Ping"
			],
			"DOI": "10.4137/BCBCR.S25460",
			"date": "2015-09-18",
			"PMC": "",
			"citation": "",
			"abstract": "Metastasis is the leading cause of breast cancer-associated deaths. Despite the significant improvement in current therapies in extending patient life, 30-40% of patients may eventually suffer from distant relapse and succumb to the disease. Consequently, a deeper understanding of the metastasis biology is key to developing better treatment strategies and achieving long-lasting therapeutic efficacies against breast cancer. This review covers recent breakthroughs in the discovery of various metastatic traits that contribute to the metastasis cascade of breast cancer, which may provide novel avenues for therapeutic targeting.",
			"category": 2,
			"name": "Jin Xin,2015"
		},
		{
			"PMID": 26375816,
			"title": "High Prevalence and Clinical Relevance of Genes Affected by Chromosomal Breaks in Colorectal Cancer.",
			"journal": "PloS one",
			"authorList": [
				"van den Broek Evert",
				"Dijkstra Maurits J J",
				"Krijgsman Oscar",
				"Sie Daoud",
				"Haan Josien C",
				"Traets Joleen J H",
				"van de Wiel Mark A",
				"Nagtegaal Iris D",
				"Punt Cornelis J A",
				"Carvalho Beatriz",
				"Ylstra Bauke",
				"Abeln Sanne",
				"Meijer Gerrit A",
				"Fijneman Remond J A"
			],
			"DOI": "10.1371/journal.pone.0138141",
			"date": "2016-05-27",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is caused by somatic DNA alterations such as gene point mutations, DNA copy number aberrations (CNA) and structural variants (SVs). Genome-wide analyses of SVs in large sample series with well-documented clinical information are still scarce. Consequently, the impact of SVs on carcinogenesis and patient outcome remains poorly understood. This study aimed to perform a systematic analysis of genes that are affected by CNA-associated chromosomal breaks in colorectal cancer (CRC) and to determine the clinical relevance of recurrent breakpoint genes.",
			"category": 2,
			"name": "van den Broek Evert,2016"
		},
		{
			"PMID": 26351634,
			"title": "Towards a Next-Generation Sequencing Diagnostic Service for Tumour Genotyping: A Comparison of Panels and Platforms.",
			"journal": "BioMed research international",
			"authorList": [
				"Burghel George J",
				"Hurst Carolyn D",
				"Watson Christopher M",
				"Chambers Phillip A",
				"Dickinson Helen",
				"Roberts Paul",
				"Knowles Margaret A"
			],
			"DOI": "10.1155/2015/478017",
			"date": "2016-06-09",
			"PMC": "",
			"citation": "",
			"abstract": "Detection of clinically actionable mutations in diagnostic tumour specimens aids in the selection of targeted therapeutics. With an ever increasing number of clinically significant mutations identified, tumour genetic diagnostics is moving from single to multigene analysis. As it is still not feasible for routine diagnostic laboratories to perform sequencing of the entire cancer genome, our approach was to undertake targeted mutation detection. To optimise our diagnostic workflow, we evaluated three target enrichment strategies using two next-generation sequencing (NGS) platforms (Illumina MiSeq and Ion PGM). The target enrichment strategies were Fluidigm Access Array custom amplicon panel including 13 genes (MiSeq sequencing), the Oxford Gene Technologies (OGT) SureSeq Solid Tumour hybridisation panel including 60 genes (MiSeq sequencing), and an Ion AmpliSeq Cancer Hotspot Panel including 50 genes (Ion PGM sequencing). DNA extracted from formalin-fixed paraffin-embedded (FFPE) blocks of eight previously characterised cancer cell lines was tested using the three panels. Matching genomic DNA from fresh cultures of these cell lines was also tested using the custom Fluidigm panel and the OGT SureSeq Solid Tumour panel. Each panel allowed mutation detection of core cancer genes including KRAS, BRAF, and EGFR. Our results indicate that the panels enable accurate variant detection despite sequencing from FFPE DNA.",
			"category": 2,
			"name": "Burghel George J,2016"
		},
		{
			"PMID": 26325016,
			"title": "How do oncoprotein mutations rewire protein-protein interaction networks?",
			"journal": "Expert review of proteomics",
			"authorList": [
				"Bowler Emily H",
				"Wang Zhenghe",
				"Ewing Rob M"
			],
			"DOI": "10.1586/14789450.2015.1084875",
			"date": "2016-06-27",
			"PMC": "",
			"citation": "",
			"abstract": "The acquisition of mutations that activate oncogenes or inactivate tumor suppressors is a primary feature of most cancers. Mutations that directly alter protein sequence and structure drive the development of tumors through aberrant expression and modification of proteins, in many cases directly impacting components of signal transduction pathways and cellular architecture. Cancer-associated mutations may have direct or indirect effects on proteins and their interactions and while the effects of mutations on signaling pathways have been widely studied, how mutations alter underlying protein-protein interaction networks is much less well understood. Systematic mapping of oncoprotein protein interactions using proteomics techniques as well as computational network analyses is revealing how oncoprotein mutations perturb protein-protein interaction networks and drive the cancer phenotype.",
			"category": 2,
			"name": "Bowler Emily H,2016"
		},
		{
			"PMID": 26317543,
			"title": "The sum of gains and losses of genes encoding the protein tyrosine kinase targets predicts response to multi-kinase inhibitor treatment: Characterization, validation, and prognostic value.",
			"journal": "Oncotarget",
			"authorList": [
				"Jiang Xiaojun",
				"Pissaloux Daniel",
				"De La Fouchardiere Christelle",
				"Desseigne Fran\u00e7oise",
				"Wang Qing",
				"Attignon Valery",
				"Fondrevelle Marie-Eve",
				"De La Fouchardiere Arnaud",
				"Perol Maurice",
				"Cassier Philippe",
				"Seigne Christelle",
				"Perol David",
				"Ray-Coquard Isabelle",
				"Meeus Pierre",
				"Fayette Jerome",
				"Flechon Aude",
				"Le Cesne Axel",
				"Penel Nicolas",
				"Tredan Olivier",
				"Blay Jean-Yves"
			],
			"DOI": "10.18632/oncotarget.4557",
			"date": "2016-07-22",
			"PMC": "",
			"citation": "",
			"abstract": "Validated predictive biomarkers for multi-tyrosine kinase inhibitors (MTKI) efficacy are lacking. We hypothesized that interindividual response variability is partially dependent on somatic DNA copy number alterations (SCNAs), particularly those of genes encoding the protein tyrosines targeted by MTKI (called target genes). Genomic alterations were investigated in MTKI responsive and non responsive patients with different histological subtypes included in the ProfiLER protocol (NCT 01774409). From March 2013 to August 2014, 58 patients with advanced cancer treated with one of 7 MTKIs were included in the ProfiLER trial and split into one discovery cohort (n = 13), and 2 validation cohorts (n = 12 and 33). An analysis of the copy number alterations of kinase-coding genes for each of 7 MTKIs was conducted. A prediction algorithm (SUMSCAN) based on the presence of specific gene gains (Tumor Target Charge, TTC) and losses (Tumor Target Losses, TTL) was conceived and validated in 2 independent validation cohorts. MTKI sensitive tumors present a characteristic SCNA profile including a global gain profile, and specific gains for target genes while MTKI resistant tumors present the opposite. SUMSCAN favorable patients achieved longer progression-free and overall survival. This work shows that the copy number sum of kinase-coding genes enables the prediction of response of cancer patients to MTKI, opening a novel paradigm for the treatment selection of these patients.",
			"category": 2,
			"name": "Jiang Xiaojun,2016"
		},
		{
			"PMID": 26300997,
			"title": "Next-generation sequencing for genetic testing of familial colorectal cancer syndromes.",
			"journal": "Hereditary cancer in clinical practice",
			"authorList": [
				"Simbolo Michele",
				"Mafficini Andrea",
				"Agostini Marco",
				"Pedrazzani Corrado",
				"Bedin Chiara",
				"Urso Emanuele D",
				"Nitti Donato",
				"Turri Giona",
				"Scardoni Maria",
				"Fassan Matteo",
				"Scarpa Aldo"
			],
			"DOI": "10.1186/s13053-015-0039-9",
			"date": "2015-08-24",
			"PMC": "",
			"citation": "",
			"abstract": "Genetic screening in families with high risk to develop colorectal cancer (CRC) prevents incurable disease and permits personalized therapeutic and follow-up strategies. The advancement of next-generation sequencing (NGS) technologies has revolutionized the throughput of DNA sequencing.",
			"category": 2,
			"name": "Simbolo Michele,2015"
		},
		{
			"PMID": 26292924,
			"title": "Large-scale RNA-Seq Transcriptome Analysis of 4043 Cancers and 548 Normal Tissue Controls across 12 TCGA Cancer Types.",
			"journal": "Scientific reports",
			"authorList": [
				"Peng Li",
				"Bian Xiu Wu",
				"Li Di Kang",
				"Xu Chuan",
				"Wang Guang Ming",
				"Xia Qing You",
				"Xiong Qing"
			],
			"DOI": "10.1038/srep13413",
			"date": "2016-09-13",
			"PMC": "",
			"citation": "",
			"abstract": "The Cancer Genome Atlas (TCGA) has accrued RNA-Seq-based transcriptome data for more than 4000 cancer tissue samples across 12 cancer types, translating these data into biological insights remains a major challenge. We analyzed and compared the transcriptomes of 4043 cancer and 548 normal tissue samples from 21 TCGA cancer types, and created a comprehensive catalog of gene expression alterations for each cancer type. By clustering genes into co-regulated gene sets, we identified seven cross-cancer gene signatures altered across a diverse panel of primary human cancer samples. A 14-gene signature extracted from these seven cross-cancer gene signatures precisely differentiated between cancerous and normal samples, the predictive accuracy of leave-one-out cross-validation (LOOCV) were 92.04%, 96.23%, 91.76%, 90.05%, 88.17%, 94.29%, and 99.10% for BLCA, BRCA, COAD, HNSC, LIHC, LUAD, and LUSC, respectively. A lung cancer-specific gene signature, containing SFTPA1 and SFTPA2 genes, accurately distinguished lung cancer from other cancer samples, the predictive accuracy of LOOCV for TCGA and GSE5364 data were 95.68% and 100%, respectively. These gene signatures provide rich insights into the transcriptional programs that trigger tumorigenesis and metastasis, and many genes in the signature gene panels may be of significant value to the diagnosis and treatment of cancer.",
			"category": 2,
			"name": "Peng Li,2016"
		},
		{
			"PMID": 26282678,
			"title": "Harmful somatic amino acid substitutions affect key pathways in cancers.",
			"journal": "BMC medical genomics",
			"authorList": [
				"Niroula Abhishek",
				"Vihinen Mauno"
			],
			"DOI": "10.1186/s12920-015-0125-x",
			"date": "2016-04-25",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is characterized by the accumulation of large numbers of genetic variations and alterations of multiple biological phenomena. Cancer genomics has largely focused on the identification of such genetic alterations and the genes containing them, known as 'cancer genes'. However, the non-functional somatic variations out-number functional variations and remain as a major challenge. Recurrent somatic variations are thought to be cancer drivers but they are present in only a small fraction of patients.",
			"category": 2,
			"name": "Niroula Abhishek,2016"
		},
		{
			"PMID": 26253570,
			"title": "Comprehensive assembly of novel transcripts from unmapped human RNA-Seq data and their association with cancer.",
			"journal": "Molecular systems biology",
			"authorList": [
				"Kazemian Majid",
				"Ren Min",
				"Lin Jian-Xin",
				"Liao Wei",
				"Spolski Rosanne",
				"Leonard Warren J"
			],
			"DOI": "10.15252/msb.156172",
			"date": "2016-05-17",
			"PMC": "",
			"citation": "",
			"abstract": "Crucial parts of the genome including genes encoding microRNAs and noncoding RNAs went unnoticed for years, and even now, despite extensive annotation and assembly of the human genome, RNA-sequencing continues to yield millions of unmappable and thus uncharacterized reads. Here, we examined > 300 billion reads from 536 normal donors and 1,873 patients encompassing 21 cancer types, identified ~300 million such uncharacterized reads, and using a distinctive approach de novo assembled 2,550 novel human transcripts, which mainly represent long noncoding RNAs. Of these, 230 exhibited relatively specific expression or non-expression in certain cancer types, making them potential markers for those cancers, whereas 183 exhibited tissue specificity. Moreover, we used lentiviral-mediated expression of three selected transcripts that had higher expression in normal than in cancer patients and found that each inhibited the growth of HepG2 cells. Our analysis provides a comprehensive and unbiased resource of unmapped human transcripts and reveals their associations with specific cancers, providing potentially important new genes for therapeutic targeting.",
			"category": 2,
			"name": "Kazemian Majid,2016"
		},
		{
			"PMID": 26212640,
			"title": "Genome-wide mutational spectra analysis reveals significant cancer-specific heterogeneity.",
			"journal": "Scientific reports",
			"authorList": [
				"Tan Hua",
				"Bao Jiguang",
				"Zhou Xiaobo"
			],
			"DOI": "10.1038/srep12566",
			"date": "2016-07-01",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is widely recognized as a genetic disease in which somatic mutations are sequentially accumulated to drive tumor progression. Although genomic landscape studies are informative for individual cancer types, a comprehensive comparative study of tumorigenic mutations across cancer types based on integrative data sources is still a pressing need. We systematically analyzed ~10(6) non-synonymous mutations extracted from COSMIC, involving ~8000 genome-wide screened samples across 23 major human cancers at both the amino acid and gene levels. Our analysis identified cancer-specific heterogeneity that traditional nucleotide variation analysis alone usually overlooked. Particularly, the amino acid arginine (R) turns out to be the most favorable target of amino acid alteration in most cancer types studied (P\u2009<\u200910(-9), binomial test), reflecting its important role in cellular physiology. The tumor suppressor gene TP53 is mutated exclusively with the HYDIN, KRAS, and PTEN genes in large intestine, lung, and endometrial cancers respectively, indicating that TP53 takes part in different signaling pathways in different cancers. While some of our analyses corroborated previous observations, others indicated relevant candidates with high priority for further experimental validation. Our findings have many ramifications in understanding the etiology of cancer and the underlying molecular mechanisms in particular cancers.",
			"category": 2,
			"name": "Tan Hua,2016"
		},
		{
			"PMID": 26197069,
			"title": "Precise Classification of Cervical Carcinomas Combined with Somatic Mutation Profiling Contributes to Predicting Disease Outcome.",
			"journal": "PloS one",
			"authorList": [
				"Spaans Vivian M",
				"Trietsch Marjolijn D",
				"Peters Alexander A W",
				"Osse Michelle",
				"Ter Haar Natalja",
				"Fleuren Gert J",
				"Jordanova Ekaterina S"
			],
			"DOI": "10.1371/journal.pone.0133670",
			"date": "2016-05-13",
			"PMC": "",
			"citation": "",
			"abstract": "Squamous cell carcinoma (SCC), adenocarcinoma (AC), and adenosquamous carcinoma (ASC) are the most common histological subtypes of cervical cancer. Differences in the somatic mutation profiles of these subtypes have been suggested. We investigated the prevalence of somatic hot-spot mutations in three well-defined cohorts of SCC, AC, and ASC and determined the additional value of mutation profiling in predicting disease outcome relative to well-established prognostic parameters.",
			"category": 2,
			"name": "Spaans Vivian M,2016"
		},
		{
			"PMID": 26177635,
			"title": "Integrated sequence and expression analysis of ovarian cancer structural variants underscores the importance of gene fusion regulation.",
			"journal": "BMC medical genomics",
			"authorList": [
				"Mittal Vinay K",
				"McDonald John F"
			],
			"DOI": "10.1186/s12920-015-0118-9",
			"date": "2016-03-03",
			"PMC": "",
			"citation": "",
			"abstract": "Genomic rearrangements or structural variants (SVs) are one of the most common classes of mutations in cancer.",
			"category": 2,
			"name": "Mittal Vinay K,2016"
		},
		{
			"PMID": 26170328,
			"title": "Mutation-induced protein interaction kinetics changes affect apoptotic network dynamic properties and facilitate oncogenesis.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Zhao Linjie",
				"Sun Tanlin",
				"Pei Jianfeng",
				"Ouyang Qi"
			],
			"DOI": "10.1073/pnas.1502126112",
			"date": "2015-10-27",
			"PMC": "",
			"citation": "",
			"abstract": "It has been a consensus in cancer research that cancer is a disease caused primarily by genomic alterations, especially somatic mutations. However, the mechanism of mutation-induced oncogenesis is not fully understood. Here, we used the mitochondrial apoptotic pathway as a case study and performed a systematic analysis of integrating pathway dynamics with protein interaction kinetics to quantitatively investigate the causal molecular mechanism of mutation-induced oncogenesis. A mathematical model of the regulatory network was constructed to establish the functional role of dynamic bifurcation in the apoptotic process. The oncogenic mutation enrichment of each of the protein functional domains involved was found strongly correlated with the parameter sensitivity of the bifurcation point. We further dissected the causal mechanism underlying this correlation by evaluating the mutational influence on protein interaction kinetics using molecular dynamics simulation. We analyzed 29 matched mutant-wild-type and 16 matched SNP--wild-type protein systems. We found that the binding kinetics changes reflected by the changes of free energy changes induced by protein interaction mutations, which induce variations in the sensitive parameters of the bifurcation point, were a major cause of apoptosis pathway dysfunction, and mutations involved in sensitive interaction domains show high oncogenic potential. Our analysis provided a molecular basis for connecting protein mutations, protein interaction kinetics, network dynamics properties, and physiological function of a regulatory network. These insights provide a framework for coupling mutation genotype to tumorigenesis phenotype and help elucidate the logic of cancer initiation.",
			"category": 2,
			"name": "Zhao Linjie,2015"
		},
		{
			"PMID": 26132936,
			"title": "Prevalence of the Prefoldin Subunit 5 Gene Deletion in Canine Mammary Tumors.",
			"journal": "PloS one",
			"authorList": [
				"Hennecke Silvia",
				"Beck Julia",
				"Bornemann-Kolatzki Kirsten",
				"Neumann Stephan",
				"Murua Escobar Hugo",
				"Nolte Ingo",
				"Hammer Susanne Conradine",
				"Hewicker-Trautwein Marion",
				"Junginger Johannes",
				"Kaup Franz-Josef",
				"Brenig Bertram",
				"Sch\u00fctz Ekkehard"
			],
			"DOI": "10.1371/journal.pone.0131280",
			"date": "2016-04-06",
			"PMC": "",
			"citation": "",
			"abstract": "A somatic deletion at the proximal end of canine chromosome 27 (CFA27) was recently reported in 50% of malignant mammary tumors. This region harbours the tumor suppressor gene prefoldin subunit 5 (PFDN5) and the deletion correlated with a higher Ki-67 score. PFDN5 has been described to repress c-MYC and is, therefore, a candidate tumor-suppressor and cancer-driver gene in canine mammary cancer. Aim of this study was to confirm the recurrent deletion in a larger number of tumors.",
			"category": 2,
			"name": "Hennecke Silvia,2016"
		},
		{
			"PMID": 26130253,
			"title": "Assessment of Esophageal Adenocarcinoma Risk Using Somatic Chromosome Alterations in Longitudinal Samples in Barrett's Esophagus.",
			"journal": "Cancer prevention research (Philadelphia, Pa.)",
			"authorList": [
				"Li Xiaohong",
				"Paulson Thomas G",
				"Galipeau Patricia C",
				"Sanchez Carissa A",
				"Liu Karen",
				"Kuhner Mary K",
				"Maley Carlo C",
				"Self Steven G",
				"Vaughan Thomas L",
				"Reid Brian J",
				"Blount Patricia L"
			],
			"DOI": "10.1158/1940-6207.CAPR-15-0130",
			"date": "2016-06-21",
			"PMC": "",
			"citation": "",
			"abstract": "Cancers detected at a late stage are often refractory to treatments and ultimately lethal. Early detection can significantly increase survival probability, but attempts to reduce mortality by early detection have frequently increased overdiagnosis of indolent conditions that do not progress over a lifetime. Study designs that incorporate biomarker trajectories in time and space are needed to distinguish patients who progress to an early cancer from those who follow an indolent course. Esophageal adenocarcinoma is characterized by evolution of punctuated and catastrophic somatic chromosomal alterations and high levels of overall mutations but few recurrently mutated genes aside from TP53. Endoscopic surveillance of Barrett's esophagus for early cancer detection provides an opportunity for assessment of alterations for cancer risk in patients who progress to esophageal adenocarcinoma compared with nonprogressors. We investigated 1,272 longitudinally collected esophageal biopsies in a 248 Barrett's patient case-cohort study with 20,425 person-months of follow-up, including 79 who progressed to early-stage esophageal adenocarcinoma. Cancer progression risk was assessed for total chromosomal alterations, diversity, and chromosomal region-specific alterations measured with single-nucleotide polymorphism arrays in biopsies obtained over esophageal space and time. A model using 29 chromosomal features was developed for cancer risk prediction (area under receiver operator curve, 0.94). The model prediction performance was robust in two independent esophageal adenocarcinoma sets and outperformed TP53 mutation, flow cytometric DNA content, and histopathologic diagnosis of dysplasia. This study offers a strategy to reduce overdiagnosis in Barrett's esophagus and improve early detection of esophageal adenocarcinoma and potentially other cancers characterized by punctuated and catastrophic chromosomal evolution.",
			"category": 2,
			"name": "Li Xiaohong,2016"
		},
		{
			"PMID": 26126604,
			"title": "An online tool for evaluating diagnostic and prognostic gene expression biomarkers in bladder cancer.",
			"journal": "BMC urology",
			"authorList": [
				"Dancik Garrett M"
			],
			"DOI": "10.1186/s12894-015-0056-z",
			"date": "2016-03-02",
			"PMC": "",
			"citation": "",
			"abstract": "In the past ~15\u00a0years, the identification of diagnostic and prognostic biomarkers from gene expression data has increased our understanding of cancer biology and has led to advances in the personalized treatment of many cancers. A diagnostic biomarker is indicative of tumor status such as tumor stage, while a prognostic biomarker is indicative of disease outcome. Despite these advances, however, there are no clinically approved biomarkers for the treatment of bladder cancer, which is the fourth most common cancer in males in the United States and one of the most expensive cancers to treat. Although gene expression profiles of bladder cancer patients are publicly available, biomarker identification requires bioinformatics expertise that is not available to many research laboratories.",
			"category": 2,
			"name": "Dancik Garrett M,2016"
		},
		{
			"PMID": 26117318,
			"title": "Functional polymorphisms in Nrf2: implications for human disease.",
			"journal": "Free radical biology & medicine",
			"authorList": [
				"Cho Hye-Youn",
				"Marzec Jacqui",
				"Kleeberger Steven R"
			],
			"DOI": "10.1016/j.freeradbiomed.2015.06.012",
			"date": "2016-08-18",
			"PMC": "",
			"citation": "",
			"abstract": "Nuclear factor (erythroid derived)-2 like 2 (NFE2L2), also known as nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), is a ubiquitous transcription factor essential for protecting cells and tissues from oxidative stress-induced injury. Positional cloning and studies with Nrf2 knockout mice have identified important roles for this transcription factor in disease phenotypes for many organ systems. Studies have also characterized the means through which human Nrf2 is regulated and the mechanisms of interaction with antioxidant response elements (ARE) in promoters of effector genes. Moreover, single nucleotide polymorphisms (SNPs) in Nrf2 have been identified and evaluated for effects on gene expression and function, and translational investigations have sought to determine whether loss of function SNPs associate with disease progression. In this review, we present 1) an overview of the human Nrf2 gene and protein domain, 2) identification of genetic mutations in Nrf2 and associations of the mutations with multiple diseases, and 3) the role of somatic mutations in Nrf2 in diseases, primarily various cancers.",
			"category": 2,
			"name": "Cho Hye-Youn,2016"
		},
		{
			"PMID": 26111339,
			"title": "Dynamics of preventive vs post-diagnostic cancer control using low-impact measures.",
			"journal": "eLife",
			"authorList": [
				"Akhmetzhanov Andrei R",
				"Hochberg Michael E"
			],
			"DOI": "10.7554/eLife.06266",
			"date": "2016-04-07",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer poses danger because of its unregulated growth, development of resistance, and metastatic spread to vital organs. We currently lack quantitative theory for how preventive measures and post-diagnostic interventions are predicted to affect risks of a life threatening cancer. Here we evaluate how continuous measures, such as life style changes and traditional treatments, affect both neoplastic growth and the frequency of resistant clones. We then compare and contrast preventive and post-diagnostic interventions assuming that only a single lesion progresses to invasive carcinoma during the life of an individual, and resection either leaves residual cells or metastases are undetected. Whereas prevention generally results in more positive therapeutic outcomes than post-diagnostic interventions, this advantage is substantially lowered should prevention initially fail to arrest tumour growth. We discuss these results and other important mitigating factors that should be taken into consideration in a comparative understanding of preventive and post-diagnostic interventions.",
			"category": 2,
			"name": "Akhmetzhanov Andrei R,2016"
		},
		{
			"PMID": 26111056,
			"title": "Computational methods and resources for the interpretation of genomic variants in cancer.",
			"journal": "BMC genomics",
			"authorList": [
				"Tian Rui",
				"Basu Malay K",
				"Capriotti Emidio"
			],
			"DOI": "10.1186/1471-2164-16-S8-S7",
			"date": "2016-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "The recent improvement of the high-throughput sequencing technologies is having a strong impact on the detection of genetic variations associated with cancer. Several institutions worldwide have been sequencing the whole exomes and or genomes of cancer patients in the thousands, thereby providing an invaluable collection of new somatic mutations in different cancer types. These initiatives promoted the development of methods and tools for the analysis of cancer genomes that are aimed at studying the relationship between genotype and phenotype in cancer. In this article we review the online resources and computational tools for the analysis of cancer genome. First, we describe the available repositories of cancer genome data. Next, we provide an overview of the methods for the detection of genetic variation and computational tools for the prioritization of cancer related genes and causative somatic variations. Finally, we discuss the future perspectives in cancer genomics focusing on the impact of computational methods and quantitative approaches for defining personalized strategies to improve the diagnosis and treatment of cancer.",
			"category": 2,
			"name": "Tian Rui,2016"
		},
		{
			"PMID": 26111017,
			"title": "TAFFYS: An Integrated Tool for Comprehensive Analysis of Genomic Aberrations in Tumor Samples.",
			"journal": "PloS one",
			"authorList": [
				"Liu Yuanning",
				"Li Ao",
				"Feng Huanqing",
				"Wang Minghui"
			],
			"DOI": "10.1371/journal.pone.0129835",
			"date": "2016-04-06",
			"PMC": "",
			"citation": "",
			"abstract": "Tumor single nucleotide polymorphism (SNP) array is a common platform for investigating the cancer genomic aberration and the functionally important altered genes. Original SNP array signals are usually corrupted by noise, and need to be de-convoluted into absolute copy number profile by analytical methods. Unfortunately, in contrast with the popularity of tumor Affymetrix SNP array, the methods that are specifically designed for this platform are still limited. The complicated characteristics of noise in signals is one of the difficulties for dissecting tumor Affymetrix SNP array data, as they inevitably blur the distinction between aberrations and create an obstacle for the copy number aberration (CNA) identification.",
			"category": 2,
			"name": "Liu Yuanning,2016"
		},
		{
			"PMID": 26099335,
			"title": "Oncogenes and tumor suppressor genes: comparative genomics and network perspectives.",
			"journal": "BMC genomics",
			"authorList": [
				"Zhu Kevin",
				"Liu Qi",
				"Zhou Yubo",
				"Tao Cui",
				"Zhao Zhongming",
				"Sun Jingchun",
				"Xu Hua"
			],
			"DOI": "10.1186/1471-2164-16-S7-S8",
			"date": "2016-03-23",
			"PMC": "",
			"citation": "",
			"abstract": "Defective tumor suppressor genes (TSGs) and hyperactive oncogenes (OCGs) heavily contribute to cell proliferation and apoptosis during cancer development through genetic variations such as somatic mutations and deletions. Moreover, they usually do not perform their cellular functions individually but rather execute jointly. Therefore, a comprehensive comparison of their mutation patterns and network properties may provide a deeper understanding of their roles in the cancer development and provide some clues for identification of novel targets.",
			"category": 2,
			"name": "Zhu Kevin,2016"
		},
		{
			"PMID": 26092435,
			"title": "Identification of cancer predisposition variants in apparently healthy individuals using a next-generation sequencing-based family genomics approach.",
			"journal": "Human genomics",
			"authorList": [
				"Karageorgos Ioannis",
				"Mizzi Clint",
				"Giannopoulou Efstathia",
				"Pavlidis Cristiana",
				"Peters Brock A",
				"Zagoriti Zoi",
				"Stenson Peter D",
				"Mitropoulos Konstantinos",
				"Borg Joseph",
				"Kalofonos Haralabos P",
				"Drmanac Radoje",
				"Stubbs Andrew",
				"van der Spek Peter",
				"Cooper David N",
				"Katsila Theodora",
				"Patrinos George P"
			],
			"DOI": "10.1186/s40246-015-0034-2",
			"date": "2016-01-08",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer, like many common disorders, has a complex etiology, often with a strong genetic component and with multiple environmental factors contributing to susceptibility. A considerable number of genomic variants have been previously reported to be causative of, or associated with, an increased risk for various types of cancer. Here, we adopted a next-generation sequencing approach in 11 members of two families of Greek descent to identify all genomic variants with the potential to predispose family members to cancer. Cross-comparison with data from the Human Gene Mutation Database identified a total of 571 variants, from which 47\u00a0% were disease-associated polymorphisms, 26\u00a0% disease-associated polymorphisms with additional supporting functional evidence, 19\u00a0% functional polymorphisms with in vitro/laboratory or in vivo supporting evidence but no known disease association, 4\u00a0% putative disease-causing mutations but with some residual doubt as to their pathological significance, and 3\u00a0% disease-causing mutations. Subsequent analysis, focused on the latter variant class most likely to be involved in cancer predisposition, revealed two variants of prime interest, namely MSH2 c.2732T>A (p.L911R) and BRCA1 c.2955delC, the first of which is novel. KMT2D c.13895delC and c.1940C>A variants are additionally reported as incidental findings. The next-generation sequencing-based family genomics approach described herein has the potential to be applied to other types of complex genetic disorder in order to identify variants of potential pathological significance.",
			"category": 2,
			"name": "Karageorgos Ioannis,2016"
		},
		{
			"PMID": 26076459,
			"title": "Combined Targeted DNA Sequencing in Non-Small Cell Lung Cancer (NSCLC) Using UNCseq and NGScopy, and RNA Sequencing Using UNCqeR for the Detection of Genetic Aberrations in NSCLC.",
			"journal": "PloS one",
			"authorList": [
				"Zhao Xiaobei",
				"Wang Anyou",
				"Walter Vonn",
				"Patel Nirali M",
				"Eberhard David A",
				"Hayward Michele C",
				"Salazar Ashley H",
				"Jo Heejoon",
				"Soloway Matthew G",
				"Wilkerson Matthew D",
				"Parker Joel S",
				"Yin Xiaoying",
				"Zhang Guosheng",
				"Siegel Marni B",
				"Rosson Gary B",
				"Earp H Shelton",
				"Sharpless Norman E",
				"Gulley Margaret L",
				"Weck Karen E",
				"Hayes D Neil",
				"Moschos Stergios J"
			],
			"DOI": "10.1371/journal.pone.0129280",
			"date": "2016-03-04",
			"PMC": "",
			"citation": "",
			"abstract": "The recent FDA approval of the MiSeqDx platform provides a unique opportunity to develop targeted next generation sequencing (NGS) panels for human disease, including cancer. We have developed a scalable, targeted panel-based assay termed UNCseq, which involves a NGS panel of over 200 cancer-associated genes and a standardized downstream bioinformatics pipeline for detection of single nucleotide variations (SNV) as well as small insertions and deletions (indel). In addition, we developed a novel algorithm, NGScopy, designed for samples with sparse sequencing coverage to detect large-scale copy number variations (CNV), similar to human SNP Array 6.0 as well as small-scale intragenic CNV. Overall, we applied this assay to 100 snap-frozen lung cancer specimens lacking same-patient germline DNA (07-0120 tissue cohort) and validated our results against Sanger sequencing, SNP Array, and our recently published integrated DNA-seq/RNA-seq assay, UNCqeR, where RNA-seq of same-patient tumor specimens confirmed SNV detected by DNA-seq, if RNA-seq coverage depth was adequate. In addition, we applied the UNCseq assay on an independent lung cancer tumor tissue collection with available same-patient germline DNA (11-1115 tissue cohort) and confirmed mutations using assays performed in a CLIA-certified laboratory. We conclude that UNCseq can identify SNV, indel, and CNV in tumor specimens lacking germline DNA in a cost-efficient fashion.",
			"category": 2,
			"name": "Zhao Xiaobei,2016"
		},
		{
			"PMID": 26071483,
			"title": "Exome Sequencing Reveals AMER1 as a Frequently Mutated Gene in Colorectal Cancer.",
			"journal": "Clinical cancer research : an official journal of the American Association for Cancer Research",
			"authorList": [
				"Sanz-Pamplona Rebeca",
				"Lopez-Doriga Adriana",
				"Par\u00e9-Brunet Laia",
				"L\u00e1zaro Kira",
				"Bellido Fernando",
				"Alonso M Henar",
				"Auss\u00f3 Susanna",
				"Guin\u00f3 Elisabet",
				"Beltr\u00e1n Sergi",
				"Castro-Giner Francesc",
				"Gut Marta",
				"Sanjuan Xavier",
				"Closa Adria",
				"Cordero David",
				"Mor\u00f3n-Duran Francisco D",
				"Soriano Antonio",
				"Salazar Ram\u00f3n",
				"Valle Laura",
				"Moreno Victor"
			],
			"DOI": "10.1158/1078-0432.CCR-15-0159",
			"date": "2016-08-01",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic mutations occur at early stages of adenoma and accumulate throughout colorectal cancer progression. The aim of this study was to characterize the mutational landscape of stage II tumors and to search for novel recurrent mutations likely implicated in colorectal cancer tumorigenesis.",
			"category": 2,
			"name": "Sanz-Pamplona Rebeca,2016"
		},
		{
			"PMID": 26066710,
			"title": "Cell Fusion Connects Oncogenesis with Tumor Evolution.",
			"journal": "The American journal of pathology",
			"authorList": [
				"Zhou Xiaofeng",
				"Merchak Kevin",
				"Lee Woojin",
				"Grande Joseph P",
				"Cascalho Marilia",
				"Platt Jeffrey L"
			],
			"DOI": "10.1016/j.ajpath.2015.03.014",
			"date": "2016-06-07",
			"PMC": "",
			"citation": "",
			"abstract": "Cell fusion likely drives tumor evolution by undermining chromosomal and DNA stability and/or by generating phenotypic diversity; however, whether a cell fusion event can initiate malignancy and direct tumor evolution is unknown. We report that a fusion event involving normal, nontransformed, cytogenetically stable epithelial cells can initiate chromosomal instability, DNA damage, cell transformation, and malignancy. Clonal analysis of fused cells reveals that the karyotypic and phenotypic potential of tumors formed by cell fusion is established immediately or within a few cell divisions after the fusion event, without further ongoing genetic and phenotypic plasticity, and that subsequent evolution of such tumors reflects selection from the initial diverse population rather than ongoing plasticity of the progeny. Thus, one cell fusion event can both initiate malignancy and fuel evolution of the tumor that ensues.",
			"category": 2,
			"name": "Zhou Xiaofeng,2016"
		},
		{
			"PMID": 26052355,
			"title": "The GALNT9, BNC1 and CCDC8 genes are frequently epigenetically dysregulated in breast tumours that metastasise to the brain.",
			"journal": "Clinical epigenetics",
			"authorList": [
				"Pangeni Rajendra P",
				"Channathodiyil Prasanna",
				"Huen David S",
				"Eagles Lawrence W",
				"Johal Balraj K",
				"Pasha Dawar",
				"Hadjistephanou Natasa",
				"Nevell Oliver",
				"Davies Claire L",
				"Adewumi Ayobami I",
				"Khanom Hamida",
				"Samra Ikroop S",
				"Buzatto Vanessa C",
				"Chandrasekaran Preethi",
				"Shinawi Thoraia",
				"Dawson Timothy P",
				"Ashton Katherine M",
				"Davis Charles",
				"Brodbelt Andrew R",
				"Jenkinson Michael D",
				"Bi\u00e8che Ivan",
				"Latif Farida",
				"Darling John L",
				"Warr Tracy J",
				"Morris Mark R"
			],
			"DOI": "10.1186/s13148-015-0089-x",
			"date": "2015-06-08",
			"PMC": "",
			"citation": "",
			"abstract": "Tumour metastasis to the brain is a common and deadly development in certain cancers; 18-30\u00a0% of breast tumours metastasise to the brain. The contribution that gene silencing through epigenetic mechanisms plays in these metastatic tumours is not well understood.",
			"category": 2,
			"name": "Pangeni Rajendra P,2015"
		},
		{
			"PMID": 26041968,
			"title": "Integrative analyses of cancer data: a review from a statistical perspective.",
			"journal": "Cancer informatics",
			"authorList": [
				"Wei Yingying"
			],
			"DOI": "10.4137/CIN.S17303",
			"date": "2015-06-04",
			"PMC": "",
			"citation": "",
			"abstract": "It has become increasingly common for large-scale public data repositories and clinical settings to have multiple types of data, including high-dimensional genomics, epigenomics, and proteomics data as well as survival data, measured simultaneously for the same group of biological samples, which provides unprecedented opportunities to understand cancer mechanisms from a more comprehensive scope and to develop new cancer therapies. Nevertheless, how to interpret a wealth of data into biologically and clinically meaningful information remains very challenging. In this paper, I review recent development in statistics for integrative analyses of cancer data. Topics will cover meta-analysis of homogeneous type of data across multiple studies, integrating multiple heterogeneous genomic data types, survival analysis with high-or ultrahigh-dimensional genomic profiles, and cross-data-type prediction where both predictors and responses are high-or ultrahigh-dimensional vectors. I compare existing statistical methods and comment on potential future research problems.",
			"category": 2,
			"name": "Wei Yingying,2015"
		},
		{
			"PMID": 26031775,
			"title": "miR-16 promotes the apoptosis of human cancer cells by targeting FEAT.",
			"journal": "BMC cancer",
			"authorList": [
				"Liang Hongwei",
				"Fu Zheng",
				"Jiang Xueyuan",
				"Wang Nan",
				"Wang Feng",
				"Wang Xueliang",
				"Zhang Suyang",
				"Wang Yanbo",
				"Yan Xin",
				"Guan Wen-xian",
				"Zhang Chen-Yu",
				"Zen Ke",
				"Zhang Yujing",
				"Chen Xi",
				"Zhou Guangxin"
			],
			"DOI": "10.1186/s12885-015-1458-8",
			"date": "2016-03-01",
			"PMC": "",
			"citation": "",
			"abstract": "Although human cancers have heterogeneous combinations of altered oncogenes, some crucial genes are universally dysregulated in most cancers. One such gene, FEAT (faint expression in normal tissues, aberrant overexpression in tumors), is uniformly overexpressed in a variety of human cancers and plays an important role in tumorigenesis by suppressing apoptosis. However, the precise molecular mechanism through which FEAT is upregulated during tumorigenesis remains largely unknown.",
			"category": 2,
			"name": "Liang Hongwei,2016"
		},
		{
			"PMID": 26028031,
			"title": "Rethinking pheochromocytomas and paragangliomas from a genomic perspective.",
			"journal": "Oncogene",
			"authorList": [
				"Castro-Vega L J",
				"Lepoutre-Lussey C",
				"Gimenez-Roqueplo A-P",
				"Favier J"
			],
			"DOI": "10.1038/onc.2015.172",
			"date": "2016-08-01",
			"PMC": "",
			"citation": "",
			"abstract": "Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors of neural crest origin. These tumors are caused by germline or somatic mutations in known susceptibility genes in up to 70% of cases. Over the past few years, the emergence of high-throughput technologies has enabled the unprecedented characterization of genomic alterations in PCC/PGL, and has improved our understanding of the molecular mechanisms that distinguish the different tumor subtypes. Integrated genomic analyses have shown that the mutation status of PCC/PGL susceptibility genes strongly correlates with multi-omics data. These observations not only emphasize the role of the long-standing susceptibility genes as the main drivers of PCC/PGL tumorigenesis, but also illustrate the functional interdependence between genomic and epigenomic alterations. In this review, we discuss the genomic landscape underlying PCC/PGL, its functional consequences for tumorigenesis and tumor progression, and the potential clinical relevance of this knowledge for the application of precision medicine for patients with PCC/PGL.",
			"category": 2,
			"name": "Castro-Vega L J,2016"
		},
		{
			"PMID": 26015801,
			"title": "Aneuploidy and chromosomal instability in cancer: a jackpot to chaos.",
			"journal": "Cell division",
			"authorList": [
				"Giam Maybelline",
				"Rancati Giulia"
			],
			"DOI": "10.1186/s13008-015-0009-7",
			"date": "2015-05-27",
			"PMC": "",
			"citation": "",
			"abstract": "Genomic instability (GIN) is a hallmark of cancer cells that facilitates the acquisition of mutations conferring aggressive or drug-resistant phenotypes during cancer evolution. Chromosomal instability (CIN) is a form of GIN that involves frequent cytogenetic changes leading to changes in chromosome copy number (aneuploidy). While both CIN and aneuploidy are common characteristics of cancer cells, their roles in tumor initiation and progression are unclear. On the one hand, CIN and aneuploidy are known to provide genetic variation to allow cells to adapt in changing environments such as nutrient fluctuations and hypoxia. Patients with constitutive aneuploidies are more susceptible to certain types of cancers, suggesting that changes in chromosome copy number could positively contribute to cancer evolution. On the other hand, chromosomal imbalances have been observed to have detrimental effects on cellular fitness and might trigger cell cycle arrest or apoptosis. Furthermore, mouse models for CIN have led to conflicting results. Taken together these findings suggest that the relationship between CIN, aneuploidy and cancer is more complex than what was previously anticipated. Here we review what is known about this complex m\u00e9nage \u00e0 trois, discuss recent evidence suggesting that aneuploidy, CIN and GIN together promote a vicious cycle of genome chaos. Lastly, we propose a working hypothesis to reconcile the conflicting observations regarding the role of aneuploidy and CIN in tumorigenesis.",
			"category": 2,
			"name": "Giam Maybelline,2015"
		},
		{
			"PMID": 26013811,
			"title": "DeAnnCNV: a tool for online detection and annotation of copy number variations from whole-exome sequencing data.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Zhang Yuanwei",
				"Yu Zhenhua",
				"Ban Rongjun",
				"Zhang Huan",
				"Iqbal Furhan",
				"Zhao Aiwu",
				"Li Ao",
				"Shi Qinghua"
			],
			"DOI": "10.1093/nar/gkv556",
			"date": "2015-12-17",
			"PMC": "",
			"citation": "",
			"abstract": "With the decrease in costs, whole-exome sequencing (WES) has become a very popular and powerful tool for the identification of genetic variants underlying human diseases. However, integrated tools to precisely detect and systematically annotate copy number variations (CNVs) from WES data are still in great demand. Here, we present an online tool, DeAnnCNV (Detection and Annotation of Copy Number Variations from WES data), to meet the current demands of WES users. Upon submitting the file generated from WES data by an in-house tool that can be downloaded from our server, DeAnnCNV can detect CNVs in each sample and extract the shared CNVs among multiple samples. DeAnnCNV also provides additional useful supporting information for the detected CNVs and associated genes to help users to find the potential candidates for further experimental study. The web server is implemented in PHP + Perl + MATLAB and is online available to all users for free at http://mcg.ustc.edu.cn/db/cnv/.",
			"category": 2,
			"name": "Zhang Yuanwei,2015"
		},
		{
			"PMID": 26011628,
			"title": "CEMP1 Induces Transformation in Human Gingival Fibroblasts.",
			"journal": "PloS one",
			"authorList": [
				"Berm\u00fadez Mercedes",
				"Imaz-Rosshandler Ivan",
				"Rangel-Escare\u00f1o Claudia",
				"Zeichner-David Margarita",
				"Arzate Higinio",
				"Mercado-Celis Gabriela E"
			],
			"DOI": "10.1371/journal.pone.0127286",
			"date": "2016-02-11",
			"PMC": "",
			"citation": "",
			"abstract": "Cementum Protein 1 (CEMP1) is a key regulator of cementogenesis. CEMP1 promotes cell attachment, differentiation, deposition rate, composition, and morphology of hydroxyapatite crystals formed by human cementoblastic cells. Its expression is restricted to cementoblasts and progenitor cell subpopulations present in the periodontal ligament. CEMP1 transfection into non-osteogenic cells such as adult human gingival fibroblasts results in differentiation of these cells into a \"mineralizing\" cell phenotype. Other studies have shown evidence that CEMP1 could have a therapeutic potential for the treatment of bone defects and regeneration of other mineralized tissues. To better understand CEMP1's biological effects in vitro we investigated the consequences of its expression in human gingival fibroblasts (HGF) growing in non-mineralizing media by comparing gene expression profiles. We identified several mRNAs whose expression is modified by CEMP1 induction in HGF cells. Enrichment analysis showed that several of these newly expressed genes are involved in oncogenesis. Our results suggest that CEMP1 causes the transformation of HGF and NIH3T3 cells. CEMP1 is overexpressed in cancer cell lines. We also determined that the region spanning the CEMP1 locus is commonly amplified in a variety of cancers, and finally we found significant overexpression of CEMP1 in leukemia, cervix, breast, prostate and lung cancer. Our findings suggest that CEMP1 exerts modulation of a number of cellular genes, cellular development, cellular growth, cell death, and cell cycle, and molecules associated with cancer.",
			"category": 2,
			"name": "Berm\u00fadez Mercedes,2016"
		},
		{
			"PMID": 26001532,
			"title": "The somatic autosomal mutation matrix in cancer genomes.",
			"journal": "Human genetics",
			"authorList": [
				"Temiz Nuri A",
				"Donohue Duncan E",
				"Bacolla Albino",
				"Vasquez Karen M",
				"Cooper David N",
				"Mudunuri Uma",
				"Ivanic Joseph",
				"Cer Regina Z",
				"Yi Ming",
				"Stephens Robert M",
				"Collins Jack R",
				"Luke Brian T"
			],
			"DOI": "10.1007/s00439-015-1566-1",
			"date": "2015-09-18",
			"PMC": "",
			"citation": "",
			"abstract": "DNA damage in somatic cells originates from both environmental and endogenous sources, giving rise to mutations through multiple mechanisms. When these mutations affect the function of critical genes, cancer may ensue. Although identifying genomic subsets of mutated genes may inform therapeutic options, a systematic survey of tumor mutational spectra is required to improve our understanding of the underlying mechanisms of mutagenesis involved in cancer etiology. Recent studies have presented genome-wide sets of somatic mutations as a 96-element vector, a procedure that only captures the immediate neighbors of the mutated nucleotide. Herein, we present a 32 \u00d7 12 mutation matrix that captures the nucleotide pattern two nucleotides upstream and downstream of the mutation. A somatic autosomal mutation matrix (SAMM) was constructed from tumor-specific mutations derived from each of 909 individual cancer genomes harboring a total of 10,681,843 single-base substitutions. In addition, mechanistic template mutation matrices (MTMMs) representing oxidative DNA damage, ultraviolet-induced DNA damage, (5m)CpG deamination, and APOBEC-mediated cytosine mutation, are presented. MTMMs were mapped to the individual tumor SAMMs to determine the maximum contribution of each mutational mechanism to the overall mutation pattern. A Manhattan distance across all SAMM elements between any two tumor genomes was used to determine their relative distance. Employing this metric, 89.5% of all tumor genomes were found to have a nearest neighbor from the same tissue of origin. When a distance-dependent 6-nearest neighbor classifier was used, 10.4% of the SAMMs had an Undetermined tissue of origin, and 92.2% of the remaining SAMMs were assigned to the correct tissue of origin. [corrected]. Thus, although tumors from different tissues may have similar mutation patterns, their SAMMs often display signatures that are characteristic of specific tissues.",
			"category": 2,
			"name": "Temiz Nuri A,2015"
		},
		{
			"PMID": 25995187,
			"title": "Hypoxia drives transient site-specific copy gain and drug-resistant gene expression.",
			"journal": "Genes & development",
			"authorList": [
				"Black Joshua C",
				"Atabakhsh Elnaz",
				"Kim Jaegil",
				"Biette Kelly M",
				"Van Rechem Capucine",
				"Ladd Brendon",
				"Burrowes Paul D",
				"Donado Carlos",
				"Mattoo Hamid",
				"Kleinstiver Benjamin P",
				"Song Bing",
				"Andriani Grasiella",
				"Joung J Keith",
				"Iliopoulos Othon",
				"Montagna Cristina",
				"Pillai Shiv",
				"Getz Gad",
				"Whetstine Johnathan R"
			],
			"DOI": "10.1101/gad.259796.115",
			"date": "2015-07-21",
			"PMC": "",
			"citation": "",
			"abstract": "Copy number heterogeneity is a prominent feature within tumors. The molecular basis for this heterogeneity remains poorly characterized. Here, we demonstrate that hypoxia induces transient site-specific copy gains (TSSGs) in primary, nontransformed, and transformed human cells. Hypoxia-driven copy gains are not dependent on HIF1\u03b1 or HIF2\u03b1; however, they are dependent on the KDM4A histone demethylase and are blocked by inhibition of KDM4A with a small molecule or the natural metabolite succinate. Furthermore, this response is conserved at a syntenic region in zebrafish cells. Regions with site-specific copy gain are also enriched for amplifications in hypoxic primary tumors. These tumors exhibited amplification and overexpression of the drug resistance gene CKS1B, which we recapitulated in hypoxic breast cancer cells. Our results demonstrate that hypoxia provides a biological stimulus to create transient site-specific copy alterations that could result in heterogeneity within tumors and cell populations. These findings have major implications in our understanding of copy number heterogeneity and the emergence of drug resistance genes in cancer.",
			"category": 2,
			"name": "Black Joshua C,2015"
		},
		{
			"PMID": 25993148,
			"title": "New and promising strategies in the management of bladder cancer.",
			"journal": "American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting",
			"authorList": [
				"Apolo Andrea B",
				"Vogelzang Nicholas J",
				"Theodorescu Dan"
			],
			"DOI": "10.14694/EdBook_AM.2015.35.105",
			"date": "2016-02-17",
			"PMC": "",
			"citation": "",
			"abstract": "Bladder cancer is a complex and aggressive disease for which treatment strategies have had limited success. Improvements in detection, treatment, and outcomes in bladder cancer will require the integration of multiple new approaches, including genomic profiling, immunotherapeutics, and large randomized clinical trials. New and promising strategies are being tested in all disease states, including nonmuscle-invasive bladder cancer (NMIBC), muscle-invasive bladder cancer (MIBC), and metastatic urothelial carcinoma (UC). Efforts are underway to develop better noninvasive urine biomarkers for use in primary or secondary detection of NMIBC, exploiting our genomic knowledge of mutations in genes such as RAS, FGFR3, PIK3CA, and TP53 and methylation pathways alone or in combination. Recent data from a large, randomized phase III trial of adjuvant cisplatin-based chemotherapy add to our knowledge of the value of perioperative chemotherapy in patients with MIBC. Finally, bladder cancer is one of a growing list of tumor types that respond to immune checkpoint inhibition, opening the potential for new therapeutic strategies for treatment of this complex and aggressive disease.",
			"category": 2,
			"name": "Apolo Andrea B,2016"
		},
		{
			"PMID": 25992881,
			"title": "A network flow-based method to predict anticancer drug sensitivity.",
			"journal": "PloS one",
			"authorList": [
				"Qin Yufang",
				"Chen Ming",
				"Wang Haiyun",
				"Zheng Xiaoqi"
			],
			"DOI": "10.1371/journal.pone.0127380",
			"date": "2016-04-14",
			"PMC": "",
			"citation": "",
			"abstract": "Predicting anticancer drug sensitivity can enhance the ability to individualize patient treatment, thus making development of cancer therapies more effective and safe. In this paper, we present a new network flow-based method, which utilizes the topological structure of pathways, for predicting anticancer drug sensitivities. Mutations and copy number alterations of cancer-related genes are assumed to change the pathway activity, and pathway activity difference before and after drug treatment is used as a measure of drug response. In our model, Contributions from different genetic alterations are considered as free parameters, which are optimized by the drug response data from the Cancer Genome Project (CGP). 10-fold cross validation on CGP data set showed that our model achieved comparable prediction results with existing elastic net model using much less input features.",
			"category": 2,
			"name": "Qin Yufang,2016"
		},
		{
			"PMID": 25989697,
			"title": "Personalized radiotherapy: concepts, biomarkers and trial design.",
			"journal": "The British journal of radiology",
			"authorList": [
				"Ree A H",
				"Redalen K R"
			],
			"DOI": "10.1259/bjr.20150009",
			"date": "2015-10-29",
			"PMC": "",
			"citation": "",
			"abstract": "In the past decade, and pointing onwards to the immediate future, clinical radiotherapy has undergone considerable developments, essentially including technological advances to sculpt radiation delivery, the demonstration of the benefit of adding concomitant cytotoxic agents to radiotherapy for a range of tumour types and, intriguingly, the increasing integration of targeted therapeutics for biological optimization of radiation effects. Recent molecular and imaging insights into radiobiology will provide a unique opportunity for rational patient treatment, enabling the parallel design of next-generation trials that formally examine the therapeutic outcome of adding targeted drugs to radiation, together with the critically important assessment of radiation volume and dose-limiting treatment toxicities. In considering the use of systemic agents with presumed radiosensitizing activity, this may also include the identification of molecular, metabolic and imaging markers of treatment response and tolerability, and will need particular attention on patient eligibility. In addition to providing an overview of clinical biomarker studies relevant for personalized radiotherapy, this communication will highlight principles in addressing clinical evaluation of combined-modality-targeted therapeutics and radiation. The increasing number of translational studies that bridge large-scale omics sciences with quality-assured phenomics end points-given the imperative development of open-source data repositories to allow investigators the access to the complex data sets-will enable radiation oncology to continue to position itself with the highest level of evidence within existing clinical practice.",
			"category": 2,
			"name": "Ree A H,2015"
		},
		{
			"PMID": 25982339,
			"title": "Cancer susceptibility syndromes in children in the area of broad clinical use of massive parallel sequencing.",
			"journal": "European journal of pediatrics",
			"authorList": [
				"Kuhlen Michaela",
				"Borkhardt Arndt"
			],
			"DOI": "10.1007/s00431-015-2565-x",
			"date": "2016-06-24",
			"PMC": "",
			"citation": "",
			"abstract": "Children diagnosed with cancer are considered for inherited cancer susceptibility testing according to well-established clinical criteria. With increasing efforts to personalize cancer medicine, comprehensive genome analyses will find its way into daily clinical routine in pediatric oncology. Whole genome and exome sequencing unavoidably generates incidental findings. The somatic \"molecular make-up\" of a tumor genome may suggest a germline mutation in a cancer susceptibility syndrome. At least two mechanisms are well-known, (a) chromothripsis (Li-Fraumeni syndrome) and (b) a high total number of mutational events which exceeds that of other samples of the same tumor type (defective DNA mismatch repair). Hence, pediatricians are faced with the fact that genetic events within the tumor genome itself can point toward underlying germline cancer susceptibility. Whenever genetic testing including next-generation sequencing (NGS) is initiated, the pediatrician has to inform about the benefits, risks, and alternatives, discuss the possibility of incidental findings and its disclosure, and to obtain informed consent prior to testing.",
			"category": 2,
			"name": "Kuhlen Michaela,2016"
		},
		{
			"PMID": 25973395,
			"title": "Misfolding, Aggregation, and Disordered Segments in c-Abl and p53 in Human Cancer.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"de Oliveira Guilherme A P",
				"Rangel Luciana P",
				"Costa Danielly C",
				"Silva Jerson L"
			],
			"DOI": "10.3389/fonc.2015.00097",
			"date": "2015-05-14",
			"PMC": "",
			"citation": "",
			"abstract": "The current understanding of the molecular mechanisms that lead to cancer is not sufficient to explain the loss or gain of function in proteins related to tumorigenic processes. Among them, more than 100 oncogenes, 20-30 tumor-suppressor genes, and hundreds of genes participating in DNA repair and replication have been found to play a role in the origins of cancer over the last 25\u2009years. The phosphorylation of serine, threonine, or tyrosine residues is a critical step in cellular growth and development and is achieved through the tight regulation of protein kinases. Phosphorylation plays a major role in eukaryotic signaling as kinase domains are found in 2% of our genes. The deregulation of kinase control mechanisms has disastrous consequences, often leading to gains of function, cell transformation, and cancer. The c-Abl kinase protein is one of the most studied targets in the fight against cancer and is a hotspot for drug development because it participates in several solid tumors and is the hallmark of chronic myelogenous leukemia. Tumor suppressors have the opposite effects. Their fundamental role in the maintenance of genomic integrity has awarded them a role as the guardians of DNA. Among the tumor suppressors, p53 is the most studied. The p53 protein has been shown to be a transcription factor that recognizes and binds to specific DNA response elements and activates gene transcription. Stress triggered by ionizing radiation or other mutagenic events leads to p53 phosphorylation and cell-cycle arrest, senescence, or programed cell death. The p53 gene is the most frequently mutated gene in cancer. Mutations in the DNA-binding domain are classified as class I or class II depending on whether substitutions occur in the DNA contact sites or in the protein core, respectively. Tumor-associated p53 mutations often lead to the loss of protein function, but recent investigations have also indicated gain-of-function mutations. The prion-like aggregation of mutant p53 is associated with loss-of-function, dominant-negative, and gain-of-function effects. In the current review, we focused on the most recent insights into the protein structure and function of the c-Abl and p53 proteins that will provide us guidance to understand the loss and gain of function of these misfolded tumor-associated proteins.",
			"category": 2,
			"name": "de Oliveira Guilherme A P,2015"
		},
		{
			"PMID": 25955013,
			"title": "Canine Mammary Tumours Are Affected by Frequent Copy Number Aberrations, including Amplification of MYC and Loss of PTEN.",
			"journal": "PloS one",
			"authorList": [
				"Borge Kaja S",
				"Nord Silje",
				"Van Loo Peter",
				"Lingj\u00e6rde Ole C",
				"Gunnes Gjermund",
				"Aln\u00e6s Grethe I G",
				"Solvang Hiroko K",
				"L\u00fcders Torben",
				"Kristensen Vessela N",
				"B\u00f8rresen-Dale Anne-Lise",
				"Lingaas Frode"
			],
			"DOI": "10.1371/journal.pone.0126371",
			"date": "2016-02-02",
			"PMC": "",
			"citation": "",
			"abstract": "Copy number aberrations frequently occur during the development of many cancers. Such events affect dosage of involved genes and may cause further genomic instability and progression of cancer. In this survey, canine SNP microarrays were used to study 117 canine mammary tumours from 69 dogs.",
			"category": 2,
			"name": "Borge Kaja S,2016"
		},
		{
			"PMID": 25915121,
			"title": "G&T-seq: parallel sequencing of single-cell genomes and transcriptomes.",
			"journal": "Nature methods",
			"authorList": [
				"Macaulay Iain C",
				"Haerty Wilfried",
				"Kumar Parveen",
				"Li Yang I",
				"Hu Tim Xiaoming",
				"Teng Mabel J",
				"Goolam Mubeen",
				"Saurat Nathalie",
				"Coupland Paul",
				"Shirley Lesley M",
				"Smith Miriam",
				"Van der Aa Niels",
				"Banerjee Ruby",
				"Ellis Peter D",
				"Quail Michael A",
				"Swerdlow Harold P",
				"Zernicka-Goetz Magdalena",
				"Livesey Frederick J",
				"Ponting Chris P",
				"Voet Thierry"
			],
			"DOI": "10.1038/nmeth.3370",
			"date": "2015-08-11",
			"PMC": "",
			"citation": "",
			"abstract": "The simultaneous sequencing of a single cell's genome and transcriptome offers a powerful means to dissect genetic variation and its effect on gene expression. Here we describe G&T-seq, a method for separating and sequencing genomic DNA and full-length mRNA from single cells. By applying G&T-seq to over 220 single cells from mice and humans, we discovered cellular properties that could not be inferred from DNA or RNA sequencing alone.",
			"category": 2,
			"name": "Macaulay Iain C,2015"
		},
		{
			"PMID": 25892662,
			"title": "Sustained proliferation in cancer: Mechanisms and novel therapeutic targets.",
			"journal": "Seminars in cancer biology",
			"authorList": [
				"Feitelson Mark A",
				"Arzumanyan Alla",
				"Kulathinal Rob J",
				"Blain Stacy W",
				"Holcombe Randall F",
				"Mahajna Jamal",
				"Marino Maria",
				"Martinez-Chantar Maria L",
				"Nawroth Roman",
				"Sanchez-Garcia Isidro",
				"Sharma Dipali",
				"Saxena Neeraj K",
				"Singh Neetu",
				"Vlachostergios Panagiotis J",
				"Guo Shanchun",
				"Honoki Kanya",
				"Fujii Hiromasa",
				"Georgakilas Alexandros G",
				"Bilsland Alan",
				"Amedei Amedeo",
				"Niccolai Elena",
				"Amin Amr",
				"Ashraf S Salman",
				"Boosani Chandra S",
				"Guha Gunjan",
				"Ciriolo Maria Rosa",
				"Aquilano Katia",
				"Chen Sophie",
				"Mohammed Sulma I",
				"Azmi Asfar S",
				"Bhakta Dipita",
				"Halicka Dorota",
				"Keith W Nicol",
				"Nowsheen Somaira"
			],
			"DOI": "10.1016/j.semcancer.2015.02.006",
			"date": "2016-09-07",
			"PMC": "",
			"citation": "",
			"abstract": "Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression.",
			"category": 2,
			"name": "Feitelson Mark A,2016"
		},
		{
			"PMID": 25883951,
			"title": "PVT1: a rising star among oncogenic long noncoding RNAs.",
			"journal": "BioMed research international",
			"authorList": [
				"Colombo Teresa",
				"Farina Lorenzo",
				"Macino Giuseppe",
				"Paci Paola"
			],
			"DOI": "10.1155/2015/304208",
			"date": "2016-02-04",
			"PMC": "",
			"citation": "",
			"abstract": "It is becoming increasingly clear that short and long noncoding RNAs critically participate in the regulation of cell growth, differentiation, and (mis)function. However, while the functional characterization of short non-coding RNAs has been reaching maturity, there is still a paucity of well characterized long noncoding RNAs, even though large studies in recent years are rapidly increasing the number of annotated ones. The long noncoding RNA PVT1 is encoded by a gene that has been long known since it resides in the well-known cancer risk region 8q24. However, a couple of accidental concurrent conditions have slowed down the study of this gene, that is, a preconception on the primacy of the protein-coding over noncoding RNAs and the prevalent interest in its neighbor MYC oncogene. Recent studies have brought PVT1 under the spotlight suggesting interesting models of functioning, such as competing endogenous RNA activity and regulation of protein stability of important oncogenes, primarily of the MYC oncogene. Despite some advancements in modelling the PVT1 role in cancer, there are many questions that remain unanswered concerning the precise molecular mechanisms underlying its functioning.",
			"category": 2,
			"name": "Colombo Teresa,2016"
		},
		{
			"PMID": 25876174,
			"title": "A simple strategy for reducing false negatives in calling variants from single-cell sequencing data.",
			"journal": "PloS one",
			"authorList": [
				"Ji Cong",
				"Miao Zong",
				"He Xionglei"
			],
			"DOI": "10.1371/journal.pone.0123789",
			"date": "2016-01-13",
			"PMC": "",
			"citation": "",
			"abstract": "Due to the growth of interest in single-cell genomics, computational methods for distinguishing true variants from artifacts are highly desirable. While special attention has been paid to false positives in variant or mutation calling from single-cell sequencing data, an equally important but often neglected issue is that of false negatives derived from allele dropout during the amplification of single cell genomes. In this paper, we propose a simple strategy to reduce the false negatives in single-cell sequencing data analysis. Simulation results show that this method is highly reliable, with an error rate of 4.94\u00d710-5, which is orders of magnitude lower than the expected false negative rate (~34%) estimated from a single-cell exome dataset, though the method is limited by the low SNP density in the human genome. We applied this method to analyze the exome data of a few dozen single tumor cells generated in previous studies, and extracted cell specific mutation information for a small set of sites. Interestingly, we found that there are difficulties in using the classical clonal model of tumor cell growth to explain the mutation patterns observed in some tumor cells.",
			"category": 2,
			"name": "Ji Cong,2016"
		},
		{
			"PMID": 25832647,
			"title": "Molecular portraits: the evolution of the concept of transcriptome-based cancer signatures.",
			"journal": "Briefings in bioinformatics",
			"authorList": [
				"Modelska Angelika",
				"Quattrone Alessandro",
				"Re Angela"
			],
			"DOI": "10.1093/bib/bbv013",
			"date": "2016-09-15",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer results from dysregulation of multiple steps of gene expression programs. We review how transcriptome profiling has been widely explored for cancer classification and biomarker discovery but resulted in limited clinical impact. Therefore, we discuss alternative and complementary omics approaches.",
			"category": 2,
			"name": "Modelska Angelika,2016"
		},
		{
			"PMID": 25825654,
			"title": "How bioinformatics influences health informatics: usage of biomolecular sequences, expression profiles and automated microscopic image analyses for clinical needs and public health.",
			"journal": "Health information science and systems",
			"authorList": [
				"Kuznetsov Vladimir",
				"Lee Hwee Kuan",
				"Maurer-Stroh Sebastian",
				"Moln\u00e1r Maria Judit",
				"Pongor Sandor",
				"Eisenhaber Birgit",
				"Eisenhaber Frank"
			],
			"DOI": "10.1186/2047-2501-1-2",
			"date": "2015-03-31",
			"PMC": "",
			"citation": "",
			"abstract": "The currently hyped expectation of personalized medicine is often associated with just achieving the information technology led integration of biomolecular sequencing, expression and histopathological bioimaging data with clinical records at the individual patients' level as if the significant biomedical conclusions would be its more or less mandatory result. It remains a sad fact that many, if not most biomolecular mechanisms that translate the human genomic information into phenotypes are not known and, thus, most of the molecular and cellular data cannot be interpreted in terms of biomedically relevant conclusions. Whereas the historical trend will certainly be into the general direction of personalized diagnostics and cures, the temperate view suggests that biomedical applications that rely either on the comparison of biomolecular sequences and/or on the already known biomolecular mechanisms have much greater chances to enter clinical practice soon. In addition to considering the general trends, we exemplarily review advances in the area of cancer biomarker discovery, in the clinically relevant characterization of patient-specific viral and bacterial pathogens (with emphasis on drug selection for influenza and enterohemorrhagic E. coli) as well as progress in the automated assessment of histopathological images. As molecular and cellular data analysis will become instrumental for achieving desirable clinical outcomes, the role of bioinformatics and computational biology approaches will dramatically grow.",
			"category": 2,
			"name": "Kuznetsov Vladimir,2015"
		},
		{
			"PMID": 25823020,
			"title": "Cancer whole-genome sequencing: present and future.",
			"journal": "Oncogene",
			"authorList": [
				"Nakagawa H",
				"Wardell C P",
				"Furuta M",
				"Taniguchi H",
				"Fujimoto A"
			],
			"DOI": "10.1038/onc.2015.90",
			"date": "2016-03-28",
			"PMC": "",
			"citation": "",
			"abstract": "Recent explosive advances in next-generation sequencing technology and computational approaches to massive data enable us to analyze a number of cancer genome profiles by whole-genome sequencing (WGS). To explore cancer genomic alterations and their diversity comprehensively, global and local cancer genome-sequencing projects, including ICGC and TCGA, have been analyzing many types of cancer genomes mainly by exome sequencing. However, there is limited information on somatic mutations in non-coding regions including untranslated regions, introns, regulatory elements and non-coding RNAs, and rearrangements, sometimes producing fusion genes, and pathogen detection in cancer genomes remain widely unexplored. WGS approaches can detect these unexplored mutations, as well as coding mutations and somatic copy number alterations, and help us to better understand the whole landscape of cancer genomes and elucidate functions of these unexplored genomic regions. Analysis of cancer genomes using the present WGS platforms is still primitive and there are substantial improvements to be made in sequencing technologies, informatics and computer resources. Taking account of the extreme diversity of cancer genomes and phenotype, it is also required to analyze much more WGS data and integrate these with multi-omics data, functional data and clinical-pathological data in a large number of sample sets to interpret them more fully and efficiently.",
			"category": 2,
			"name": "Nakagawa H,2016"
		},
		{
			"PMID": 25800737,
			"title": "Cells deficient in base-excision repair reveal cancer hallmarks originating from adjustments to genetic instability.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Markkanen Enni",
				"Fischer Roman",
				"Ledentcova Marina",
				"Kessler Benedikt M",
				"Dianov Grigory L"
			],
			"DOI": "10.1093/nar/gkv222",
			"date": "2015-07-07",
			"PMC": "",
			"citation": "",
			"abstract": "Genetic instability, provoked by exogenous mutagens, is well linked to initiation of cancer. However, even in unstressed cells, DNA undergoes a plethora of spontaneous alterations provoked by its inherent chemical instability and the intracellular milieu. Base excision repair (BER) is the major cellular pathway responsible for repair of these lesions, and as deficiency in BER activity results in DNA damage it has been proposed that it may trigger the development of sporadic cancers. Nevertheless, experimental evidence for this model remains inconsistent and elusive. Here, we performed a proteomic analysis of BER deficient human cells using stable isotope labelling with amino acids in cell culture (SILAC), and demonstrate that BER deficiency, which induces genetic instability, results in dramatic changes in gene expression, resembling changes found in many cancers. We observed profound alterations in tissue homeostasis, serine biosynthesis, and one-carbon- and amino acid metabolism, all of which have been identified as cancer cell 'hallmarks'. For the first time, this study describes gene expression changes characteristic for cells deficient in repair of endogenous DNA lesions by BER. These expression changes resemble those observed in cancer cells, suggesting that genetically unstable BER deficient cells may be a source of pre-cancerous cells.",
			"category": 2,
			"name": "Markkanen Enni,2015"
		},
		{
			"PMID": 25794193,
			"title": "DISIS: prediction of drug response through an iterative sure independence screening.",
			"journal": "PloS one",
			"authorList": [
				"Fang Yun",
				"Qin Yufang",
				"Zhang Naiqian",
				"Wang Jun",
				"Wang Haiyun",
				"Zheng Xiaoqi"
			],
			"DOI": "10.1371/journal.pone.0120408",
			"date": "2016-02-09",
			"PMC": "",
			"citation": "",
			"abstract": "Prediction of drug response based on genomic alterations is an important task in the research of personalized medicine. Current elastic net model utilized a sure independence screening to select relevant genomic features with drug response, but it may neglect the combination effect of some marginally weak features. In this work, we applied an iterative sure independence screening scheme to select drug response relevant features from the Cancer Cell Line Encyclopedia (CCLE) dataset. For each drug in CCLE, we selected up to 40 features including gene expressions, mutation and copy number alterations of cancer-related genes, and some of them are significantly strong features but showing weak marginal correlation with drug response vector. Lasso regression based on the selected features showed that our prediction accuracies are higher than those by elastic net regression for most drugs.",
			"category": 2,
			"name": "Fang Yun,2016"
		},
		{
			"PMID": 25774356,
			"title": "Beyond Mutations: Additional Mechanisms and Implications of SWI/SNF Complex Inactivation.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Marquez Stefanie B",
				"Thompson Kenneth W",
				"Lu Li",
				"Reisman David"
			],
			"DOI": "10.3389/fonc.2014.00372",
			"date": "2015-03-16",
			"PMC": "",
			"citation": "",
			"abstract": "SWI/SNF is a major regulator of gene expression. Its role is to facilitate the shifting and exposure of DNA segments within the promoter and other key domains to transcription factors and other essential cellular proteins. This complex interacts with a wide range of proteins and does not function within a single, specific pathway; thus, it is involved in a multitude of cellular processes, including DNA repair, differentiation, development, cell adhesion, and growth control. Given SWI/SNF's prominent role in these processes, many of which are important for blocking cancer development, it is not surprising that the SWI/SNF complex is targeted during cancer initiation and progression both by mutations and by non-mutational mechanisms. Currently, the understanding of the types of alterations, their frequency, and their impact on the SWI/SNF subunits is an area of intense research that has been bolstered by a recent cadre of NextGen sequencing studies. These studies have revealed mutations in SWI/SNF subunits, indicating that this complex is thus important for cancer development. The purpose of this review is to put into perspective the role of mutations versus other mechanisms in the silencing of SWI/SNF subunits, in particular, BRG1 and BRM. In addition, this review explores the recent development of synthetic lethality and how it applies to this complex, as well as how BRM polymorphisms are becoming recognized as potential clinical biomarkers for cancer risk.",
			"category": 2,
			"name": "Marquez Stefanie B,2015"
		},
		{
			"PMID": 25725369,
			"title": "Cell death in genome evolution.",
			"journal": "Seminars in cell & developmental biology",
			"authorList": [
				"Teng Xinchen",
				"Hardwick J Marie"
			],
			"DOI": "10.1016/j.semcdb.2015.02.014",
			"date": "2015-12-15",
			"PMC": "",
			"citation": "",
			"abstract": "Inappropriate survival of abnormal cells underlies tumorigenesis. Most discoveries about programmed cell death have come from studying model organisms. Revisiting the experimental contexts that inspired these discoveries helps explain confounding biases that inevitably accompany such discoveries. Amending early biases has added a newcomer to the collection of cell death models. Analysis of gene-dependent death in yeast revealed the surprising influence of single gene mutations on subsequent eukaryotic genome evolution. Similar events may influence the selection for mutations during early tumorigenesis. The possibility that any early random mutation might drive the selection for a cancer driver mutation is conceivable but difficult to demonstrate. This was tested in yeast, revealing that mutation of almost any gene appears to specify the selection for a new second mutation. Some human tumors contain pairs of mutant genes homologous to co-occurring mutant genes in yeast. Here we consider how yeast again provide novel insights into tumorigenesis.",
			"category": 2,
			"name": "Teng Xinchen,2015"
		},
		{
			"PMID": 25712261,
			"title": "Biological databases for human research.",
			"journal": "Genomics, proteomics & bioinformatics",
			"authorList": [
				"Zou Dong",
				"Ma Lina",
				"Yu Jun",
				"Zhang Zhang"
			],
			"DOI": "10.1016/j.gpb.2015.01.006",
			"date": "2015-07-07",
			"PMC": "",
			"citation": "",
			"abstract": "The completion of the Human Genome Project lays a foundation for systematically studying the human genome from evolutionary history to precision medicine against diseases. With the explosive growth of biological data, there is an increasing number of biological databases that have been developed in aid of human-related research. Here we present a collection of human-related biological databases and provide a mini-review by classifying them into different categories according to their data types. As human-related databases continue to grow not only in count but also in volume, challenges are ahead in big data storage, processing, exchange and curation.",
			"category": 2,
			"name": "Zou Dong,2015"
		},
		{
			"PMID": 25695218,
			"title": "Recent insights emerging from malignant mesothelioma genome sequencing.",
			"journal": "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer",
			"authorList": [
				"Carbone Michele",
				"Gaudino Giovanni",
				"Yang Haining"
			],
			"DOI": "10.1097/JTO.0000000000000466",
			"date": "2015-08-06",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Carbone Michele,2015"
		},
		{
			"PMID": 25692096,
			"title": "Endoplasmic reticulum stress, genome damage, and cancer.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Dicks Naomi",
				"Gutierrez Karina",
				"Michalak Marek",
				"Bordignon Vilceu",
				"Agellon Luis B"
			],
			"DOI": "10.3389/fonc.2015.00011",
			"date": "2015-02-18",
			"PMC": "",
			"citation": "",
			"abstract": "Endoplasmic reticulum (ER) stress has been linked to many diseases, including cancer. A large body of work has focused on the activation of the ER stress response in cancer cells to facilitate their survival and tumor growth; however, there are some studies suggesting that the ER stress response can also mitigate cancer progression. Despite these contradictions, it is clear that the ER stress response is closely associated with cancer biology. The ER stress response classically encompasses activation of three separate pathways, which are collectively categorized the unfolded protein response (UPR). The UPR has been extensively studied in various cancers and appears to confer a selective advantage to tumor cells to facilitate their enhanced growth and resistance to anti-cancer agents. It has also been shown that ER stress induces chromatin changes, which can also facilitate cell survival. Chromatin remodeling has been linked with many cancers through repression of tumor suppressor and apoptosis genes. Interplay between the classic UPR and genome damage repair mechanisms may have important implications in the transformation process of normal cells into cancer cells.",
			"category": 2,
			"name": "Dicks Naomi,2015"
		},
		{
			"PMID": 25691825,
			"title": "The Cancer Genome Atlas (TCGA): an immeasurable source of knowledge.",
			"journal": "Contemporary oncology (Poznan, Poland)",
			"authorList": [
				"Tomczak Katarzyna",
				"Czerwi\u0144ska Patrycja",
				"Wiznerowicz Maciej"
			],
			"DOI": "10.5114/wo.2014.47136",
			"date": "2015-02-18",
			"PMC": "",
			"citation": "",
			"abstract": "The Cancer Genome Atlas (TCGA) is a public funded project that aims to catalogue and discover major cancer-causing genomic alterations to create a comprehensive \"atlas\" of cancer genomic profiles. So far, TCGA researchers have analysed large cohorts of over 30 human tumours through large-scale genome sequencing and integrated multi-dimensional analyses. Studies of individual cancer types, as well as comprehensive pan-cancer analyses have extended current knowledge of tumorigenesis. A major goal of the project was to provide publicly available datasets to help improve diagnostic methods, treatment standards, and finally to prevent cancer. This review discusses the current status of TCGA Research Network structure, purpose, and achievements.",
			"category": 2,
			"name": "Tomczak Katarzyna,2015"
		},
		{
			"PMID": 25636233,
			"title": "Association of PALB2 sequence variants with the risk of familial and early-onset breast cancer in a South-American population.",
			"journal": "BMC cancer",
			"authorList": [
				"Leyton Yessica",
				"Gonzalez-Hormazabal Patricio",
				"Blanco Rafael",
				"Bravo Teresa",
				"Fernandez-Ramires Ricardo",
				"Morales Sebastian",
				"Landeros Natalia",
				"Reyes Jose M",
				"Peralta Octavio",
				"Tapia Julio C",
				"Gomez Fernando",
				"Waugh Enrique",
				"Iba\u00f1ez Gladys",
				"Pakomio Janara",
				"Grau Gilberto",
				"Jara Lilian"
			],
			"DOI": "10.1186/s12885-015-1033-3",
			"date": "2016-01-01",
			"PMC": "",
			"citation": "",
			"abstract": "Germline mutations in PALB2 have been identified in approximately 1% of familial breast cancer (BC) in several populations. Nevertheless its contribution in the South-American population is unknown. The goal of this study was to determine the prevalence of PALB2 mutations in the Chilean population.",
			"category": 2,
			"name": "Leyton Yessica,2016"
		},
		{
			"PMID": 25630433,
			"title": "Molecular pathogenesis of CLL and its evolution.",
			"journal": "International journal of hematology",
			"authorList": [
				"Rodr\u00edguez David",
				"Bretones Gabriel",
				"Arango Javier R",
				"Valdespino V\u00edctor",
				"Campo El\u00edas",
				"Quesada V\u00edctor",
				"L\u00f3pez-Ot\u00edn Carlos"
			],
			"DOI": "10.1007/s12185-015-1733-0",
			"date": "2015-09-23",
			"PMC": "",
			"citation": "",
			"abstract": "In spite of being the most prevalent adult leukemia in Western countries, the molecular mechanisms driving the establishment and progression of chronic lymphocytic leukemia (CLL) remain largely unknown. In recent years, the use of next-generation sequencing techniques has uncovered new and, in some cases, unexpected driver genes with prognostic and therapeutic value. The mutational landscape of CLL is characterized by high-genetic and epigenetic heterogeneity, low mutation recurrence and a long tail of cases with undefined driver genes. On the other hand, the use of deep sequencing has also revealed high intra-tumor heterogeneity and provided a detailed picture of clonal evolution processes. This phenomenon, in which aberrant DNA methylation can also participate, appears to be tightly associated to poor outcomes and chemo-refractoriness, thus providing a new subject for therapeutic intervention. Hence, and having in mind the limitations derived from the CLL complexity thus described, the application of massively parallel sequencing studies has unveiled a wealth of information that is expected to substantially improve patient staging schemes and CLL clinical management.",
			"category": 2,
			"name": "Rodr\u00edguez David,2015"
		},
		{
			"PMID": 25626454,
			"title": "Quantitative analysis of differences in copy numbers using read depth obtained from PCR-enriched samples and controls.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"Reinecke Frank",
				"Satya Ravi Vijaya",
				"DiCarlo John"
			],
			"DOI": "10.1186/s12859-014-0428-5",
			"date": "2015-08-18",
			"PMC": "",
			"citation": "",
			"abstract": "Next-generation sequencing (NGS) is rapidly becoming common practice in clinical diagnostics and cancer research. In addition to the detection of single nucleotide variants (SNVs), information on copy number variants (CNVs) is of great interest. Several algorithms exist to detect CNVs by analyzing whole genome sequencing data or data from samples enriched by hybridization-capture. PCR-enriched amplicon-sequencing data have special characteristics that have been taken into account by only one publicly available algorithm so far.",
			"category": 2,
			"name": "Reinecke Frank,2015"
		},
		{
			"PMID": 25597408,
			"title": "Integrative genomics identifies YY1AP1 as an oncogenic driver in EpCAM(+) AFP(+) hepatocellular carcinoma.",
			"journal": "Oncogene",
			"authorList": [
				"Zhao X",
				"Parpart S",
				"Takai A",
				"Roessler S",
				"Budhu A",
				"Yu Z",
				"Blank M",
				"Zhang Y E",
				"Jia H-L",
				"Ye Q-H",
				"Qin L-X",
				"Tang Z-Y",
				"Thorgeirsson S S",
				"Wang X W"
			],
			"DOI": "10.1038/onc.2014.438",
			"date": "2015-12-15",
			"PMC": "",
			"citation": "",
			"abstract": "Identification of key drivers and new therapeutic targets is important given the poor prognosis for hepatocellular carcinoma (HCC) patients, particularly those ineligible for surgical resection or liver transplant. However, the approach to identify such driver genes is facing significant challenges due to the genomically heterogenous nature of HCC. Here we tested whether the integrative genomic profiling of a well-defined HCC subset that is classified by an extreme EpCAM(+) AFP(+) gene expression signature and associated with poor prognosis, all attributes of a stem cell-like phenotype, could uncover survival-related driver genes in HCC. Following transcriptomic analysis of the well-defined HCC cases, a Gene Set Enrichment Analysis coupled with genomic copy number alteration assessment revealed that YY1-associated protein 1 (YY1AP1) is a critical oncoprotein specifically activated in EpCAM(+) AFP(+) HCC. YY1AP1 silencing eliminates oncogene addiction by altering the chromatin landscape and triggering massive apoptosis in vitro and tumor suppression in vivo. YY1AP1 expression promotes HCC proliferation and is required for the maintenance of stem cell features. We revealed that YY1AP1 cooperates with YY1 to alter the chromatin landscape and activate transcription of stemness regulators. Thus YY1AP1 may serve as a key molecular target for EpCAM(+) AFP(+) HCC subtype. Our results demonstrate the feasibility and power of a new strategy by utilizing well-defined patient samples and integrative genomics to uncover critical pathways linked to HCC subtypes with prognostic impact.",
			"category": 2,
			"name": "Zhao X,2015"
		},
		{
			"PMID": 25587136,
			"title": "The value of monitoring to control evolving populations.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Fischer Andrej",
				"V\u00e1zquez-Garc\u00eda Ignacio",
				"Mustonen Ville"
			],
			"DOI": "10.1073/pnas.1409403112",
			"date": "2015-04-23",
			"PMC": "",
			"citation": "",
			"abstract": "Populations can evolve to adapt to external changes. The capacity to evolve and adapt makes successful treatment of infectious diseases and cancer difficult. Indeed, therapy resistance has become a key challenge for global health. Therefore, ideas of how to control evolving populations to overcome this threat are valuable. Here we use the mathematical concepts of stochastic optimal control to study what is needed to control evolving populations. Following established routes to calculate control strategies, we first study how a polymorphism can be maintained in a finite population by adaptively tuning selection. We then introduce a minimal model of drug resistance in a stochastically evolving cancer cell population and compute adaptive therapies. When decisions are in this manner based on monitoring the response of the tumor, this can outperform established therapy paradigms. For both case studies, we demonstrate the importance of high-resolution monitoring of the target population to achieve a given control objective, thus quantifying the intuition that to control, one must monitor.",
			"category": 2,
			"name": "Fischer Andrej,2015"
		},
		{
			"PMID": 25572314,
			"title": "Patient-specific driver gene prediction and risk assessment through integrated network analysis of cancer omics profiles.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Bertrand Denis",
				"Chng Kern Rei",
				"Sherbaf Faranak Ghazi",
				"Kiesel Anja",
				"Chia Burton K H",
				"Sia Yee Yen",
				"Huang Sharon K",
				"Hoon Dave S B",
				"Liu Edison T",
				"Hillmer Axel",
				"Nagarajan Niranjan"
			],
			"DOI": "10.1093/nar/gku1393",
			"date": "2015-07-07",
			"PMC": "",
			"citation": "",
			"abstract": "Extensive and multi-dimensional data sets generated from recent cancer omics profiling projects have presented new challenges and opportunities for unraveling the complexity of cancer genome landscapes. In particular, distinguishing the unique complement of genes that drive tumorigenesis in each patient from a sea of passenger mutations is necessary for translating the full benefit of cancer genome sequencing into the clinic. We address this need by presenting a data integration framework (OncoIMPACT) to nominate patient-specific driver genes based on their phenotypic impact. Extensive in silico and in vitro validation helped establish OncoIMPACT's robustness, improved precision over competing approaches and verifiable patient and cell line specific predictions (2/2 and 6/7 true positives and negatives, respectively). In particular, we computationally predicted and experimentally validated the gene TRIM24 as a putative novel amplified driver in a melanoma patient. Applying OncoIMPACT to more than 1000 tumor samples, we generated patient-specific driver gene lists in five different cancer types to identify modes of synergistic action. We also provide the first demonstration that computationally derived driver mutation signatures can be overall superior to single gene and gene expression based signatures in enabling patient stratification and prognostication. Source code and executables for OncoIMPACT are freely available from http://sourceforge.net/projects/oncoimpact.",
			"category": 2,
			"name": "Bertrand Denis,2015"
		},
		{
			"PMID": 25562700,
			"title": "Trends in Personalized Therapies in Oncology: The (Venture) Capitalist's Perspective.",
			"journal": "Journal of personalized medicine",
			"authorList": [
				"Fleck Roman",
				"Bach Daniel"
			],
			"DOI": "10.3390/jpm2010015",
			"date": "2015-01-07",
			"PMC": "",
			"citation": "",
			"abstract": "Oncology is one of the most important fields of personalized medicine as a majority of efforts in this field have recently centered on targeted cancer drug development. New tools are continuously being developed that promise to make cancer treatment more efficacious while causing fewer side effects. Like most industries, the biopharmaceutical industry is also following certain global trends and these are analyzed in this article. As academia and industry are mutually dependent on each other, researchers in the field should be aware of those trends and the immediate consequences for their research. It is important for the future of this field that there is a healthy relationship among all interested parties as the challenges of personalized medicine are becoming ever more complex.",
			"category": 2,
			"name": "Fleck Roman,2015"
		},
		{
			"PMID": 25554788,
			"title": "Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions.",
			"journal": "Science (New York, N.Y.)",
			"authorList": [
				"Tomasetti Cristian",
				"Vogelstein Bert"
			],
			"DOI": "10.1126/science.1260825",
			"date": "2015-01-20",
			"PMC": "",
			"citation": "",
			"abstract": "Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue's homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to \"bad luck,\" that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes.",
			"category": 2,
			"name": "Tomasetti Cristian,2015"
		},
		{
			"PMID": 25535351,
			"title": "Only three driver gene mutations are required for the development of lung and colorectal cancers.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Tomasetti Cristian",
				"Marchionni Luigi",
				"Nowak Martin A",
				"Parmigiani Giovanni",
				"Vogelstein Bert"
			],
			"DOI": "10.1073/pnas.1421839112",
			"date": "2015-04-23",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer arises through the sequential accumulation of mutations in oncogenes and tumor suppressor genes. However, how many such mutations are required for a normal human cell to progress to an advanced cancer? The best estimates for this number have been provided by mathematical models based on the relation between age and incidence. For example, the classic studies of Nordling [Nordling CO (1953) Br J Cancer 7(1):68-72] and Armitage and Doll [Armitage P, Doll R (1954) Br J Cancer 8(1):1-12] suggest that six or seven sequential mutations are required. Here, we describe a different approach to derive this estimate that combines conventional epidemiologic studies with genome-wide sequencing data: incidence data for different groups of patients with the same cancer type were compared with respect to their somatic mutation rates. In two well-documented cancer types (lung and colon adenocarcinomas), we find that only three sequential mutations are required to develop cancer. This conclusion deepens our understanding of the process of carcinogenesis and has important implications for the design of future cancer genome-sequencing efforts.",
			"category": 2,
			"name": "Tomasetti Cristian,2015"
		},
		{
			"PMID": 25528755,
			"title": "A cancer theory kerfuffle can lead to new lines of research.",
			"journal": "Journal of the National Cancer Institute",
			"authorList": [
				"Baker Stuart G"
			],
			"DOI": "10.1093/jnci/dju405",
			"date": "2015-02-19",
			"PMC": "",
			"citation": "",
			"abstract": "The standard viewpoint that cancer is a genetic disease is often stated as a fact rather than a theory. By not acknowledging that it is a theory, namely the Somatic Mutation Theory (SMT), researchers are limiting their progress. An attractive alternative to SMT is the tissue organization field theory (TOFT), which is summarized as \"development gone awry.\" To initiate a kerfuffle, I discuss the interpretation of various results under both TOFT and SMT, including recurrent mutations, hereditary cancers, induction of tumors in transgenic experiments, remission of tumors following the inhibition of enzymes activated by mutated genes, nongenotoxic carcinogens, denervation experiments, foreign-body carcinogenesis, transplantation experiments, and tumors with zero mutations. Thinking in terms of TOFT can spur new lines of research; examples are given related to the early detection of cancer.",
			"category": 2,
			"name": "Baker Stuart G,2015"
		},
		{
			"PMID": 25524504,
			"title": "Safety and diagnostic accuracy of tumor biopsies in children with cancer.",
			"journal": "Cancer",
			"authorList": [
				"Interiano Rodrigo B",
				"Loh Amos H P",
				"Hinkle Nathan",
				"Wahid Fazal N",
				"Malkan Alpin D",
				"Bahrami Armita",
				"Jenkins Jesse J",
				"Mao Shenghua",
				"Wu Jianrong",
				"Proctor Kimberly",
				"Santana Victor M",
				"Pappo Alberto S",
				"Gold Robert E",
				"Davidoff Andrew M"
			],
			"DOI": "10.1002/cncr.29167",
			"date": "2015-05-22",
			"PMC": "",
			"citation": "",
			"abstract": "Tumor biopsies are central to the diagnosis and management of cancer and are critical to efforts in personalized medicine and targeted therapeutics. In the current study, the authors sought to evaluate the safety and accuracy of biopsies in children with cancer.",
			"category": 2,
			"name": "Interiano Rodrigo B,2015"
		},
		{
			"PMID": 25513881,
			"title": "Somatic mosaicism in the human genome.",
			"journal": "Genes",
			"authorList": [
				"Freed Donald",
				"Stevens Eric L",
				"Pevsner Jonathan"
			],
			"DOI": "10.3390/genes5041064",
			"date": "2014-12-17",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic mosaicism refers to the occurrence of two genetically distinct populations of cells within an individual, derived from a postzygotic mutation. In contrast to inherited mutations, somatic mosaic mutations may affect only a portion of the body and are not transmitted to progeny. These mutations affect varying genomic sizes ranging from single nucleotides to entire chromosomes and have been implicated in disease, most prominently cancer. The phenotypic consequences of somatic mosaicism are dependent upon many factors including the developmental time at which the mutation occurs, the areas of the body that are affected, and the pathophysiological effect(s) of the mutation. The advent of second-generation sequencing technologies has augmented existing array-based and cytogenetic approaches for the identification of somatic mutations. We outline the strengths and weaknesses of these techniques and highlight recent insights into the role of somatic mosaicism in causing cancer, neurodegenerative, monogenic, and complex disease.",
			"category": 2,
			"name": "Freed Donald,2014"
		},
		{
			"PMID": 25501392,
			"title": "Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes.",
			"journal": "Nature genetics",
			"authorList": [
				"Leiserson Mark D M",
				"Vandin Fabio",
				"Wu Hsin-Ta",
				"Dobson Jason R",
				"Eldridge Jonathan V",
				"Thomas Jacob L",
				"Papoutsaki Alexandra",
				"Kim Younhun",
				"Niu Beifang",
				"McLellan Michael",
				"Lawrence Michael S",
				"Gonzalez-Perez Abel",
				"Tamborero David",
				"Cheng Yuwei",
				"Ryslik Gregory A",
				"Lopez-Bigas Nuria",
				"Getz Gad",
				"Ding Li",
				"Raphael Benjamin J"
			],
			"DOI": "10.1038/ng.3168",
			"date": "2015-04-14",
			"PMC": "",
			"citation": "",
			"abstract": "Cancers exhibit extensive mutational heterogeneity, and the resulting long-tail phenomenon complicates the discovery of genes and pathways that are significantly mutated in cancer. We perform a pan-cancer analysis of mutated networks in 3,281 samples from 12 cancer types from The Cancer Genome Atlas (TCGA) using HotNet2, a new algorithm to find mutated subnetworks that overcomes the limitations of existing single-gene, pathway and network approaches. We identify 16 significantly mutated subnetworks that comprise well-known cancer signaling pathways as well as subnetworks with less characterized roles in cancer, including cohesin, condensin and others. Many of these subnetworks exhibit co-occurring mutations across samples. These subnetworks contain dozens of genes with rare somatic mutations across multiple cancers; many of these genes have additional evidence supporting a role in cancer. By illuminating these rare combinations of mutations, pan-cancer network analyses provide a roadmap to investigate new diagnostic and therapeutic opportunities across cancer types.",
			"category": 2,
			"name": "Leiserson Mark D M,2015"
		},
		{
			"PMID": 25493071,
			"title": "A novel pathogenic classification of cancers.",
			"journal": "Cancer cell international",
			"authorList": [
				"Sonnenschein Carlos",
				"Davis Barbara",
				"Soto Ana M"
			],
			"DOI": "10.1186/s12935-014-0113-9",
			"date": "2014-12-10",
			"PMC": "",
			"citation": "",
			"abstract": "According to contemporary epidemiological and experimental evidence, we propose a novel classification of cancers based on pathogenesis instead of classifications based on histological appearance of cancer. This new scheme first defines cancers as either 1. inborn errors of development or 2. sporadic ones, and then sub-defines the former into 1A. inborn inherited errors of development, being those due to mutations contributed by one or both parents' gametes to the developing conceptus, and 1B. inborn induced errors of development when the malformations and/or cancers are due to environmental carcinogenic exposure during pregnancy. It is anticipated that the origin of an increasing number of so-called sporadic cancers will turn out to be linked to the inborn induced errors of development group.",
			"category": 2,
			"name": "Sonnenschein Carlos,2014"
		},
		{
			"PMID": 25484456,
			"title": "From Physics to Pharmacology?",
			"journal": "Reports on progress in physics. Physical Society (Great Britain)",
			"authorList": [
				"Allen Richard J",
				"Elston Timothy C"
			],
			"DOI": "",
			"date": "2019-11-20",
			"PMC": "",
			"citation": "",
			"abstract": "Over the last fifty years there has been an explosion of biological data, leading to the realization that to fully explain biological mechanisms it is necessary to interpret them as complex dynamical systems. The first stage of this interpretation is to determine which components (proteins, genes or metabolites) of the system interact. This is usually represented by a graph, or network. The behavior of this network can then be investigated using mathematical modeling. In vivo these biological networks show several remarkable (and seemingly paradoxical) properties including robustness, plasticity and sensitivity. Erroneous behavior of these networks is often associated with disease. Hence understanding the system-level properties can have important implications for the treatment of disease. Systems biology is an organized approach to quantitatively describe and elucidate the behavior of these complex networks. This review focuses on the progress and future challenges of a systems approach to biology.",
			"category": 2,
			"name": "Allen Richard J,2019"
		},
		{
			"PMID": 25435801,
			"title": "Congenital heart disease: the crossroads of genetics, epigenetics and environment.",
			"journal": "Current genomics",
			"authorList": [
				"Vecoli Cecilia",
				"Pulignani Silvia",
				"Foffa Ilenia",
				"Andreassi Maria Grazia"
			],
			"DOI": "10.2174/1389202915666140716175634",
			"date": "2014-12-01",
			"PMC": "",
			"citation": "",
			"abstract": "Congenital heart diseases (CHDs) are recognized as the most common type of birth malformations. Although recent advances in pre- and neonatal diagnosis as well as in surgical procedures have reduced the morbidity and mortality for many CHD, the etiology for CHD remains undefined. In non-syndromic and isolated (without a familial history or a Mendelian inheritance) forms of CHDs, a multifactorial pathogenesis with interplay between inherited and non-inherited causes is recognized. In this paper, we discuss the current knowledge of the potential molecular mechanisms, mediating abnormal cardiac development in non-syndromic and isolated CHD, including mutations in cardiac transcription factors, the role of somatic mutations and epigenetic alterations as well as the influence of gene-environment interactions. In the near future, the advent of high-throughput genomic technologies with the integration of system biology will expand our understanding of isolated, non-syndromic CHDs for their prevention, early diagnosis and therapy.",
			"category": 2,
			"name": "Vecoli Cecilia,2014"
		},
		{
			"PMID": 25435088,
			"title": "HotSpotter: efficient visualization of driver mutations.",
			"journal": "BMC genomics",
			"authorList": [
				"Roszik Jason",
				"Woodman Scott E"
			],
			"DOI": "10.1186/1471-2164-15-1044",
			"date": "2015-07-08",
			"PMC": "",
			"citation": "",
			"abstract": "Driver mutations are positively selected during the evolution of cancers. The relative frequency of a particular mutation within a gene is typically used as a criterion for identifying a driver mutation. However, driver mutations may occur with relative infrequency at a particular site, but cluster within a region of the gene. When analyzing across different cancers, particular mutation sites or mutations within a particular region of the gene may be of relatively low frequency in some cancers, but still provide selective growth advantage.",
			"category": 2,
			"name": "Roszik Jason,2015"
		},
		{
			"PMID": 25431261,
			"title": "Individualized chemotherapy for osteosarcoma and identification of gene mutations in osteosarcoma.",
			"journal": "Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine",
			"authorList": [
				"Xiao Xin",
				"Wang Wei",
				"Zhang Haoqiang",
				"Gao Peng",
				"Fan Bo",
				"Huang Chen",
				"Fu Jun",
				"Chen Guojing",
				"Shi Lei",
				"Zhu Haodong",
				"Li Xiangdong",
				"Li Jing",
				"Fan Hongbin",
				"Wu Zhigang",
				"Guo Zheng",
				"Hu Yongcheng",
				"Wu Sujia",
				"Yu Xiuchun",
				"Xu Cheng",
				"Wang Zhen"
			],
			"DOI": "10.1007/s13277-014-2853-5",
			"date": "2015-07-09",
			"PMC": "",
			"citation": "",
			"abstract": "The study aims to identify novel gene mutations in osteosarcoma and to guide individualized preoperative chemotherapy for osteosarcoma based on the analysis of expression and mutations of the drug-metabolism-related genes. Twenty-eight osteosarcoma patients received individualized preoperative chemotherapy regimens. Expression levels and mutations of chemotherapy-related genes in samples collected from the patients were determined using real-time PCR and DNA sequencing, respectively. Patient sensitivity to chemotherapeutic agents was evaluated by systematic analysis of the PCR and sequencing results. Novel mutations were identified via high-throughput sequencing of 339 genes in 10 osteosarcoma samples. Individualized preoperative chemotherapy outcomes were valid for nine patients (n\u2009=\u20099/28, 32.1%). Chemosensitivity assays showed that all 28 patients were sensitive to ifosfamide, whereas 46.4 and 39.2% were sensitive to docetaxel and platinum, respectively. More importantly, patients receiving highly chemosensitive chemotherapy agents had better prognosis and treatment outcomes than those receiving less chemosensitive agents (P\u2009<\u20090.05). In addition, 39 gene mutations were detected in at least five osteosarcoma tumor samples. Analysis of the expression and mutation of drug-metabolism-related genes will aid in the design of effective individualized preoperative chemotherapy regimens for osteosarcoma. Determining the chemosensitivity of individual tumors to chemotherapeutic agents will facilitate the development of better therapeutic approaches. Individualized treatment of osteosarcoma may improve chemotherapy efficacy and the survival rate of osteosarcoma patients. High-throughput genotyping allows mapping of osteosarcoma mutations, and novel gene mutations offered new candidates for diagnosis and therapeutic targeting.",
			"category": 2,
			"name": "Xiao Xin,2015"
		},
		{
			"PMID": 25428357,
			"title": "arrayMap 2014: an updated cancer genome resource.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Cai Haoyang",
				"Gupta Saumya",
				"Rath Prisni",
				"Ai Ni",
				"Baudis Michael"
			],
			"DOI": "10.1093/nar/gku1123",
			"date": "2015-06-29",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic copy number aberrations (CNA) represent a mutation type encountered in the majority of cancer genomes. Here, we present the 2014 edition of arrayMap (http://www.arraymap.org), a publicly accessible collection of pre-processed oncogenomic array data sets and CNA profiles, representing a vast range of human malignancies. Since the initial release, we have enhanced this resource both in content and especially with regard to data mining support. The 2014 release of arrayMap contains more than 64,000 genomic array data sets, representing about 250 tumor diagnoses. Data sets included in arrayMap have been assembled from public repositories as well as additional resources, and integrated by applying custom processing pipelines. Online tools have been upgraded for a more flexible array data visualization, including options for processing user provided, non-public data sets. Data integration has been improved by mapping to multiple editions of the human reference genome, with the majority of the data now being available for the UCSC hg18 as well as GRCh37 versions. The large amount of tumor CNA data in arrayMap can be freely downloaded by users to promote data mining projects, and to explore special events such as chromothripsis-like genome patterns.",
			"category": 2,
			"name": "Cai Haoyang,2015"
		},
		{
			"PMID": 25418858,
			"title": "Insights into a Critical Role of the FOXO3a-FOXM1 Axis in DNA Damage Response and Genotoxic Drug Resistance.",
			"journal": "Current drug targets",
			"authorList": [
				"Nestal de Moraes Gabriela",
				"Bella Laura",
				"Zona Stefania",
				"Burton Matthew J",
				"Lam Eric W-F"
			],
			"DOI": "",
			"date": "2016-10-13",
			"PMC": "",
			"citation": "",
			"abstract": "FOXO3a and FOXM1 are two forkhead transcription factors with antagonistic roles in cancer and DNA damage response. FOXO3a functions like a typical tumour suppressor, whereas FOXM1 is a potent oncogene aberrantly overexpressed in genotoxic resistant cancers. FOXO3a not only represses FOXM1 expression but also its transcriptional output. Recent research has provided novel insights into a central role for FOXO3a and FOXM1 in DNA damage response. The FOXO3a-FOXM1 axis plays a pivotal role in DNA damage repair and the accompanied cellular response through regulating the expression of genes essential for DNA damage sensing, mediating, signalling and repair as well as for senescence, cell cycle and cell death control. In this manner, the FOXO3a-FOXM1 axis also holds the key to cell fate decision in response to genotoxic therapeutic agents and controls the equilibrium between DNA repair and cell termination by cell death or senescence. As a consequence, inhibition of FOXM1 or reactivation of FOXO3a in cancer cells could enhance the efficacy of DNA damaging cancer therapies by decreasing the rate of DNA repair and cell survival while increasing senescence and cell death. Conceptually, targeting FOXO3a and FOXM1 may represent a promising molecular therapeutic option for improving the efficacy and selectivity of DNA damage agents, particularly in genotoxic agent resistant cancer. In addition, FOXO3a, FOXM1 and their downstream transcriptional targets may also be reliable diagnostic biomarkers for predicting outcome, for selecting therapeutic options, and for monitoring treatments in DNA-damaging agent therapy.",
			"category": 2,
			"name": "Nestal de Moraes Gabriela,2016"
		},
		{
			"PMID": 25407411,
			"title": "Evolutionary triage governs fitness in driver and passenger mutations and suggests targeting never mutations.",
			"journal": "Nature communications",
			"authorList": [
				"Gatenby R A",
				"Cunningham J J",
				"Brown J S"
			],
			"DOI": "10.1038/ncomms6499",
			"date": "2015-11-16",
			"PMC": "",
			"citation": "",
			"abstract": "Genetic and epigenetic changes in cancer cells are typically divided into 'drivers' and 'passengers'. Drug development strategies target driver mutations, but inter- and intratumoral heterogeneity usually results in emergence of resistance. Here we model intratumoral evolution in the context of a fecundity/survivorship trade-off. Simulations demonstrate that the fitness value of any genetic change is not fixed but dependent on evolutionary triage governed by initial cell properties, current selection forces and prior genotypic/phenotypic trajectories. We demonstrate that spatial variations in molecular properties of tumour cells are the result of changes in environmental selection forces such as blood flow. Simulated therapies targeting fitness-increasing (driver) mutations usually decrease the tumour burden but almost inevitably fail due to population heterogeneity. An alternative strategy targets gene mutations that are never observed. Because up or downregulation of these genes unconditionally reduces cellular fitness, they are eliminated by evolutionary triage but can be exploited for targeted therapy.",
			"category": 2,
			"name": "Gatenby R A,2015"
		},
		{
			"PMID": 25363767,
			"title": "The mutational landscapes of genetic and chemical models of Kras-driven lung cancer.",
			"journal": "Nature",
			"authorList": [
				"Westcott Peter M K",
				"Halliwill Kyle D",
				"To Minh D",
				"Rashid Mamunur",
				"Rust Alistair G",
				"Keane Thomas M",
				"Delrosario Reyno",
				"Jen Kuang-Yu",
				"Gurley Kay E",
				"Kemp Christopher J",
				"Fredlund Erik",
				"Quigley David A",
				"Adams David J",
				"Balmain Allan"
			],
			"DOI": "10.1038/nature13898",
			"date": "2015-02-12",
			"PMC": "",
			"citation": "",
			"abstract": "Next-generation sequencing of human tumours has refined our understanding of the mutational processes operative in cancer initiation and progression, yet major questions remain regarding the factors that induce driver mutations and the processes that shape mutation selection during tumorigenesis. Here we performed whole-exome sequencing on adenomas from three mouse models of non-small-cell lung cancer, which were induced either by exposure to carcinogens (methyl-nitrosourea (MNU) and urethane) or by genetic activation of Kras (Kras(LA2)). Although the MNU-induced tumours carried exactly the same initiating mutation in Kras as seen in the Kras(LA2) model (G12D), MNU tumours had an average of 192 non-synonymous, somatic single-nucleotide variants, compared with only six in tumours from the Kras(LA2) model. By contrast, the Kras(LA2) tumours exhibited a significantly higher level of aneuploidy and copy number alterations compared with the carcinogen-induced tumours, suggesting that carcinogen-induced and genetically engineered models lead to tumour development through different routes. The wild-type allele of Kras has been shown to act as a tumour suppressor in mouse models of non-small-cell lung cancer. We demonstrate that urethane-induced tumours from wild-type mice carry mostly (94%) Kras Q61R mutations, whereas those from Kras heterozygous animals carry mostly (92%) Kras Q61L mutations, indicating a major role for germline Kras status in mutation selection during initiation. The exome-wide mutation spectra in carcinogen-induced tumours overwhelmingly display signatures of the initiating carcinogen, while adenocarcinomas acquire additional C > T mutations at CpG sites. These data provide a basis for understanding results from human tumour genome sequencing, which has identified two broad categories of tumours based on the relative frequency of single-nucleotide variations and copy number alterations, and underline the importance of carcinogen models for understanding the complex mutation spectra seen in human cancers.",
			"category": 2,
			"name": "Westcott Peter M K,2015"
		},
		{
			"PMID": 25348012,
			"title": "Benchmarking mutation effect prediction algorithms using functionally validated cancer-related missense mutations.",
			"journal": "Genome biology",
			"authorList": [
				"Martelotto Luciano G",
				"Ng Charlotte Ky",
				"De Filippo Maria R",
				"Zhang Yan",
				"Piscuoglio Salvatore",
				"Lim Raymond S",
				"Shen Ronglai",
				"Norton Larry",
				"Reis-Filho Jorge S",
				"Weigelt Britta"
			],
			"DOI": "10.1186/s13059-014-0484-1",
			"date": "2015-10-26",
			"PMC": "",
			"citation": "",
			"abstract": "Massively parallel sequencing studies have led to the identification of a large number of mutations present in a minority of cancers of a given site. Hence, methods to identify the likely pathogenic mutations that are worth exploring experimentally and clinically are required. We sought to compare the performance of 15 mutation effect prediction algorithms and their agreement. As a hypothesis-generating aim, we sought to define whether combinations of prediction algorithms would improve the functional effect predictions of specific mutations.",
			"category": 2,
			"name": "Martelotto Luciano G,2015"
		},
		{
			"PMID": 25337557,
			"title": "Recent advances in in vivo genotoxicity testing: prediction of carcinogenic potential using comet and micronucleus assay in animal models.",
			"journal": "Journal of cancer prevention",
			"authorList": [
				"Kang Seung Hun",
				"Kwon Jee Young",
				"Lee Jong Kwon",
				"Seo Young Rok"
			],
			"DOI": "",
			"date": "2014-10-22",
			"PMC": "",
			"citation": "",
			"abstract": "Genotoxic events have been known as crucial step in the initiation of cancer. To assess the risk of cancer, genotoxicity assays, including comet, micronucleus (MN), chromosomal aberration, bacterial reverse, and sister chromatid exchange assay, can be performed. Compared with in vitro genotoxicity assay, in vivo genotoxicity assay has been used to verify in vitro assay result and definitely provide biological significance for certain organs or cell types. The comet assay can detect DNA strand breaks as markers of genotoxicity. Methods of the in vivo comet assay have been established by Japanese Center for the Validation of Alternative Methods (JaCVAM) validation studies depending on tissue and sample types. The MN can be initiated by segregation error and lagging acentric chromosome fragment. Methods of the in vivo MN assay have been established by Organization for Economic Co-operation and Development (OECD) test guidelines and many studies. Combining the in vivo comet and MN assay has been regarded as useful methodology for evaluating genetic damage, and it has been used in the assessment of potential carcinogenicity by complementarily presenting two distinct endpoints of the in vivo genotoxicity individual test. Few studies have investigated the quantitative relation between in vivo genotoxicity results and carcinogenicity. Extensive studies emphasizes that positive correlation is detectable. This review summarizes the results of the in vivo comet and MN assays that have investigated the genotoxicity of carcinogens as classified by the International Agency for Research on Cancer (IARC) carcinogenicity database. As a result, these genotoxicity data may provide meaningful information for the assessment of potential carcinogenicity and for implementation in the prevention of cancer.",
			"category": 2,
			"name": "Kang Seung Hun,2014"
		},
		{
			"PMID": 25332972,
			"title": "The significance of genetics for cholangiocarcinoma development.",
			"journal": "Annals of translational medicine",
			"authorList": [
				"Maroni Luca",
				"Pierantonelli Irene",
				"Banales Jesus M",
				"Benedetti Antonio",
				"Marzioni Marco"
			],
			"DOI": "10.3978/j.issn.2305-5839.2012.10.04",
			"date": "2014-10-21",
			"PMC": "",
			"citation": "",
			"abstract": "Cholangiocarcinoma (CCA) is a rare malignancy of the liver, arising from bile ducts. The incidence is increasing worldwide, but the prognosis has remained dismal and virtually unchanged in the past 30 years. Although several risk factors have been associated with the development of this cancer, none of them are normally identified in most patients. Diagnosis in advanced stages of the disease and limited therapeutic options contribute to poor survival rates. The recent analysis of genetic and epigenetic alterations occurring in CCA has shed new light in the understanding of the molecular mechanisms leading to the malignant transformation of biliary cells. Further studies in this direction may foster new diagnostic, prognostic and therapeutic approaches. This review provides a global overview of recent advances in CCA and describes the most important genetic mutations and epigenetic alterations so far reported in CCA.",
			"category": 2,
			"name": "Maroni Luca,2014"
		},
		{
			"PMID": 25300573,
			"title": "Enhanced expression of retinoic acid receptor alpha (RARA) induces epithelial-to-mesenchymal transition and disruption of mammary acinar structures.",
			"journal": "Molecular oncology",
			"authorList": [
				"Doi Ayano",
				"Ishikawa Kosuke",
				"Shibata Nao",
				"Ito Emi",
				"Fujimoto Jiro",
				"Yamamoto Mizuki",
				"Shiga Hatsuki",
				"Mochizuki Hiromi",
				"Kawamura Yoshifumi",
				"Goshima Naoki",
				"Semba Kentaro",
				"Watanabe Shinya"
			],
			"DOI": "10.1016/j.molonc.2014.09.005",
			"date": "2015-09-16",
			"PMC": "",
			"citation": "",
			"abstract": "The early steps of mammary tumorigenesis include loss of epithelial cell polarity, escape from anoikis, and acquisition of proliferative capacity. The genes responsible for these processes are predicted to be early diagnostic markers or new therapeutic targets. Here we tested 51 genes coamplified with ERBB2 in the 17q12-21 amplicon for these tumorigenic activities using an MCF10A 3D culture-based screening system. We found that overexpression of retinoic acid receptor \u03b1 (RARA) disrupted normal acinar structure and induced epithelial-to-mesenchymal transition (EMT). The mRNA levels of known EMT-inducing factors, including SLUG, FOXC2, ZEB1, and ZEB2, were significantly increased upon RARA overexpression. Knockdown of ZEB1 suppressed the RARA-mediated EMT phenotype. These results suggest that overexpression of RARA enhances malignant transformation during mammary tumorigenesis.",
			"category": 2,
			"name": "Doi Ayano,2015"
		},
		{
			"PMID": 25293804,
			"title": "Cancer evolution: mathematical models and computational inference.",
			"journal": "Systematic biology",
			"authorList": [
				"Beerenwinkel Niko",
				"Schwarz Roland F",
				"Gerstung Moritz",
				"Markowetz Florian"
			],
			"DOI": "10.1093/sysbio/syu081",
			"date": "2015-06-04",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a somatic evolutionary process characterized by the accumulation of mutations, which contribute to tumor growth, clinical progression, immune escape, and drug resistance development. Evolutionary theory can be used to analyze the dynamics of tumor cell populations and to make inference about the evolutionary history of a tumor from molecular data. We review recent approaches to modeling the evolution of cancer, including population dynamics models of tumor initiation and progression, phylogenetic methods to model the evolutionary relationship between tumor subclones, and probabilistic graphical models to describe dependencies among mutations. Evolutionary modeling helps to understand how tumors arise and will also play an increasingly important prognostic role in predicting disease progression and the outcome of medical interventions, such as targeted therapy.",
			"category": 2,
			"name": "Beerenwinkel Niko,2015"
		},
		{
			"PMID": 25275295,
			"title": "Chemoradiation provides a physiological selective pressure that increases the expansion of aberrant TP53 tumor variants in residual rectal cancerous regions.",
			"journal": "Oncotarget",
			"authorList": [
				"Sakai Kazuko",
				"Kazama Shinsuke",
				"Nagai Yuzo",
				"Murono Koji",
				"Tanaka Toshiaki",
				"Ishihara Soichiro",
				"Sunami Eiji",
				"Tomida Shuta",
				"Nishio Kazuto",
				"Watanabe Toshiaki"
			],
			"DOI": "",
			"date": "2015-07-13",
			"PMC": "",
			"citation": "",
			"abstract": "Neoadjuvant chemoradiotherapy has been introduced in patients with surgically resected rectal cancer and reduced the local recurrence. Heterogeneity exists in rectal cancer, and we hypothesized that there are subclones resistant to chemoradiotherapy within the cancer mass. We performed DNA-targeted sequencing of pre- and post-treatment tumor tissues obtained from 20 rectal cancer patients who received chemoradiotherapy. The variant frequency of the mutant clones was compared between pre- and post-treatment samples of nine non-responder patients. RNA-targeted sequencing of 57 genes related to sensitivity to chemotherapy and radiotherapy was performed for the paired samples. Immunohistochemical analyses of p53 expression were also performed on the paired samples from the nine non-responder patients. DNA-sequencing detected frequent mutations of suppressor genes including TP53, APC and FBXW7 in the post-treatment samples of the nine non-responders. The frequency of TP53 mutations showed significant increases after chemoradiotherapy. RNA-targeted sequencing of 29 tumor tissues demonstrated that decreased expression of three genes and increased expression of four genes were detected in the post-treatment samples. Significantly increased expression of TP53 was observed in the post-treatment samples. Immunohistochemical staining for p53 revealed that increased p53 intensity scores were observed after chemoradiotherapy. These results suggest that the tumors with TP53 mutations tend to accumulate through chemoradiotherapy.",
			"category": 2,
			"name": "Sakai Kazuko,2015"
		},
		{
			"PMID": 25271376,
			"title": "Origins and functional consequences of somatic mitochondrial DNA mutations in human cancer.",
			"journal": "eLife",
			"authorList": [
				"Ju Young Seok",
				"Alexandrov Ludmil B",
				"Gerstung Moritz",
				"Martincorena Inigo",
				"Nik-Zainal Serena",
				"Ramakrishna Manasa",
				"Davies Helen R",
				"Papaemmanuil Elli",
				"Gundem Gunes",
				"Shlien Adam",
				"Bolli Niccolo",
				"Behjati Sam",
				"Tarpey Patrick S",
				"Nangalia Jyoti",
				"Massie Charles E",
				"Butler Adam P",
				"Teague Jon W",
				"Vassiliou George S",
				"Green Anthony R",
				"Du Ming-Qing",
				"Unnikrishnan Ashwin",
				"Pimanda John E",
				"Teh Bin Tean",
				"Munshi Nikhil",
				"Greaves Mel",
				"Vyas Paresh",
				"El-Naggar Adel K",
				"Santarius Tom",
				"Collins V Peter",
				"Grundy Richard",
				"Taylor Jack A",
				"Hayes D Neil",
				"Malkin David",
				"ICGC Breast Cancer Group",
				"ICGC Chronic Myeloid Disorders Group",
				"ICGC Prostate Cancer Group",
				"Foster Christopher S",
				"Warren Anne Y",
				"Whitaker Hayley C",
				"Brewer Daniel",
				"Eeles Rosalind",
				"Cooper Colin",
				"Neal David",
				"Visakorpi Tapio",
				"Isaacs William B",
				"Bova G Steven",
				"Flanagan Adrienne M",
				"Futreal P Andrew",
				"Lynch Andy G",
				"Chinnery Patrick F",
				"McDermott Ultan",
				"Stratton Michael R",
				"Campbell Peter J"
			],
			"DOI": "10.7554/eLife.02935",
			"date": "2015-06-23",
			"PMC": "",
			"citation": "",
			"abstract": "Recent sequencing studies have extensively explored the somatic alterations present in the nuclear genomes of cancers. Although mitochondria control energy metabolism and apoptosis, the origins and impact of cancer-associated mutations in mtDNA are unclear. In this study, we analyzed somatic alterations in mtDNA from 1675 tumors. We identified 1907 somatic substitutions, which exhibited dramatic replicative strand bias, predominantly C > T and A > G on the mitochondrial heavy strand. This strand-asymmetric signature differs from those found in nuclear cancer genomes but matches the inferred germline process shaping primate mtDNA sequence content. A number of mtDNA mutations showed considerable heterogeneity across tumor types. Missense mutations were selectively neutral and often gradually drifted towards homoplasmy over time. In contrast, mutations resulting in protein truncation undergo negative selection and were almost exclusively heteroplasmic. Our findings indicate that the endogenous mutational mechanism has far greater impact than any other external mutagens in mitochondria and is fundamentally linked to mtDNA replication.",
			"category": 2,
			"name": "Ju Young Seok,2015"
		},
		{
			"PMID": 25260652,
			"title": "Polygenic in vivo validation of cancer mutations using transposons.",
			"journal": "Genome biology",
			"authorList": [
				"Chew Su Kit",
				"Lu Dong",
				"Campos Lia S",
				"Scott Kenneth L",
				"Saci Abdel",
				"Wang Juexuan",
				"Collinson Adam",
				"Raine Keiran",
				"Hinton Jonathan",
				"Teague Jon W",
				"Jones David",
				"Menzies Andrew",
				"Butler Adam P",
				"Gamble John",
				"O'Meara Sarah",
				"McLaren Stuart",
				"Chin Lynda",
				"Liu Pentao",
				"Futreal P Andrew"
			],
			"DOI": "10.1186/s13059-014-0455-6",
			"date": "2015-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "The in vivo validation of cancer mutations and genes identified in cancer genomics is resource-intensive because of the low throughput of animal experiments. We describe a mouse model that allows multiple cancer mutations to be validated in each animal line. Animal lines are generated with multiple candidate cancer mutations using transposons. The candidate cancer genes are tagged and randomly expressed in somatic cells, allowing easy identification of the cancer genes involved in the generated tumours. This system presents a useful, generalised and efficient means for animal validation of cancer genes.",
			"category": 2,
			"name": "Chew Su Kit,2015"
		},
		{
			"PMID": 25250338,
			"title": "Identification and analysis of driver missense mutations using rotation forest with feature selection.",
			"journal": "BioMed research international",
			"authorList": [
				"Du Xiuquan",
				"Cheng Jiaxing"
			],
			"DOI": "10.1155/2014/905951",
			"date": "2015-06-15",
			"PMC": "",
			"citation": "",
			"abstract": "Identifying cancer-associated mutations (driver mutations) is critical for understanding the cellular function of cancer genome that leads to activation of oncogenes or inactivation of tumor suppressor genes. Many approaches are proposed which use supervised machine learning techniques for prediction with features obtained by some databases. However, often we do not know which features are important for driver mutations prediction. In this study, we propose a novel feature selection method (called DX) from 126 candidate features' set. In order to obtain the best performance, rotation forest algorithm was adopted to perform the experiment. On the train dataset which was collected from COSMIC and Swiss-Prot databases, we are able to obtain high prediction performance with 88.03% accuracy, 93.9% precision, and 81.35% recall when the 11 top-ranked features were used. Comparison with other various techniques in the TP53, EGFR, and Cosmic2plus datasets shows the generality of our method.",
			"category": 2,
			"name": "Du Xiuquan,2015"
		},
		{
			"PMID": 25243403,
			"title": "Combining structural modeling with ensemble machine learning to accurately predict protein fold stability and binding affinity effects upon mutation.",
			"journal": "PloS one",
			"authorList": [
				"Berliner Niklas",
				"Teyra Joan",
				"Colak Recep",
				"Garcia Lopez Sebastian",
				"Kim Philip M"
			],
			"DOI": "10.1371/journal.pone.0107353",
			"date": "2015-06-16",
			"PMC": "",
			"citation": "",
			"abstract": "Advances in sequencing have led to a rapid accumulation of mutations, some of which are associated with diseases. However, to draw mechanistic conclusions, a biochemical understanding of these mutations is necessary. For coding mutations, accurate prediction of significant changes in either the stability of proteins or their affinity to their binding partners is required. Traditional methods have used semi-empirical force fields, while newer methods employ machine learning of sequence and structural features. Here, we show how combining both of these approaches leads to a marked boost in accuracy. We introduce ELASPIC, a novel ensemble machine learning approach that is able to predict stability effects upon mutation in both, domain cores and domain-domain interfaces. We combine semi-empirical energy terms, sequence conservation, and a wide variety of molecular details with a Stochastic Gradient Boosting of Decision Trees (SGB-DT) algorithm. The accuracy of our predictions surpasses existing methods by a considerable margin, achieving correlation coefficients of 0.77 for stability, and 0.75 for affinity predictions. Notably, we integrated homology modeling to enable proteome-wide prediction and show that accurate prediction on modeled structures is possible. Lastly, ELASPIC showed significant differences between various types of disease-associated mutations, as well as between disease and common neutral mutations. Unlike pure sequence-based prediction methods that try to predict phenotypic effects of mutations, our predictions unravel the molecular details governing the protein instability, and help us better understand the molecular causes of diseases.",
			"category": 2,
			"name": "Berliner Niklas,2015"
		},
		{
			"PMID": 25232094,
			"title": "Human germline and pan-cancer variomes and their distinct functional profiles.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Pan Yang",
				"Karagiannis Konstantinos",
				"Zhang Haichen",
				"Dingerdissen Hayley",
				"Shamsaddini Amirhossein",
				"Wan Quan",
				"Simonyan Vahan",
				"Mazumder Raja"
			],
			"DOI": "10.1093/nar/gku772",
			"date": "2015-01-15",
			"PMC": "",
			"citation": "",
			"abstract": "Identification of non-synonymous single nucleotide variations (nsSNVs) has exponentially increased due to advances in Next-Generation Sequencing technologies. The functional impacts of these variations have been difficult to ascertain because the corresponding knowledge about sequence functional sites is quite fragmented. It is clear that mapping of variations to sequence functional features can help us better understand the pathophysiological role of variations. In this study, we investigated the effect of nsSNVs on more than 17 common types of post-translational modification (PTM) sites, active sites and binding sites. Out of 1 705 285 distinct nsSNVs on 259 216 functional sites we identified 38 549 variations that significantly affect 10 major functional sites. Furthermore, we found distinct patterns of site disruptions due to germline and somatic nsSNVs. Pan-cancer analysis across 12 different cancer types led to the identification of 51 genes with 106 nsSNV affected functional sites found in 3 or more cancer types. 13 of the 51 genes overlap with previously identified Significantly Mutated Genes (Nature. 2013 Oct 17;502(7471)). 62 mutations in these 13 genes affecting functional sites such as DNA, ATP binding and various PTM sites occur across several cancers and can be prioritized for additional validation and investigations.",
			"category": 2,
			"name": "Pan Yang,2015"
		},
		{
			"PMID": 25221514,
			"title": "Iron and thiols as two major players in carcinogenesis: friends or foes?",
			"journal": "Frontiers in pharmacology",
			"authorList": [
				"Toyokuni Shinya"
			],
			"DOI": "10.3389/fphar.2014.00200",
			"date": "2014-09-15",
			"PMC": "",
			"citation": "",
			"abstract": "Iron is the most abundant metal in the human body and mainly works as a cofactor for proteins such as hemoglobin and various enzymes. No independent life forms on earth can survive without iron. However, excess iron is intimately associated with carcinogenesis by increasing oxidative stress via its catalytic activity to generate hydroxyl radicals. Biomolecules with redox-active sulfhydryl function(s) (thiol compounds) are necessary for the maintenance of mildly reductive cellular environments to counteract oxidative stress, and for the execution of redox reactions for metabolism and detoxification. Involvement of glutathione S-transferase and thioredoxin has long attracted the attention of cancer researchers. Here, I update recent findings on the involvement of iron and thiol compounds during carcinogenesis and in cancer cells. It is now recognized that the cystine/glutamate transporter (antiporter) is intimately associated with ferroptosis, an iron-dependent, non-apoptotic form of cell death, observed in cancer cells, and also with cancer stem cells; the former with transporter blockage but the latter with its stabilization. Excess iron in the presence of oxygen appears the most common known mutagen. Ironically, the persistent activation of antioxidant systems via genetic alterations in Nrf2 and Keap1 also contributes to carcinogenesis. Therefore, it is difficult to conclude the role of iron and thiol compounds as friends or foes, which depends on the quantity/distribution and induction/flexibility, respectively. Avoiding further mutation would be the most helpful strategy for cancer prevention, and myriad of efforts are being made to sort out the weaknesses of cancer cells.",
			"category": 2,
			"name": "Toyokuni Shinya,2014"
		},
		{
			"PMID": 25202140,
			"title": "Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis.",
			"journal": "Blood",
			"authorList": [
				"Chakraborty Rikhia",
				"Hampton Oliver A",
				"Shen Xiaoyun",
				"Simko Stephen J",
				"Shih Albert",
				"Abhyankar Harshal",
				"Lim Karen Phaik Har",
				"Covington Kyle R",
				"Trevino Lisa",
				"Dewal Ninad",
				"Muzny Donna M",
				"Doddapaneni Harshavardhan",
				"Hu Jianhong",
				"Wang Linghua",
				"Lupo Philip J",
				"Hicks M John",
				"Bonilla Diana L",
				"Dwyer Karen C",
				"Berres Marie-Luise",
				"Poulikakos Poulikos I",
				"Merad Miriam",
				"McClain Kenneth L",
				"Wheeler David A",
				"Allen Carl E",
				"Parsons D Williams"
			],
			"DOI": "10.1182/blood-2014-05-577825",
			"date": "2015-01-05",
			"PMC": "",
			"citation": "",
			"abstract": "Langerhans cell histiocytosis (LCH) is a myeloproliferative disorder characterized by lesions composed of pathological CD207(+) dendritic cells with an inflammatory infiltrate. BRAFV600E remains the only recurrent mutation reported in LCH. In order to evaluate the spectrum of somatic mutations in LCH, whole exome sequencing was performed on matched LCH and normal tissue samples obtained from 41 patients. Lesions from other histiocytic disorders, juvenile xanthogranuloma, Erdheim-Chester disease, and Rosai-Dorfman disease were also evaluated. All of the lesions from histiocytic disorders were characterized by an extremely low overall rate of somatic mutations. Notably, 33% (7/21) of LCH cases with wild-type BRAF and none (0/20) with BRAFV600E harbored somatic mutations in MAP2K1 (6 in-frame deletions and 1 missense mutation) that induced extracellular signal-regulated kinase (ERK) phosphorylation in vitro. Single cases of somatic mutations of the mitogen-activated protein kinase (MAPK) pathway genes ARAF and ERBB3 were also detected. The ability of MAPK pathway inhibitors to suppress MAPK kinase and ERK phosphorylation in cell culture and primary tumor models was dependent on the specific LCH mutation. The findings of this study support a model in which ERK activation is a universal end point in LCH arising from pathological activation of upstream signaling proteins.",
			"category": 2,
			"name": "Chakraborty Rikhia,2015"
		},
		{
			"PMID": 25201439,
			"title": "Towards accurate characterization of clonal heterogeneity based on structural variation.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"Fan Xian",
				"Zhou Wanding",
				"Chong Zechen",
				"Nakhleh Luay",
				"Chen Ken"
			],
			"DOI": "10.1186/1471-2105-15-299",
			"date": "2014-11-08",
			"PMC": "",
			"citation": "",
			"abstract": "Recent advances in deep digital sequencing have unveiled an unprecedented degree of clonal heterogeneity within a single tumor DNA sample. Resolving such heterogeneity depends on accurate estimation of fractions of alleles that harbor somatic mutations. Unlike substitutions or small indels, structural variants such as deletions, duplications, inversions and translocations involve segments of DNAs and are potentially more accurate for allele fraction estimations. However, no systematic method exists that can support such analysis.",
			"category": 2,
			"name": "Fan Xian,2014"
		},
		{
			"PMID": 25183062,
			"title": "Pegasus: a comprehensive annotation and prediction tool for detection of driver gene fusions in cancer.",
			"journal": "BMC systems biology",
			"authorList": [
				"Abate Francesco",
				"Zairis Sakellarios",
				"Ficarra Elisa",
				"Acquaviva Andrea",
				"Wiggins Chris H",
				"Frattini Veronique",
				"Lasorella Anna",
				"Iavarone Antonio",
				"Inghirami Giorgio",
				"Rabadan Raul"
			],
			"DOI": "10.1186/s12918-014-0097-z",
			"date": "2015-10-13",
			"PMC": "",
			"citation": "",
			"abstract": "The extraordinary success of imatinib in the treatment of BCR-ABL1 associated cancers underscores the need to identify novel functional gene fusions in cancer. RNA sequencing offers a genome-wide view of expressed transcripts, uncovering biologically functional gene fusions. Although several bioinformatics tools are already available for the detection of putative fusion transcripts, candidate event lists are plagued with non-functional read-through events, reverse transcriptase template switching events, incorrect mapping, and other systematic errors. Such lists lack any indication of oncogenic relevance, and they are too large for exhaustive experimental validation.",
			"category": 2,
			"name": "Abate Francesco,2015"
		},
		{
			"PMID": 25167919,
			"title": "Inferring copy number and genotype in tumour exome data.",
			"journal": "BMC genomics",
			"authorList": [
				"Amarasinghe Kaushalya C",
				"Li Jason",
				"Hunter Sally M",
				"Ryland Georgina L",
				"Cowin Prue A",
				"Campbell Ian G",
				"Halgamuge Saman K"
			],
			"DOI": "10.1186/1471-2164-15-732",
			"date": "2015-05-28",
			"PMC": "",
			"citation": "",
			"abstract": "Using whole exome sequencing to predict aberrations in tumours is a cost effective alternative to whole genome sequencing, however is predominantly used for variant detection and infrequently utilised for detection of somatic copy number variation.",
			"category": 2,
			"name": "Amarasinghe Kaushalya C,2015"
		},
		{
			"PMID": 25164877,
			"title": "Somatically mutated tumor antigens in the quest for a more efficacious patient-oriented immunotherapy of cancer.",
			"journal": "Cancer immunology, immunotherapy : CII",
			"authorList": [
				"Trajanoski Zlatko",
				"Maccalli Cristina",
				"Mennonna Daniele",
				"Casorati Giulia",
				"Parmiani Giorgio",
				"Dellabona Paolo"
			],
			"DOI": "10.1007/s00262-014-1599-7",
			"date": "2015-03-16",
			"PMC": "",
			"citation": "",
			"abstract": "Although cancer immunotherapy shows efficacy with adoptive T cell therapy (ACT) and antibody-based immune checkpoint blockade, efficacious therapeutic vaccination of cancer patients with tumor-associated antigens (TAAs) remains largely unmet. Current cancer vaccines utilize nonmutated shared TAAs that may have suboptimal immunogenicity. Experimental evidence underscores the strong immunogenicity of unique TAAs derived from somatically mutated cancer proteins, whose massive characterization has been precluded until recently by technical limitations. The development of cost-effective, high-throughput DNA sequencing approaches makes now possible the rapid identification of all the somatic mutations contained in a cancer cell genome. This method, combined with robust bioinformatics platforms for T cell epitope prediction and established reverse immunology approaches, provides us with an integrated strategy to identify patient-specific unique TAAs in a relatively short time, compatible with their potential use in the clinic. Hence, it is now for the first time possible to quantitatively define the patient's unique tumor antigenome and exploit it for vaccination, possibly in combination with ACT and/or immune checkpoint blockade to further increase immunotherapy efficacy.",
			"category": 2,
			"name": "Trajanoski Zlatko,2015"
		},
		{
			"PMID": 25161255,
			"title": "Fast randomization of large genomic datasets while preserving alteration counts.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Gobbi Andrea",
				"Iorio Francesco",
				"Dawson Kevin J",
				"Wedge David C",
				"Tamborero David",
				"Alexandrov Ludmil B",
				"Lopez-Bigas Nuria",
				"Garnett Mathew J",
				"Jurman Giuseppe",
				"Saez-Rodriguez Julio"
			],
			"DOI": "10.1093/bioinformatics/btu474",
			"date": "2015-01-15",
			"PMC": "",
			"citation": "",
			"abstract": "Studying combinatorial patterns in cancer genomic datasets has recently emerged as a tool for identifying novel cancer driver networks. Approaches have been devised to quantify, for example, the tendency of a set of genes to be mutated in a 'mutually exclusive' manner. The significance of the proposed metrics is usually evaluated by computing P-values under appropriate null models. To this end, a Monte Carlo method (the switching-algorithm) is used to sample simulated datasets under a null model that preserves patient- and gene-wise mutation rates. In this method, a genomic dataset is represented as a bipartite network, to which Markov chain updates (switching-steps) are applied. These steps modify the network topology, and a minimal number of them must be executed to draw simulated datasets independently under the null model. This number has previously been deducted empirically to be a linear function of the total number of variants, making this process computationally expensive.",
			"category": 2,
			"name": "Gobbi Andrea,2015"
		},
		{
			"PMID": 25161249,
			"title": "ContrastRank: a new method for ranking putative cancer driver genes and classification of tumor samples.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Tian Rui",
				"Basu Malay K",
				"Capriotti Emidio"
			],
			"DOI": "10.1093/bioinformatics/btu466",
			"date": "2015-01-15",
			"PMC": "",
			"citation": "",
			"abstract": "The recent advance in high-throughput sequencing technologies is generating a huge amount of data that are becoming an important resource for deciphering the genotype underlying a given phenotype. Genome sequencing has been extensively applied to the study of the cancer genomes. Although a few methods have been already proposed for the detection of cancer-related genes, their automatic identification is still a challenging task. Using the genomic data made available by The Cancer Genome Atlas Consortium (TCGA), we propose a new prioritization approach based on the analysis of the distribution of putative deleterious variants in a large cohort of cancer samples.",
			"category": 2,
			"name": "Tian Rui,2015"
		},
		{
			"PMID": 25156108,
			"title": "Molecular heterogeneity of glioblastoma and its clinical relevance.",
			"journal": "Pathology oncology research : POR",
			"authorList": [
				"Eder Katalin",
				"Kalman Bernadette"
			],
			"DOI": "10.1007/s12253-014-9833-3",
			"date": "2015-07-07",
			"PMC": "",
			"citation": "",
			"abstract": "Glioblastoma is the most common intracranial malignancy and constitutes about 50 % of all gliomas. Both inter-tumor and intra-tumor histological heterogeneity had been recognized by the early 1980-ies. Recent works using novel molecular platforms provided molecular definitions of these tumors. Based on comprehensive genomic sequence analyses, The Cancer Genome Atlas Research Network (TCGA) cataloged somatic mutations and recurrent copy number alterations in glioblastoma. Robust transcriptome and epigenome studies also revealed inter-tumor heterogeneity. Integration and cluster analyses of multi-dimensional genomic data lead to a new classification of glioblastoma tumors into subtypes with distinct biological features and clinical correlates. However, multiple observations also revealed tumor area-specific patterns of genomic imbalance. In addition, genetic alterations have been identified that were common to all areas analyzed and other alterations that were area specific. Analyses of intra-tumor transcriptome variations revealed that in more than half of the examined cases, fragments from the same tumor mass could be classified into at least two different glioblastoma molecular subgroups. Intra-tumor heterogeneity of molecular genetic profiles in glioblastoma may explain the difficulties encountered in the validation of oncologic biomarkers, and contribute to a biased selection of patients for single target therapies, treatment failure or drug resistance. In this paper, we summarize the currently available literature concerning inter- and intra-tumor molecular heterogeneity of glioblastomas, and call attention to the importance of this topic in relation to the growing efforts in routine molecular diagnostics and personalized therapy.",
			"category": 2,
			"name": "Eder Katalin,2015"
		},
		{
			"PMID": 25129480,
			"title": "In vivo proteomic imaging analysis of caveolae reveals pumping system to penetrate solid tumors.",
			"journal": "Nature medicine",
			"authorList": [
				"Oh Phil",
				"Testa Jacqueline E",
				"Borgstrom Per",
				"Witkiewicz Halina",
				"Li Yan",
				"Schnitzer Jan E"
			],
			"DOI": "10.1038/nm.3623",
			"date": "2014-11-03",
			"PMC": "",
			"citation": "",
			"abstract": "Technologies are needed to map and image biological barriers in vivo that limit solid tumor delivery and, ultimately, the effectiveness of imaging and therapeutic agents. Here we integrate proteomic and imaging analyses of caveolae at the blood-tumor interface to discover an active transendothelial portal to infiltrate tumors. A post-translationally modified form of annexin A1 (AnnA1) is selectively concentrated in human and rodent tumor caveolae. To follow trafficking, we generated a specific AnnA1 antibody that targets caveolae in the tumor endothelium. Intravital microscopy of caveolae-immunotargeted fluorophores even at low intravenous doses showed rapid and robust pumping across the endothelium to enter mammary, prostate and lung tumors. Within 1 h, the fluorescence signal concentrated throughout tumors to exceed the peak levels in blood. This transvascular pumping required the expression of caveolin 1 and annexin A1. Tumor uptake with other antibodies were >100-fold less. This proteomic imaging strategy reveals a unique target, antibody and caveolae pumping system for solid tumor penetration.",
			"category": 2,
			"name": "Oh Phil,2014"
		},
		{
			"PMID": 25122662,
			"title": "Genomic analysis of fibrolamellar hepatocellular carcinoma.",
			"journal": "Human molecular genetics",
			"authorList": [
				"Xu Lei",
				"Hazard Florette K",
				"Zmoos Anne-Flore",
				"Jahchan Nadine",
				"Chaib Hassan",
				"Garfin Phillip M",
				"Rangaswami Arun",
				"Snyder Michael P",
				"Sage Julien"
			],
			"DOI": "10.1093/hmg/ddu418",
			"date": "2015-08-24",
			"PMC": "",
			"citation": "",
			"abstract": "Pediatric tumors are relatively infrequent, but are often associated with significant lethality and lifelong morbidity. A major goal of pediatric cancer research has been to identify key drivers of tumorigenesis to eventually develop targeted therapies to enhance cure rate and minimize acute and long-term toxic effects. Here, we used genomic approaches to identify biomarkers and candidate drivers for fibrolamellar hepatocellular carcinoma (FL-HCC), a very rare subtype of pediatric liver cancer for which limited therapeutic options exist. In-depth genomic analyses of one tumor followed by immunohistochemistry validation on seven other tumors showed expression of neuroendocrine markers in FL-HCC. DNA and RNA sequencing data further showed that common cancer pathways are not visibly altered in FL-HCC but identified two novel structural variants, both resulting in fusion transcripts. The first, a 400 kb deletion, results in a DNAJB1-PRKCA fusion transcript, which leads to increased cAMP-dependent protein kinase (PKA) activity in the index tumor case and other FL-HCC cases compared with normal liver. This PKA fusion protein is oncogenic in HCC cells. The second gene fusion event, a translocation between the CLPTM1L and GLIS3 genes, generates a transcript whose product also promotes cancer phenotypes in HCC cell lines. These experiments further highlight the tumorigenic role of gene fusions in the etiology of pediatric solid tumors and identify both candidate biomarkers and possible therapeutic targets for this lethal pediatric disease.",
			"category": 2,
			"name": "Xu Lei,2015"
		},
		{
			"PMID": 25106096,
			"title": "Discovery of co-occurring driver pathways in cancer.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"Zhang Junhua",
				"Wu Ling-Yun",
				"Zhang Xiang-Sun",
				"Zhang Shihua"
			],
			"DOI": "10.1186/1471-2105-15-271",
			"date": "2014-10-12",
			"PMC": "",
			"citation": "",
			"abstract": "It has been widely realized that pathways rather than individual genes govern the course of carcinogenesis. Therefore, discovering driver pathways is becoming an important step to understand the molecular mechanisms underlying cancer and design efficient treatments for cancer patients. Previous studies have focused mainly on observation of the alterations in cancer genomes at the individual gene or single pathway level. However, a great deal of evidence has indicated that multiple pathways often function cooperatively in carcinogenesis and other key biological processes.",
			"category": 2,
			"name": "Zhang Junhua,2014"
		},
		{
			"PMID": 25084359,
			"title": "Can we negotiate with a tumor?",
			"journal": "PloS one",
			"authorList": [
				"Wolfrom Claire M",
				"Laurent Michel",
				"Deschatrette Jean"
			],
			"DOI": "10.1371/journal.pone.0103834",
			"date": "2015-04-23",
			"PMC": "",
			"citation": "",
			"abstract": "Recent progress in deciphering the molecular portraits of tumors promises an era of more personalized drug choices. However, current protocols still follow standard fixed-time schedules, which is not entirely coherent with the common observation that most tumors do not grow continuously. This unpredictability of the increases in tumor mass is not necessarily an obstacle to therapeutic efficiency, particularly if tumor dynamics could be exploited. We propose a model of tumor mass evolution as the integrated result of the dynamics of two linked complex systems, tumor cell population and tumor microenvironment, and show the practical relevance of this nonlinear approach.",
			"category": 2,
			"name": "Wolfrom Claire M,2015"
		},
		{
			"PMID": 25079325,
			"title": "Cancer: One cell at a time.",
			"journal": "Nature",
			"authorList": [
				"Fox Edward J",
				"Loeb Lawrence A"
			],
			"DOI": "10.1038/nature13650",
			"date": "2014-09-05",
			"PMC": "",
			"citation": "",
			"abstract": "Single-cell DNA sequencing of two breast-cancer types has shown extensive mutational variation in individual tumours, confirming that generation of genetic diversity may be inherent in how tumours evolve.",
			"category": 2,
			"name": "Fox Edward J,2014"
		},
		{
			"PMID": 25072550,
			"title": "The impracticality of biomedical rejuvenation therapies: translational and pharmacological barriers.",
			"journal": "Rejuvenation research",
			"authorList": [
				"Kyriazis Marios"
			],
			"DOI": "10.1089/rej.2014.1588",
			"date": "2015-05-26",
			"PMC": "",
			"citation": "",
			"abstract": "The notion that it is possible to eradicate age-related degeneration and live a life with a negligible rate of senescence solely by using a physical \"repair-oriented\" approach is flawed on a number of fronts. Here, I will argue that there are so many unknown variables embedded in this line of thinking that make the final result impossible to predict. Two relatively easy-to-research areas are the search for successful cross-link breakers and an effective lysosomal degradation therapy. A more complex and speculative strategy is whole-body interdiction of lengthening of telomeres (WILT). Highlighting these as examples, I argue that it is unlikely that such rejuvenation biotechnologies will be used meaningfully by the general public. The discussion assumes that although such therapies may in theory one day be developed in the laboratory, and even possibly be formulated as physical clinical therapies, these will be unusable in practical terms when applied upon humans at large. Due to inherent characteristics of our biological, evolutionary, and psychological heritage, it is implausible that curing aging will occur by using physical interventions alone.",
			"category": 2,
			"name": "Kyriazis Marios,2015"
		},
		{
			"PMID": 25056697,
			"title": "Acute myeloid leukaemia: a paradigm for the clonal evolution of cancer?",
			"journal": "Disease models & mechanisms",
			"authorList": [
				"Grove Carolyn S",
				"Vassiliou George S"
			],
			"DOI": "10.1242/dmm.015974",
			"date": "2015-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "Acute myeloid leukaemia (AML) is an uncontrolled clonal proliferation of abnormal myeloid progenitor cells in the bone marrow and blood. Advances in cancer genomics have revealed the spectrum of somatic mutations that give rise to human AML and drawn our attention to its molecular evolution and clonal architecture. It is now evident that most AML genomes harbour small numbers of mutations, which are acquired in a stepwise manner. This characteristic, combined with our ability to identify mutations in individual leukaemic cells and our detailed understanding of normal human and murine haematopoiesis, makes AML an excellent model for understanding the principles of cancer evolution. Furthermore, a better understanding of how AML evolves can help us devise strategies to improve the therapy and prognosis of AML patients. Here, we draw from recent advances in genomics, clinical studies and experimental models to describe the current knowledge of the clonal evolution of AML and its implications for the biology and treatment of leukaemias and other cancers.",
			"category": 2,
			"name": "Grove Carolyn S,2015"
		},
		{
			"PMID": 25047600,
			"title": "Clinical phenotype-based gene prioritization: an initial study using semantic similarity and the human phenotype ontology.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"Masino Aaron J",
				"Dechene Elizabeth T",
				"Dulik Matthew C",
				"Wilkens Alisha",
				"Spinner Nancy B",
				"Krantz Ian D",
				"Pennington Jeffrey W",
				"Robinson Peter N",
				"White Peter S"
			],
			"DOI": "10.1186/1471-2105-15-248",
			"date": "2014-10-12",
			"PMC": "",
			"citation": "",
			"abstract": "Exome sequencing is a promising method for diagnosing patients with a complex phenotype. However, variant interpretation relative to patient phenotype can be challenging in some scenarios, particularly clinical assessment of rare complex phenotypes. Each patient's sequence reveals many possibly damaging variants that must be individually assessed to establish clear association with patient phenotype. To assist interpretation, we implemented an algorithm that ranks a given set of genes relative to patient phenotype. The algorithm orders genes by the semantic similarity computed between phenotypic descriptors associated with each gene and those describing the patient. Phenotypic descriptor terms are taken from the Human Phenotype Ontology (HPO) and semantic similarity is derived from each term's information content.",
			"category": 2,
			"name": "Masino Aaron J,2014"
		},
		{
			"PMID": 25044326,
			"title": "Missing genetic risk in neural tube defects: can exome sequencing yield an insight?",
			"journal": "Birth defects research. Part A, Clinical and molecular teratology",
			"authorList": [
				"Krupp Deidre R",
				"Soldano Karen L",
				"Garrett Melanie E",
				"Cope Heidi",
				"Ashley-Koch Allison E",
				"Gregory Simon G"
			],
			"DOI": "10.1002/bdra.23276",
			"date": "2015-05-12",
			"PMC": "",
			"citation": "",
			"abstract": "Neural tube defects (NTD) have a strong genetic component, with up to 70% of variance in human prevalence determined by heritable factors. Although the identification of causal DNA variants by sequencing candidate genes from functionally relevant pathways and model organisms has provided some success, alternative approaches are demanded.",
			"category": 2,
			"name": "Krupp Deidre R,2015"
		},
		{
			"PMID": 25033876,
			"title": "Computational analysis identifies a sponge interaction network between long non-coding RNAs and messenger RNAs in human breast cancer.",
			"journal": "BMC systems biology",
			"authorList": [
				"Paci Paola",
				"Colombo Teresa",
				"Farina Lorenzo"
			],
			"DOI": "10.1186/1752-0509-8-83",
			"date": "2015-02-27",
			"PMC": "",
			"citation": "",
			"abstract": "Non-coding RNAs (ncRNAs) are emerging as key regulators of many cellular processes in both physiological and pathological states. Moreover, the constant discovery of new non-coding RNA species suggests that the study of their complex functions is still in its very early stages. This variegated class of RNA species encompasses the well-known microRNAs (miRNAs) and the most recently acknowledged long non-coding RNAs (lncRNAs). Interestingly, in the last couple of years, a few studies have shown that some lncRNAs can act as miRNA sponges, i.e. as competing endogenous RNAs (ceRNAs), able to reduce the amount of miRNAs available to target messenger RNAs (mRNAs).",
			"category": 2,
			"name": "Paci Paola,2015"
		},
		{
			"PMID": 25030888,
			"title": "C. elegans whole-genome sequencing reveals mutational signatures related to carcinogens and DNA repair deficiency.",
			"journal": "Genome research",
			"authorList": [
				"Meier Bettina",
				"Cooke Susanna L",
				"Weiss Joerg",
				"Bailly Aymeric P",
				"Alexandrov Ludmil B",
				"Marshall John",
				"Raine Keiran",
				"Maddison Mark",
				"Anderson Elizabeth",
				"Stratton Michael R",
				"Gartner Anton",
				"Campbell Peter J"
			],
			"DOI": "10.1101/gr.175547.114",
			"date": "2015-06-15",
			"PMC": "",
			"citation": "",
			"abstract": "Mutation is associated with developmental and hereditary disorders, aging, and cancer. While we understand some mutational processes operative in human disease, most remain mysterious. We used Caenorhabditis elegans whole-genome sequencing to model mutational signatures, analyzing 183 worm populations across 17 DNA repair-deficient backgrounds propagated for 20 generations or exposed to carcinogens. The baseline mutation rate in C. elegans was approximately one per genome per generation, not overtly altered across several DNA repair deficiencies over 20 generations. Telomere erosion led to complex chromosomal rearrangements initiated by breakage-fusion-bridge cycles and completed by simultaneously acquired, localized clusters of breakpoints. Aflatoxin B1 induced substitutions of guanines in a GpC context, as observed in aflatoxin-induced liver cancers. Mutational burden increased with impaired nucleotide excision repair. Cisplatin and mechlorethamine, DNA crosslinking agents, caused dose- and genotype-dependent signatures among indels, substitutions, and rearrangements. Strikingly, both agents induced clustered rearrangements resembling \"chromoanasynthesis,\" a replication-based mutational signature seen in constitutional genomic disorders, suggesting that interstrand crosslinks may play a pathogenic role in such events. Cisplatin mutagenicity was most pronounced in xpf-1 mutants, suggesting that this gene critically protects cells against platinum chemotherapy. Thus, experimental model systems combined with genome sequencing can recapture and mechanistically explain mutational signatures associated with human disease.",
			"category": 2,
			"name": "Meier Bettina,2015"
		},
		{
			"PMID": 25024164,
			"title": "Unique mutation portraits and frequent COL2A1 gene alteration in chondrosarcoma.",
			"journal": "Genome research",
			"authorList": [
				"Totoki Yasushi",
				"Yoshida Akihiko",
				"Hosoda Fumie",
				"Nakamura Hiromi",
				"Hama Natsuko",
				"Ogura Koichi",
				"Yoshida Aki",
				"Fujiwara Tomohiro",
				"Arai Yasuhito",
				"Toguchida Junya",
				"Tsuda Hitoshi",
				"Miyano Satoru",
				"Kawai Akira",
				"Shibata Tatsuhiro"
			],
			"DOI": "10.1101/gr.160598.113",
			"date": "2015-05-26",
			"PMC": "",
			"citation": "",
			"abstract": "Chondrosarcoma is the second most frequent malignant bone tumor. However, the etiological background of chondrosarcomagenesis remains largely unknown, along with details on molecular alterations and potential therapeutic targets. Massively parallel paired-end sequencing of whole genomes of 10 primary chondrosarcomas revealed that the process of accumulation of somatic mutations is homogeneous irrespective of the pathological subtype or the presence of IDH1 mutations, is unique among a range of cancer types, and shares significant commonalities with that of prostate cancer. Clusters of structural alterations localized within a single chromosome were observed in four cases. Combined with targeted resequencing of additional cartilaginous tumor cohorts, we identified somatic alterations of the COL2A1 gene, which encodes an essential extracellular matrix protein in chondroskeletal development, in 19.3% of chondrosarcoma and 31.7% of enchondroma cases. Epigenetic regulators (IDH1 and YEATS2) and an activin/BMP signal component (ACVR2A) were recurrently altered. Furthermore, a novel FN1-ACVR2A fusion transcript was observed in both chondrosarcoma and osteochondromatosis cases. With the characteristic accumulative process of somatic changes as a background, molecular defects in chondrogenesis and aberrant epigenetic control are primarily causative of both benign and malignant cartilaginous tumors.",
			"category": 2,
			"name": "Totoki Yasushi,2015"
		},
		{
			"PMID": 25014222,
			"title": "Comprehensive study of tumour single nucleotide polymorphism array data reveals significant driver aberrations and disrupted signalling pathways in human hepatocellular cancer.",
			"journal": "IET systems biology",
			"authorList": [
				"Liu Yuanning",
				"Wang Minghui",
				"Feng Huanqing",
				"Li Ao"
			],
			"DOI": "10.1049/iet-syb.2013.0027",
			"date": "2014-09-04",
			"PMC": "",
			"citation": "",
			"abstract": "The authors describe an integrated method for analysing cancer driver aberrations and disrupted pathways by using tumour single nucleotide polymorphism (SNP) arrays. The authors new method adopts a novel statistical model to explicitly quantify the SNP signals, and therefore infers the genomic aberrations, including copy number alteration and loss of heterozygosity. Examination on the dilution series dataset shows that this method can correctly identify the genomic aberrations even with the existence of severe normal cell contamination in tumour sample. Furthermore, with the results of the aberration identification obtained from multiple tumour samples, a permutation-based approach is proposed for identifying the statistically significant driver aberrations, which are further incorporated with the known signalling pathways for pathway enrichment analysis. By applying the approach to 286 hepatocellular tumour samples, they successfully uncover numerous driver aberration regions across the cancer genome, for example, chromosomes 4p and 5q, which harbour many known hepatocellular cancer related genes such as alpha-fetoprotein (AFP) and ectodermal-neural cortex (ENC1). In addition, they identify nine disrupted pathways that are highly enriched by the driver aberrations, including the systemic lupus erythematosus pathway, the vascular endothelial growth factor (VEGF) signalling pathway and so on. These results support the feasibility and the utility of the proposed method on the characterisation of the cancer genome and the downstream analysis of the driver aberrations and the disrupted signalling pathways.",
			"category": 2,
			"name": "Liu Yuanning,2014"
		},
		{
			"PMID": 25006808,
			"title": "Induction of cancer stem cell properties in colon cancer cells by defined factors.",
			"journal": "PloS one",
			"authorList": [
				"Oshima Nobu",
				"Yamada Yasuhiro",
				"Nagayama Satoshi",
				"Kawada Kenji",
				"Hasegawa Suguru",
				"Okabe Hiroshi",
				"Sakai Yoshiharu",
				"Aoi Takashi"
			],
			"DOI": "10.1371/journal.pone.0101735",
			"date": "2015-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer stem cells (CSCs) are considered to be responsible for the dismal prognosis of cancer patients. However, little is known about the molecular mechanisms underlying the acquisition and maintenance of CSC properties in cancer cells because of their rarity in clinical samples. We herein induced CSC properties in cancer cells using defined factors. We retrovirally introduced a set of defined factors (OCT3/4, SOX2 and KLF4) into human colon cancer cells, followed by culture with conventional serum-containing medium, not human embryonic stem cell medium. We then evaluated the CSC properties in the cells. The colon cancer cells transduced with the three factors showed significantly enhanced CSC properties in terms of the marker gene expression, sphere formation, chemoresistance and tumorigenicity. We designated the cells with CSC properties induced by the factors, a subset of the transduced cells, as induced CSCs (iCSCs). Moreover, we established a novel technology to isolate and collect the iCSCs based on the differences in the degree of the dye-effluxing activity enhancement. The xenografts derived from our iCSCs were not teratomas. Notably, in contrast to the tumors from the parental cancer cells, the iCSC-based tumors mimicked actual human colon cancer tissues in terms of their immunohistological findings, which showed colonic lineage differentiation. In addition, we confirmed that the phenotypes of our iCSCs were reproducible in serial transplantation experiments. By introducing defined factors, we generated iCSCs with lineage specificity directly from cancer cells, not via an induced pluripotent stem cell state. The novel method enables us to obtain abundant materials of CSCs that not only have enhanced tumorigenicity, but also the ability to differentiate to recapitulate a specific type of cancer tissues. Our method can be of great value to fully understand CSCs and develop new therapies targeting CSCs.",
			"category": 2,
			"name": "Oshima Nobu,2015"
		},
		{
			"PMID": 24981601,
			"title": "Mechanisms underlying mutational signatures in human cancers.",
			"journal": "Nature reviews. Genetics",
			"authorList": [
				"Helleday Thomas",
				"Eshtad Saeed",
				"Nik-Zainal Serena"
			],
			"DOI": "10.1038/nrg3729",
			"date": "2014-10-08",
			"PMC": "",
			"citation": "",
			"abstract": "The collective somatic mutations observed in a cancer are the outcome of multiple mutagenic processes that have been operative over the lifetime of a patient. Each process leaves a characteristic imprint--a mutational signature--on the cancer genome, which is defined by the type of DNA damage and DNA repair processes that result in base substitutions, insertions and deletions or structural variations. With the advent of whole-genome sequencing, researchers are identifying an increasing array of these signatures. Mutational signatures can be used as a physiological readout of the biological history of a cancer and also have potential use for discerning ongoing mutational processes from historical ones, thus possibly revealing new targets for anticancer therapies.",
			"category": 2,
			"name": "Helleday Thomas,2014"
		},
		{
			"PMID": 24970867,
			"title": "Integrated RNA and DNA sequencing improves mutation detection in low purity tumors.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Wilkerson Matthew D",
				"Cabanski Christopher R",
				"Sun Wei",
				"Hoadley Katherine A",
				"Walter Vonn",
				"Mose Lisle E",
				"Troester Melissa A",
				"Hammerman Peter S",
				"Parker Joel S",
				"Perou Charles M",
				"Hayes D Neil"
			],
			"DOI": "10.1093/nar/gku489",
			"date": "2014-10-14",
			"PMC": "",
			"citation": "",
			"abstract": "Identifying somatic mutations is critical for cancer genome characterization and for prioritizing patient treatment. DNA whole exome sequencing (DNA-WES) is currently the most popular technology; however, this yields low sensitivity in low purity tumors. RNA sequencing (RNA-seq) covers the expressed exome with depth proportional to expression. We hypothesized that integrating DNA-WES and RNA-seq would enable superior mutation detection versus DNA-WES alone. We developed a first-of-its-kind method, called UNCeqR, that detects somatic mutations by integrating patient-matched RNA-seq and DNA-WES. In simulation, the integrated DNA and RNA model outperformed the DNA-WES only model. Validation by patient-matched whole genome sequencing demonstrated superior performance of the integrated model over DNA-WES only models, including a published method and published mutation profiles. Genome-wide mutational analysis of breast and lung cancer cohorts (n = 871) revealed remarkable tumor genomics properties. Low purity tumors experienced the largest gains in mutation detection by integrating RNA-seq and DNA-WES. RNA provided greater mutation signal than DNA in expressed mutations. Compared to earlier studies on this cohort, UNCeqR increased mutation rates of driver and therapeutically targeted genes (e.g. PIK3CA, ERBB2 and FGFR2). In summary, integrating RNA-seq with DNA-WES increases mutation detection performance, especially for low purity tumors.",
			"category": 2,
			"name": "Wilkerson Matthew D,2014"
		},
		{
			"PMID": 24966870,
			"title": "Is homologous recombination really an error-free process?",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Guirouilh-Barbat Jos\u00e9e",
				"Lambert Sarah",
				"Bertrand Pascale",
				"Lopez Bernard S"
			],
			"DOI": "10.3389/fgene.2014.00175",
			"date": "2014-06-26",
			"PMC": "",
			"citation": "",
			"abstract": "Homologous recombination (HR) is an evolutionarily conserved process that plays a pivotal role in the equilibrium between genetic stability and diversity. HR is commonly considered to be error-free, but several studies have shown that HR can be error-prone. Here, we discuss the actual accuracy of HR. First, we present the product of genetic exchanges (gene conversion, GC, and crossing over, CO) and the mechanisms of HR during double strand break repair and replication restart. We discuss the intrinsic capacities of HR to generate genome rearrangements by GC or CO, either during DSB repair or replication restart. During this process, abortive HR intermediates generate genetic instability and cell toxicity. In addition to genome rearrangements, HR also primes error-prone DNA synthesis and favors mutagenesis on single stranded DNA, a key DNA intermediate during the HR process. The fact that cells have developed several mechanisms protecting against HR excess emphasize its potential risks. Consistent with this duality, several pro-oncogenic situations have been consistently associated with either decreased or increased HR levels. Nevertheless, this versatility also has advantages that we outline here. We conclude that HR is a double-edged sword, which on one hand controls the equilibrium between genome stability and diversity but, on the other hand, can jeopardize the maintenance of genomic integrity. Therefore, whether non-homologous end joining (which, in contrast with HR, is not intrinsically mutagenic) or HR is the more mutagenic process is a question that should be re-evaluated. Both processes can be \"Dr. Jekyll\" in maintaining genome stability/variability and \"Mr. Hyde\" in jeopardizing genome integrity.",
			"category": 2,
			"name": "Guirouilh-Barbat Jos\u00e9e,2014"
		},
		{
			"PMID": 24959421,
			"title": "Intratumoral heterogeneity, its contribution to therapy resistance and methodological caveats to assessment.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Renovanz Mirjam",
				"Kim Ella L"
			],
			"DOI": "10.3389/fonc.2014.00142",
			"date": "2014-06-24",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Renovanz Mirjam,2014"
		},
		{
			"PMID": 24929528,
			"title": "DrugTargetSeqR: a genomics- and CRISPR-Cas9-based method to analyze drug targets.",
			"journal": "Nature chemical biology",
			"authorList": [
				"Kasap Corynn",
				"Elemento Olivier",
				"Kapoor Tarun M"
			],
			"DOI": "10.1038/nchembio.1551",
			"date": "2014-10-06",
			"PMC": "",
			"citation": "",
			"abstract": "To identify physiological targets of drugs and bioactive small molecules, we developed an approach, named DrugTargetSeqR, which combines high-throughput sequencing, computational mutation discovery and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-based genome editing. We applied this approach to ispinesib and YM155, drugs that have undergone clinical trials as anticancer agents, and uncovered mechanisms of action and identified genetic and epigenetic mechanisms likely to cause drug resistance in human cancer cells.",
			"category": 2,
			"name": "Kasap Corynn,2014"
		},
		{
			"PMID": 24905005,
			"title": "Cancer epigenetics: tumor heterogeneity, plasticity of stem-like states, and drug resistance.",
			"journal": "Molecular cell",
			"authorList": [
				"Easwaran Hariharan",
				"Tsai Hsing-Chen",
				"Baylin Stephen B"
			],
			"DOI": "10.1016/j.molcel.2014.05.015",
			"date": "2014-07-29",
			"PMC": "",
			"citation": "",
			"abstract": "The existence of subpopulations of cells in cancers with increased tumor-initiating capacities and self-renewal potential, often termed \"cancer stem cells,\" is a much discussed and key area of cancer biology. Such cellular heterogeneity is very important because of its impact on therapy and especially states of treatment resistance. A major question is whether there is plasticity for evolution of these cell states during tumorigenesis that can involve movement between cell populations in a reversible fashion. In this review, we discuss the possible role of epigenetic abnormalities as well as genetic alterations in such dynamics and in the creation of cellular heterogeneity in cancers of all types.",
			"category": 2,
			"name": "Easwaran Hariharan,2014"
		},
		{
			"PMID": 24886479,
			"title": "Novel principles of gamma-retroviral insertional transcription activation in murine leukemia virus-induced end-stage tumors.",
			"journal": "Retrovirology",
			"authorList": [
				"Sokol Martin",
				"Wabl Matthias",
				"Ruiz Irene Rius",
				"Pedersen Finn Skou"
			],
			"DOI": "10.1186/1742-4690-11-36",
			"date": "2015-03-04",
			"PMC": "",
			"citation": "",
			"abstract": "Insertional mutagenesis screens of retrovirus-induced mouse tumors have proven valuable in human cancer research and for understanding adverse effects of retroviral-based gene therapies. In previous studies, the assignment of mouse genes to individual retroviral integration sites has been based on close proximity and expression patterns of annotated genes at target positions in the genome. We here employed next-generation RNA sequencing to map retroviral-mouse chimeric junctions genome-wide, and to identify local patterns of transcription activation in T-lymphomas induced by the murine leukemia gamma-retrovirus SL3-3. Moreover, to determine epigenetic integration preferences underlying long-range gene activation by retroviruses, the colocalization propensity with common epigenetic enhancer markers (H3K4Me1 and H3K27Ac) of 6,117 integrations derived from end-stage tumors of more than 2,000 mice was examined.",
			"category": 2,
			"name": "Sokol Martin,2015"
		},
		{
			"PMID": 24885780,
			"title": "Stabilization of perturbed Boolean network attractors through compensatory interactions.",
			"journal": "BMC systems biology",
			"authorList": [
				"Campbell Colin",
				"Albert R\u00e9ka"
			],
			"DOI": "10.1186/1752-0509-8-53",
			"date": "2014-09-22",
			"PMC": "",
			"citation": "",
			"abstract": "Understanding and ameliorating the effects of network damage are of significant interest, due in part to the variety of applications in which network damage is relevant. For example, the effects of genetic mutations can cascade through within-cell signaling and regulatory networks and alter the behavior of cells, possibly leading to a wide variety of diseases. The typical approach to mitigating network perturbations is to consider the compensatory activation or deactivation of system components. Here, we propose a complementary approach wherein interactions are instead modified to alter key regulatory functions and prevent the network damage from triggering a deregulatory cascade.",
			"category": 2,
			"name": "Campbell Colin,2014"
		},
		{
			"PMID": 24882574,
			"title": "Targeting the oncogenic Met receptor by antibodies and gene therapy.",
			"journal": "Oncogene",
			"authorList": [
				"Vigna E",
				"Comoglio P M"
			],
			"DOI": "10.1038/onc.2014.142",
			"date": "2015-06-22",
			"PMC": "",
			"citation": "",
			"abstract": "The receptor for hepatocyte growth factor (HGF), a tyrosine kinase encoded by the Met oncogene, has a crucial role in cancer growth, invasion and metastasis. It is a validated therapeutic target for 'personalized' treatment of a number of malignancies. Therapeutic tools prompting selective, robust and highly effective Met inhibition potentially represent a major step in the battle against cancer. Antibodies targeting either Met or its ligand HGF, although challenging, demonstrate to be endowed with promising features. Here we briefly review and discuss the state of the art in the field.",
			"category": 2,
			"name": "Vigna E,2015"
		},
		{
			"PMID": 24882004,
			"title": "High-definition reconstruction of clonal composition in cancer.",
			"journal": "Cell reports",
			"authorList": [
				"Fischer Andrej",
				"V\u00e1zquez-Garc\u00eda Ignacio",
				"Illingworth Christopher J R",
				"Mustonen Ville"
			],
			"DOI": "10.1016/j.celrep.2014.04.055",
			"date": "2015-08-21",
			"PMC": "",
			"citation": "",
			"abstract": "The extensive genetic heterogeneity of cancers can greatly affect therapy success due to the existence of subclonal mutations conferring resistance. However, the characterization of subclones in mixed-cell populations is computationally challenging due to the short length of sequence reads that are generated by current sequencing technologies. Here, we report cloneHD, a probabilistic algorithm for the performance of subclone reconstruction from data generated by high-throughput DNA sequencing: read depth, B-allele counts at germline heterozygous loci, and somatic mutation counts. The algorithm can exploit the added information present in correlated longitudinal or multiregion samples and takes into account correlations along genomes caused by events such as copy-number changes. We apply cloneHD to two case studies: a breast cancer sample and time-resolved samples of chronic lymphocytic leukemia, where we demonstrate that monitoring the response of a patient to therapy regimens is feasible. Our work provides new opportunities for tracking cancer development.",
			"category": 2,
			"name": "Fischer Andrej,2015"
		},
		{
			"PMID": 24875441,
			"title": "Toxicogenomics and cancer susceptibility: advances with next-generation sequencing.",
			"journal": "Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews",
			"authorList": [
				"Ning Baitang",
				"Su Zhenqiang",
				"Mei Nan",
				"Hong Huixiao",
				"Deng Helen",
				"Shi Leming",
				"Fuscoe James C",
				"Tolleson William H"
			],
			"DOI": "10.1080/10590501.2014.907460",
			"date": "2015-01-09",
			"PMC": "",
			"citation": "",
			"abstract": "The aim of this review is to comprehensively summarize the recent achievements in the field of toxicogenomics and cancer research regarding genetic-environmental interactions in carcinogenesis and detection of genetic aberrations in cancer genomes by next-generation sequencing technology. Cancer is primarily a genetic disease in which genetic factors and environmental stimuli interact to cause genetic and epigenetic aberrations in human cells. Mutations in the germline act as either high-penetrance alleles that strongly increase the risk of cancer development, or as low-penetrance alleles that mildly change an individual's susceptibility to cancer. Somatic mutations, resulting from either DNA damage induced by exposure to environmental mutagens or from spontaneous errors in DNA replication or repair are involved in the development or progression of the cancer. Induced or spontaneous changes in the epigenome may also drive carcinogenesis. Advances in next-generation sequencing technology provide us opportunities to accurately, economically, and rapidly identify genetic variants, somatic mutations, gene expression profiles, and epigenetic alterations with single-base resolution. Whole genome sequencing, whole exome sequencing, and RNA sequencing of paired cancer and adjacent normal tissue present a comprehensive picture of the cancer genome. These new findings should benefit public health by providing insights in understanding cancer biology, and in improving cancer diagnosis and therapy.",
			"category": 2,
			"name": "Ning Baitang,2015"
		},
		{
			"PMID": 24859469,
			"title": "Examining the impact of gene variants on histone lysine methylation.",
			"journal": "Biochimica et biophysica acta",
			"authorList": [
				"Van Rechem Capucine",
				"Whetstine Johnathan R"
			],
			"DOI": "10.1016/j.bbagrm.2014.05.014",
			"date": "2015-03-03",
			"PMC": "",
			"citation": "",
			"abstract": "In recent years, there has been a boom in the amount of genome-wide sequencing data that has uncovered important and unappreciated links between certain genes, families of genes and enzymatic processes and diseases such as cancer. Such studies have highlighted the impact that chromatin modifying enzymes could have in cancer and other genetic diseases. In this review, we summarize characterized mutations and single nucleotide polymorphisms (SNPs) in histone lysine methyltransferases (KMTs), histone lysine demethylases (KDMs) and histones. We primarily focus on variants with strong disease correlations and discuss how they could impact histone lysine methylation dynamics and gene regulation.",
			"category": 2,
			"name": "Van Rechem Capucine,2015"
		},
		{
			"PMID": 24845652,
			"title": "CLImAT: accurate detection of copy number alteration and loss of heterozygosity in impure and aneuploid tumor samples using whole-genome sequencing data.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Yu Zhenhua",
				"Liu Yuanning",
				"Shen Yi",
				"Wang Minghui",
				"Li Ao"
			],
			"DOI": "10.1093/bioinformatics/btu346",
			"date": "2014-11-14",
			"PMC": "",
			"citation": "",
			"abstract": "Whole-genome sequencing of tumor samples has been demonstrated as an efficient approach for comprehensive analysis of genomic aberrations in cancer genome. Critical issues such as tumor impurity and aneuploidy, GC-content and mappability bias have been reported to complicate identification of copy number alteration and loss of heterozygosity in complex tumor samples. Therefore, efficient computational methods are required to address these issues.",
			"category": 2,
			"name": "Yu Zhenhua,2014"
		},
		{
			"PMID": 24829462,
			"title": "DUET: a server for predicting effects of mutations on protein stability using an integrated computational approach.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Pires Douglas E V",
				"Ascher David B",
				"Blundell Tom L"
			],
			"DOI": "10.1093/nar/gku411",
			"date": "2014-09-18",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer genome and other sequencing initiatives are generating extensive data on non-synonymous single nucleotide polymorphisms (nsSNPs) in human and other genomes. In order to understand the impacts of nsSNPs on the structure and function of the proteome, as well as to guide protein engineering, accurate in silicomethodologies are required to study and predict their effects on protein stability. Despite the diversity of available computational methods in the literature, none has proven accurate and dependable on its own under all scenarios where mutation analysis is required. Here we present DUET, a web server for an integrated computational approach to study missense mutations in proteins. DUET consolidates two complementary approaches (mCSM and SDM) in a consensus prediction, obtained by combining the results of the separate methods in an optimized predictor using Support Vector Machines (SVM). We demonstrate that the proposed method improves overall accuracy of the predictions in comparison with either method individually and performs as well as or better than similar methods. The DUET web server is freely and openly available at http://structure.bioc.cam.ac.uk/duet.",
			"category": 2,
			"name": "Pires Douglas E V,2014"
		},
		{
			"PMID": 24823667,
			"title": "Somatic retrotransposition in human cancer revealed by whole-genome and exome sequencing.",
			"journal": "Genome research",
			"authorList": [
				"Helman Elena",
				"Lawrence Michael S",
				"Stewart Chip",
				"Sougnez Carrie",
				"Getz Gad",
				"Meyerson Matthew"
			],
			"DOI": "10.1101/gr.163659.113",
			"date": "2015-02-20",
			"PMC": "",
			"citation": "",
			"abstract": "Retrotransposons constitute a major source of genetic variation, and somatic retrotransposon insertions have been reported in cancer. Here, we applied TranspoSeq, a computational framework that identifies retrotransposon insertions from sequencing data, to whole genomes from 200 tumor/normal pairs across 11 tumor types as part of The Cancer Genome Atlas (TCGA) Pan-Cancer Project. In addition to novel germline polymorphisms, we find 810 somatic retrotransposon insertions primarily in lung squamous, head and neck, colorectal, and endometrial carcinomas. Many somatic retrotransposon insertions occur in known cancer genes. We find that high somatic retrotransposition rates in tumors are associated with high rates of genomic rearrangement and somatic mutation. Finally, we developed TranspoSeq-Exome to interrogate an additional 767 tumor samples with hybrid-capture exome data and discovered 35 novel somatic retrotransposon insertions into exonic regions, including an insertion into an exon of the PTEN tumor suppressor gene. The results of this large-scale, comprehensive analysis of retrotransposon movement across tumor types suggest that somatic retrotransposon insertions may represent an important class of structural variation in cancer.",
			"category": 2,
			"name": "Helman Elena,2015"
		},
		{
			"PMID": 24806839,
			"title": "Identification of 2R-ohnologue gene families displaying the same mutation-load skew in multiple cancers.",
			"journal": "Open biology",
			"authorList": [
				"Tinti Michele",
				"Dissanayake Kumara",
				"Synowsky Silvia",
				"Albergante Luca",
				"MacKintosh Carol"
			],
			"DOI": "10.1098/rsob.140029",
			"date": "2014-09-12",
			"PMC": "",
			"citation": "",
			"abstract": "The complexity of signalling pathways was boosted at the origin of the vertebrates, when two rounds of whole genome duplication (2R-WGD) occurred. Those genes and proteins that have survived from the 2R-WGD-termed 2R-ohnologues-belong to families of two to four members, and are enriched in signalling components relevant to cancer. Here, we find that while only approximately 30% of human transcript-coding genes are 2R-ohnologues, they carry 42-60% of the gene mutations in 30 different cancer types. Across a subset of cancer datasets, including melanoma, breast, lung adenocarcinoma, liver and medulloblastoma, we identified 673 2R-ohnologue families in which one gene carries mutations at multiple positions, while sister genes in the same family are relatively mutation free. Strikingly, in 315 of the 322 2R-ohnologue families displaying such a skew in multiple cancers, the same gene carries the heaviest mutation load in each cancer, and usually the second-ranked gene is also the same in each cancer. Our findings inspire the hypothesis that in certain cancers, heterogeneous combinations of genetic changes impair parts of the 2R-WGD signalling networks and force information flow through a limited set of oncogenic pathways in which specific non-mutated 2R-ohnologues serve as effectors. The non-mutated 2R-ohnologues are therefore potential therapeutic targets. These include proteins linked to growth factor signalling, neurotransmission and ion channels.",
			"category": 2,
			"name": "Tinti Michele,2014"
		},
		{
			"PMID": 24759209,
			"title": "Principles and methods of integrative genomic analyses in cancer.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Kristensen Vessela N",
				"Lingj\u00e6rde Ole Christian",
				"Russnes Hege G",
				"Vollan Hans Kristian M",
				"Frigessi Arnoldo",
				"B\u00f8rresen-Dale Anne-Lise"
			],
			"DOI": "10.1038/nrc3721",
			"date": "2014-06-09",
			"PMC": "",
			"citation": "",
			"abstract": "Combined analyses of molecular data, such as DNA copy-number alteration, mRNA and protein expression, point to biological functions and molecular pathways being deregulated in multiple cancers. Genomic, metabolomic and clinical data from various solid cancers and model systems are emerging and can be used to identify novel patient subgroups for tailored therapy and monitoring. The integrative genomics methodologies that are used to interpret these data require expertise in different disciplines, such as biology, medicine, mathematics, statistics and bioinformatics, and they can seem daunting. The objectives, methods and computational tools of integrative genomics that are available to date are reviewed here, as is their implementation in cancer research.",
			"category": 2,
			"name": "Kristensen Vessela N,2014"
		},
		{
			"PMID": 24743239,
			"title": "Prediction and prioritization of rare oncogenic mutations in the cancer Kinome using novel features and multiple classifiers.",
			"journal": "PLoS computational biology",
			"authorList": [
				"U ManChon",
				"Talevich Eric",
				"Katiyar Samiksha",
				"Rasheed Khaled",
				"Kannan Natarajan"
			],
			"DOI": "10.1371/journal.pcbi.1003545",
			"date": "2014-12-08",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a genetic disease that develops through a series of somatic mutations, a subset of which drive cancer progression. Although cancer genome sequencing studies are beginning to reveal the mutational patterns of genes in various cancers, identifying the small subset of \"causative\" mutations from the large subset of \"non-causative\" mutations, which accumulate as a consequence of the disease, is a challenge. In this article, we present an effective machine learning approach for identifying cancer-associated mutations in human protein kinases, a class of signaling proteins known to be frequently mutated in human cancers. We evaluate the performance of 11 well known supervised learners and show that a multiple-classifier approach, which combines the performances of individual learners, significantly improves the classification of known cancer-associated mutations. We introduce several novel features related specifically to structural and functional characteristics of protein kinases and find that the level of conservation of the mutated residue at specific evolutionary depths is an important predictor of oncogenic effect. We consolidate the novel features and the multiple-classifier approach to prioritize and experimentally test a set of rare unconfirmed mutations in the epidermal growth factor receptor tyrosine kinase (EGFR). Our studies identify T725M and L861R as rare cancer-associated mutations inasmuch as these mutations increase EGFR activity in the absence of the activating EGF ligand in cell-based assays.",
			"category": 2,
			"name": "U ManChon,2014"
		},
		{
			"PMID": 24736160,
			"title": "Competing views on cancer.",
			"journal": "Journal of biosciences",
			"authorList": [
				"Sonnenschein Carlos",
				"Soto Ana M",
				"Rangarajan Annapoorni",
				"Kulkarni Prakash"
			],
			"DOI": "",
			"date": "2014-12-10",
			"PMC": "",
			"citation": "",
			"abstract": "Despite intense research efforts that have provided enormous insight, cancer continues to be a poorly understood disease. There has been much debate over whether the cancerous state can be said to originate in a single cell or whether it is a reflection of aberrant behaviour on the part of a 'society of cells'. This article presents, in the form of a debate conducted among the authors, three views of how the problem might be addressed. We do not claim that the views exhaust all possibilities. These views are (a) the tissue organization field theory (TOFT) that is based on a breakdown of tissue organization involving many cells from different embryological layers, (b) the cancer stem cell (CSC) hypothesis that focuses on genetic and epigenetic changes that take place within single cells, and (c) the proposition that rewiring of the cell's protein interaction networks mediated by intrinsically disordered proteins (IDPs) drives the tumorigenic process. The views are based on different philosophical approaches. In detail, they differ on some points and agree on others. It is left to the reader to decide whether one approach to understanding cancer appears more promising than the other.",
			"category": 2,
			"name": "Sonnenschein Carlos,2014"
		},
		{
			"PMID": 24728294,
			"title": "Association of a germline copy number polymorphism of APOBEC3A and APOBEC3B with burden of putative APOBEC-dependent mutations in breast cancer.",
			"journal": "Nature genetics",
			"authorList": [
				"Nik-Zainal Serena",
				"Wedge David C",
				"Alexandrov Ludmil B",
				"Petljak Mia",
				"Butler Adam P",
				"Bolli Niccolo",
				"Davies Helen R",
				"Knappskog Stian",
				"Martin Sancha",
				"Papaemmanuil Elli",
				"Ramakrishna Manasa",
				"Shlien Adam",
				"Simonic Ingrid",
				"Xue Yali",
				"Tyler-Smith Chris",
				"Campbell Peter J",
				"Stratton Michael R"
			],
			"DOI": "10.1038/ng.2955",
			"date": "2014-06-16",
			"PMC": "",
			"citation": "",
			"abstract": "The somatic mutations in a cancer genome are the aggregate outcome of one or more mutational processes operative through the lifetime of the individual with cancer. Each mutational process leaves a characteristic mutational signature determined by the mechanisms of DNA damage and repair that constitute it. A role was recently proposed for the APOBEC family of cytidine deaminases in generating particular genome-wide mutational signatures and a signature of localized hypermutation called kataegis. A germline copy number polymorphism involving APOBEC3A and APOBEC3B, which effectively deletes APOBEC3B, has been associated with modestly increased risk of breast cancer. Here we show that breast cancers in carriers of the deletion show more mutations of the putative APOBEC-dependent genome-wide signatures than cancers in non-carriers. The results suggest that the APOBEC3A-APOBEC3B germline deletion allele confers cancer susceptibility through increased activity of APOBEC-dependent mutational processes, although the mechanism by which this increase in activity occurs remains unknown.",
			"category": 2,
			"name": "Nik-Zainal Serena,2014"
		},
		{
			"PMID": 24714652,
			"title": "Processed pseudogenes acquired somatically during cancer development.",
			"journal": "Nature communications",
			"authorList": [
				"Cooke Susanna L",
				"Shlien Adam",
				"Marshall John",
				"Pipinikas Christodoulos P",
				"Martincorena Inigo",
				"Tubio Jose M C",
				"Li Yilong",
				"Menzies Andrew",
				"Mudie Laura",
				"Ramakrishna Manasa",
				"Yates Lucy",
				"Davies Helen",
				"Bolli Niccolo",
				"Bignell Graham R",
				"Tarpey Patrick S",
				"Behjati Sam",
				"Nik-Zainal Serena",
				"Papaemmanuil Elli",
				"Teixeira Vitor H",
				"Raine Keiran",
				"O'Meara Sarah",
				"Dodoran Maryam S",
				"Teague Jon W",
				"Butler Adam P",
				"Iacobuzio-Donahue Christine",
				"Santarius Thomas",
				"Grundy Richard G",
				"Malkin David",
				"Greaves Mel",
				"Munshi Nikhil",
				"Flanagan Adrienne M",
				"Bowtell David",
				"Martin Sancha",
				"Larsimont Denis",
				"Reis-Filho Jorge S",
				"Boussioutas Alex",
				"Taylor Jack A",
				"Hayes Neil D",
				"Janes Sam M",
				"Futreal P Andrew",
				"Stratton Michael R",
				"McDermott Ultan",
				"Campbell Peter J",
				"ICGC Breast Cancer Group"
			],
			"DOI": "10.1038/ncomms4644",
			"date": "2015-11-02",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen sequencing data from 660 cancer samples for somatically acquired pseudogenes. We find 42 events in 17 samples, especially non-small cell lung cancer (5/27) and colorectal cancer (2/11). Genomic features mirror those of germline LINE element retrotranspositions, with frequent target-site duplications (67%), consensus TTTTAA sites at insertion points, inverted rearrangements (21%), 5' truncation (74%) and polyA tails (88%). Transcriptional consequences include expression of pseudogenes from UTRs or introns of target genes. In addition, a somatic pseudogene that integrated into the promoter and first exon of the tumour suppressor gene, MGA, abrogated expression from that allele. Thus, formation of processed pseudogenes represents a new class of mutation occurring during cancer development, with potentially diverse functional consequences depending on genomic context.",
			"category": 2,
			"name": "Cooke Susanna L,2015"
		},
		{
			"PMID": 24671188,
			"title": "Designing a high-throughput somatic mutation profiling panel specifically for gynaecological cancers.",
			"journal": "PloS one",
			"authorList": [
				"Spaans Vivian M",
				"Trietsch Marjolijn D",
				"Crobach Stijn",
				"Stelloo Ellen",
				"Kremer Dennis",
				"Osse Elisabeth M",
				"Haar Natalja T ter",
				"van Eijk Ronald",
				"Muller Susanne",
				"van Wezel Tom",
				"Trimbos J Baptist",
				"Bosse Tjalling",
				"Smit Vincent T H B M",
				"Fleuren Gert Jan"
			],
			"DOI": "10.1371/journal.pone.0093451",
			"date": "2015-06-01",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic mutations play a major role in tumour initiation and progression. The mutation status of a tumour may predict prognosis and guide targeted therapies. The majority of techniques to study oncogenic mutations require high quality and quantity DNA or are analytically challenging. Mass-spectrometry based mutation analysis however is a relatively simple and high-throughput method suitable for formalin-fixed, paraffin-embedded (FFPE) tumour material. Targeted gene panels using this technique have been developed for several types of cancer. These current cancer hotspot panels are not focussed on the genes that are most relevant in gynaecological cancers. In this study, we report the design and validation of a novel, mass-spectrometry based panel specifically for gynaecological malignancies and present the frequencies of detected mutations. Using frequency data from the online Catalogue of Somatic Mutations in Cancer, we selected 171 somatic hotspot mutations in the 13 most important genes for gynaecological cancers, being BRAF, CDKN2A, CTNNB1, FBXW7, FGFR2, FGFR3, FOXL2, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A and PTEN. A total of 546 tumours (205 cervical, 227 endometrial, 89 ovarian, and 25 vulvar carcinomas) were used to test and validate our panel, and to study the prevalence and spectrum of somatic mutations in these types of cancer. The results were validated by testing duplicate samples and by allele-specific qPCR. The panel presented here using mass-spectrometry shows to be reproducible and high-throughput, and is usefull in FFPE material of low quality and quantity. It provides new possibilities for studying large numbers of gynaecological tumour samples in daily practice, and could be useful in guided therapy selection.",
			"category": 2,
			"name": "Spaans Vivian M,2015"
		},
		{
			"PMID": 24670643,
			"title": "Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia.",
			"journal": "Nature",
			"authorList": [
				"Li Yilong",
				"Schwab Claire",
				"Ryan Sarra",
				"Papaemmanuil Elli",
				"Robinson Hazel M",
				"Jacobs Patricia",
				"Moorman Anthony V",
				"Dyer Sara",
				"Borrow Julian",
				"Griffiths Mike",
				"Heerema Nyla A",
				"Carroll Andrew J",
				"Talley Polly",
				"Bown Nick",
				"Telford Nick",
				"Ross Fiona M",
				"Gaunt Lorraine",
				"McNally Richard J Q",
				"Young Bryan D",
				"Sinclair Paul",
				"Rand Vikki",
				"Teixeira Manuel R",
				"Joseph Olivia",
				"Robinson Ben",
				"Maddison Mark",
				"Dastugue Nicole",
				"Vandenberghe Peter",
				"Stephens Philip J",
				"Cheng Jiqiu",
				"Van Loo Peter",
				"Stratton Michael R",
				"Campbell Peter J",
				"Harrison Christine J"
			],
			"DOI": "10.1038/nature13115",
			"date": "2014-04-22",
			"PMC": "",
			"citation": "",
			"abstract": "Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21). We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes.",
			"category": 2,
			"name": "Li Yilong,2014"
		},
		{
			"PMID": 24669031,
			"title": "Identification of human tissue kallikrein 6 as a potential marker of laryngeal cancer based on the relevant secretory/releasing protein database.",
			"journal": "Disease markers",
			"authorList": [
				"Zhang Ying",
				"Zhang Zaixing",
				"Yang Lei",
				"Xu Bin",
				"Li Weihua",
				"Tang Pingzhang",
				"Zhang Zongmin",
				"Han Naijun",
				"Gao Yanning",
				"Cheng Shujun",
				"Xiao Ting"
			],
			"DOI": "10.1155/2014/594093",
			"date": "2015-01-19",
			"PMC": "",
			"citation": "",
			"abstract": "This study was aimed to create a large-scale laryngeal cancer relevant secretory/releasing protein database and further discover candidate biomarkers.",
			"category": 2,
			"name": "Zhang Ying,2015"
		},
		{
			"PMID": 24657537,
			"title": "Mutational signatures: the patterns of somatic mutations hidden in cancer genomes.",
			"journal": "Current opinion in genetics & development",
			"authorList": [
				"Alexandrov Ludmil B",
				"Stratton Michael R"
			],
			"DOI": "10.1016/j.gde.2013.11.014",
			"date": "2014-10-31",
			"PMC": "",
			"citation": "",
			"abstract": "All cancers originate from a single cell that starts to behave abnormally due to the acquired somatic mutations in its genome. Until recently, the knowledge of the mutational processes that cause these somatic mutations has been very limited. Recent advances in sequencing technologies and the development of novel mathematical approaches have allowed deciphering the patterns of somatic mutations caused by different mutational processes. Here, we summarize our current understanding of mutational patterns and mutational signatures in light of both the somatic cell paradigm of cancer research and the recent developments in the field of cancer genomics.",
			"category": 2,
			"name": "Alexandrov Ludmil B,2014"
		},
		{
			"PMID": 24622842,
			"title": "Driver mutations of cancer epigenomes.",
			"journal": "Protein & cell",
			"authorList": [
				"Roy David M",
				"Walsh Logan A",
				"Chan Timothy A"
			],
			"DOI": "10.1007/s13238-014-0031-6",
			"date": "2014-11-28",
			"PMC": "",
			"citation": "",
			"abstract": "Epigenetic alterations are associated with all aspects of cancer, from tumor initiation to cancer progression and metastasis. It is now well understood that both losses and gains of DNA methylation as well as altered chromatin organization contribute significantly to cancer-associated phenotypes. More recently, new sequencing technologies have allowed the identification of driver mutations in epigenetic regulators, providing a mechanistic link between the cancer epigenome and genetic alterations. Oncogenic activating mutations are now known to occur in a number of epigenetic modifiers (i.e. IDH1/2, EZH2, DNMT3A), pinpointing epigenetic pathways that are involved in tumorigenesis. Similarly, investigations into the role of inactivating mutations in chromatin modifiers (i.e. KDM6A, CREBBP/EP300, SMARCB1) implicate many of these genes as tumor suppressors. Intriguingly, a number of neoplasms are defined by a plethora of mutations in epigenetic regulators, including renal, bladder, and adenoid cystic carcinomas. Particularly striking is the discovery of frequent histone H3.3 mutations in pediatric glioma, a particularly aggressive neoplasm that has long remained poorly understood. Cancer epigenetics is a relatively new, promising frontier with much potential for improving cancer outcomes. Already, therapies such as 5-azacytidine and decitabine have proven that targeting epigenetic alterations in cancer can lead to tangible benefits. Understanding how genetic alterations give rise to the cancer epigenome will offer new possibilities for developing better prognostic and therapeutic strategies.",
			"category": 2,
			"name": "Roy David M,2014"
		},
		{
			"PMID": 24608173,
			"title": "NCG 4.0: the network of cancer genes in the era of massive mutational screenings of cancer genomes.",
			"journal": "Database : the journal of biological databases and curation",
			"authorList": [
				"An Omer",
				"Pendino Vera",
				"D'Antonio Matteo",
				"Ratti Emanuele",
				"Gentilini Marco",
				"Ciccarelli Francesca D"
			],
			"DOI": "10.1093/database/bau015",
			"date": "2014-08-26",
			"PMC": "",
			"citation": "",
			"abstract": "NCG 4.0 is the latest update of the Network of Cancer Genes, a web-based repository of systems-level properties of cancer genes. In its current version, the database collects information on 537 known (i.e. experimentally supported) and 1463 candidate (i.e. inferred using statistical methods) cancer genes. Candidate cancer genes derive from the manual revision of 67 original publications describing the mutational screening of 3460 human exomes and genomes in 23 different cancer types. For all 2000 cancer genes, duplicability, evolutionary origin, expression, functional annotation, interaction network with other human proteins and with microRNAs are reported. In addition to providing a substantial update of cancer-related information, NCG 4.0 also introduces two new features. The first is the annotation of possible false-positive cancer drivers, defined as candidate cancer genes inferred from large-scale screenings whose association with cancer is likely to be spurious. The second is the description of the systems-level properties of 64 human microRNAs that are causally involved in cancer progression (oncomiRs). Owing to the manual revision of all information, NCG 4.0 constitutes a complete and reliable resource on human coding and non-coding genes whose deregulation drives cancer onset and/or progression. NCG 4.0 can also be downloaded as a free application for Android smart phones. Database URL: http://bio.ieo.eu/ncg/.",
			"category": 2,
			"name": "An Omer,2014"
		},
		{
			"PMID": 24607840,
			"title": "The evolving role of cancer cell line-based screens to define the impact of cancer genomes on drug response.",
			"journal": "Current opinion in genetics & development",
			"authorList": [
				"Garnett Mathew J",
				"McDermott Ultan"
			],
			"DOI": "10.1016/j.gde.2013.12.002",
			"date": "2014-10-31",
			"PMC": "",
			"citation": "",
			"abstract": "Over the last decade we have witnessed the convergence of two powerful experimental designs toward a common goal of defining the molecular subtypes that underpin the likelihood of a cancer patient responding to treatment in the clinic. The first of these 'experiments' has been the systematic sequencing of large numbers of cancer genomes through the International Cancer Genome Consortium and The Cancer Genome Atlas. This endeavour is beginning to yield a complete catalogue of the cancer genes that are critical for tumourigenesis and amongst which we will find tomorrow's biomarkers and drug targets. The second 'experiment' has been the use of large-scale biological models such as cancer cell lines to correlate mutations in cancer genes with drug sensitivity, such that one could begin to develop rationale clinical trials to begin to test these hypotheses. It is at this intersection of cancer genome sequencing and biological models that there exists the opportunity to completely transform how we stratify cancer patients in the clinic for treatment.",
			"category": 2,
			"name": "Garnett Mathew J,2014"
		},
		{
			"PMID": 24597965,
			"title": "seqCNA: an R package for DNA copy number analysis in cancer using high-throughput sequencing.",
			"journal": "BMC genomics",
			"authorList": [
				"Mosen-Ansorena David",
				"Telleria Naiara",
				"Veganzones Silvia",
				"De la Orden Virginia",
				"Maestro Maria Luisa",
				"Aransay Ana M"
			],
			"DOI": "10.1186/1471-2164-15-178",
			"date": "2014-10-17",
			"PMC": "",
			"citation": "",
			"abstract": "Deviations in the amount of genomic content that arise during tumorigenesis, called copy number alterations, are structural rearrangements that can critically affect gene expression patterns. Additionally, copy number alteration profiles allow insight into cancer discrimination, progression and complexity. On data obtained from high-throughput sequencing, improving quality through GC bias correction and keeping false positives to a minimum help build reliable copy number alteration profiles.",
			"category": 2,
			"name": "Mosen-Ansorena David,2014"
		},
		{
			"PMID": 24565034,
			"title": "Identification of mutated core cancer modules by integrating somatic mutation, copy number variation, and gene expression data.",
			"journal": "BMC systems biology",
			"authorList": [
				"Zhang Junhua",
				"Zhang Shihua",
				"Wang Yong",
				"Zhang Xiang-Sun"
			],
			"DOI": "10.1186/1752-0509-7-S2-S4",
			"date": "2014-11-12",
			"PMC": "",
			"citation": "",
			"abstract": "Understanding the molecular mechanisms underlying cancer is an important step for the effective diagnosis and treatment of cancer patients. With the huge volume of data from the large-scale cancer genomics projects, an open challenge is to distinguish driver mutations, pathways, and gene sets (or core modules) that contribute to cancer formation and progression from random passengers which accumulate in somatic cells but do not contribute to tumorigenesis. Due to mutational heterogeneity, current analyses are often restricted to known pathways and functional modules for enrichment of somatic mutations. Therefore, discovery of new pathways and functional modules is a pressing need.",
			"category": 2,
			"name": "Zhang Junhua,2014"
		},
		{
			"PMID": 24564980,
			"title": "SAVI: a statistical algorithm for variant frequency identification.",
			"journal": "BMC systems biology",
			"authorList": [
				"Trifonov Vladimir",
				"Pasqualucci Laura",
				"Tiacci Enrico",
				"Falini Brunangelo",
				"Rabadan Raul"
			],
			"DOI": "10.1186/1752-0509-7-S2-S2",
			"date": "2014-11-12",
			"PMC": "",
			"citation": "",
			"abstract": "Many problems in biomedical research can be posed as a comparison between related samples (healthy vs. disease, subtypes of the same disease, longitudinal data representing the progression of a disease, etc). In the cases in which the distinction has a genetic or epigenetic basis, next-generation sequencing technologies have become a major tool for obtaining the difference between the samples. A commonly occurring application is the identification of somatic mutations occurring in tumor tissue samples driving a single cell to expand clonally. In this case, the progression of the disease can be traced through the trajectory of the frequency of the oncogenic alleles. Thus obtaining precise estimates of the frequency of abnormal alleles at various stages of the disease is paramount to understanding the processes driving it. Although the procedure is conceptually simple, technical difficulties arise due to inhomogeneous samples, existence of competing subclonal populations, and systematic and non-systematic errors introduced by the sequencing technologies.",
			"category": 2,
			"name": "Trifonov Vladimir,2014"
		},
		{
			"PMID": 24564548,
			"title": "Identification of gene fusions from human lung cancer mass spectrometry data.",
			"journal": "BMC genomics",
			"authorList": [
				"Sun Han",
				"Xing Xiaobin",
				"Li Jing",
				"Zhou Fengli",
				"Chen Yunqin",
				"He Ying",
				"Li Wei",
				"Wei Guangwu",
				"Chang Xiao",
				"Jia Jia",
				"Li Yixue",
				"Xie Lu"
			],
			"DOI": "10.1186/1471-2164-14-S8-S5",
			"date": "2014-11-05",
			"PMC": "",
			"citation": "",
			"abstract": "Tandem mass spectrometry (MS/MS) technology has been applied to identify proteins, as an ultimate approach to confirm the original genome annotation. To be able to identify gene fusion proteins, a special database containing peptides that cross over gene fusion breakpoints is needed.",
			"category": 2,
			"name": "Sun Han,2014"
		},
		{
			"PMID": 24564171,
			"title": "A gene signature based method for identifying subtypes and subtype-specific drivers in cancer with an application to medulloblastoma.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"Chen Peikai",
				"Fan Yubo",
				"Man Tsz-kwong",
				"Hung Y S",
				"Lau Ching C",
				"Wong Stephen T C"
			],
			"DOI": "10.1186/1471-2105-14-S18-S1",
			"date": "2014-05-05",
			"PMC": "",
			"citation": "",
			"abstract": "Subtypes are widely found in cancer. They are characterized with different behaviors in clinical and molecular profiles, such as survival rates, gene signature and copy number aberrations (CNAs). While cancer is generally believed to have been caused by genetic aberrations, the number of such events is tremendous in the cancer tissue and only a small subset of them may be tumorigenic. On the other hand, gene expression signature of a subtype represents residuals of the subtype-specific cancer mechanisms. Using high-throughput data to link these factors to define subtype boundaries and identify subtype-specific drivers, is a promising yet largely unexplored topic.",
			"category": 2,
			"name": "Chen Peikai,2014"
		},
		{
			"PMID": 24552141,
			"title": "Patterns and processes of somatic mutations in nine major cancers.",
			"journal": "BMC medical genomics",
			"authorList": [
				"Jia Peilin",
				"Pao William",
				"Zhao Zhongming"
			],
			"DOI": "10.1186/1755-8794-7-11",
			"date": "2014-09-03",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer genomes harbor hundreds to thousands of somatic nonsynonymous mutations. DNA damage and deficiency of DNA repair systems are two major forces to cause somatic mutations, marking cancer genomes with specific somatic mutation patterns. Recently, several pan-cancer genome studies revealed more than 20 mutation signatures across multiple cancer types. However, detailed cancer-type specific mutation signatures and their different features within (intra-) and between (inter-) cancer types remain largely unexplored.",
			"category": 2,
			"name": "Jia Peilin,2014"
		},
		{
			"PMID": 24498620,
			"title": "Identification of novel point mutations in splicing sites integrating whole-exome and RNA-seq data in myeloproliferative diseases.",
			"journal": "Molecular genetics & genomic medicine",
			"authorList": [
				"Spinelli Roberta",
				"Pirola Alessandra",
				"Redaelli Sara",
				"Sharma Nitesh",
				"Raman Hima",
				"Valletta Simona",
				"Magistroni Vera",
				"Piazza Rocco",
				"Gambacorti-Passerini Carlo"
			],
			"DOI": "10.1002/mgg3.23",
			"date": "2014-02-05",
			"PMC": "",
			"citation": "",
			"abstract": "Point mutations in intronic regions near mRNA splice junctions can affect the splicing process. To identify novel splicing variants from exome sequencing data, we developed a bioinformatics splice-site prediction procedure to analyze next-generation sequencing (NGS) data (SpliceFinder). SpliceFinder integrates two functional annotation tools for NGS, ANNOVAR and MutationTaster and two canonical splice site prediction programs for single mutation analysis, SSPNN and NetGene2. By SpliceFinder, we identified somatic mutations affecting RNA splicing in a colon cancer sample, in eight atypical chronic myeloid leukemia (aCML), and eight CML patients. A novel homozygous splicing mutation was found in APC (NM_000038.4:c.1312+5G>A) and six heterozygous in GNAQ (NM_002072.2:c.735+1C>T), ABCC 3 (NM_003786.3:c.1783-1G>A), KLHDC 1 (NM_172193.1:c.568-2A>G), HOOK 1 (NM_015888.4:c.1662-1G>A), SMAD 9 (NM_001127217.2:c.1004-1C>T), and DNAH 9 (NM_001372.3:c.10242+5G>A). Integrating whole-exome and RNA sequencing in aCML and CML, we assessed the phenotypic effect of mutations on mRNA splicing for GNAQ, ABCC 3, HOOK 1. In ABCC 3 and HOOK 1, RNA-Seq showed the presence of aberrant transcripts with activation of a cryptic splice site or intron retention, validated by the reverse transcription-polymerase chain reaction (RT-PCR) in the case of HOOK 1. In GNAQ, RNA-Seq showed 22% of wild-type transcript and 78% of mRNA skipping exon 5, resulting in a 4-6 frameshift fusion confirmed by RT-PCR. The pipeline can be useful to identify intronic variants affecting RNA sequence by complementing conventional exome analysis.",
			"category": 2,
			"name": "Spinelli Roberta,2014"
		},
		{
			"PMID": 24498045,
			"title": "Genome-wide identification of somatic aberrations from paired normal-tumor samples.",
			"journal": "PloS one",
			"authorList": [
				"Li Ao",
				"Liu Yuanning",
				"Zhao Qihong",
				"Feng Huanqing",
				"Harris Lyndsay",
				"Wang Minghui"
			],
			"DOI": "10.1371/journal.pone.0087212",
			"date": "2014-09-08",
			"PMC": "",
			"citation": "",
			"abstract": "Genomic copy number alteration and allelic imbalance are distinct features of cancer cells, and recent advances in the genotyping technology have greatly boosted the research in the cancer genome. However, the complicated nature of tumor usually hampers the dissection of the SNP arrays. In this study, we describe a bioinformatic tool, named GIANT, for genome-wide identification of somatic aberrations from paired normal-tumor samples measured with SNP arrays. By efficiently incorporating genotype information of matched normal sample, it accurately detects different types of aberrations in cancer genome, even for aneuploid tumor samples with severe normal cell contamination. Furthermore, it allows for discovery of recurrent aberrations with critical biological properties in tumorigenesis by using statistical significance test. We demonstrate the superior performance of the proposed method on various datasets including tumor replicate pairs, simulated SNP arrays and dilution series of normal-cancer cell lines. Results show that GIANT has the potential to detect the genomic aberration even when the cancer cell proportion is as low as 5\u223c10%. Application on a large number of paired tumor samples delivers a genome-wide profile of the statistical significance of the various aberrations, including amplification, deletion and LOH. We believe that GIANT represents a powerful bioinformatic tool for interpreting the complex genomic aberration, and thus assisting both academic study and the clinical treatment of cancer.",
			"category": 2,
			"name": "Li Ao,2014"
		},
		{
			"PMID": 24497842,
			"title": "Single cell genomics: advances and future perspectives.",
			"journal": "PLoS genetics",
			"authorList": [
				"Macaulay Iain C",
				"Voet Thierry"
			],
			"DOI": "10.1371/journal.pgen.1004126",
			"date": "2014-06-17",
			"PMC": "",
			"citation": "",
			"abstract": "Advances in whole-genome and whole-transcriptome amplification have permitted the sequencing of the minute amounts of DNA and RNA present in a single cell, offering a window into the extent and nature of genomic and transcriptomic heterogeneity which occurs in both normal development and disease. Single-cell approaches stand poised to revolutionise our capacity to understand the scale of genomic, epigenomic, and transcriptomic diversity that occurs during the lifetime of an individual organism. Here, we review the major technological and biological breakthroughs achieved, describe the remaining challenges to overcome, and provide a glimpse into the promise of recent and future developments.",
			"category": 2,
			"name": "Macaulay Iain C,2014"
		},
		{
			"PMID": 24497559,
			"title": "B-cell lymphoma mutations: improving diagnostics and enabling targeted therapies.",
			"journal": "Haematologica",
			"authorList": [
				"Vaqu\u00e9 Jos\u00e9 P",
				"Mart\u00ednez Nerea",
				"Batlle-L\u00f3pez Ana",
				"P\u00e9rez Cristina",
				"Montes-Moreno Santiago",
				"S\u00e1nchez-Beato Margarita",
				"Piris Miguel A"
			],
			"DOI": "10.3324/haematol.2013.096248",
			"date": "2014-07-24",
			"PMC": "",
			"citation": "",
			"abstract": "B-cell lymphomas comprise an increasing number of clinicopathological entities whose characterization has historically been based mainly on histopathological features. In recent decades, the analysis of chromosomal aberrations as well as gene and miRNA expression profile studies have helped distinguish particular tumor types and also enabled the detection of a number of targets with therapeutic implications, such as those activated downstream of the B-cell receptor. Our ability to identify the mechanisms involved in B-cell lymphoma pathogenesis has been boosted recently through the use of Next Generation Sequencing techniques in the analysis of human cancer. This work summarizes the recent findings in the molecular pathogenesis of B-cell neoplasms with special focus on those clinically relevant somatic mutations with the potential to be explored as candidates for the development of new targeted therapies. Our work includes a comparison between the mutational indexes and ranges observed in B-cell lymphomas and also with other solid tumors and describes the most striking mutational data for the major B-cell neoplasms. This review describes a highly dynamic field that currently offers many opportunities for personalized therapy, although there is still much to be gained from the further molecular characterization of these clinicopathological entities.",
			"category": 2,
			"name": "Vaqu\u00e9 Jos\u00e9 P,2014"
		},
		{
			"PMID": 24454733,
			"title": "Deriving a mutation index of carcinogenicity using protein structure and protein interfaces.",
			"journal": "PloS one",
			"authorList": [
				"Espinosa Octavio",
				"Mitsopoulos Konstantinos",
				"Hakas Jarle",
				"Pearl Frances",
				"Zvelebil Marketa"
			],
			"DOI": "10.1371/journal.pone.0084598",
			"date": "2014-12-28",
			"PMC": "",
			"citation": "",
			"abstract": "With the advent of Next Generation Sequencing the identification of mutations in the genomes of healthy and diseased tissues has become commonplace. While much progress has been made to elucidate the aetiology of disease processes in cancer, the contributions to disease that many individual mutations make remain to be characterised and their downstream consequences on cancer phenotypes remain to be understood. Missense mutations commonly occur in cancers and their consequences remain challenging to predict. However, this knowledge is becoming more vital, for both assessing disease progression and for stratifying drug treatment regimes. Coupled with structural data, comprehensive genomic databases of mutations such as the 1000 Genomes project and COSMIC give an opportunity to investigate general principles of how cancer mutations disrupt proteins and their interactions at the molecular and network level. We describe a comprehensive comparison of cancer and neutral missense mutations; by combining features derived from structural and interface properties we have developed a carcinogenicity predictor, InCa (Index of Carcinogenicity). Upon comparison with other methods, we observe that InCa can predict mutations that might not be detected by other methods. We also discuss general limitations shared by all predictors that attempt to predict driver mutations and discuss how this could impact high-throughput predictions. A web interface to a server implementation is publicly available at http://inca.icr.ac.uk/.",
			"category": 2,
			"name": "Espinosa Octavio,2014"
		},
		{
			"PMID": 24404425,
			"title": "Immune response to mutant neo-antigens: Cancer's lessons for aging.",
			"journal": "Oncoimmunology",
			"authorList": [
				"Geyer Rory J",
				"Tobet Rebecca",
				"Berlin Richard D",
				"Srivastava Pramod K"
			],
			"DOI": "",
			"date": "2021-02-03",
			"PMC": "",
			"citation": "",
			"abstract": "Extending observations on the immunogenicity of neo-antigens that arise in the course of oncogenesis and tumor progression, we suggest that somatic mutations affecting normal tissues also lead to generation of new epitopes. We hypothesize that, at least under inflammatory conditions, immune responses against such neo-antigens may lead to the elimination or functional impairment of normal cells, thus contributing to aging.",
			"category": 2,
			"name": "Geyer Rory J,2021"
		},
		{
			"PMID": 24379610,
			"title": "Target genes discovery through copy number alteration analysis in human hepatocellular carcinoma.",
			"journal": "World journal of gastroenterology",
			"authorList": [
				"Gu De-Leung",
				"Chen Yen-Hsieh",
				"Shih Jou-Ho",
				"Lin Chi-Hung",
				"Jou Yuh-Shan",
				"Chen Chian-Feng"
			],
			"DOI": "10.3748/wjg.v19.i47.8873",
			"date": "2014-06-25",
			"PMC": "",
			"citation": "",
			"abstract": "High-throughput short-read sequencing of exomes and whole cancer genomes in multiple human hepatocellular carcinoma (HCC) cohorts confirmed previously identified frequently mutated somatic genes, such as TP53, CTNNB1 and AXIN1, and identified several novel genes with moderate mutation frequencies, including ARID1A, ARID2, MLL, MLL2, MLL3, MLL4, IRF2, ATM, CDKN2A, FGF19, PIK3CA, RPS6KA3, JAK1, KEAP1, NFE2L2, C16orf62, LEPR, RAC2, and IL6ST. Functional classification of these mutated genes suggested that alterations in pathways participating in chromatin remodeling, Wnt/\u03b2-catenin signaling, JAK/STAT signaling, and oxidative stress play critical roles in HCC tumorigenesis. Nevertheless, because there are few druggable genes used in HCC therapy, the identification of new therapeutic targets through integrated genomic approaches remains an important task. Because a large amount of HCC genomic data genotyped by high density single nucleotide polymorphism arrays is deposited in the public domain, copy number alteration (CNA) analyses of these arrays is a cost-effective way to reveal target genes through profiling of recurrent and overlapping amplicons, homozygous deletions and potentially unbalanced chromosomal translocations accumulated during HCC progression. Moreover, integration of CNAs with other high-throughput genomic data, such as aberrantly coding transcriptomes and non-coding gene expression in human HCC tissues and rodent HCC models, provides lines of evidence that can be used to facilitate the identification of novel HCC target genes with the potential of improving the survival of HCC patients.",
			"category": 2,
			"name": "Gu De-Leung,2014"
		},
		{
			"PMID": 24362839,
			"title": "Interaction-based discovery of functionally important genes in cancers.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Ghersi Dario",
				"Singh Mona"
			],
			"DOI": "10.1093/nar/gkt1305",
			"date": "2014-04-15",
			"PMC": "",
			"citation": "",
			"abstract": "A major challenge in cancer genomics is uncovering genes with an active role in tumorigenesis from a potentially large pool of mutated genes across patient samples. Here we focus on the interactions that proteins make with nucleic acids, small molecules, ions and peptides, and show that residues within proteins that are involved in these interactions are more frequently affected by mutations observed in large-scale cancer genomic data than are other residues. We leverage this observation to predict genes that play a functionally important role in cancers by introducing a computational pipeline (http://canbind.princeton.edu) for mapping large-scale cancer exome data across patients onto protein structures, and automatically extracting proteins with an enriched number of mutations affecting their nucleic acid, small molecule, ion or peptide binding sites. Using this computational approach, we show that many previously known genes implicated in cancers are enriched in mutations within the binding sites of their encoded proteins. By focusing on functionally relevant portions of proteins--specifically those known to be involved in molecular interactions--our approach is particularly well suited to detect infrequent mutations that may nonetheless be important in cancer, and should aid in expanding our functional understanding of the genomic landscape of cancer.",
			"category": 2,
			"name": "Ghersi Dario,2014"
		},
		{
			"PMID": 24362534,
			"title": "TRAF2 is an NF-\u03baB-activating oncogene in epithelial cancers.",
			"journal": "Oncogene",
			"authorList": [
				"Shen R R",
				"Zhou A Y",
				"Kim E",
				"O'Connell J T",
				"Hagerstrand D",
				"Beroukhim R",
				"Hahn W C"
			],
			"DOI": "10.1038/onc.2013.543",
			"date": "2015-04-28",
			"PMC": "",
			"citation": "",
			"abstract": "Aberrant nuclear factor (NF)-\u03baB activation is frequently observed in human cancers. Genome characterization efforts have identified genetic alterations in multiple components of the NF-\u03baB pathway, some of which have been shown to be essential for cancer initiation and tumor maintenance. Here, using patient tumors and cancer cell lines, we identify the NF-\u03baB regulator, TRAF2 (tumor necrosis factor (TNF) receptor-associated factor 2), as an oncogene that is recurrently amplified and rearranged in 15% of human epithelial cancers. Suppression of TRAF2 in cancer cells harboring TRAF2 copy number gain inhibits proliferation, NF-\u03baB activation, anchorage-independent growth and tumorigenesis. Cancer cells that are dependent on TRAF2 also require NF-\u03baB for survival. The phosphorylation of TRAF2 at serine 11 is essential for the survival of cancer cells harboring TRAF2 amplification. Together, these observations identify TRAF2 as a frequently amplified oncogene.",
			"category": 2,
			"name": "Shen R R,2015"
		},
		{
			"PMID": 24346768,
			"title": "Identifying potential cancer driver genes by genomic data integration.",
			"journal": "Scientific reports",
			"authorList": [
				"Chen Yong",
				"Hao Jingjing",
				"Jiang Wei",
				"He Tong",
				"Zhang Xuegong",
				"Jiang Tao",
				"Jiang Rui"
			],
			"DOI": "10.1038/srep03538",
			"date": "2014-10-10",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a genomic disease associated with a plethora of gene mutations resulting in a loss of control over vital cellular functions. Among these mutated genes, driver genes are defined as being causally linked to oncogenesis, while passenger genes are thought to be irrelevant for cancer development. With increasing numbers of large-scale genomic datasets available, integrating these genomic data to identify driver genes from aberration regions of cancer genomes becomes an important goal of cancer genome analysis and investigations into mechanisms responsible for cancer development. A computational method, MAXDRIVER, is proposed here to identify potential driver genes on the basis of copy number aberration (CNA) regions of cancer genomes, by integrating publicly available human genomic data. MAXDRIVER employs several optimization strategies to construct a heterogeneous network, by means of combining a fused gene functional similarity network, gene-disease associations and a disease phenotypic similarity network. MAXDRIVER was validated to effectively recall known associations among genes and cancers. Previously identified as well as novel driver genes were detected by scanning CNAs of breast cancer, melanoma and liver carcinoma. Three predicted driver genes (CDKN2A, AKT1, RNF139) were found common in these three cancers by comparative analysis.",
			"category": 2,
			"name": "Chen Yong,2014"
		},
		{
			"PMID": 24344357,
			"title": "The genotype-dependent influence of functionalized multiwalled carbon nanotubes on fetal development.",
			"journal": "Biomaterials",
			"authorList": [
				"Huang Xinglu",
				"Zhang Fan",
				"Sun Xiaolian",
				"Choi Ki-Young",
				"Niu Gang",
				"Zhang Guofeng",
				"Guo Jinxia",
				"Lee Seulki",
				"Chen Xiaoyuan"
			],
			"DOI": "",
			"date": "2014-06-18",
			"PMC": "",
			"citation": "",
			"abstract": "In many cases cancer is caused by gene deficiency that is being passed along from generation to generation. Soluble carbon nanotubes (CNTs) have shown promising applications in the diagnosis and therapy of cancer, however, the potential relationship between cancer-prone individuals and response to CNT exposure as a prerequisite for development of personalized nanomedicine, is still poorly understood. Here we report that intravenous injections of multi-walled carbon nanotubes into p53 (a well-known cancer-susceptible gene) heterozygous pregnant mice can induce p53- dependent responses in fetal development. Larger sized multi-walled carbon nanotubes moved across the blood-placenta barrier (BPB), restricted the development of fetuses, and induced brain deformity, whereas single-walled and smaller sized multi-walled carbon nanotubes showed no or less fetotoxicity. A molecular mechanism study found that multi-walled carbon nanotubes directly triggered p53-dependent apoptosis and cell cycle arrest in response to DNA damage. Based on the molecular mechanism, we also incorporated N-acetylcysteine (NAC), an FDA approved antioxidant, to prevent CNTs induced nuclear DNA damage and reduce brain development abnormalities. Our findings suggest that CNTs might have genetic background-dependent toxic effect on the normal development of the embryo, and provide new insights into protection against nanoparticle-induced toxicity in potential clinical applications.",
			"category": 2,
			"name": "Huang Xinglu,2014"
		},
		{
			"PMID": 24343361,
			"title": "Cancer as a metabolic disease: implications for novel therapeutics.",
			"journal": "Carcinogenesis",
			"authorList": [
				"Seyfried Thomas N",
				"Flores Roberto E",
				"Poff Angela M",
				"D'Agostino Dominic P"
			],
			"DOI": "10.1093/carcin/bgt480",
			"date": "2014-05-14",
			"PMC": "",
			"citation": "",
			"abstract": "Emerging evidence indicates that cancer is primarily a metabolic disease involving disturbances in energy production through respiration and fermentation. The genomic instability observed in tumor cells and all other recognized hallmarks of cancer are considered downstream epiphenomena of the initial disturbance of cellular energy metabolism. The disturbances in tumor cell energy metabolism can be linked to abnormalities in the structure and function of the mitochondria. When viewed as a mitochondrial metabolic disease, the evolutionary theory of Lamarck can better explain cancer progression than can the evolutionary theory of Darwin. Cancer growth and progression can be managed following a whole body transition from fermentable metabolites, primarily glucose and glutamine, to respiratory metabolites, primarily ketone bodies. As each individual is a unique metabolic entity, personalization of metabolic therapy as a broad-based cancer treatment strategy will require fine-tuning to match the therapy to an individual's unique physiology.",
			"category": 2,
			"name": "Seyfried Thomas N,2014"
		},
		{
			"PMID": 24336748,
			"title": "Genome destabilizing mutator alleles drive specific mutational trajectories in Saccharomyces cerevisiae.",
			"journal": "Genetics",
			"authorList": [
				"Stirling Peter C",
				"Shen Yaoqing",
				"Corbett Richard",
				"Jones Steven J M",
				"Hieter Philip"
			],
			"DOI": "10.1534/genetics.113.159806",
			"date": "2014-10-09",
			"PMC": "",
			"citation": "",
			"abstract": "In addition to environmental factors and intrinsic variations in base substitution rates, specific genome-destabilizing mutations can shape the mutational trajectory of genomes. How specific alleles influence the nature and position of accumulated mutations in a genomic context is largely unknown. Understanding the impact of genome-destabilizing alleles is particularly relevant to cancer genomes where biased mutational signatures are identifiable. We first created a more complete picture of cellular pathways that impact mutation rate using a primary screen to identify essential Saccharomyces cerevisiae gene mutations that cause mutator phenotypes. Drawing primarily on new alleles identified in this resource, we measure the impact of diverse mutator alleles on mutation patterns directly by whole-genome sequencing of 68 mutation-accumulation strains derived from wild-type and 11 parental mutator genotypes. The accumulated mutations differ across mutator strains, displaying base-substitution biases, allele-specific mutation hotspots, and break-associated mutation clustering. For example, in mutants of POL\u03b1 and the Cdc13-Stn1-Ten1 complex, we find a distinct subtelomeric bias for mutations that we show is independent of the target sequence. Together our data suggest that specific genome-instability mutations are sufficient to drive discrete mutational signatures, some of which share properties with mutation patterns seen in tumors. Thus, in a population of cells, genome-instability mutations could influence clonal evolution by establishing discrete mutational trajectories for genomes.",
			"category": 2,
			"name": "Stirling Peter C,2014"
		},
		{
			"PMID": 24294611,
			"title": "Side population cells as prototype of chemoresistant, tumor-initiating cells.",
			"journal": "BioMed research international",
			"authorList": [
				"Richard Vinitha",
				"Nair Madhumathy G",
				"Santhosh Kumar T R",
				"Pillai M Radhakrishna"
			],
			"DOI": "10.1155/2013/517237",
			"date": "2014-06-09",
			"PMC": "",
			"citation": "",
			"abstract": "Classically, isolation of CSCs from tumors exploits the detection of cell surface markers associated with normal stem cells. Invariable expression of these cell surface markers in almost all proliferating tumor cells that albeit impart specific functionality, the universality, and clinical credibility of CSC phenotype based on markers is still dubious. Side Population (SP) cells, as defined by Hoechst dye exclusion in flow cytometry, have been identified in many solid tumors and cell lines and the SP phenotype can be considered as an enriched source of stem cells as well as an alternative source for the isolation of cancer stem cells especially when molecular markers for stem cells are unknown. SP cells may be responsible for the maintenance and propagation of tumors and the proportion of SP cells may be a predictor of patient outcome. Several of these markers used in cell sorting have emerged as prognostic markers of disease progression though it is seen that the development of new CSC-targeted strategies is often hindered by poor understanding of their regulatory networks and functions. This review intends to appraise the experimental progress towards enhanced isolation and drug screening based on property of acquired chemoresistance of cancer stem cells.",
			"category": 2,
			"name": "Richard Vinitha,2014"
		},
		{
			"PMID": 24289158,
			"title": "wKinMut: an integrated tool for the analysis and interpretation of mutations in human protein kinases.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"Izarzugaza Jose M G",
				"Vazquez Miguel",
				"del Pozo Angela",
				"Valencia Alfonso"
			],
			"DOI": "10.1186/1471-2105-14-345",
			"date": "2014-02-28",
			"PMC": "",
			"citation": "",
			"abstract": "Protein kinases are involved in relevant physiological functions and a broad number of mutations in this superfamily have been reported in the literature to affect protein function and stability. Unfortunately, the exploration of the consequences on the phenotypes of each individual mutation remains a considerable challenge.",
			"category": 2,
			"name": "Izarzugaza Jose M G,2014"
		},
		{
			"PMID": 24225322,
			"title": "Progenetix: 12 years of oncogenomic data curation.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Cai Haoyang",
				"Kumar Nitin",
				"Ai Ni",
				"Gupta Saumya",
				"Rath Prisni",
				"Baudis Michael"
			],
			"DOI": "10.1093/nar/gkt1108",
			"date": "2014-03-17",
			"PMC": "",
			"citation": "",
			"abstract": "DNA copy number aberrations (CNAs) can be found in the majority of cancer genomes and are crucial for understanding the potential mechanisms underlying tumor initiation and progression. Since the first release in 2001, the Progenetix project (http://www.progenetix.org) has provided a reference resource dedicated to provide the most comprehensive collection of genome-wide CNA profiles. Reflecting the application of comparative genomic hybridization techniques to tens of thousands of cancer genomes, over the past 12 years our data curation efforts have resulted in a more than 60-fold increase in the number of cancer samples presented through Progenetix. In addition, new data exploration tools and visualization options have been added. In particular, the gene-specific CNA frequency analysis should facilitate the assignment of cancer genes to related cancer types. In addition, the new user file processing interface allows users to take advantage of the online tools, including various data representation options for proprietary data pre-publication. In this update article, we report recent improvements of the database in terms of content, user interface and online tools.",
			"category": 2,
			"name": "Cai Haoyang,2014"
		},
		{
			"PMID": 24214964,
			"title": "DriverDB: an exome sequencing database for cancer driver gene identification.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Cheng Wei-Chung",
				"Chung I-Fang",
				"Chen Chen-Yang",
				"Sun Hsing-Jen",
				"Fen Jun-Jeng",
				"Tang Wei-Chun",
				"Chang Ting-Yu",
				"Wong Tai-Tong",
				"Wang Hsei-Wei"
			],
			"DOI": "10.1093/nar/gkt1025",
			"date": "2014-03-17",
			"PMC": "",
			"citation": "",
			"abstract": "Exome sequencing (exome-seq) has aided in the discovery of a huge amount of mutations in cancers, yet challenges remain in converting oncogenomics data into information that is interpretable and accessible for clinical care. We constructed DriverDB (http://ngs.ym.edu.tw/driverdb/), a database which incorporates 6079 cases of exome-seq data, annotation databases (such as dbSNP, 1000 Genome and Cosmic) and published bioinformatics algorithms dedicated to driver gene/mutation identification. We provide two points of view, 'Cancer' and 'Gene', to help researchers to visualize the relationships between cancers and driver genes/mutations. The 'Cancer' section summarizes the calculated results of driver genes by eight computational methods for a specific cancer type/dataset and provides three levels of biological interpretation for realization of the relationships between driver genes. The 'Gene' section is designed to visualize the mutation information of a driver gene in five different aspects. Moreover, a 'Meta-Analysis' function is provided so researchers may identify driver genes in customer-defined samples. The novel driver genes/mutations identified hold potential for both basic research and biotech applications.",
			"category": 2,
			"name": "Cheng Wei-Chung,2014"
		},
		{
			"PMID": 24212657,
			"title": "Retrotransposon-encoded reverse transcriptase in the genesis, progression and cellular plasticity of human cancer.",
			"journal": "Cancers",
			"authorList": [
				"Sinibaldi-Vallebona Paola",
				"Matteucci Claudia",
				"Spadafora Corrado"
			],
			"DOI": "10.3390/cancers3011141",
			"date": "2013-11-11",
			"PMC": "",
			"citation": "",
			"abstract": "LINE-1 (Long Interspersed Nuclear Elements) and HERVs (Human Endogenous Retroviruses) are two families of autonomously replicating retrotransposons that together account for about 28% of the human genome. Genes harbored within LINE-1 and HERV retrotransposons, particularly those encoding the reverse transcriptase (RT) enzyme, are generally expressed at low levels in differentiated cells, but their expression is upregulated in transformed cells and embryonic tissues. Here we discuss a recently discovered RT-dependent mechanism that operates in tumorigenesis and reversibly modulates phenotypic and functional variations associated with tumor progression. Downregulation of active LINE-1 elements drastically reduces the tumorigenic potential of cancer cells, paralleled by reduced proliferation and increased differentiation. Pharmacological RT inhibitors (e.g., nevirapine and efavirenz) exert similar effects on tumorigenic cell lines, both in culture and in animal models. The HERV-K family play a distinct complementary role in stress-dependent transition of melanoma cells from an adherent, non-aggressive, to a non-adherent, highly malignant, growth phenotype. In synthesis, the retrotransposon-encoded RT is increasingly emerging as a key regulator of tumor progression and a promising target in a novel anti-cancer therapy.",
			"category": 2,
			"name": "Sinibaldi-Vallebona Paola,2013"
		},
		{
			"PMID": 24204395,
			"title": "Destruxin B Isolated from Entomopathogenic Fungus Metarhizium anisopliae Induces Apoptosis via a Bcl-2 Family-Dependent Mitochondrial Pathway in Human Nonsmall Cell Lung Cancer Cells.",
			"journal": "Evidence-based complementary and alternative medicine : eCAM",
			"authorList": [
				"Wu Chun-Chi",
				"Chen Tzu-Hsiu",
				"Liu Bing-Lan",
				"Wu Li-Chen",
				"Chen Yung-Ching",
				"Tzeng Yew-Min",
				"Hsu Shih-Lan"
			],
			"DOI": "10.1155/2013/548929",
			"date": "2013-11-08",
			"PMC": "",
			"citation": "",
			"abstract": "Destruxin B, isolated from entomopathogenic fungus Metarhizium anisopliae, is one of the cyclodepsipeptides with insecticidal and anticancer activities. In this study, destruxin B was extracted and purified by ion-exchange chromatography, silica gel chromatography, and semipreparative high-performance liquid chromatography. The potential anticancer effects and molecular mechanisms of destruxin B in human nonsmall cell lung cancer cell lines were characterized. Our results showed that destruxin B induced apoptotic cell death in A549 cells. This event was accompanied by the activation of caspase-2, -3, and -9. Moreover, destruxin B increased the expression level of proapoptotic molecule, PUMA, while decreased antiapoptotic molecule Mcl-1. Additionally, the translocation of Bax from cytosol to mitochondrial membrane was observed upon destruxin B treatment. Knockdown of Bax by shRNA effectively attenuated destruxin-B-triggered apoptosis in A549 cells. Interestingly, similar toxic effects and underlying mechanisms including caspase activation, upregulation of PUMA, and downregulation of Mcl-1 were also observed in a p53-null lung cancer H1299 cell line upon destruxin B treatment. Taken together, our findings suggest that destruxin-B-induced apoptosis in human nonsmall cell lung cancer cells is via a Bcl-2 family-dependent mitochondrial pathway.",
			"category": 2,
			"name": "Wu Chun-Chi,2013"
		},
		{
			"PMID": 24195709,
			"title": "Inference of tumor phylogenies with improved somatic mutation discovery.",
			"journal": "Journal of computational biology : a journal of computational molecular cell biology",
			"authorList": [
				"Salari Raheleh",
				"Saleh Syed Shayon",
				"Kashef-Haghighi Dorna",
				"Khavari David",
				"Newburger Daniel E",
				"West Robert B",
				"Sidow Arend",
				"Batzoglou Serafim"
			],
			"DOI": "10.1089/cmb.2013.0106",
			"date": "2014-06-10",
			"PMC": "",
			"citation": "",
			"abstract": "Next-generation sequencing technologies provide a powerful tool for studying genome evolution during progression of advanced diseases such as cancer. Although many recent studies have employed new sequencing technologies to detect mutations across multiple, genetically related tumors, current methods do not exploit available phylogenetic information to improve the accuracy of their variant calls. Here, we present a novel algorithm that uses somatic single-nucleotide variations (SNVs) in multiple, related tissue samples as lineage markers for phylogenetic tree reconstruction. Our method then leverages the inferred phylogeny to improve the accuracy of SNV discovery. Experimental analyses demonstrate that our method achieves up to 32% improvement for somatic SNV calling of multiple, related samples over the accuracy of GATK's Unified Genotyper, the state-of-the-art multisample SNV caller.",
			"category": 2,
			"name": "Salari Raheleh,2014"
		},
		{
			"PMID": 24192750,
			"title": "Detecting somatic genetic alterations in tumor specimens by exon capture and massively parallel sequencing.",
			"journal": "Journal of visualized experiments : JoVE",
			"authorList": [
				"Won Helen H",
				"Scott Sasinya N",
				"Brannon A Rose",
				"Shah Ronak H",
				"Berger Michael F"
			],
			"DOI": "10.3791/50710",
			"date": "2014-05-29",
			"PMC": "",
			"citation": "",
			"abstract": "Efforts to detect and investigate key oncogenic mutations have proven valuable to facilitate the appropriate treatment for cancer patients. The establishment of high-throughput, massively parallel \"next-generation\" sequencing has aided the discovery of many such mutations. To enhance the clinical and translational utility of this technology, platforms must be high-throughput, cost-effective, and compatible with formalin-fixed paraffin embedded (FFPE) tissue samples that may yield small amounts of degraded or damaged DNA. Here, we describe the preparation of barcoded and multiplexed DNA libraries followed by hybridization-based capture of targeted exons for the detection of cancer-associated mutations in fresh frozen and FFPE tumors by massively parallel sequencing. This method enables the identification of sequence mutations, copy number alterations, and select structural rearrangements involving all targeted genes. Targeted exon sequencing offers the benefits of high throughput, low cost, and deep sequence coverage, thus conferring high sensitivity for detecting low frequency mutations.",
			"category": 2,
			"name": "Won Helen H,2014"
		},
		{
			"PMID": 24187453,
			"title": "Clinical applications of next-generation sequencing in colorectal cancers.",
			"journal": "World journal of gastroenterology",
			"authorList": [
				"Kim Tae-Min",
				"Lee Sug-Hyung",
				"Chung Yeun-Jun"
			],
			"DOI": "10.3748/wjg.v19.i40.6784",
			"date": "2014-04-08",
			"PMC": "",
			"citation": "",
			"abstract": "Like other solid tumors, colorectal cancer (CRC) is a genomic disorder in which various types of genomic alterations, such as point mutations, genomic rearrangements, gene fusions, or chromosomal copy number alterations, can contribute to the initiation and progression of the disease. The advent of a new DNA sequencing technology known as next-generation sequencing (NGS) has revolutionized the speed and throughput of cataloguing such cancer-related genomic alterations. Now the challenge is how to exploit this advanced technology to better understand the underlying molecular mechanism of colorectal carcinogenesis and to identify clinically relevant genetic biomarkers for diagnosis and personalized therapeutics. In this review, we will introduce NGS-based cancer genomics studies focusing on those of CRC, including a recent large-scale report from the Cancer Genome Atlas. We will mainly discuss how NGS-based exome-, whole genome- and methylome-sequencing have extended our understanding of colorectal carcinogenesis. We will also introduce the unique genomic features of CRC discovered by NGS technologies, such as the relationship with bacterial pathogens and the massive genomic rearrangements of chromothripsis. Finally, we will discuss the necessary steps prior to development of a clinical application of NGS-related findings for the advanced management of patients with CRC.",
			"category": 2,
			"name": "Kim Tae-Min,2014"
		},
		{
			"PMID": 24185402,
			"title": "DNA sequence analysis with droplet-based microfluidics.",
			"journal": "Lab on a chip",
			"authorList": [
				"Abate Adam R",
				"Hung Tony",
				"Sperling Ralph A",
				"Mary Pascaline",
				"Rotem Assaf",
				"Agresti Jeremy J",
				"Weiner Michael A",
				"Weitz David A"
			],
			"DOI": "10.1039/c3lc50905b",
			"date": "2014-06-15",
			"PMC": "",
			"citation": "",
			"abstract": "Droplet-based microfluidic techniques can form and process micrometer scale droplets at thousands per second. Each droplet can house an individual biochemical reaction, allowing millions of reactions to be performed in minutes with small amounts of total reagent. This versatile approach has been used for engineering enzymes, quantifying concentrations of DNA in solution, and screening protein crystallization conditions. Here, we use it to read the sequences of DNA molecules with a FRET-based assay. Using probes of different sequences, we interrogate a target DNA molecule for polymorphisms. With a larger probe set, additional polymorphisms can be interrogated as well as targets of arbitrary sequence.",
			"category": 2,
			"name": "Abate Adam R,2014"
		},
		{
			"PMID": 24183448,
			"title": "Cumulative haploinsufficiency and triplosensitivity drive aneuploidy patterns and shape the cancer genome.",
			"journal": "Cell",
			"authorList": [
				"Davoli Teresa",
				"Xu Andrew Wei",
				"Mengwasser Kristen E",
				"Sack Laura M",
				"Yoon John C",
				"Park Peter J",
				"Elledge Stephen J"
			],
			"DOI": "10.1016/j.cell.2013.10.011",
			"date": "2014-01-23",
			"PMC": "",
			"citation": "",
			"abstract": "Aneuploidy has been recognized as a hallmark of cancer for more than 100 years, yet no general theory to explain the recurring patterns of aneuploidy in cancer has emerged. Here, we develop Tumor Suppressor and Oncogene (TUSON) Explorer, a computational method that analyzes the patterns of mutational signatures in tumors and predicts the likelihood that any individual gene functions as a tumor suppressor (TSG) or oncogene (OG). By analyzing >8,200 tumor-normal pairs, we provide statistical evidence suggesting that many more genes possess cancer driver properties than anticipated, forming a continuum of oncogenic potential. Integrating our driver predictions with information on somatic copy number alterations, we find that the distribution and potency of TSGs (STOP genes), OGs, and essential genes (GO genes) on chromosomes can predict the complex patterns of aneuploidy and copy number variation characteristic of cancer genomes. We propose that the cancer genome is shaped through a process of cumulative haploinsufficiency and triplosensitivity.",
			"category": 2,
			"name": "Davoli Teresa,2014"
		},
		{
			"PMID": 24155772,
			"title": "Normal Sequence and Activity but Reduced Levels of DNA-Pkcs in Human Lymphoblastic Cells Implicate Impaired Protein Stability with Radiosensitive Phenotype.",
			"journal": "Journal of Cancer",
			"authorList": [
				"Yap Seow Fong",
				"Boo Cynthia Sk",
				"Loong Susan LE",
				"Baskar Rajamanickam"
			],
			"DOI": "10.7150/jca.6453",
			"date": "2015-10-26",
			"PMC": "",
			"citation": "",
			"abstract": "Non-homologous end joining (NHEJ) is the main repair pathway for DNA double strand breaks (DSBs) induced by ionizing radiation in mammalian cells. Subsets of cancer patients are hypersensitive to radiotherapy after standard doses. We sought to determine the radiosensitivity of human lymphoblastic cells (LB0005) for the abnormality in NHEJ components.",
			"category": 2,
			"name": "Yap Seow Fong,2015"
		},
		{
			"PMID": 24142049,
			"title": "Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing.",
			"journal": "Nature biotechnology",
			"authorList": [
				"Frampton Garrett M",
				"Fichtenholtz Alex",
				"Otto Geoff A",
				"Wang Kai",
				"Downing Sean R",
				"He Jie",
				"Schnall-Levin Michael",
				"White Jared",
				"Sanford Eric M",
				"An Peter",
				"Sun James",
				"Juhn Frank",
				"Brennan Kristina",
				"Iwanik Kiel",
				"Maillet Ashley",
				"Buell Jamie",
				"White Emily",
				"Zhao Mandy",
				"Balasubramanian Sohail",
				"Terzic Selmira",
				"Richards Tina",
				"Banning Vera",
				"Garcia Lazaro",
				"Mahoney Kristen",
				"Zwirko Zac",
				"Donahue Amy",
				"Beltran Himisha",
				"Mosquera Juan Miguel",
				"Rubin Mark A",
				"Dogan Snjezana",
				"Hedvat Cyrus V",
				"Berger Michael F",
				"Pusztai Lajos",
				"Lechner Matthias",
				"Boshoff Chris",
				"Jarosz Mirna",
				"Vietz Christine",
				"Parker Alex",
				"Miller Vincent A",
				"Ross Jeffrey S",
				"Curran John",
				"Cronin Maureen T",
				"Stephens Philip J",
				"Lipson Doron",
				"Yelensky Roman"
			],
			"DOI": "10.1038/nbt.2696",
			"date": "2014-10-24",
			"PMC": "",
			"citation": "",
			"abstract": "As more clinically relevant cancer genes are identified, comprehensive diagnostic approaches are needed to match patients to therapies, raising the challenge of optimization and analytical validation of assays that interrogate millions of bases of cancer genomes altered by multiple mechanisms. Here we describe a test based on massively parallel DNA sequencing to characterize base substitutions, short insertions and deletions (indels), copy number alterations and selected fusions across 287 cancer-related genes from routine formalin-fixed and paraffin-embedded (FFPE) clinical specimens. We implemented a practical validation strategy with reference samples of pooled cell lines that model key determinants of accuracy, including mutant allele frequency, indel length and amplitude of copy change. Test sensitivity achieved was 95-99% across alteration types, with high specificity (positive predictive value >99%). We confirmed accuracy using 249 FFPE cancer specimens characterized by established assays. Application of the test to 2,221 clinical cases revealed clinically actionable alterations in 76% of tumors, three times the number of actionable alterations detected by current diagnostic tests.",
			"category": 2,
			"name": "Frampton Garrett M,2014"
		},
		{
			"PMID": 24139898,
			"title": "Hypermutation of the inactive X chromosome is a frequent event in cancer.",
			"journal": "Cell",
			"authorList": [
				"J\u00e4ger Natalie",
				"Schlesner Matthias",
				"Jones David T W",
				"Raffel Simon",
				"Mallm Jan-Philipp",
				"Junge Kristin M",
				"Weichenhan Dieter",
				"Bauer Tobias",
				"Ishaque Naveed",
				"Kool Marcel",
				"Northcott Paul A",
				"Korshunov Andrey",
				"Drews Ruben M",
				"Koster Jan",
				"Versteeg Rogier",
				"Richter Julia",
				"Hummel Michael",
				"Mack Stephen C",
				"Taylor Michael D",
				"Witt Hendrik",
				"Swartman Benedict",
				"Schulte-Bockholt Dietrich",
				"Sultan Marc",
				"Yaspo Marie-Laure",
				"Lehrach Hans",
				"Hutter Barbara",
				"Brors Benedikt",
				"Wolf Stephan",
				"Plass Christoph",
				"Siebert Reiner",
				"Trumpp Andreas",
				"Rippe Karsten",
				"Lehmann Irina",
				"Lichter Peter",
				"Pfister Stefan M",
				"Eils Roland"
			],
			"DOI": "10.1016/j.cell.2013.09.042",
			"date": "2014-01-02",
			"PMC": "",
			"citation": "",
			"abstract": "Mutation is a fundamental process in tumorigenesis. However, the degree to which the rate of somatic mutation varies across the human genome and the mechanistic basis underlying this variation remain to be fully elucidated. Here, we performed a cross-cancer comparison of 402 whole genomes comprising a diverse set of childhood and adult tumors, including both solid and hematopoietic malignancies. Surprisingly, we found that the inactive X chromosome of many female cancer genomes accumulates on average twice and up to four times as many somatic mutations per megabase, as compared to the individual autosomes. Whole-genome sequencing of clonally expanded hematopoietic stem/progenitor cells (HSPCs) from healthy individuals and a premalignant myelodysplastic syndrome (MDS) sample revealed no X chromosome hypermutation. Our data suggest that hypermutation of the inactive X chromosome is an early and frequent feature of tumorigenesis resulting from DNA replication stress in aberrantly proliferating cells.",
			"category": 2,
			"name": "J\u00e4ger Natalie,2014"
		},
		{
			"PMID": 24135425,
			"title": "Clinical application of high-throughput genomic technologies for treatment selection in breast cancer.",
			"journal": "Breast cancer research : BCR",
			"authorList": [
				"Hansen Aaron R",
				"Bedard Philippe L"
			],
			"DOI": "",
			"date": "2014-09-11",
			"PMC": "",
			"citation": "",
			"abstract": "Large-scale collaborative initiatives using next-generation DNA sequencing and other high-throughput technologies have begun to characterize the genomic landscape of breast cancer. These landmark studies have identified infrequent driver mutations that are potential targets for therapeutic intervention with approved or investigational drug treatments, among other important discoveries. Recently, many institutions have launched molecular screening programs that apply high-throughput genomic technologies to patients with advanced solid malignancies, including breast cancer, to inform clinical decision-making. This article provides an overview of the recent molecular insights in breast cancer, including potentially actionable somatic alterations, the technological platforms currently available in a clinical diagnostics setting to detect these alterations, and ongoing institutional or regional molecular screening programs in advanced breast cancer.",
			"category": 2,
			"name": "Hansen Aaron R,2014"
		},
		{
			"PMID": 24135279,
			"title": "Origins of metastatic traits.",
			"journal": "Cancer cell",
			"authorList": [
				"Vanharanta Sakari",
				"Massagu\u00e9 Joan"
			],
			"DOI": "10.1016/j.ccr.2013.09.007",
			"date": "2013-12-12",
			"PMC": "",
			"citation": "",
			"abstract": "How cancer cells acquire the competence to colonize distant organs remains a central question in cancer biology. Tumors can release large numbers of cancer cells into the circulation, but only a small proportion of these cells survive on infiltrating distant organs and even fewer form clinically meaningful metastases. During the past decade, many predictive gene signatures and specific mediators of metastasis have been identified, yet how cancer cells acquire these traits has remained obscure. Recent experimental work and high-resolution sequencing of human tissues have started to reveal the molecular and tumor evolutionary principles that underlie the emergence of metastatic traits.",
			"category": 2,
			"name": "Vanharanta Sakari,2013"
		},
		{
			"PMID": 24134916,
			"title": "Individual karyotypes at the origins of cervical carcinomas.",
			"journal": "Molecular cytogenetics",
			"authorList": [
				"McCormack Amanda",
				"Fan Jiang Lan",
				"Duesberg Max",
				"Bloomfield Mathew",
				"Fiala Christian",
				"Duesberg Peter"
			],
			"DOI": "10.1186/1755-8166-6-44",
			"date": "2013-12-20",
			"PMC": "",
			"citation": "",
			"abstract": "In 1952 Papanicolaou et al. first diagnosed and graded cervical carcinomas based on individual \"abnormal DNA contents\" and cellular phenotypes. Surprisingly current papilloma virus and mutation theories of carcinomas do not mention these individualities. The viral theory holds that randomly integrated, defective genomes of papilloma viruses, which are often untranscribed, cause cervical carcinomas with unknown cofactors 20-50 years after infection. Virus-free carcinomas are attributed to mutations of a few tumor-suppressor genes, especially the p53 gene. But the paradox of how a few mutations or latent defective viral DNAs would generate carcinomas with endless individual DNA contents, degrees of malignancies and cellular phenotypes is unsolved. Since speciation predicts individuality, we test here the theory that cancers are autonomous species with individual clonal karyotypes and phenotypes. This theory postulates that carcinogens induce aneuploidy. By unbalancing mitosis genes aneuploidy catalyzes chain reactions of karyotypic evolutions. Most such evolutions end with non-viable karyotypes but a few become new cancer karyotypes. Despite congenitally unbalanced mitosis genes cancer karyotypes are stabilized by clonal selections for cancer-specific autonomy.",
			"category": 2,
			"name": "McCormack Amanda,2013"
		},
		{
			"PMID": 24096148,
			"title": "Review of mass spectrometry-based metabolomics in cancer research.",
			"journal": "Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology",
			"authorList": [
				"Liesenfeld David B",
				"Habermann Nina",
				"Owen Robert W",
				"Scalbert Augustin",
				"Ulrich Cornelia M"
			],
			"DOI": "10.1158/1055-9965.EPI-13-0584",
			"date": "2014-10-02",
			"PMC": "",
			"citation": "",
			"abstract": "Metabolomics, the systematic investigation of all metabolites present within a biologic system, is used in biomarker development for many human diseases, including cancer. In this review, we investigate the current role of mass spectrometry-based metabolomics in cancer research. A literature review was carried out within the databases PubMed, Embase, and Web of Knowledge. We included 106 studies reporting on 21 different types of cancer in 7 different sample types. Metabolomics in cancer research is most often used for case-control comparisons. Secondary applications include translational areas, such as patient prognosis, therapy control and tumor classification, or grading. Metabolomics is at a developmental stage with respect to epidemiology, with the majority of studies including less than 100 patients. Standardization is required especially concerning sample preparation and data analysis. In the second part of this review, we reconstructed a metabolic network of patients with cancer by quantitatively extracting all reports of altered metabolites: Alterations in energy metabolism, membrane, and fatty acid synthesis emerged, with tryptophan levels changed most frequently in various cancers. Metabolomics has the potential to evolve into a standard tool for future applications in epidemiology and translational cancer research, but further, large-scale studies including prospective validation are needed.",
			"category": 2,
			"name": "Liesenfeld David B,2014"
		},
		{
			"PMID": 24089052,
			"title": "The comprehensive neuro-oncology data repository (CONDR): a research infrastructure to develop and validate imaging biomarkers.",
			"journal": "Neurosurgery",
			"authorList": [
				"Fouke Sarah Jost",
				"Benzinger Tammie L",
				"Milchenko Mikhail",
				"LaMontagne Pamela",
				"Shimony Joshua S",
				"Chicoine Michael R",
				"Rich Keith M",
				"Kim Albert H",
				"Leuthardt Eric C",
				"Keogh Bart",
				"Marcus Daniel S"
			],
			"DOI": "10.1227/NEU.0000000000000201",
			"date": "2014-09-04",
			"PMC": "",
			"citation": "",
			"abstract": "Advanced imaging methods have the potential to serve as quantitative biomarkers in neuro-oncology research. However, a lack of standardization of image acquisition, processing, and analysis limits their application in clinical research. Standardization of these methods and an organized archival platform are required to better validate and apply these markers in research settings and, ultimately, in clinical practice.",
			"category": 2,
			"name": "Fouke Sarah Jost,2014"
		},
		{
			"PMID": 24084849,
			"title": "Comprehensive identification of mutational cancer driver genes across 12 tumor types.",
			"journal": "Scientific reports",
			"authorList": [
				"Tamborero David",
				"Gonzalez-Perez Abel",
				"Perez-Llamas Christian",
				"Deu-Pons Jordi",
				"Kandoth Cyriac",
				"Reimand J\u00fcri",
				"Lawrence Michael S",
				"Getz Gad",
				"Bader Gary D",
				"Ding Li",
				"Lopez-Bigas Nuria"
			],
			"DOI": "10.1038/srep02650",
			"date": "2014-07-06",
			"PMC": "",
			"citation": "",
			"abstract": "With the ability to fully sequence tumor genomes/exomes, the quest for cancer driver genes can now be undertaken in an unbiased manner. However, obtaining a complete catalog of cancer genes is difficult due to the heterogeneous molecular nature of the disease and the limitations of available computational methods. Here we show that the combination of complementary methods allows identifying a comprehensive and reliable list of cancer driver genes. We provide a list of 291 high-confidence cancer driver genes acting on 3,205 tumors from 12 different cancer types. Among those genes, some have not been previously identified as cancer drivers and 16 have clear preference to sustain mutations in one specific tumor type. The novel driver candidates complement our current picture of the emergence of these diseases. In summary, the catalog of driver genes and the methodology presented here open new avenues to better understand the mechanisms of tumorigenesis.",
			"category": 2,
			"name": "Tamborero David,2014"
		},
		{
			"PMID": 24071852,
			"title": "Pan-cancer patterns of somatic copy number alteration.",
			"journal": "Nature genetics",
			"authorList": [
				"Zack Travis I",
				"Schumacher Stephen E",
				"Carter Scott L",
				"Cherniack Andre D",
				"Saksena Gordon",
				"Tabak Barbara",
				"Lawrence Michael S",
				"Zhsng Cheng-Zhong",
				"Wala Jeremiah",
				"Mermel Craig H",
				"Sougnez Carrie",
				"Gabriel Stacey B",
				"Hernandez Bryan",
				"Shen Hui",
				"Laird Peter W",
				"Getz Gad",
				"Meyerson Matthew",
				"Beroukhim Rameen"
			],
			"DOI": "10.1038/ng.2760",
			"date": "2015-08-19",
			"PMC": "",
			"citation": "",
			"abstract": "Determining how somatic copy number alterations (SCNAs) promote cancer is an important goal. We characterized SCNA patterns in 4,934 cancers from The Cancer Genome Atlas Pan-Cancer data set. Whole-genome doubling, observed in 37% of cancers, was associated with higher rates of every other type of SCNA, TP53 mutations, CCNE1 amplifications and alterations of the PPP2R complex. SCNAs that were internal to chromosomes tended to be shorter than telomere-bounded SCNAs, suggesting different mechanisms underlying their generation. Significantly recurrent focal SCNAs were observed in 140 regions, including 102 without known oncogene or tumor suppressor gene targets and 50 with significantly mutated genes. Amplified regions without known oncogenes were enriched for genes involved in epigenetic regulation. When levels of genomic disruption were accounted for, 7% of region pairs were anticorrelated, and these regions tended to encompass genes whose proteins physically interact, suggesting related functions. These results provide insights into mechanisms of generation and functional consequences of cancer-related SCNAs.",
			"category": 2,
			"name": "Zack Travis I,2015"
		},
		{
			"PMID": 24063528,
			"title": "Cancer: tilting at windmills?",
			"journal": "Molecular cancer",
			"authorList": [
				"Kulkarni Prakash",
				"Shiraishi Takumi",
				"Kulkarni Rahul V"
			],
			"DOI": "10.1186/1476-4598-12-108",
			"date": "2014-07-08",
			"PMC": "",
			"citation": "",
			"abstract": "One of the striking characteristics of cancer cells is their phenotypic diversity and ability to switch phenotypes in response to environmental fluctuations. Such phenotypic changes (e.g. from drug-sensitive to drug-resistant), which are critical for survival and proliferation, are widely believed to arise due to mutations in the cancer cell's genome. However, there is growing concern that such a deterministic view is not entirely consistent with multiple lines of evidence which indicate that cancer can arise in the absence of mutations and can even be reversed to normalcy despite the mutations. In this Commentary, we wish to present an alternate view that highlights how stochasticity in protein interaction networks (PINs) may play a key role in cancer initiation and progression. We highlight the potential role of intrinsically disordered proteins (IDPs) and submit that targeting IDPs can lead to new insights and treatment protocols for cancer.",
			"category": 2,
			"name": "Kulkarni Prakash,2014"
		},
		{
			"PMID": 24063399,
			"title": "Fractal dimension of chromatin: potential molecular diagnostic applications for cancer prognosis.",
			"journal": "Expert review of molecular diagnostics",
			"authorList": [
				"Metze Konradin"
			],
			"DOI": "10.1586/14737159.2013.828889",
			"date": "2014-04-17",
			"PMC": "",
			"citation": "",
			"abstract": "Fractal characteristics of chromatin, revealed by light or electron microscopy, have been reported during the last 20 years. Fractal features can easily be estimated in digitalized microscopic images and are helpful for diagnosis and prognosis of neoplasias. During carcinogenesis and tumor progression, an increase of the fractal dimension (FD) of stained nuclei has been shown in intraepithelial lesions of the uterine cervix and the anus, oral squamous cell carcinomas or adenocarcinomas of the pancreas. Furthermore, an increased FD of chromatin is an unfavorable prognostic factor in squamous cell carcinomas of the oral cavity and the larynx, melanomas and multiple myelomas. High goodness-of-fit of the regression line of the FD is a favorable prognostic factor in acute leukemias and multiple myelomas. The nucleus has fractal and power-law organization in several different levels, which might in part be interrelated. Some possible relations between modifications of the chromatin organization during carcinogenesis and tumor progression and an increase of the FD of stained chromatin are suggested. Furthermore, increased complexity of the chromatin structure, loss of heterochromatin and a less-perfect self-organization of the nucleus in aggressive neoplasias are discussed.",
			"category": 2,
			"name": "Metze Konradin,2014"
		},
		{
			"PMID": 24041470,
			"title": "Integrative genomic and functional profiling of the pancreatic cancer genome.",
			"journal": "BMC genomics",
			"authorList": [
				"Shain A Hunter",
				"Salari Keyan",
				"Giacomini Craig P",
				"Pollack Jonathan R"
			],
			"DOI": "10.1186/1471-2164-14-624",
			"date": "2014-11-10",
			"PMC": "",
			"citation": "",
			"abstract": "Pancreatic cancer is a deadly disease with a five-year survival of less than 5%. A better understanding of the underlying biology may suggest novel therapeutic targets. Recent surveys of the pancreatic cancer genome have uncovered numerous new alterations; yet systematic functional characterization of candidate cancer genes has lagged behind. To address this challenge, here we have devised a highly-parallel RNA interference-based functional screen to evaluate many genomically-nominated candidate pancreatic cancer genes simultaneously.",
			"category": 2,
			"name": "Shain A Hunter,2014"
		},
		{
			"PMID": 24030381,
			"title": "Clinical and biological implications of driver mutations in myelodysplastic syndromes.",
			"journal": "Blood",
			"authorList": [
				"Papaemmanuil Elli",
				"Gerstung Moritz",
				"Malcovati Luca",
				"Tauro Sudhir",
				"Gundem Gunes",
				"Van Loo Peter",
				"Yoon Chris J",
				"Ellis Peter",
				"Wedge David C",
				"Pellagatti Andrea",
				"Shlien Adam",
				"Groves Michael John",
				"Forbes Simon A",
				"Raine Keiran",
				"Hinton Jon",
				"Mudie Laura J",
				"McLaren Stuart",
				"Hardy Claire",
				"Latimer Calli",
				"Della Porta Matteo G",
				"O'Meara Sarah",
				"Ambaglio Ilaria",
				"Galli Anna",
				"Butler Adam P",
				"Walldin Gunilla",
				"Teague Jon W",
				"Quek Lynn",
				"Sternberg Alex",
				"Gambacorti-Passerini Carlo",
				"Cross Nicholas C P",
				"Green Anthony R",
				"Boultwood Jacqueline",
				"Vyas Paresh",
				"Hellstrom-Lindberg Eva",
				"Bowen David",
				"Cazzola Mario",
				"Stratton Michael R",
				"Campbell Peter J",
				"Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium"
			],
			"DOI": "10.1182/blood-2013-08-518886",
			"date": "2014-01-21",
			"PMC": "",
			"citation": "",
			"abstract": "Myelodysplastic syndromes (MDS) are a heterogeneous group of chronic hematological malignancies characterized by dysplasia, ineffective hematopoiesis and a variable risk of progression to acute myeloid leukemia. Sequencing of MDS genomes has identified mutations in genes implicated in RNA splicing, DNA modification, chromatin regulation, and cell signaling. We sequenced 111 genes across 738 patients with MDS or closely related neoplasms (including chronic myelomonocytic leukemia and MDS-myeloproliferative neoplasms) to explore the role of acquired mutations in MDS biology and clinical phenotype. Seventy-eight percent of patients had 1 or more oncogenic mutations. We identify complex patterns of pairwise association between genes, indicative of epistatic interactions involving components of the spliceosome machinery and epigenetic modifiers. Coupled with inferences on subclonal mutations, these data suggest a hypothesis of genetic \"predestination,\" in which early driver mutations, typically affecting genes involved in RNA splicing, dictate future trajectories of disease evolution with distinct clinical phenotypes. Driver mutations had equivalent prognostic significance, whether clonal or subclonal, and leukemia-free survival deteriorated steadily as numbers of driver mutations increased. Thus, analysis of oncogenic mutations in large, well-characterized cohorts of patients illustrates the interconnections between the cancer genome and disease biology, with considerable potential for clinical application.",
			"category": 2,
			"name": "Papaemmanuil Elli,2014"
		},
		{
			"PMID": 24024216,
			"title": "Emerging metabolic targets in the therapy of hematological malignancies.",
			"journal": "BioMed research international",
			"authorList": [
				"Leni Zaira",
				"Parakkal Geetha",
				"Arcaro Alexandre"
			],
			"DOI": "10.1155/2013/946206",
			"date": "2014-04-07",
			"PMC": "",
			"citation": "",
			"abstract": "During the last decade, the development of anticancer therapies has focused on targeting neoplastic-related metabolism. Cancer cells display a variety of changes in their metabolism, which enable them to satisfy the high bioenergetic and biosynthetic demands for rapid cell division. One of the crucial alterations is referred to as the \"Warburg effect\", which involves a metabolic shift from oxidative phosphorylation towards the less efficient glycolysis, independent of the presence of oxygen. Although there are many examples of solid tumors having altered metabolism with high rates of glucose uptake and glycolysis, it was only recently reported that this phenomenon occurs in hematological malignancies. This review presents evidence that targeting the glycolytic pathway at different levels in hematological malignancies can inhibit cancer cell proliferation by restoring normal metabolic conditions. However, to achieve cancer regression, high concentrations of glycolytic inhibitors are used due to limited solubility and biodistribution, which may result in toxicity. Besides using these inhibitors as monotherapies, combinatorial approaches using standard chemotherapeutic agents could display enhanced efficacy at eradicating malignant cells. The identification of the metabolic enzymes critical for hematological cancer cell proliferation and survival appears to be an interesting new approach for the targeted therapy of hematological malignancies.",
			"category": 2,
			"name": "Leni Zaira,2014"
		},
		{
			"PMID": 24009526,
			"title": "Comparative oncogenomic analysis of copy number alterations in human and zebrafish tumors enables cancer driver discovery.",
			"journal": "PLoS genetics",
			"authorList": [
				"Zhang GuangJun",
				"Hoersch Sebastian",
				"Amsterdam Adam",
				"Whittaker Charles A",
				"Beert Eline",
				"Catchen Julian M",
				"Farrington Sarah",
				"Postlethwait John H",
				"Legius Eric",
				"Hopkins Nancy",
				"Lees Jacqueline A"
			],
			"DOI": "10.1371/journal.pgen.1003734",
			"date": "2014-03-20",
			"PMC": "",
			"citation": "",
			"abstract": "The identification of cancer drivers is a major goal of current cancer research. Finding driver genes within large chromosomal events is especially challenging because such alterations encompass many genes. Previously, we demonstrated that zebrafish malignant peripheral nerve sheath tumors (MPNSTs) are highly aneuploid, much like human tumors. In this study, we examined 147 zebrafish MPNSTs by massively parallel sequencing and identified both large and focal copy number alterations (CNAs). Given the low degree of conserved synteny between fish and mammals, we reasoned that comparative analyses of CNAs from fish versus human MPNSTs would enable elimination of a large proportion of passenger mutations, especially on large CNAs. We established a list of orthologous genes between human and zebrafish, which includes approximately two-thirds of human protein-coding genes. For the subset of these genes found in human MPNST CNAs, only one quarter of their orthologues were co-gained or co-lost in zebrafish, dramatically narrowing the list of candidate cancer drivers for both focal and large CNAs. We conclude that zebrafish-human comparative analysis represents a powerful, and broadly applicable, tool to enrich for evolutionarily conserved cancer drivers.",
			"category": 2,
			"name": "Zhang GuangJun,2014"
		},
		{
			"PMID": 23977391,
			"title": "Human APOBEC3A isoforms translocate to the nucleus and induce DNA double strand breaks leading to cell stress and death.",
			"journal": "PloS one",
			"authorList": [
				"Mussil Bianka",
				"Susp\u00e8ne Rodolphe",
				"Aynaud Marie-Ming",
				"Gauvrit Anne",
				"Vartanian Jean-Pierre",
				"Wain-Hobson Simon"
			],
			"DOI": "10.1371/journal.pone.0073641",
			"date": "2015-01-15",
			"PMC": "",
			"citation": "",
			"abstract": "Human APOBEC3 enzymes deaminate single stranded DNA. At least five can deaminate mitochondrial DNA in the cytoplasm, while three can deaminate viral DNA in the nucleus. However, only one, APOBEC3A, can hypermutate genomic DNA. We analysed the distribution and function of the two APOBEC3A isoforms p1 and p2 in transfected cell lines. Both can translocate to the nucleus and hypermutate CMYC DNA and induce DNA double strand breaks as visualized by the detection of \u00a9H2AX or Chk2. APOBEC3A induced G1 phase cell cycle arrest and triggered several members of the intrinsic apoptosis pathway. Activation of purified human CD4+ T lymphocytes with PHA, IL2 and interferon \u03b1 resulted in C->T hypermutation of genomic DNA and double stranded breaks suggesting a role for APOBEC3A in pro-inflammatory conditions. As chronic inflammation underlies many diseases including numerous cancers, it is possible that APOBEC3A induction may generate many of the lesions typical of a cancer genome.",
			"category": 2,
			"name": "Mussil Bianka,2015"
		},
		{
			"PMID": 23974363,
			"title": "Chromoplexy: a new paradigm in genome remodeling and evolution.",
			"journal": "Asian journal of andrology",
			"authorList": [
				"Wang Kendric",
				"Wang Yuzhuo",
				"Collins Colin C"
			],
			"DOI": "10.1038/aja.2013.109",
			"date": "2014-06-23",
			"PMC": "",
			"citation": "",
			"abstract": "Early massively-parallel sequencing studies have revealed the mutational landscape of protein-coding genes in prostate cancer. However, most of these studies have not explored the extensive influence of genomic rearrangement in prostate cancer. In a recent Cell article, Baca and colleagues used whole-genome sequencing to tackle this issue, comprehensively surveying the abundance of genomic rearrangements present in a large cohort of 57 prostate cancers. They characterized a wide-spread phenomenon termed 'chromoplexy', which may drive cancer evolution through the phenomena of punctuated equilibrium by concurrently dysregulating numerous cancer genes across multiple chromosomes. While the causes of this event still require elucidation, this defining discovery undoubtedly offers an important glimpse into the evolutionary process of prostate cancer.",
			"category": 2,
			"name": "Wang Kendric,2014"
		},
		{
			"PMID": 23954162,
			"title": "DrGaP: a powerful tool for identifying driver genes and pathways in cancer sequencing studies.",
			"journal": "American journal of human genetics",
			"authorList": [
				"Hua Xing",
				"Xu Haiming",
				"Yang Yaning",
				"Zhu Jun",
				"Liu Pengyuan",
				"Lu Yan"
			],
			"DOI": "10.1016/j.ajhg.2013.07.003",
			"date": "2013-11-05",
			"PMC": "",
			"citation": "",
			"abstract": "Cancers are caused by the accumulation of genomic alterations. Driver mutations are required for the cancer phenotype, whereas passenger mutations are irrelevant to tumor development and accumulate through DNA replication. A major challenge facing the field of cancer genome sequencing is to identify cancer-associated genes with mutations that drive the cancer phenotype. Here, we describe a powerful and flexible statistical framework for identifying driver genes and driver signaling pathways in cancer genome-sequencing studies. Biological knowledge of the mutational process in tumors is fully integrated into our statistical models and includes such variables as the length of protein-coding regions, transcript isoforms, variation in mutation types, differences in background mutation rates, the redundancy of genetic code, and multiple mutations in one gene. This framework provides several significant features that are not addressed or naively obtained by previous methods. In particular, on the observation of low prevalence of somatic mutations in individual tumors, we propose a heuristic strategy to estimate the mixture proportion of chi-square distribution of likelihood ratio test (LRT) statistics. This provides significantly increased statistical power compared to regular LRT. Through a combination of simulation and analysis of TCGA cancer sequencing study data, we demonstrate high accuracy and sensitivity in our methods. Our statistical methods and several auxiliary bioinformatics tools have been incorporated into a computational tool, DrGaP. The newly developed tool is immediately applicable to cancer genome-sequencing studies and will lead to a more complete identification of altered driver genes and driver signaling pathways in cancer.",
			"category": 2,
			"name": "Hua Xing,2013"
		},
		{
			"PMID": 23945592,
			"title": "Signatures of mutational processes in human cancer.",
			"journal": "Nature",
			"authorList": [
				"Alexandrov Ludmil B",
				"Nik-Zainal Serena",
				"Wedge David C",
				"Aparicio Samuel A J R",
				"Behjati Sam",
				"Biankin Andrew V",
				"Bignell Graham R",
				"Bolli Niccol\u00f2",
				"Borg Ake",
				"B\u00f8rresen-Dale Anne-Lise",
				"Boyault Sandrine",
				"Burkhardt Birgit",
				"Butler Adam P",
				"Caldas Carlos",
				"Davies Helen R",
				"Desmedt Christine",
				"Eils Roland",
				"Eyfj\u00f6rd J\u00f3runn Erla",
				"Foekens John A",
				"Greaves Mel",
				"Hosoda Fumie",
				"Hutter Barbara",
				"Ilicic Tomislav",
				"Imbeaud Sandrine",
				"Imielinski Marcin",
				"J\u00e4ger Natalie",
				"Jones David T W",
				"Jones David",
				"Knappskog Stian",
				"Kool Marcel",
				"Lakhani Sunil R",
				"L\u00f3pez-Ot\u00edn Carlos",
				"Martin Sancha",
				"Munshi Nikhil C",
				"Nakamura Hiromi",
				"Northcott Paul A",
				"Pajic Marina",
				"Papaemmanuil Elli",
				"Paradiso Angelo",
				"Pearson John V",
				"Puente Xose S",
				"Raine Keiran",
				"Ramakrishna Manasa",
				"Richardson Andrea L",
				"Richter Julia",
				"Rosenstiel Philip",
				"Schlesner Matthias",
				"Schumacher Ton N",
				"Span Paul N",
				"Teague Jon W",
				"Totoki Yasushi",
				"Tutt Andrew N J",
				"Vald\u00e9s-Mas Rafael",
				"van Buuren Marit M",
				"van 't Veer Laura",
				"Vincent-Salomon Anne",
				"Waddell Nicola",
				"Yates Lucy R",
				"Australian Pancreatic Cancer Genome Initiative",
				"ICGC Breast Cancer Consortium",
				"ICGC MMML-Seq Consortium",
				"ICGC PedBrain",
				"Zucman-Rossi Jessica",
				"Futreal P Andrew",
				"McDermott Ultan",
				"Lichter Peter",
				"Meyerson Matthew",
				"Grimmond Sean M",
				"Siebert Reiner",
				"Campo El\u00edas",
				"Shibata Tatsuhiro",
				"Pfister Stefan M",
				"Campbell Peter J",
				"Stratton Michael R"
			],
			"DOI": "10.1038/nature12477",
			"date": "2013-10-29",
			"PMC": "",
			"citation": "",
			"abstract": "All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.",
			"category": 2,
			"name": "Alexandrov Ludmil B,2013"
		},
		{
			"PMID": 23922675,
			"title": "Boolean network model for cancer pathways: predicting carcinogenesis and targeted therapy outcomes.",
			"journal": "PloS one",
			"authorList": [
				"Fumi\u00e3 Herman F",
				"Martins Marcelo L"
			],
			"DOI": "10.1371/journal.pone.0069008",
			"date": "2014-04-29",
			"PMC": "",
			"citation": "",
			"abstract": "A Boolean dynamical system integrating the main signaling pathways involved in cancer is constructed based on the currently known protein-protein interaction network. This system exhibits stationary protein activation patterns--attractors--dependent on the cell's microenvironment. These dynamical attractors were determined through simulations and their stabilities against mutations were tested. In a higher hierarchical level, it was possible to group the network attractors into distinct cell phenotypes and determine driver mutations that promote phenotypic transitions. We find that driver nodes are not necessarily central in the network topology, but at least they are direct regulators of central components towards which converge or through which crosstalk distinct cancer signaling pathways. The predicted drivers are in agreement with those pointed out by diverse census of cancer genes recently performed for several human cancers. Furthermore, our results demonstrate that cell phenotypes can evolve towards full malignancy through distinct sequences of accumulated mutations. In particular, the network model supports routes of carcinogenesis known for some tumor types. Finally, the Boolean network model is employed to evaluate the outcome of molecularly targeted cancer therapies. The major find is that monotherapies were additive in their effects and that the association of targeted drugs is necessary for cancer eradication.",
			"category": 2,
			"name": "Fumi\u00e3 Herman F,2014"
		},
		{
			"PMID": 23913938,
			"title": "Targeting the tumor microenvironment: from understanding pathways to effective clinical trials.",
			"journal": "Cancer research",
			"authorList": [
				"Fang Hua",
				"Declerck Yves A"
			],
			"DOI": "10.1158/0008-5472.CAN-13-0661",
			"date": "2014-02-20",
			"PMC": "",
			"citation": "",
			"abstract": "It is clear that tumor cells do not act alone but in close interaction with the extracellular matrix and with stromal cells in the tumor microenvironment (TME). As our understanding of tumor cell-stroma interactions increased over the last two decades, significant efforts have been made to develop agents that interfere with these interactions. Here, we discuss four different therapeutic strategies that target the TME, focusing on agents that are at the most advanced stage of preclinical or clinical development. We end this review by outlining some of the lessons we have learned so far from the development of TME-targeting agents.",
			"category": 2,
			"name": "Fang Hua,2014"
		},
		{
			"PMID": 23900255,
			"title": "Computational approaches to identify functional genetic variants in cancer genomes.",
			"journal": "Nature methods",
			"authorList": [
				"Gonzalez-Perez Abel",
				"Mustonen Ville",
				"Reva Boris",
				"Ritchie Graham R S",
				"Creixell Pau",
				"Karchin Rachel",
				"Vazquez Miguel",
				"Fink J Lynn",
				"Kassahn Karin S",
				"Pearson John V",
				"Bader Gary D",
				"Boutros Paul C",
				"Muthuswamy Lakshmi",
				"Ouellette B F Francis",
				"Reimand J\u00fcri",
				"Linding Rune",
				"Shibata Tatsuhiro",
				"Valencia Alfonso",
				"Butler Adam",
				"Dronov Serge",
				"Flicek Paul",
				"Shannon Nick B",
				"Carter Hannah",
				"Ding Li",
				"Sander Chris",
				"Stuart Josh M",
				"Stein Lincoln D",
				"Lopez-Bigas Nuria",
				"International Cancer Genome Consortium Mutation Pathways and Consequences Subgroup of the Bioinformatics Analyses Working Group"
			],
			"DOI": "10.1038/nmeth.2562",
			"date": "2013-12-11",
			"PMC": "",
			"citation": "",
			"abstract": "The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor but only a minority of these drive tumor progression. We present the result of discussions within the ICGC on how to address the challenge of identifying mutations that contribute to oncogenesis, tumor maintenance or response to therapy, and recommend computational techniques to annotate somatic variants and predict their impact on cancer phenotype.",
			"category": 2,
			"name": "Gonzalez-Perez Abel,2013"
		},
		{
			"PMID": 23887607,
			"title": "Technical and implementation issues in using next-generation sequencing of cancers in clinical practice.",
			"journal": "British journal of cancer",
			"authorList": [
				"Ulahannan D",
				"Kovac M B",
				"Mulholland P J",
				"Cazier J-B",
				"Tomlinson I"
			],
			"DOI": "10.1038/bjc.2013.416",
			"date": "2013-11-04",
			"PMC": "",
			"citation": "",
			"abstract": "Next-generation sequencing (NGS) of cancer genomes promises to revolutionise oncology, with the ability to design and use targeted drugs, to predict outcome and response, and to classify tumours. It is continually becoming cheaper, faster and more reliable, with the capability to identify rare yet clinically important somatic mutations. Technical challenges include sequencing samples of low quality and/or quantity, reliable identification of structural and copy number variation, and assessment of intratumour heterogeneity. Once these problems are overcome, the use of the data to guide clinical decision making is not straightforward, and there is a risk of premature use of molecular changes to guide patient management in the absence of supporting evidence. Paradoxically, NGS may simply move the bottleneck of personalised medicine from data acquisition to the identification of reliable biomarkers. Standardised cancer NGS data collection on an international scale would be a significant step towards optimising patient care.",
			"category": 2,
			"name": "Ulahannan D,2013"
		},
		{
			"PMID": 23879537,
			"title": "Vitamin D and microRNAs in bone.",
			"journal": "Critical reviews in eukaryotic gene expression",
			"authorList": [
				"Lisse Thomas S",
				"Adams John S",
				"Hewison Martin"
			],
			"DOI": "",
			"date": "2014-02-27",
			"PMC": "",
			"citation": "",
			"abstract": "MicroRNAs (miRNAs) are short noncoding RNAs that orchestrate complex posttranscriptional regulatory networks essential to the regulation of gene expression. Through complementarity with messenger RNA (mRNA) sequences, miRNAs act primarily to silence gene expression through either degradation or inhibited translation of target transcripts. In this way, miRNAs can act to fine-tune the transcriptional regulation of gene expression, but they may also play distinct roles in the proliferation, differentiation, and function of specific cell types. miRNA regulatory networks may be particularly important for signaling molecules such as vitamin D that exert pleiotropic effects on tissues throughout the body. The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D) functions as a steroid hormone that, when bound to its nuclear vitamin D receptor, is able to regulate target gene expression. However, recent studies have also implicated 1,25(OH)2D in epigenetic regulation of genes most notably as a modulator of miRNA function. The current review details our understanding of vitamin D and miRNAs with specific emphasis on the implications of this interaction for biological responses to vitamin D in one of its classical target tissues, i.e., bone.",
			"category": 2,
			"name": "Lisse Thomas S,2014"
		},
		{
			"PMID": 23871696,
			"title": "KDM4A lysine demethylase induces site-specific copy gain and rereplication of regions amplified in tumors.",
			"journal": "Cell",
			"authorList": [
				"Black Joshua C",
				"Manning Amity L",
				"Van Rechem Capucine",
				"Kim Jaegil",
				"Ladd Brendon",
				"Cho Juok",
				"Pineda Cristiana M",
				"Murphy Nancy",
				"Daniels Danette L",
				"Montagna Cristina",
				"Lewis Peter W",
				"Glass Kimberly",
				"Allis C David",
				"Dyson Nicholas J",
				"Getz Gad",
				"Whetstine Johnathan R"
			],
			"DOI": "10.1016/j.cell.2013.06.051",
			"date": "2013-10-28",
			"PMC": "",
			"citation": "",
			"abstract": "Acquired chromosomal instability and copy number alterations are hallmarks of cancer. Enzymes capable of promoting site-specific copy number changes have yet to be identified. Here, we demonstrate that H3K9/36me3 lysine demethylase KDM4A/JMJD2A overexpression leads to localized copy gain of 1q12, 1q21, and Xq13.1 without global chromosome instability. KDM4A-amplified tumors have increased copy gains for these same regions. 1q12h copy gain occurs within a single cell cycle, requires S phase, and is not stable but is regenerated each cell division. Sites with increased copy number are rereplicated and have increased KDM4A, MCM, and DNA polymerase occupancy. Suv39h1/KMT1A or HP1\u03b3 overexpression suppresses the copy gain, whereas H3K9/K36 methylation interference promotes gain. Our results demonstrate that overexpression of a chromatin modifier results in site-specific copy gains. This begins to establish how copy number changes could originate during tumorigenesis and demonstrates that transient overexpression of specific chromatin modulators could promote these events.",
			"category": 2,
			"name": "Black Joshua C,2013"
		},
		{
			"PMID": 23836920,
			"title": "Fusion peptides from oncogenic chimeric proteins as putative specific biomarkers of cancer.",
			"journal": "Molecular & cellular proteomics : MCP",
			"authorList": [
				"Conlon Kevin P",
				"Basrur Venkatesha",
				"Rolland Delphine",
				"Wolfe Thomas",
				"Nesvizhskii Alexey I",
				"MacCoss Michael J",
				"Lim Megan S",
				"Elenitoba-Johnson Kojo S J"
			],
			"DOI": "10.1074/mcp.M113.029926",
			"date": "2014-05-09",
			"PMC": "",
			"citation": "",
			"abstract": "Chromosomal translocations encoding chimeric fusion proteins constitute one of the most common mechanisms underlying oncogenic transformation in human cancer. Fusion peptides resulting from such oncogenic chimeric fusions, though unique to specific cancer subtypes, are unexplored as cancer biomarkers. Here we show, using an approach termed fusion peptide multiple reaction monitoring mass spectrometry, the direct identification of different cancer-specific fusion peptides arising from protein chimeras that are generated from the juxtaposition of heterologous genes fused by recurrent chromosomal translocations. Using fusion peptide multiple reaction monitoring mass spectrometry in a clinically relevant scenario, we demonstrate the specific, sensitive, and unambiguous detection of a specific diagnostic fusion peptide in clinical samples of anaplastic large cell lymphoma, but not in a diverse array of benign lymph nodes or other forms of primary malignant lymphomas and cancer-derived cell lines. Our studies highlight the utility of fusion peptides as cancer biomarkers and carry broad implications for the use of protein biomarkers in cancer detection and monitoring.",
			"category": 2,
			"name": "Conlon Kevin P,2014"
		},
		{
			"PMID": 23832661,
			"title": "Cooperation and antagonism among cancer genes: the renal cancer paradigm.",
			"journal": "Cancer research",
			"authorList": [
				"Pe\u00f1a-Llopis Samuel",
				"Christie Alana",
				"Xie Xian-Jin",
				"Brugarolas James"
			],
			"DOI": "10.1158/0008-5472.CAN-13-0360",
			"date": "2014-02-06",
			"PMC": "",
			"citation": "",
			"abstract": "It is poorly understood how driver mutations in cancer genes work together to promote tumor development. Renal cell carcinoma (RCC) offers a unique opportunity to study complex relationships among cancer genes. The four most commonly mutated genes in RCC of clear-cell type (the most common type) are two-hit tumor suppressor genes, and they cluster in a 43-Mb region on chromosome 3p that is deleted in approximately 90% of tumors: VHL (mutated in \u223c80%), PBRM1 (\u223c50%), BAP1 (\u223c15%), and SETD2 (\u223c15%). Meta-analyses that we conducted show that mutations in PBRM1 and SETD2 co-occur in tumors at a frequency higher than expected by chance alone, indicating that these mutations may cooperate in tumorigenesis. In contrast, consistent with our previous results, mutations in PBRM1 and BAP1 tend to be mutually exclusive. Mutation exclusivity analyses (often confounded by lack of statistical power) raise the possibility of functional redundancy. However, mutation exclusivity may indicate negative genetic interactions, as proposed herein for PBRM1 and BAP1, and mutations in these genes define RCC with different pathologic features, gene expression profiles, and outcomes. Negative genetic interactions among cancer genes point toward broader context dependencies of cancer gene action beyond tissue dependencies. An enhanced understanding of cancer gene dependencies may help to unravel vulnerabilities that can be exploited therapeutically.",
			"category": 2,
			"name": "Pe\u00f1a-Llopis Samuel,2014"
		},
		{
			"PMID": 23818585,
			"title": "The mTOR pathway negatively controls ATM by up-regulating miRNAs.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Shen Changxian",
				"Houghton Peter J"
			],
			"DOI": "10.1073/pnas.1220898110",
			"date": "2013-09-25",
			"PMC": "",
			"citation": "",
			"abstract": "The ataxia telangiectasia mutated (ATM) checkpoint is the central surveillance system that maintains genome integrity. We found that in the context of childhood sarcoma, mammalian target of rapamycin (mTOR) signaling suppresses ATM by up-regulating miRNAs targeting ATM. Pharmacological inhibition or genetic down-regulation of the mTOR pathway resulted in increase of ATM mRNA and protein both in mouse sarcoma xenografts and cultured cells. mTOR Complex 1 (mTORC1) suppresses ATM via S6K1/2 signaling pathways. microRNA-18a and microRNA-421, both of which target ATM, are positively controlled by mTOR signaling. Our findings have identified a negative feedback loop for the signaling between ATM and mTOR pathways and suggest that oncogenic growth signals may promote tumorigenesis by dampening the ATM checkpoint.",
			"category": 2,
			"name": "Shen Changxian,2013"
		},
		{
			"PMID": 23811269,
			"title": "Integrated network analyses for functional genomic studies in cancer.",
			"journal": "Seminars in cancer biology",
			"authorList": [
				"Wilson Jennifer L",
				"Hemann Michael T",
				"Fraenkel Ernest",
				"Lauffenburger Douglas A"
			],
			"DOI": "10.1016/j.semcancer.2013.06.004",
			"date": "2014-03-03",
			"PMC": "",
			"citation": "",
			"abstract": "RNA-interference (RNAi) studies hold great promise for functional investigation of the significance of genetic variations and mutations, as well as potential synthetic lethalities, for understanding and treatment of cancer, yet technical and conceptual issues currently diminish the potential power of this approach. While numerous research groups are usefully employing this kind of functional genomic methodology to identify molecular mediators of disease severity, response, and resistance to treatment, findings are generally confounded by \"off-target\" effects. These effects arise from a variety of issues beyond non-specific reagent behavior, such as biological cross-talk and feedback processes so thus can occur even with specific perturbation. Interpreting RNAi results in a network framework instead of merely as individual \"hits\" or \"targets\" leverages contributions from all hit/target contributions to pathways via their relationships with other network nodes. This interpretation can ameliorate dependence upon individual reagent performance and increase confidence in biological validation. Here we provide background on RNAi studies in cancer applications, review key challenges with functional genomics, and motivate the use of network models grounded in pathway analyses.",
			"category": 2,
			"name": "Wilson Jennifer L,2014"
		},
		{
			"PMID": 23780408,
			"title": "Distinct evolutionary trajectories of primary high-grade serous ovarian cancers revealed through spatial mutational profiling.",
			"journal": "The Journal of pathology",
			"authorList": [
				"Bashashati Ali",
				"Ha Gavin",
				"Tone Alicia",
				"Ding Jiarui",
				"Prentice Leah M",
				"Roth Andrew",
				"Rosner Jamie",
				"Shumansky Karey",
				"Kalloger Steve",
				"Senz Janine",
				"Yang Winnie",
				"McConechy Melissa",
				"Melnyk Nataliya",
				"Anglesio Michael",
				"Luk Margaret T Y",
				"Tse Kane",
				"Zeng Thomas",
				"Moore Richard",
				"Zhao Yongjun",
				"Marra Marco A",
				"Gilks Blake",
				"Yip Stephen",
				"Huntsman David G",
				"McAlpine Jessica N",
				"Shah Sohrab P"
			],
			"DOI": "10.1002/path.4230",
			"date": "2013-10-18",
			"PMC": "",
			"citation": "",
			"abstract": "High-grade serous ovarian cancer (HGSC) is characterized by poor outcome, often attributed to the emergence of treatment-resistant subclones. We sought to measure the degree of genomic diversity within primary, untreated HGSCs to examine the natural state of tumour evolution prior to therapy. We performed exome sequencing, copy number analysis, targeted amplicon deep sequencing and gene expression profiling on 31 spatially and temporally separated HGSC tumour specimens (six patients), including ovarian masses, distant metastases and fallopian tube lesions. We found widespread intratumoural variation in mutation, copy number and gene expression profiles, with key driver alterations in genes present in only a subset of samples (eg PIK3CA, CTNNB1, NF1). On average, only 51.5% of mutations were present in every sample of a given case (range 10.2-91.4%), with TP53 as the only somatic mutation consistently present in all samples. Complex segmental aneuploidies, such as whole-genome doubling, were present in a subset of samples from the same individual, with divergent copy number changes segregating independently of point mutation acquisition. Reconstruction of evolutionary histories showed one patient with mixed HGSC and endometrioid histology, with common aetiologic origin in the fallopian tube and subsequent selection of different driver mutations in the histologically distinct samples. In this patient, we observed mixed cell populations in the early fallopian tube lesion, indicating that diversity arises at early stages of tumourigenesis. Our results revealed that HGSCs exhibit highly individual evolutionary trajectories and diverse genomic tapestries prior to therapy, exposing an essential biological characteristic to inform future design of personalized therapeutic solutions and investigation of drug-resistance mechanisms.",
			"category": 2,
			"name": "Bashashati Ali,2013"
		},
		{
			"PMID": 23754386,
			"title": "Effects of oncogenic mutations on the conformational free-energy landscape of EGFR kinase.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Sutto Ludovico",
				"Gervasio Francesco Luigi"
			],
			"DOI": "10.1073/pnas.1221953110",
			"date": "2013-09-06",
			"PMC": "",
			"citation": "",
			"abstract": "Activating mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase are frequently found in many cancers. It has been suggested that changes in the equilibrium between its active and inactive conformations are linked to its oncogenic potential. Here, we quantify the effects of some of the most common single (L858R and T790M) and double (T790M-L858R) oncogenic mutations on the conformational free-energy landscape of the EGFR kinase domain by using massive molecular dynamics simulations together with parallel tempering, metadynamics, and one of the best force-fields available. Whereas the wild-type EGFR catalytic domain monomer is mostly found in an inactive conformation, our results show a clear shift toward the active conformation for all of the mutants. The L858R mutation stabilizes the active conformation at the expense of the inactive conformation and rigidifies the \u03b1C-helix. The T790M gatekeeper mutant favors activation by stabilizing a hydrophobic cluster. Finally, T790M with L858R shows a significant positive epistasis effect. This combination not only stabilizes the active conformation, but in nontrivial ways changes the free-energy landscape lowering the transition barriers.",
			"category": 2,
			"name": "Sutto Ludovico,2013"
		},
		{
			"PMID": 23740488,
			"title": "A deterministic model for the occurrence and dynamics of multiple mutations in hierarchically organized tissues.",
			"journal": "Journal of the Royal Society, Interface",
			"authorList": [
				"Werner Benjamin",
				"Dingli David",
				"Traulsen Arne"
			],
			"DOI": "10.1098/rsif.2013.0349",
			"date": "2013-12-09",
			"PMC": "",
			"citation": "",
			"abstract": "Cancers are rarely caused by single mutations, but often develop as a result of the combined effects of multiple mutations. For most cells, the number of possible cell divisions is limited because of various biological constraints, such as progressive telomere shortening, cell senescence cascades or a hierarchically organized tissue structure. Thus, the risk of accumulating cells carrying multiple mutations is low. Nonetheless, many diseases are based on the accumulation of such multiple mutations. We model a general, hierarchically organized tissue by a multi-compartment approach, allowing any number of mutations within a cell. We derive closed solutions for the deterministic clonal dynamics and the reproductive capacity of single clones. Our results hold for the average dynamics in a hierarchical tissue characterized by an arbitrary combination of proliferation parameters. We show that hierarchically organized tissues strongly suppress cells carrying multiple mutations and derive closed solutions for the expected size and diversity of clonal populations founded by a single mutant within the hierarchy. We discuss the example of childhood acute lymphoblastic leukaemia in detail and find good agreement between our predicted results and recently observed clonal diversities in patients. This result can contribute to the explanation of very diverse mutation profiles observed by whole genome sequencing of many different cancers.",
			"category": 2,
			"name": "Werner Benjamin,2013"
		},
		{
			"PMID": 23718799,
			"title": "Integrated analysis of recurrent properties of cancer genes to identify novel drivers.",
			"journal": "Genome biology",
			"authorList": [
				"D'Antonio Matteo",
				"Ciccarelli Francesca D"
			],
			"DOI": "10.1186/gb-2013-14-5-r52",
			"date": "2015-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "The heterogeneity of cancer genomes in terms of acquired mutations complicates the identification of genes whose modification may exert a driver role in tumorigenesis. In this study, we present a novel method that integrates expression profiles, mutation effects, and systemic properties of mutated genes to identify novel cancer drivers. We applied our method to ovarian cancer samples and were able to identify putative drivers in the majority of carcinomas without mutations in known cancer genes, thus suggesting that it can be used as a complementary approach to find rare driver mutations that cannot be detected using frequency-based approaches.",
			"category": 2,
			"name": "D'Antonio Matteo,2015"
		},
		{
			"PMID": 23713780,
			"title": "Druggable orthosteric and allosteric hot spots to target protein-protein interactions.",
			"journal": "Current pharmaceutical design",
			"authorList": [
				"Ma Buyong",
				"Nussinov Ruth"
			],
			"DOI": "",
			"date": "2014-12-01",
			"PMC": "",
			"citation": "",
			"abstract": "Drug designing targeting protein-protein interactions is challenging. Because structural elucidation and computational analysis have revealed the importance of hot spot residues in stabilizing these interactions, there have been on-going efforts to develop drugs which bind the hot spots and out-compete the native protein partners. The question arises as to what are the key 'druggable' properties of hot spots in protein-protein interactions and whether these mimic the general hot spot definition. Identification of orthosteric (at the protein- protein interaction site) and allosteric (elsewhere) druggable hot spots is expected to help in discovering compounds that can more effectively modulate protein-protein interactions. For example, are there any other significant features beyond their location in pockets in the interface? The interactions of protein-protein hot spots are coupled with conformational dynamics of protein complexes. Currently increasing efforts focus on the allosteric drug discovery. Allosteric drugs bind away from the native binding site and can modulate the native interactions. We propose that identification of allosteric hot spots could similarly help in more effective allosteric drug discovery. While detection of allosteric hot spots is challenging, targeting drugs to these residues has the potential of greatly increasing the hot spot and protein druggability.",
			"category": 2,
			"name": "Ma Buyong,2014"
		},
		{
			"PMID": 23710360,
			"title": "Label-Free Quantitation and Mapping of the ErbB2 Tumor Receptor by Multiple Protease Digestion with Data-Dependent (MS1) and Data-Independent (MS2) Acquisitions.",
			"journal": "International journal of proteomics",
			"authorList": [
				"Held Jason M",
				"Schilling Birgit",
				"D'Souza Alexandria K",
				"Srinivasan Tara",
				"Behring Jessica B",
				"Sorensen Dylan J",
				"Benz Christopher C",
				"Gibson Bradford W"
			],
			"DOI": "10.1155/2013/791985",
			"date": "2013-05-28",
			"PMC": "",
			"citation": "",
			"abstract": "The receptor tyrosine kinase ErbB2 is a breast cancer biomarker whose posttranslational modifications (PTMs) are a key indicator of its activation. Quantifying the expression and PTMs of biomarkers such as ErbB2 by selected reaction monitoring (SRM) mass spectrometry has several limitations, including minimal coverage and extensive assay development time. Therefore, we assessed the utility of two high resolution, full scan mass spectrometry approaches, MS1 Filtering and SWATH MS2, for targeted ErbB2 proteomics. Endogenous ErbB2 immunoprecipitated from SK-BR-3 cells was in-gel digested with trypsin, chymotrypsin, Asp-N, or trypsin plus Asp-N in triplicate. Data-dependent acquisition with an AB SCIEX TripleTOF 5600 and MS1 Filtering data processing was used to assess peptide and PTM coverage as well as the reproducibility of enzyme digestion. Data-independent acquisition (SWATH) was also performed for MS2 quantitation. MS1 Filtering and SWATH MS2 allow quantitation of all detected analytes after acquisition, enabling the use of multiple proteases for quantitative assessment of target proteins. Combining high resolution proteomics with multiprotease digestion enabled quantitative mapping of ErbB2 with excellent reproducibility, improved amino acid sequence and PTM coverage, and decreased assay development time compared to typical SRM assays. These results demonstrate that high resolution quantitative proteomic approaches are an effective tool for targeted biomarker quantitation.",
			"category": 2,
			"name": "Held Jason M,2013"
		},
		{
			"PMID": 23702683,
			"title": "Detailed molecular characterisation of acute myeloid leukaemia with a normal karyotype using targeted DNA capture.",
			"journal": "Leukemia",
			"authorList": [
				"Conte N",
				"Varela I",
				"Grove C",
				"Manes N",
				"Yusa K",
				"Moreno T",
				"Segonds-Pichon A",
				"Bench A",
				"Gudgin E",
				"Herman B",
				"Bolli N",
				"Ellis P",
				"Haddad D",
				"Costeas P",
				"Rad R",
				"Scott M",
				"Huntly B",
				"Bradley A",
				"Vassiliou G S"
			],
			"DOI": "10.1038/leu.2013.117",
			"date": "2013-10-21",
			"PMC": "",
			"citation": "",
			"abstract": "Advances in sequencing technologies are giving unprecedented insights into the spectrum of somatic mutations underlying acute myeloid leukaemia with a normal karyotype (AML-NK). It is clear that the prognosis of individual patients is strongly influenced by the combination of mutations in their leukaemia and that many leukaemias are composed of multiple subclones, with differential susceptibilities to treatment. Here, we describe a method, employing targeted capture coupled with next-generation sequencing and tailored bioinformatic analysis, for the simultaneous study of 24 genes recurrently mutated in AML-NK. Mutational analysis was performed using open source software and an in-house script (Mutation Identification and Analysis Software), which identified dominant clone mutations with 100% specificity. In each of seven cases of AML-NK studied, we identified and verified mutations in 2-4 genes in the main leukaemic clone. Additionally, high sequencing depth enabled us to identify putative subclonal mutations and detect leukaemia-specific mutations in DNA from remission marrow. Finally, we used normalised read depths to detect copy number changes and identified and subsequently verified a tandem duplication of exons 2-9 of MLL and at least one deletion involving PTEN. This methodology reliably detects sequence and copy number mutations, and can thus greatly facilitate the classification, clinical research, diagnosis and management of AML-NK.",
			"category": 2,
			"name": "Conte N,2013"
		},
		{
			"PMID": 23690930,
			"title": "Analysis of tumor heterogeneity and cancer gene networks using deep sequencing of MMTV-induced mouse mammary tumors.",
			"journal": "PloS one",
			"authorList": [
				"Klijn Christiaan",
				"Koudijs Marco J",
				"Kool Jaap",
				"ten Hoeve Jelle",
				"Boer Mandy",
				"de Moes Joost",
				"Akhtar Waseem",
				"van Miltenburg Martine",
				"Vendel-Zwaagstra Annabel",
				"Reinders Marcel J T",
				"Adams David J",
				"van Lohuizen Maarten",
				"Hilkens John",
				"Wessels Lodewyk F A",
				"Jonkers Jos"
			],
			"DOI": "10.1371/journal.pone.0062113",
			"date": "2013-12-30",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer develops through a multistep process in which normal cells progress to malignant tumors via the evolution of their genomes as a result of the acquisition of mutations in cancer driver genes. The number, identity and mode of action of cancer driver genes, and how they contribute to tumor evolution is largely unknown. This study deployed the Mouse Mammary Tumor Virus (MMTV) as an insertional mutagen to find both the driver genes and the networks in which they function. Using deep insertion site sequencing we identified around 31000 retroviral integration sites in 604 MMTV-induced mammary tumors from mice with mammary gland-specific deletion of Trp53, Pten heterozygous knockout mice, or wildtype strains. We identified 18 known common integration sites (CISs) and 12 previously unknown CISs marking new candidate cancer genes. Members of the Wnt, Fgf, Fgfr, Rspo and Pdgfr gene families were commonly mutated in a mutually exclusive fashion. The sequence data we generated yielded also information on the clonality of insertions in individual tumors, allowing us to develop a data-driven model of MMTV-induced tumor development. Insertional mutations near Wnt and Fgf genes mark the earliest \"initiating\" events in MMTV induced tumorigenesis, whereas Fgfr genes are targeted later during tumor progression. Our data shows that insertional mutagenesis can be used to discover the mutational networks, the timing of mutations, and the genes that initiate and drive tumor evolution.",
			"category": 2,
			"name": "Klijn Christiaan,2013"
		},
		{
			"PMID": 23656622,
			"title": "The genomic landscape of chronic lymphocytic leukemia: clinical implications.",
			"journal": "BMC medicine",
			"authorList": [
				"Quesada V\u00edctor",
				"Ramsay Andrew J",
				"Rodr\u00edguez David",
				"Puente Xose S",
				"Campo El\u00edas",
				"L\u00f3pez-Ot\u00edn Carlos"
			],
			"DOI": "10.1186/1741-7015-11-124",
			"date": "2013-09-25",
			"PMC": "",
			"citation": "",
			"abstract": "A precise understanding of the genomic and epigenomic features of chronic lymphocytic leukemia (CLL) may benefit the study of the disease's staging and treatment. While recent reports have shed some light on these aspects, several challenges need to be addressed before translating this research into clinical practice. Thus, even the best candidate driver genes display low mutational rates compared to other tumors. This means that a large percentage of cases do not display clear tumor-driving point mutations, or show candidate driving point mutations with no obvious biochemical relationship to the more frequently mutated genes. This genomic landscape probably reflects either an unknown underlying biochemical mechanism playing a key role in CLL or multiple biochemical pathways independently driving the development of this tumor. The elucidation of either scenario will have important consequences on the clinical management of CLL. Herein, we review the recent advances in the definition of the genomic landscape of CLL and the ongoing research to characterize the underlying biochemical events that drive this disease.",
			"category": 2,
			"name": "Quesada V\u00edctor,2013"
		},
		{
			"PMID": 23642077,
			"title": "Identification of somatic mutations in cancer through Bayesian-based analysis of sequenced genome pairs.",
			"journal": "BMC genomics",
			"authorList": [
				"Christoforides Alexis",
				"Carpten John D",
				"Weiss Glen J",
				"Demeure Michael J",
				"Von Hoff Daniel D",
				"Craig David W"
			],
			"DOI": "10.1186/1471-2164-14-302",
			"date": "2013-10-30",
			"PMC": "",
			"citation": "",
			"abstract": "The field of cancer genomics has rapidly adopted next-generation sequencing (NGS) in order to study and characterize malignant tumors with unprecedented resolution. In particular for cancer, one is often trying to identify somatic mutations--changes specific to a tumor and not within an individual's germline. However, false positive and false negative detections often result from lack of sufficient variant evidence, contamination of the biopsy by stromal tissue, sequencing errors, and the erroneous classification of germline variation as tumor-specific.",
			"category": 2,
			"name": "Christoforides Alexis,2013"
		},
		{
			"PMID": 23640184,
			"title": "Challenges in pharmacogenetics.",
			"journal": "European journal of clinical pharmacology",
			"authorList": [
				"Cascorbi Ingolf",
				"Bruhn Oliver",
				"Werk Anneke N"
			],
			"DOI": "10.1007/s00228-013-1492-x",
			"date": "2013-11-01",
			"PMC": "",
			"citation": "",
			"abstract": "The attempt to optimize drug treatment of patients by using evidenced-based medicine considering individual physiological and disease-related conditions is standard of modern medicine. Pharmacogenetics (PGx) has contributed to individualization considering hereditary genetic information; however, increasingly, pharmacogenomics is becoming essential, particularly in relation to modern oncology. New technologies such as next-generation sequencing and rapid development of computational and information sciences will help to better elucidate the consequences of genetic variation, considering also epigenetics and gene-environmental interactions and their translation into clinically relevant individual phenotypes. This review highlights the current challenging and most promising examples of PGx.",
			"category": 2,
			"name": "Cascorbi Ingolf,2013"
		},
		{
			"PMID": 23633940,
			"title": "Distinct types of disorder in the human proteome: functional implications for alternative splicing.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Colak Recep",
				"Kim TaeHyung",
				"Michaut Magali",
				"Sun Mark",
				"Irimia Manuel",
				"Bellay Jeremy",
				"Myers Chad L",
				"Blencowe Benjamin J",
				"Kim Philip M"
			],
			"DOI": "10.1371/journal.pcbi.1003030",
			"date": "2013-12-19",
			"PMC": "",
			"citation": "",
			"abstract": "Intrinsically disordered regions have been associated with various cellular processes and are implicated in several human diseases, but their exact roles remain unclear. We previously defined two classes of conserved disordered regions in budding yeast, referred to as \"flexible\" and \"constrained\" conserved disorder. In flexible disorder, the property of disorder has been positionally conserved during evolution, whereas in constrained disorder, both the amino acid sequence and the property of disorder have been conserved. Here, we show that flexible and constrained disorder are widespread in the human proteome, and are particularly common in proteins with regulatory functions. Both classes of disordered sequences are highly enriched in regions of proteins that undergo tissue-specific (TS) alternative splicing (AS), but not in regions of proteins that undergo general (i.e., not tissue-regulated) AS. Flexible disorder is more highly enriched in TS alternative exons, whereas constrained disorder is more highly enriched in exons that flank TS alternative exons. These latter regions are also significantly more enriched in potential phosphosites and other short linear motifs associated with cell signaling. We further show that cancer driver mutations are significantly enriched in regions of proteins associated with TS and general AS. Collectively, our results point to distinct roles for TS alternative exons and flanking exons in the dynamic regulation of protein interaction networks in response to signaling activity, and they further suggest that alternatively spliced regions of proteins are often functionally altered by mutations responsible for cancer.",
			"category": 2,
			"name": "Colak Recep,2013"
		},
		{
			"PMID": 23630320,
			"title": "Single-cell paired-end genome sequencing reveals structural variation per cell cycle.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Voet Thierry",
				"Kumar Parveen",
				"Van Loo Peter",
				"Cooke Susanna L",
				"Marshall John",
				"Lin Meng-Lay",
				"Zamani Esteki Masoud",
				"Van der Aa Niels",
				"Mateiu Ligia",
				"McBride David J",
				"Bignell Graham R",
				"McLaren Stuart",
				"Teague Jon",
				"Butler Adam",
				"Raine Keiran",
				"Stebbings Lucy A",
				"Quail Michael A",
				"D'Hooghe Thomas",
				"Moreau Yves",
				"Futreal P Andrew",
				"Stratton Michael R",
				"Vermeesch Joris R",
				"Campbell Peter J"
			],
			"DOI": "10.1093/nar/gkt345",
			"date": "2013-09-10",
			"PMC": "",
			"citation": "",
			"abstract": "The nature and pace of genome mutation is largely unknown. Because standard methods sequence DNA from populations of cells, the genetic composition of individual cells is lost, de novo mutations in cells are concealed within the bulk signal and per cell cycle mutation rates and mechanisms remain elusive. Although single-cell genome analyses could resolve these problems, such analyses are error-prone because of whole-genome amplification (WGA) artefacts and are limited in the types of DNA mutation that can be discerned. We developed methods for paired-end sequence analysis of single-cell WGA products that enable (i) detecting multiple classes of DNA mutation, (ii) distinguishing DNA copy number changes from allelic WGA-amplification artefacts by the discovery of matching aberrantly mapping read pairs among the surfeit of paired-end WGA and mapping artefacts and (iii) delineating the break points and architecture of structural variants. By applying the methods, we capture DNA copy number changes acquired over one cell cycle in breast cancer cells and in blastomeres derived from a human zygote after in vitro fertilization. Furthermore, we were able to discover and fine-map a heritable inter-chromosomal rearrangement t(1;16)(p36;p12) by sequencing a single blastomere. The methods will expedite applications in basic genome research and provide a stepping stone to novel approaches for clinical genetic diagnosis.",
			"category": 2,
			"name": "Voet Thierry,2013"
		},
		{
			"PMID": 23613682,
			"title": "Genetic risk prediction for normal-karyotype acute myeloid leukemia using whole-exome sequencing.",
			"journal": "Genomics & informatics",
			"authorList": [
				"Heo Seong Gu",
				"Hong Eun Pyo",
				"Park Ji Wan"
			],
			"DOI": "10.5808/GI.2013.11.1.46",
			"date": "2013-05-08",
			"PMC": "",
			"citation": "",
			"abstract": "Normal-karyotype acute myeloid leukemia (NK-AML) is a highly malignant and cytogenetically heterogeneous hematologic cancer. We searched for somatic mutations from 10 pairs of tumor and normal cells by using a highly efficient and reliable analysis workflow for whole-exome sequencing data and performed association tests between the NK-AML and somatic mutations. We identified 21 nonsynonymous single nucleotide variants (SNVs) located in a coding region of 18 genes. Among them, the SNVs of three leukemia-related genes (MUC4, CNTNAP2, and GNAS) reported in previous studies were replicated in this study. We conducted stepwise genetic risk score (GRS) models composed of the NK-AML susceptible variants and evaluated the prediction accuracy of each GRS model by computing the area under the receiver operating characteristic curve (AUC). The GRS model that was composed of five SNVs (rs75156964, rs56213454, rs6604516, rs10888338, and rs2443878) showed 100% prediction accuracy, and the combined effect of the three reported genes was validated in the current study (AUC, 0.98; 95% confidence interval, 0.92 to 1.00). Further study with large sample sizes is warranted to validate the combined effect of these somatic point mutations, and the discovery of novel markers may provide an opportunity to develop novel diagnostic and therapeutic targets for NK-AML.",
			"category": 2,
			"name": "Heo Seong Gu,2013"
		},
		{
			"PMID": 23612016,
			"title": "Sporadic and reversible chromothripsis in chronic lymphocytic leukemia revealed by longitudinal genomic analysis.",
			"journal": "Leukemia",
			"authorList": [
				"Bassaganyas L",
				"Be\u00e0 S",
				"Escaram\u00eds G",
				"Tornador C",
				"Salaverria I",
				"Zapata L",
				"Drechsel O",
				"Ferreira P G",
				"Rodriguez-Santiago B",
				"Tubio J M C",
				"Navarro A",
				"Mart\u00edn-Garc\u00eda D",
				"L\u00f3pez C",
				"Mart\u00ednez-Trillos A",
				"L\u00f3pez-Guillermo A",
				"Gut M",
				"Ossowski S",
				"L\u00f3pez-Ot\u00edn C",
				"Campo E",
				"Estivill X"
			],
			"DOI": "10.1038/leu.2013.127",
			"date": "2014-03-10",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Bassaganyas L,2014"
		},
		{
			"PMID": 23605045,
			"title": "Meander: visually exploring the structural variome using space-filling curves.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Pavlopoulos Georgios A",
				"Kumar Parveen",
				"Sifrim Alejandro",
				"Sakai Ryo",
				"Lin Meng Lay",
				"Voet Thierry",
				"Moreau Yves",
				"Aerts Jan"
			],
			"DOI": "10.1093/nar/gkt254",
			"date": "2013-08-05",
			"PMC": "",
			"citation": "",
			"abstract": "The introduction of next generation sequencing methods in genome studies has made it possible to shift research from a gene-centric approach to a genome wide view. Although methods and tools to detect single nucleotide polymorphisms are becoming more mature, methods to identify and visualize structural variation (SV) are still in their infancy. Most genome browsers can only compare a given sequence to a reference genome; therefore, direct comparison of multiple individuals still remains a challenge. Therefore, the implementation of efficient approaches to explore and visualize SVs and directly compare two or more individuals is desirable. In this article, we present a visualization approach that uses space-filling Hilbert curves to explore SVs based on both read-depth and pair-end information. An interactive open-source Java application, called Meander, implements the proposed methodology, and its functionality is demonstrated using two cases. With Meander, users can explore variations at different levels of resolution and simultaneously compare up to four different individuals against a common reference. The application was developed using Java version 1.6 and Processing.org and can be run on any platform. It can be found at http://homes.esat.kuleuven.be/~bioiuser/meander.",
			"category": 2,
			"name": "Pavlopoulos Georgios A,2013"
		},
		{
			"PMID": 23604282,
			"title": "Heterogeneity of tumor-induced gene expression changes in the human metabolic network.",
			"journal": "Nature biotechnology",
			"authorList": [
				"Hu Jie",
				"Locasale Jason W",
				"Bielas Jason H",
				"O'Sullivan Jacintha",
				"Sheahan Kieran",
				"Cantley Lewis C",
				"Vander Heiden Matthew G",
				"Vitkup Dennis"
			],
			"DOI": "10.1038/nbt.2530",
			"date": "2014-02-14",
			"PMC": "",
			"citation": "",
			"abstract": "Reprogramming of cellular metabolism is an emerging hallmark of neoplastic transformation. However, it is not known how the expression of metabolic genes in tumors differs from that in normal tissues, or whether different tumor types exhibit similar metabolic changes. Here we compare expression patterns of metabolic genes across 22 diverse types of human tumors. Overall, the metabolic gene expression program in tumors is similar to that in the corresponding normal tissues. Although expression changes of some metabolic pathways (e.g., upregulation of nucleotide biosynthesis and glycolysis) are frequently observed across tumors, expression changes of other pathways (e.g., oxidative phosphorylation) are very heterogeneous. Our analysis also suggests that the expression changes of some metabolic genes (e.g., isocitrate dehydrogenase and fumarate hydratase) may enhance or mimic the effects of recurrent mutations in tumors. On the level of individual biochemical reactions, many hundreds of metabolic isoenzymes show significant and tumor-specific expression changes. These isoenzymes are potential targets for anticancer therapy.",
			"category": 2,
			"name": "Hu Jie,2014"
		},
		{
			"PMID": 23599619,
			"title": "Clinical relevance of cancer genome sequencing.",
			"journal": "World journal of gastroenterology",
			"authorList": [
				"Ku Chee Seng",
				"Cooper David N",
				"Roukos Dimitrios H"
			],
			"DOI": "10.3748/wjg.v19.i13.2011",
			"date": "2013-12-09",
			"PMC": "",
			"citation": "",
			"abstract": "The arrival of both high-throughput and bench-top next-generation sequencing technologies and sequence enrichment methods has revolutionized our approach to dissecting the genetic basis of cancer. These technologies have been almost invariably employed in whole-genome sequencing (WGS) and whole-exome sequencing (WES) studies. Both WGS and WES approaches have been widely applied to interrogate the somatic mutational landscape of sporadic cancers and identify novel germline mutations underlying familial cancer syndromes. The clinical implications of cancer genome sequencing have become increasingly clear, for example in diagnostics. In this editorial, we present these advances in the context of research discovery and discuss both the clinical relevance of cancer genome sequencing and the challenges associated with the adoption of these genomic technologies in a clinical setting.",
			"category": 2,
			"name": "Ku Chee Seng,2013"
		},
		{
			"PMID": 23594910,
			"title": "Cancer genome-sequencing study design.",
			"journal": "Nature reviews. Genetics",
			"authorList": [
				"Mwenifumbo Jill C",
				"Marra Marco A"
			],
			"DOI": "10.1038/nrg3445",
			"date": "2013-06-06",
			"PMC": "",
			"citation": "",
			"abstract": "Discoveries from cancer genome sequencing have the potential to translate into advances in cancer prevention, diagnostics, prognostics, treatment and basic biology. Given the diversity of downstream applications, cancer genome-sequencing studies need to be designed to best fulfil specific aims. Knowledge of second-generation cancer genome-sequencing study design also facilitates assessment of the validity and importance of the rapidly growing number of published studies. In this Review, we focus on the practical application of second-generation sequencing technology (also known as next-generation sequencing) to cancer genomics and discuss how aspects of study design and methodological considerations - such as the size and composition of the discovery cohort - can be tailored to serve specific research aims.",
			"category": 2,
			"name": "Mwenifumbo Jill C,2013"
		},
		{
			"PMID": 23594372,
			"title": "IRS2 is a candidate driver oncogene on 13q34 in colorectal cancer.",
			"journal": "International journal of experimental pathology",
			"authorList": [
				"Day Elizabeth",
				"Poulogiannis George",
				"McCaughan Frank",
				"Mulholland Shani",
				"Arends Mark J",
				"Ibrahim Ashraf E K",
				"Dear Paul H"
			],
			"DOI": "10.1111/iep.12021",
			"date": "2013-07-16",
			"PMC": "",
			"citation": "",
			"abstract": "Copy number alterations are frequently found in colorectal cancer (CRC), and recurrent gains or losses are likely to correspond to regions harbouring genes that promote or impede carcinogenesis respectively. Gain of chromosome 13q is common in CRC but, because the region of gain is frequently large, identification of the driver gene(s) has hitherto proved difficult. We used array comparative genomic hybridization to analyse 124 primary CRCs, demonstrating that 13q34 is a region of gain in 35% of CRCs, with focal gains in 4% and amplification in a further 1.6% of cases. To reduce the number of potential driver genes to consider, it was necessary to refine the boundaries of the narrowest copy number changes seen in this series and hence define the minimal copy region (MCR). This was performed using molecular copy-number counting, identifying IRS2 as the only complete gene, and therefore the likely driver oncogene, within the refined MCR. Analysis of available colorectal neoplasia data sets confirmed IRS2 gene gain as a common event. Furthermore, IRS2 protein and mRNA expression in colorectal neoplasia was assessed and was positively correlated with progression from normal through adenoma to carcinoma. In functional in vitro experiments, we demonstrate that deregulated expression of IRS2 activates the oncogenic PI3 kinase pathway and increases cell adhesion, both characteristics of invasive CRC cells. Together, these data identify IRS2 as a likely driver oncogene in the prevalent 13q34 region of gain/amplification and suggest that IRS2 over-expression may provide an additional mechanism of PI3 kinase pathway activation in CRC.",
			"category": 2,
			"name": "Day Elizabeth,2013"
		},
		{
			"PMID": 23589550,
			"title": "Advancing precision medicine for prostate cancer through genomics.",
			"journal": "Journal of clinical oncology : official journal of the American Society of Clinical Oncology",
			"authorList": [
				"Roychowdhury Sameek",
				"Chinnaiyan Arul M"
			],
			"DOI": "10.1200/JCO.2012.45.3662",
			"date": "2013-07-22",
			"PMC": "",
			"citation": "",
			"abstract": "Prostate cancer is the most common type of cancer in men and the second leading cause of cancer death in men in the United States. The recent surge of high-throughput sequencing of cancer genomes has supported an expanding molecular classification of prostate cancer. Translation of these basic science studies into clinically valuable biomarkers for diagnosis and prognosis and biomarkers that are predictive for therapy is critical to the development of precision medicine in prostate cancer. We review potential applications aimed at improving screening specificity in prostate cancer and differentiating aggressive versus indolent prostate cancers. Furthermore, we review predictive biomarker candidates involving ETS gene rearrangements, PTEN inactivation, and androgen receptor signaling. These and other putative biomarkers may signify aberrant oncogene pathway activation and provide a rationale for matching patients with molecularly targeted therapies in clinical trials. Lastly, we advocate innovations for clinical trial design to incorporate tumor biopsy and molecular characterization to develop biomarkers and understand mechanisms of resistance.",
			"category": 2,
			"name": "Roychowdhury Sameek,2013"
		},
		{
			"PMID": 23589546,
			"title": "Existing and emerging technologies for tumor genomic profiling.",
			"journal": "Journal of clinical oncology : official journal of the American Society of Clinical Oncology",
			"authorList": [
				"MacConaill Laura E"
			],
			"DOI": "10.1200/JCO.2012.46.5948",
			"date": "2013-07-22",
			"PMC": "",
			"citation": "",
			"abstract": "Ongoing global genome characterization efforts are revolutionizing our knowledge of cancer genomics and tumor biology. In parallel, information gleaned from these studies on driver cancer gene alterations--mutations, copy number alterations, translocations, and/or chromosomal rearrangements--an be leveraged, in principle, to develop a cohesive framework for individualized cancer treatment. These possibilities have been enabled, to a large degree, by revolutionary advances in genomic technologies that facilitate systematic profiling for hallmark cancer genetic alterations at increasingly fine resolutions. Ongoing innovations in existing genomics technologies, as well as the many emerging technologies, will likely continue to advance translational cancer genomics and precision cancer medicine.",
			"category": 2,
			"name": "MacConaill Laura E,2013"
		},
		{
			"PMID": 23588493,
			"title": "Identification of tumorigenic and therapeutically actionable mutations in transplantable mouse tumor cells by exome sequencing.",
			"journal": "Oncogenesis",
			"authorList": [
				"Bhadury J",
				"L\u00f3pez M D",
				"Muralidharan S V",
				"Nilsson L M",
				"Nilsson J A"
			],
			"DOI": "10.1038/oncsis.2013.8",
			"date": "2013-04-17",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer development occurs in response to the successive accumulation of mutations that eventually targets key regulators of cell proliferation. As most mutations likely occur randomly, cancer driver mutations can only be found if they are recurrent. Here we use exome sequencing of the mouse cell lines Panc02, L1210 and Colon 26 to identify genetic alterations (single-nucleotide polymorphisms and small insertion and deletions) that occurred in three different strains of mice and that resulted in tumorigenesis. We identify known mutations in genes like Kras, Cdkn2a/b, Smad4 and Trp53 and a large list of genes whose causal link to cancer is unknown. Interestingly, by screening a compound library we find that the identified oncogenic Kras mutation in Colon 26 cells correlates with its sensitivity to MEK inhibitors in vitro and in vivo. Our analysis of these mouse tumor exomes show that their manageable number of mutations could facilitate the identification of novel mutations or pathways driving tumor development. Furthermore, their use as tools is now enhanced as they can be used to create syngenic transplant models for utilization in drug discovery and validation. Finally, by showing that Kras mutant Colon 26 cells are sensitive to MEK inhibitors, we provide one proof-of-principle experiment that a platform containing targeted resequencing and drug screens could be a valuable addition in the clinic to devise anti-cancer drug schemes.",
			"category": 2,
			"name": "Bhadury J,2013"
		},
		{
			"PMID": 23587365,
			"title": "Single-cell sequencing analysis characterizes common and cell-lineage-specific mutations in a muscle-invasive bladder cancer.",
			"journal": "GigaScience",
			"authorList": [
				"Li Yingrui",
				"Xu Xun",
				"Song Luting",
				"Hou Yong",
				"Li Zesong",
				"Tsang Shirley",
				"Li Fuqiang",
				"Im Kate McGee",
				"Wu Kui",
				"Wu Hanjie",
				"Ye Xiaofei",
				"Li Guibo",
				"Wang Linlin",
				"Zhang Bo",
				"Liang Jie",
				"Xie Wei",
				"Wu Renhua",
				"Jiang Hui",
				"Liu Xiao",
				"Yu Chang",
				"Zheng Hancheng",
				"Jian Min",
				"Nie Liping",
				"Wan Lei",
				"Shi Min",
				"Sun Xiaojuan",
				"Tang Aifa",
				"Guo Guangwu",
				"Gui Yaoting",
				"Cai Zhiming",
				"Li Jingxiang",
				"Wang Wen",
				"Lu Zuhong",
				"Zhang Xiuqing",
				"Bolund Lars",
				"Kristiansen Karsten",
				"Wang Jian",
				"Yang Huanming",
				"Dean Michael",
				"Wang Jun"
			],
			"DOI": "10.1186/2047-217X-1-12",
			"date": "2013-04-17",
			"PMC": "",
			"citation": "",
			"abstract": "Cancers arise through an evolutionary process in which cell populations are subjected to selection; however, to date, the process of bladder cancer, which is one of the most common cancers in the world, remains unknown at a single-cell level.",
			"category": 2,
			"name": "Li Yingrui,2013"
		},
		{
			"PMID": 23587148,
			"title": "Preoperative chemosensitivity testing as Predictor of Treatment benefit in Adjuvant stage III colon cancer (PePiTA): protocol of a prospective BGDO (Belgian Group for Digestive Oncology) multicentric study.",
			"journal": "BMC cancer",
			"authorList": [
				"Hendlisz Alain",
				"Golfinopoulos Vassilis",
				"Deleporte Amelie",
				"Paesmans Marianne",
				"Mansy Hazem El",
				"Garcia Camilo",
				"Peeters Marc",
				"Annemans Lieven",
				"Vandeputte Caroline",
				"Maetens Marion",
				"Borbath Ivan",
				"Dresse Damien",
				"Houbiers Ghislain",
				"Fried Michael",
				"Awada Ahmad",
				"Piccart Martine",
				"Laethem Jean-Luc Van",
				"Flamen Patrick"
			],
			"DOI": "10.1186/1471-2407-13-190",
			"date": "2015-01-27",
			"PMC": "",
			"citation": "",
			"abstract": "Surgery is a curative treatment for patients with locally advanced colon cancer, but recurrences are frequent for those with stage III disease. FOLFOX adjuvant chemotherapy has been shown to improve recurrence-free survival and overall survival by more than 20% and is nowadays considered a standard of care. However, the vast majority of patients will not benefit from receiving cytotoxic drugs because they have either already been cured by surgery or because their tumor cells are resistant to the chemotherapy, for which predictive factors are still not available.",
			"category": 2,
			"name": "Hendlisz Alain,2015"
		},
		{
			"PMID": 23583620,
			"title": "Dipeptide analysis of p53 mutations and evolution of p53 family proteins.",
			"journal": "Biochimica et biophysica acta",
			"authorList": [
				"Huang Qiang",
				"Yu Long",
				"Levine Arnold J",
				"Nussinov Ruth",
				"Ma Buyong"
			],
			"DOI": "10.1016/j.bbapap.2013.04.002",
			"date": "2014-03-18",
			"PMC": "",
			"citation": "",
			"abstract": "p53 gain-of-function mutations are similar to driver mutations in cancer genes, with both promoting tumorigenesis. Most previous studies focused on residues lost by mutations, providing information related to a dominantly-negative effect. However, to understand gain-of-function mutations, it is also important to investigate what are the distributions of residues gained by mutations. We compile available p53/p63/p73 protein sequences and construct a non-redundant dataset. We analyze the amino acid and dipeptide composition of p53/p63/p73 proteins across evolution and compare them with the gain/loss of amino acids and dipeptides in human p53 following cancer-related somatic mutations. We find that the ratios of amino acids gained via somatic mutations during evolution to those lost through p53 cancer mutations correlate with the ratios found in single nucleotide polymorphisms in the human proteome. The dipeptide mutational gain/loss ratios are inversely correlated with those observed over p53 evolution but tend to follow the increasing p63/p73-like dipeptide propensities. We successfully simulated the p53 cancer mutation spectrum using the dipeptide composition across the p53 family accounting for the likelihood of mutations in p53 codons. The results revealed that the p53 mutation spectrum is dominated not only by p53 evolution but also by reversal of evolution to a certain degree. This article is part of a Special Issue entitled: Computational Proteomics, Systems Biology & Clinical Implications. Guest Editor: Yudong Cai.",
			"category": 2,
			"name": "Huang Qiang,2014"
		},
		{
			"PMID": 23578170,
			"title": "Anti-Gal: an abundant human natural antibody of multiple pathogeneses and clinical benefits.",
			"journal": "Immunology",
			"authorList": [
				"Galili Uri"
			],
			"DOI": "10.1111/imm.12110",
			"date": "2013-11-13",
			"PMC": "",
			"citation": "",
			"abstract": "Anti-Gal is the most abundant natural antibody in humans, constituting ~\u00a01% of immunoglobulins. Anti-Gal is naturally produced also in apes and Old World monkeys. The ligand of anti-Gal is a carbohydrate antigen called the '\u03b1-gal epitope' with the structure Gal\u03b11-3Gal\u03b21-4GlcNAc-R. The \u03b1-gal epitope is present as a major carbohydrate antigen in non-primate mammals, prosimians and New World monkeys. Anti-Gal can contributes to several immunological pathogeneses. Anti-Gal IgE produced in some individuals causes allergies to meat and to the therapeutic monoclonal antibody cetuximab, all presenting \u03b1-gal epitopes. Aberrant expression of the \u03b1-gal epitope or of antigens mimicking it in humans may result in autoimmune processes, as in Graves' disease. \u03b1-Gal epitopes produced by Trypanosoma cruzi interact with anti-Gal and induce 'autoimmune like' inflammatory reactions in Chagas' disease. Anti-Gal IgM and IgG further mediate rejection of xenografts expressing \u03b1-gal epitopes. Because of its abundance, anti-Gal may be exploited for various clinical uses. It increases immunogenicity of microbial vaccines (e.g. influenza vaccine) presenting \u03b1-gal epitopes by targeting them for effective uptake by antigen-presenting cells. Tumour lesions are converted into vaccines against autologous tumour-associated antigens by intra-tumoral injection of \u03b1-gal glycolipids, which insert into tumour cell membranes. Anti-Gal binding to \u03b1-gal epitopes on tumour cells targets them for uptake by antigen-presenting cells. Accelerated wound healing is achieved by application of \u03b1-gal nanoparticles, which bind anti-Gal, activate complement, and recruit and activate macrophages that induce tissue regeneration. This therapy may be of further significance in regeneration of internally injured tissues such as ischaemic myocardium and injured nerves.",
			"category": 2,
			"name": "Galili Uri,2013"
		},
		{
			"PMID": 23571731,
			"title": "Genetic analysis in neurology: the next 10 years.",
			"journal": "JAMA neurology",
			"authorList": [
				"Pittman Alan",
				"Hardy John"
			],
			"DOI": "10.1001/jamaneurol.2013.2068",
			"date": "2013-08-29",
			"PMC": "",
			"citation": "",
			"abstract": "In recent years, neurogenetics research had made some remarkable advances owing to the advent of genotyping arrays and next-generation sequencing. These improvements to the technology have allowed us to determine the whole-genome structure and its variation and to examine its effect on phenotype in an unprecedented manner. The identification of rare disease-causing mutations has led to the identification of new biochemical pathways and has facilitated a greater understanding of the etiology of many neurological diseases. Furthermore, genome-wide association studies have provided information on how common genetic variability impacts on the risk for the development of various complex neurological diseases. Herein, we review how these technological advances have changed the approaches being used to study the genetic basis of neurological disease and how the research findings will be translated into clinical utility.",
			"category": 2,
			"name": "Pittman Alan,2013"
		},
		{
			"PMID": 23568837,
			"title": "Genome evolution during progression to breast cancer.",
			"journal": "Genome research",
			"authorList": [
				"Newburger Daniel E",
				"Kashef-Haghighi Dorna",
				"Weng Ziming",
				"Salari Raheleh",
				"Sweeney Robert T",
				"Brunner Alayne L",
				"Zhu Shirley X",
				"Guo Xiangqian",
				"Varma Sushama",
				"Troxell Megan L",
				"West Robert B",
				"Batzoglou Serafim",
				"Sidow Arend"
			],
			"DOI": "10.1101/gr.151670.112",
			"date": "2013-10-22",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer evolution involves cycles of genomic damage, epigenetic deregulation, and increased cellular proliferation that eventually culminate in the carcinoma phenotype. Early neoplasias, which are often found concurrently with carcinomas and are histologically distinguishable from normal breast tissue, are less advanced in phenotype than carcinomas and are thought to represent precursor stages. To elucidate their role in cancer evolution we performed comparative whole-genome sequencing of early neoplasias, matched normal tissue, and carcinomas from six patients, for a total of 31 samples. By using somatic mutations as lineage markers we built trees that relate the tissue samples within each patient. On the basis of these lineage trees we inferred the order, timing, and rates of genomic events. In four out of six cases, an early neoplasia and the carcinoma share a mutated common ancestor with recurring aneuploidies, and in all six cases evolution accelerated in the carcinoma lineage. Transition spectra of somatic mutations are stable and consistent across cases, suggesting that accumulation of somatic mutations is a result of increased ancestral cell division rather than specific mutational mechanisms. In contrast to highly advanced tumors that are the focus of much of the current cancer genome sequencing, neither the early neoplasia genomes nor the carcinomas are enriched with potentially functional somatic point mutations. Aneuploidies that occur in common ancestors of neoplastic and tumor cells are the earliest events that affect a large number of genes and may predispose breast tissue to eventual development of invasive carcinoma.",
			"category": 2,
			"name": "Newburger Daniel E,2013"
		},
		{
			"PMID": 23568704,
			"title": "The war on cancer: are we winning?",
			"journal": "Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine",
			"authorList": [
				"Duffy M J"
			],
			"DOI": "10.1007/s13277-013-0759-2",
			"date": "2013-07-18",
			"PMC": "",
			"citation": "",
			"abstract": "Of all the diseases affecting humankind, cancer is one of the most difficult to treat and cure. One of the main reasons for this difficulty relates to the fact that cancer is not a single disease but consists of hundreds of different types. Furthermore, cancers exhibit considerable genetic complexity with more than 400 different genes implicated in their development. In addition, cancers display major inter- and intratumor heterogeneity. Despite these complexities, several successes have been achieved in recent years. Most of these successes relate to the specific targeting of driver genes involved in cancer development. These successes include imatinib for the treatment of chronic myeloid leukemia, anti-HER2 therapies (trastuzumab, pertuzumab, and lapatinib) to treat breast cancer, anti-EGFR tyrosine kinase inhibitors (gefitinib and erlotinib) to treat non-small cell lung cancer, and anti-BRAF agents (vemurafenib and dabrafenib) to treat melanoma. Although the war on cancer has not yet been won, neither has it been lost. With continued basic and clinical research, cancer is being transformed into a chronic disease in which patients have increased survival rates and better quality of life.",
			"category": 2,
			"name": "Duffy M J,2013"
		},
		{
			"PMID": 23565319,
			"title": "KRAS gene mutations are more common in colorectal villous adenomas and in situ carcinomas than in carcinomas.",
			"journal": "International journal of molecular epidemiology and genetics",
			"authorList": [
				"Zauber Peter",
				"Marotta Stephen",
				"Sabbath-Solitare Marlene"
			],
			"DOI": "",
			"date": "2013-07-04",
			"PMC": "",
			"citation": "",
			"abstract": "We have evaluated the frequency of KRAS gene mutations during the critical transition from villous adenoma to colorectal carcinoma to assess whether the adenomas contain a KRAS mutation more frequently than carcinomas. We analyzed sporadic villous and tubulovillous adenomas, in situ carcinomas, and primary colorectal carcinomas from multiple patients. The cancers were further evaluated for mucinous status and microsatellite instability. Standard PCR molecular techniques were used for KRAS and microsatellite analyses. A KRAS mutation was found in 61.9% of 134 adenomas, 67.8% of 84 in situ carcinomas, and just 31.6% of 171 carcinomas. Our study clearly demonstrates that tubulovillous and villous adenomas, as well as both the benign and malignant parts of in situ carcinomas, are statistically more likely to contain a somatic KRAS gene mutation than colorectal carcinomas. This difference is confined to the non-mucinous and the microsatellite stable tumors. Our data support the possibility that non-mucinous and microsatellite stable carcinomas with wild-type KRAS gene may have had a mutation in the KRAS gene during their earlier stages, with the mutation lost during further growth.",
			"category": 2,
			"name": "Zauber Peter,2013"
		},
		{
			"PMID": 23549172,
			"title": "The Warburg effect version 2.0: metabolic reprogramming of cancer stem cells.",
			"journal": "Cell cycle (Georgetown, Tex.)",
			"authorList": [
				"Menendez Javier A",
				"Joven Jorge",
				"Cuf\u00ed S\u00edlvia",
				"Corominas-Faja Bruna",
				"Oliveras-Ferraros Cristina",
				"Cuy\u00e0s Elisabet",
				"Martin-Castillo Bego\u00f1a",
				"L\u00f3pez-Bonet Eugeni",
				"Alarc\u00f3n Tom\u00e1s",
				"Vazquez-Martin Alejandro"
			],
			"DOI": "10.4161/cc.24479",
			"date": "2013-11-11",
			"PMC": "",
			"citation": "",
			"abstract": "When fighting cancer, knowledge on metabolism has always been important. Today, it matters more than ever. The restricted cataloging of cancer genomes is quite unlikely to achieve the task of curing cancer, unless it is integrated into metabolic networks that respond to and influence the constantly evolving cancer stem cell (CSC) cellular states. Once the genomic era of carcinogenesis had pushed the 1920s Otto Warburg's metabolic cancer hypothesis into obscurity for decades, the most recent studies begin to support a new developing paradigm, in which the molecular logic behind the conversion of non-CSCs into CSCs can be better understood in terms of the \"metabolic facilitators\" and \"metabolic impediments\" that operate as proximate openings and roadblocks, respectively, for the transcriptional events and signal transduction programs that ultimately orchestrate the intrinsic and/or microenvironmental paths to CSC cellular states. Here we propose that a profound understanding of how human carcinomas install a proper \"Warburg effect version 2.0\" allowing them to \"run\" the CSCs' \"software\" programs should guide a new era of metabolo-genomic-personalized cancer medicine. By viewing metabolic reprogramming of CSCs as an essential characteristic that allows dynamic, multidimensional and evolving cancer populations to compete successfully for their expansion on the organism, we now argue that CSCs bioenergetics might be another cancer hallmark. A definitive understanding of metabolic reprogramming in CSCs may complement or to some extent replace, the 30-y-old paradigm of targeting oncogenes to treat human carcinomas, because it can be possible to metabolically create non-permissive or \"hostile\" metabotypes to prevent the occurrence of CSC cellular states with tumor- and metastasis-initiating capacity.",
			"category": 2,
			"name": "Menendez Javier A,2013"
		},
		{
			"PMID": 23533264,
			"title": "Response to Cabozantinib in patients with RET fusion-positive lung adenocarcinomas.",
			"journal": "Cancer discovery",
			"authorList": [
				"Drilon Alexander",
				"Wang Lu",
				"Hasanovic Adnan",
				"Suehara Yoshiyuki",
				"Lipson Doron",
				"Stephens Phil",
				"Ross Jeffrey",
				"Miller Vincent",
				"Ginsberg Michelle",
				"Zakowski Maureen F",
				"Kris Mark G",
				"Ladanyi Marc",
				"Rizvi Naiyer"
			],
			"DOI": "10.1158/2159-8290.CD-13-0035",
			"date": "2014-05-01",
			"PMC": "",
			"citation": "",
			"abstract": "The discovery of RET fusions in lung cancers has uncovered a new therapeutic target for patients whose tumors harbor these changes. In an unselected population of non-small cell lung carcinomas (NSCLCs), RET fusions are present in 1% to 2% of cases. This incidence increases substantially, however, in never-smokers with lung adenocarcinomas that lack other known driver oncogenes. Although preclinical data provide experimental support for the use of RET inhibitors in the treatment of RET fusion-positive tumors, clinical data on response are lacking. We report preliminary data for the first three patients treated with the RET inhibitor cabozantinib on a prospective phase II trial for patients with RET fusion-positive NSCLCs (NCT01639508). Confirmed partial responses were observed in 2 patients, including one harboring a novel TRIM33-RET fusion. A third patient with a KIF5B-RET fusion has had prolonged stable disease approaching 8 months (31 weeks). All three patients remain progression-free on treatment.",
			"category": 2,
			"name": "Drilon Alexander,2014"
		},
		{
			"PMID": 23531354,
			"title": "Patchwork: allele-specific copy number analysis of whole-genome sequenced tumor tissue.",
			"journal": "Genome biology",
			"authorList": [
				"Mayrhofer Markus",
				"DiLorenzo Sebastian",
				"Isaksson Anders"
			],
			"DOI": "10.1186/gb-2013-14-3-r24",
			"date": "2015-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "Whole-genome sequencing of tumor tissue has the potential to provide comprehensive characterization of genomic alterations in tumor samples. We present Patchwork, a new bioinformatic tool for allele-specific copy number analysis using whole-genome sequencing data. Patchwork can be used to determine the copy number of homologous sequences throughout the genome, even in aneuploid samples with moderate sequence coverage and tumor cell content. No prior knowledge of average ploidy or tumor cell content is required. Patchwork is freely available as an R package, installable via R-Forge (http://patchwork.r-forge.r-project.org/).",
			"category": 2,
			"name": "Mayrhofer Markus,2015"
		},
		{
			"PMID": 23504227,
			"title": "Mechanisms and insights into drug resistance in cancer.",
			"journal": "Frontiers in pharmacology",
			"authorList": [
				"Zahreddine Hiba",
				"Borden Katherine L B"
			],
			"DOI": "10.3389/fphar.2013.00028",
			"date": "2013-03-19",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer drug resistance continues to be a major impediment in medical oncology. Clinically, resistance can arise prior to or as a result of cancer therapy. In this review, we discuss different mechanisms adapted by cancerous cells to resist treatment, including alteration in drug transport and metabolism, mutation and amplification of drug targets, as well as genetic rewiring which can lead to impaired apoptosis. Tumor heterogeneity may also contribute to resistance, where small subpopulations of cells may acquire or stochastically already possess some of the features enabling them to emerge under selective drug pressure. Making the problem even more challenging, some of these resistance pathways lead to multidrug resistance, generating an even more difficult clinical problem to overcome. We provide examples of these mechanisms and some insights into how understanding these processes can influence the next generation of cancer therapies.",
			"category": 2,
			"name": "Zahreddine Hiba,2013"
		},
		{
			"PMID": 23499923,
			"title": "Interpretation, stratification and evidence for sequence variants affecting mRNA splicing in complete human genome sequences.",
			"journal": "Genomics, proteomics & bioinformatics",
			"authorList": [
				"Shirley Ben C",
				"Mucaki Eliseos J",
				"Whitehead Tyson",
				"Costea Paul I",
				"Akan Pelin",
				"Rogan Peter K"
			],
			"DOI": "10.1016/j.gpb.2013.01.008",
			"date": "2013-07-25",
			"PMC": "",
			"citation": "",
			"abstract": "Information theory-based methods have been shown to be sensitive and specific for predicting and quantifying the effects of non-coding mutations in Mendelian diseases. We present the Shannon pipeline software for genome-scale mutation analysis and provide evidence that the software predicts variants affecting mRNA splicing. Individual information contents (in bits) of reference and variant splice sites are compared and significant differences are annotated and prioritized. The software has been implemented for CLC-Bio Genomics platform. Annotation indicates the context of novel mutations as well as common and rare SNPs with splicing effects. Potential natural and cryptic mRNA splicing variants are identified, and null mutations are distinguished from leaky mutations. Mutations and rare SNPs were predicted in genomes of three cancer cell lines (U2OS, U251 and A431), which were supported by expression analyses. After filtering, tractable numbers of potentially deleterious variants are predicted by the software, suitable for further laboratory investigation. In these cell lines, novel functional variants comprised 6-17 inactivating mutations, 1-5 leaky mutations and 6-13 cryptic splicing mutations. Predicted effects were validated by RNA-seq analysis of the three aforementioned cancer cell lines, and expression microarray analysis of SNPs in HapMap cell lines.",
			"category": 2,
			"name": "Shirley Ben C,2013"
		},
		{
			"PMID": 23474816,
			"title": "Increased genome instability in human DNA segments with self-chains: homology-induced structural variations via replicative mechanisms.",
			"journal": "Human molecular genetics",
			"authorList": [
				"Zhou Weichen",
				"Zhang Feng",
				"Chen Xiaoli",
				"Shen Yiping",
				"Lupski James R",
				"Jin Li"
			],
			"DOI": "10.1093/hmg/ddt113",
			"date": "2014-01-07",
			"PMC": "",
			"citation": "",
			"abstract": "Environmental factors including ionizing radiation and chemical agents have been known to be able to induce DNA rearrangements and cause genomic structural variations (SVs); however, the roles of intrinsic characteristics of the human genome, such as regional genome architecture, in SV formation and the potential mechanisms underlying genomic instability remain to be further elucidated. Recently, locus-specific observations showed that 'self-chain' (SC), a group of short low-copy repeats (LCRs) in the human genome, can induce autism-associated SV mutations of the MECP2 and NRXN1 genes. In this study, we conducted a genome-wide analysis to investigate SCs and their potential roles in genomic SV formation. Utilizing a vast amount of human SV data, we observed a significant biased distribution of human germline SV breakpoints to SC regions. Notably, the breakpoint distribution pattern is different between SV types across deletion, duplication, inversion and insertion. Our observations were coincident with a mechanism of SC-induced DNA replicative errors, whereas SC may sporadically be used as substrates of nonallelic homologous recombination (NAHR). This contention was further supported by our consistent findings in somatic SV mutations of cancer genomes, suggesting a general mechanism of SC-induced genome instability in human germ and somatic cells.",
			"category": 2,
			"name": "Zhou Weichen,2014"
		},
		{
			"PMID": 23431153,
			"title": "Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Britschgi Adrian",
				"Bill Anke",
				"Brinkhaus Heike",
				"Rothwell Christopher",
				"Clay Ieuan",
				"Duss Stephan",
				"Rebhan Michael",
				"Raman Pichai",
				"Guy Chantale T",
				"Wetzel Kristie",
				"George Elizabeth",
				"Popa M Oana",
				"Lilley Sarah",
				"Choudhury Hedaythul",
				"Gosling Martin",
				"Wang Louis",
				"Fitzgerald Stephanie",
				"Borawski Jason",
				"Baffoe Jonathan",
				"Labow Mark",
				"Gaither L Alex",
				"Bentires-Alj Mohamed"
			],
			"DOI": "10.1073/pnas.1217072110",
			"date": "2013-05-23",
			"PMC": "",
			"citation": "",
			"abstract": "The calcium-activated chloride channel anoctamin 1 (ANO1) is located within the 11q13 amplicon, one of the most frequently amplified chromosomal regions in human cancer, but its functional role in tumorigenesis has remained unclear. The 11q13 region is amplified in \u223c15% of breast cancers. Whether ANO1 is amplified in breast tumors, the extent to which gene amplification contributes to ANO1 overexpression, and whether overexpression of ANO1 is important for tumor maintenance have remained unknown. We have found that ANO1 is amplified and highly expressed in breast cancer cell lines and primary tumors. Amplification of ANO1 correlated with disease grade and poor prognosis. Knockdown of ANO1 in ANO1-amplified breast cancer cell lines and other cancers bearing 11q13 amplification inhibited proliferation, induced apoptosis, and reduced tumor growth in established cancer xenografts. Moreover, ANO1 chloride channel activity was important for cell viability. Mechanistically, ANO1 knockdown or pharmacological inhibition of its chloride-channel activity reduced EGF receptor (EGFR) and calmodulin-dependent protein kinase II (CAMKII) signaling, which subsequently attenuated AKT, v-src sarcoma viral oncogene homolog (SRC), and extracellular signal-regulated kinase (ERK) activation in vitro and in vivo. Our results highlight the involvement of the ANO1 chloride channel in tumor progression and provide insights into oncogenic signaling in human cancers with 11q13 amplification, thereby establishing ANO1 as a promising target for therapy in these highly prevalent tumor types.",
			"category": 2,
			"name": "Britschgi Adrian,2013"
		},
		{
			"PMID": 23422670,
			"title": "DNA replication timing and higher-order nuclear organization determine single-nucleotide substitution patterns in cancer genomes.",
			"journal": "Nature communications",
			"authorList": [
				"Liu Lin",
				"De Subhajyoti",
				"Michor Franziska"
			],
			"DOI": "10.1038/ncomms2502",
			"date": "2013-06-20",
			"PMC": "",
			"citation": "",
			"abstract": "Single-nucleotide substitutions are a defining characteristic of cancer genomes. Many single-nucleotide substitutions in cancer genomes arise because of errors in DNA replication, which is spatio-temporally stratified. Here we propose that DNA replication patterns help shape the mutational landscapes of normal and cancer genomes. Using data on five fully sequenced cancer types and two personal genomes, we determined that the frequency of intergenic single-nucleotide substitution is significantly higher in late DNA replication timing regions, even after controlling for a number of genomic features. Furthermore, some substitution signatures are more frequent in certain DNA replication timing zones. Finally, integrating data on higher-order nuclear organization, we found that genomic regions in close spatial proximity to late-replicating domains display similar mutation spectra as the late-replicating regions themselves. These data suggest that DNA replication timing together with higher-order genomic organization contribute to the patterns of single-nucleotide substitution in normal and cancer genomes.",
			"category": 2,
			"name": "Liu Lin,2013"
		},
		{
			"PMID": 23420281,
			"title": "Modeling tumor evolutionary dynamics.",
			"journal": "Frontiers in physiology",
			"authorList": [
				"Stransky Beatriz",
				"de Souza Sandro J"
			],
			"DOI": "10.3389/fphys.2012.00480",
			"date": "2013-02-20",
			"PMC": "",
			"citation": "",
			"abstract": "Tumorigenesis can be seen as an evolutionary process, in which the transformation of a normal cell into a tumor cell involves a number of limiting genetic and epigenetic events, occurring in a series of discrete stages. However, not all mutations in a cell are directly involved in cancer development and it is likely that most of them (passenger mutations) do not contribute in any way to tumorigenesis. Moreover, the process of tumor evolution is punctuated by selection of advantageous (driver) mutations and clonal expansions. Regarding these driver mutations, it is uncertain how many limiting events are required and/or sufficient to promote a tumorigenic process or what are the values associated with the adaptive advantage of different driver mutations. In spite of the availability of high-quality cancer data, several assumptions about the mechanistic process of cancer initiation and development remain largely untested, both mathematically and statistically. Here we review the development of recent mathematical/computational models and discuss their impact in the field of tumor biology.",
			"category": 2,
			"name": "Stransky Beatriz,2013"
		},
		{
			"PMID": 23416983,
			"title": "Cancer driver-passenger distinction via sporadic human and dog cancer comparison: a proof-of-principle study with colorectal cancer.",
			"journal": "Oncogene",
			"authorList": [
				"Tang J",
				"Li Y",
				"Lyon K",
				"Camps J",
				"Dalton S",
				"Ried T",
				"Zhao S"
			],
			"DOI": "10.1038/onc.2013.17",
			"date": "2014-04-14",
			"PMC": "",
			"citation": "",
			"abstract": "Herein we report a proof-of-principle study illustrating a novel dog-human comparison strategy that addresses a central aim of cancer research, namely cancer driver-passenger distinction. We previously demonstrated that sporadic canine colorectal cancers (CRCs) share similar molecular pathogenesis mechanisms as their human counterparts. In this study, we compared the genome-wide copy number abnormalities between 29 human and 10 canine sporadic CRCs. This led to the identification of 73 driver candidate genes (DCGs), altered in both species, and with 27 from the whole genome and 46 from dog-human genomic rearrangement breakpoint (GRB) regions, as well as 38 passenger candidate genes (PCGs), altered in humans only and located in GRB regions. We noted that DCGs significantly differ from PCGs in every analysis conducted to assess their cancer relevance and biological functions. Importantly, although PCGs are not enriched in any specific functions, DCGs possess significantly enhanced functionality closely associated with cell proliferation and death regulation, as well as with epithelial cell apicobasal polarity establishment/maintenance. These observations support the notion that, in sporadic CRCs of both species, cell polarity genes not only contribute in preventing cancer cell invasion and spreading, but also likely serve as tumor suppressors by modulating cell growth. This pilot study validates our novel strategy and has uncovered four new potential cell polarity and colorectal tumor suppressor genes (RASA3, NUPL1, DENND5A and AVL9). Expansion of this study would make more driver-passenger distinctions for cancers with large genomic amplifications or deletions, and address key questions regarding the relationship between cancer pathogenesis and epithelial cell polarity control in mammals.",
			"category": 2,
			"name": "Tang J,2014"
		},
		{
			"PMID": 23412501,
			"title": "ING1 and ING2: multifaceted tumor suppressor genes.",
			"journal": "Cellular and molecular life sciences : CMLS",
			"authorList": [
				"Gu\u00e9rillon Claire",
				"Larrieu Delphine",
				"Pedeux R\u00e9my"
			],
			"DOI": "10.1007/s00018-013-1270-z",
			"date": "2013-11-12",
			"PMC": "",
			"citation": "",
			"abstract": "Inhibitor of Growth 1 (ING1) was identified and characterized as a \"candidate\" tumor suppressor gene in 1996. Subsequently, four more genes, also characterized as \"candidate\" tumor suppressor genes, were identified by homology search: ING2, ING3, ING4, and ING5. The ING proteins are characterized by a high homology in their C-terminal domain, which contains a Nuclear Localization Sequence and a Plant HomeoDomain (PHD), which has a high affinity to Histone 3 tri-methylated on lysine 4 (H3K4Me3). The ING proteins have been involved in the control of cell growth, senescence, apoptosis, chromatin remodeling, and DNA repair. Within the ING family, ING1 and ING2 form a subgroup since they are evolutionarily and functionally close. In yeast, only one gene, Pho23, is related to ING1 and ING2 and possesses also a PHD. Recently, the ING1 and ING2 tumor suppressor status has been fully established since several studies have described the loss of ING1 and ING2 protein expression in human tumors and both ING1 and ING2 knockout mice were reported to have spontaneously developed tumors, B cell lymphomas, and soft tissue sarcomas, respectively. In this review, we will describe for the first time what is known about the ING1 and ING2 genes, proteins, their regulations in both human and mice, and their status in human tumors. Furthermore, we explore the current knowledge about identified functions involving ING1 and ING2 in tumor suppression pathways especially in the control of cell cycle and in genome stability.",
			"category": 2,
			"name": "Gu\u00e9rillon Claire,2013"
		},
		{
			"PMID": 23401433,
			"title": "Genotyping and genomic profiling of non-small-cell lung cancer: implications for current and future therapies.",
			"journal": "Journal of clinical oncology : official journal of the American Society of Clinical Oncology",
			"authorList": [
				"Li Tianhong",
				"Kung Hsing-Jien",
				"Mack Philip C",
				"Gandara David R"
			],
			"DOI": "10.1200/JCO.2012.45.3753",
			"date": "2013-05-15",
			"PMC": "",
			"citation": "",
			"abstract": "Substantial advances have been made in understanding critical molecular and cellular mechanisms driving tumor initiation, maintenance, and progression in non-small-cell lung cancer (NSCLC). Over the last decade, these findings have led to the discovery of a variety of novel drug targets and the development of new treatment strategies. Already, the standard of care for patients with advanced-stage NSCLC is shifting from selecting therapy empirically based on a patient's clinicopathologic features to using biomarker-driven treatment algorithms based on the molecular profile of a patient's tumor. This approach is currently best exemplified by treating patients with NSCLC with first-line tyrosine kinase inhibitors when their cancers harbor gain-of-function hotspot mutations in the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) gene rearrangements. These genotype-based targeted therapies represent the first step toward personalizing NSCLC therapy. Recent technology advances in multiplex genotyping and high-throughput genomic profiling by next-generation sequencing technologies now offer the possibility of rapidly and comprehensively interrogating the cancer genome of individual patients from small tumor biopsies. This advance provides the basis for categorizing molecular-defined subsets of patients with NSCLC in whom a growing list of novel molecularly targeted therapeutics are clinically evaluable and additional novel drug targets can be discovered. Increasingly, practicing oncologists are facing the challenge of determining how to select, interpret, and apply these new genetic and genomic assays. This review summarizes the evolution, early success, current status, challenges, and opportunities for clinical application of genotyping and genomic tests in therapeutic decision making for NSCLC.",
			"category": 2,
			"name": "Li Tianhong,2013"
		},
		{
			"PMID": 23390603,
			"title": "Saccharomyces cerevisiae genetics predicts candidate therapeutic genetic interactions at the mammalian replication fork.",
			"journal": "G3 (Bethesda, Md.)",
			"authorList": [
				"van Pel Derek M",
				"Stirling Peter C",
				"Minaker Sean W",
				"Sipahimalani Payal",
				"Hieter Philip"
			],
			"DOI": "10.1534/g3.112.004754",
			"date": "2013-08-14",
			"PMC": "",
			"citation": "",
			"abstract": "The concept of synthetic lethality has gained popularity as a rational guide for predicting chemotherapeutic targets based on negative genetic interactions between tumor-specific somatic mutations and a second-site target gene. One hallmark of most cancers that can be exploited by chemotherapies is chromosome instability (CIN). Because chromosome replication, maintenance, and segregation represent conserved and cell-essential processes, they can be modeled effectively in simpler eukaryotes such as Saccharomyces cerevisiae. Here we analyze and extend genetic networks of CIN cancer gene orthologs in yeast, focusing on essential genes. This identifies hub genes and processes that are candidate targets for synthetic lethal killing of cancer cells with defined somatic mutations. One hub process in these networks is DNA replication. A nonessential, fork-associated scaffold, CTF4, is among the most highly connected genes. As Ctf4 lacks enzymatic activity, potentially limiting its development as a therapeutic target, we exploited its function as a physical interaction hub to rationally predict synthetic lethal interactions between essential Ctf4-binding proteins and CIN cancer gene orthologs. We then validated a subset of predicted genetic interactions in a human colorectal cancer cell line, showing that siRNA-mediated knockdown of MRE11A sensitizes cells to depletion of various replication fork-associated proteins. Overall, this work describes methods to identify, predict, and validate in cancer cells candidate therapeutic targets for tumors with known somatic mutations in CIN genes using data from yeast. We affirm not only replication stress but also the targeting of DNA replication fork proteins themselves as potential targets for anticancer therapeutic development.",
			"category": 2,
			"name": "van Pel Derek M,2013"
		},
		{
			"PMID": 23382248,
			"title": "Recurrent reciprocal RNA chimera involving YPEL5 and PPP1CB in chronic lymphocytic leukemia.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Velusamy Thirunavukkarasu",
				"Palanisamy Nallasivam",
				"Kalyana-Sundaram Shanker",
				"Sahasrabuddhe Anagh Anant",
				"Maher Christopher A",
				"Robinson Daniel R",
				"Bahler David W",
				"Cornell Timothy T",
				"Wilson Thomas E",
				"Lim Megan S",
				"Chinnaiyan Arul M",
				"Elenitoba-Johnson Kojo S J"
			],
			"DOI": "10.1073/pnas.1214326110",
			"date": "2013-04-26",
			"PMC": "",
			"citation": "",
			"abstract": "Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults in the Western hemisphere. Tumor-specific chromosomal translocations, characteristic findings in several human malignancies that directly lead to malignant transformation, have not been identified in CLL. Using paired-end transcriptome sequencing, we identified recurrent and reciprocal RNA chimeras involving yippee like 5 (YPEL5) and serine/threonine-protein phosphatase PP1-beta-catalytic subunit (PPP1CB) in CLL. Two of seven index cases (28%) harbored the reciprocal RNA chimeras in our initial screening. Using quantitative real-time PCR (q real-time PCR), YPEL5/PPP1CB and PPP1CB/YPEL5 fusion transcripts were detected in 97 of 103 CLL samples (95%) but not in paired normal samples, benign lymphocytes, or various unrelated cancers. Whole-genome sequencing and Southern blotting demonstrated no evidence for a genomic fusion between YPEL5 and PPP1CB. YPEL5/PPP1CB chimera, when introduced into mammalian cells, expressed a truncated PPP1CB protein that demonstrated diminished phosphatase activity. PPP1CB silencing resulted in enhanced proliferation and colony formation of MEC1 and JVM3 cells, implying a role in the pathogenesis of mature B-cell leukemia. These studies uncover a potential role for recurrent RNA chimeras involving phosphatases in the pathogenesis of a common form of leukemia.",
			"category": 2,
			"name": "Velusamy Thirunavukkarasu,2013"
		},
		{
			"PMID": 23374339,
			"title": "Mechanisms of programmed DNA lesions and genomic instability in the immune system.",
			"journal": "Cell",
			"authorList": [
				"Alt Frederick W",
				"Zhang Yu",
				"Meng Fei-Long",
				"Guo Chunguang",
				"Schwer Bjoern"
			],
			"DOI": "10.1016/j.cell.2013.01.007",
			"date": "2013-03-28",
			"PMC": "",
			"citation": "",
			"abstract": "Chromosomal translocations involving antigen receptor loci are common in lymphoid malignancies. Translocations require DNA double-strand breaks (DSBs) at two chromosomal sites, their physical juxtaposition, and their fusion by end-joining. Ability of lymphocytes to generate diverse repertoires of antigen receptors and effector antibodies derives from programmed genomic alterations that produce DSBs. We discuss these lymphocyte-specific processes, with a focus on mechanisms that provide requisite DSB target specificity and mechanisms that suppress DSB translocation. We also discuss recent work that provides new insights into DSB repair pathways and the influences of three-dimensional genome organization on physiological processes and cancer genomes.",
			"category": 2,
			"name": "Alt Frederick W,2013"
		},
		{
			"PMID": 23368785,
			"title": "CoNVEX: copy number variation estimation in exome sequencing data using HMM.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"Amarasinghe Kaushalya C",
				"Li Jason",
				"Halgamuge Saman K"
			],
			"DOI": "10.1186/1471-2105-14-S2-S2",
			"date": "2013-09-16",
			"PMC": "",
			"citation": "",
			"abstract": "One of the main types of genetic variations in cancer is Copy Number Variations (CNV). Whole exome sequencing (WES) is a popular alternative to whole genome sequencing (WGS) to study disease specific genomic variations. However, finding CNV in Cancer samples using WES data has not been fully explored.",
			"category": 2,
			"name": "Amarasinghe Kaushalya C,2013"
		},
		{
			"PMID": 23345422,
			"title": "Half or more of the somatic mutations in cancers of self-renewing tissues originate prior to tumor initiation.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Tomasetti Cristian",
				"Vogelstein Bert",
				"Parmigiani Giovanni"
			],
			"DOI": "10.1073/pnas.1221068110",
			"date": "2013-04-09",
			"PMC": "",
			"citation": "",
			"abstract": "Although it has been hypothesized that some of the somatic mutations found in tumors may occur before tumor initiation, there is little experimental or conceptual data on this topic. To gain insights into this fundamental issue, we formulated a mathematical model for the evolution of somatic mutations in which all relevant phases of a tissue's history are considered. The model makes the prediction, validated by our empirical findings, that the number of somatic mutations in tumors of self-renewing tissues is positively correlated with the age of the patient at diagnosis. Importantly, our analysis indicates that half or more of the somatic mutations in certain tumors of self-renewing tissues occur before the onset of neoplasia. The model also provides a unique way to estimate the in vivo tissue-specific somatic mutation rates in normal tissues directly from the sequencing data of tumors. Our results have substantial implications for the interpretation of the large number of genome-wide cancer studies now being undertaken.",
			"category": 2,
			"name": "Tomasetti Cristian,2013"
		},
		{
			"PMID": 23342069,
			"title": "The frequency of granulocytes with spontaneous somatic mutations: a wide distribution in a normal human population.",
			"journal": "PloS one",
			"authorList": [
				"Rondelli Tommaso",
				"Berardi Margherita",
				"Peruzzi Benedetta",
				"Boni Luca",
				"Caporale Roberto",
				"Dolara Piero",
				"Notaro Rosario",
				"Luzzatto Lucio"
			],
			"DOI": "10.1371/journal.pone.0054046",
			"date": "2013-08-02",
			"PMC": "",
			"citation": "",
			"abstract": "Germ-line mutation rate has been regarded classically as a fundamental biological parameter, as it affects the prevalence of genetic disorders and the rate of evolution. Somatic mutation rate is also an important biological parameter, as it may influence the development and/or the course of acquired diseases, particularly of cancer. Estimates of this parameter have been previously obtained in few instances from dermal fibroblasts and lymphoblastoid cells. However, the methodology required has been laborious and did not lend itself to the analysis of large numbers of samples. We have previously shown that the X-linked gene PIG-A, since its product is required for glycosyl-phosphatidylinositol-anchored proteins to become surface bound, is a good sentinel gene for studying somatic mutations. We now show that by this approach we can accurately measure the proportion of PIG-A mutant peripheral blood granulocytes, which we call mutant frequency, \u0192. We found that the results are reproducible, with a variation coefficient (CV) of 45%. Repeat samples from 32 subjects also had a CV of 44%, indicating that \u0192 is a relatively stable individual characteristic. From a study of 142 normal subjects we found that log \u0192 is a normally distributed variable; \u0192 variability spans a 80-fold range, from less than 1\u00d710\u207b\u2076 to 37.5\u00d710\u207b\u2076, with a median of 4.9\u00d710\u207b\u2076. Unlike other techniques commonly employed in population studies, such as comet assay, this method can detect any kind of mutation, including point mutation, as long as it causes functional inactivation of PIG-A gene. Since the test is rapid and requires only a small sample of peripheral blood, this methodology will lend itself to investigating genetic factors that underlie the variation in the somatic mutation rate, as well as environmental factors that may affect it. It will be also possible to test whether \u0192 is a determinant of the risk of cancer.",
			"category": 2,
			"name": "Rondelli Tommaso,2013"
		},
		{
			"PMID": 23341493,
			"title": "Genomic insights into cancer-associated aberrant CpG island hypermethylation.",
			"journal": "Briefings in functional genomics",
			"authorList": [
				"Sproul Duncan",
				"Meehan Richard R"
			],
			"DOI": "10.1093/bfgp/els063",
			"date": "2013-12-12",
			"PMC": "",
			"citation": "",
			"abstract": "Carcinogenesis is thought to occur through a combination of mutational and epimutational events that disrupt key pathways regulating cellular growth and division. The DNA methylomes of cancer cells can exhibit two striking differences from normal cells; a global reduction of DNA methylation levels and the aberrant hypermethylation of some sequences, particularly CpG islands (CGIs). This aberrant hypermethylation is often invoked as a mechanism causing the transcriptional inactivation of tumour suppressor genes that directly drives the carcinogenic process. Here, we review our current understanding of this phenomenon, focusing on how global analysis of cancer methylomes indicates that most affected CGI genes are already silenced prior to aberrant hypermethylation during cancer development. We also discuss how genome-scale analyses of both normal and cancer cells have refined our understanding of the elusive mechanism(s) that may underpin aberrant CGI hypermethylation.",
			"category": 2,
			"name": "Sproul Duncan,2013"
		},
		{
			"PMID": 23340846,
			"title": "High-throughput sequencing for biology and medicine.",
			"journal": "Molecular systems biology",
			"authorList": [
				"Soon Wendy Weijia",
				"Hariharan Manoj",
				"Snyder Michael P"
			],
			"DOI": "10.1038/msb.2012.61",
			"date": "2013-09-16",
			"PMC": "",
			"citation": "",
			"abstract": "Advances in genome sequencing have progressed at a rapid pace, with increased throughput accompanied by plunging costs. But these advances go far beyond faster and cheaper. High-throughput sequencing technologies are now routinely being applied to a wide range of important topics in biology and medicine, often allowing researchers to address important biological questions that were not possible before. In this review, we discuss these innovative new approaches-including ever finer analyses of transcriptome dynamics, genome structure and genomic variation-and provide an overview of the new insights into complex biological systems catalyzed by these technologies. We also assess the impact of genotyping, genome sequencing and personal omics profiling on medical applications, including diagnosis and disease monitoring. Finally, we review recent developments in single-cell sequencing, and conclude with a discussion of possible future advances and obstacles for sequencing in biology and health.",
			"category": 2,
			"name": "Soon Wendy Weijia,2013"
		},
		{
			"PMID": 23329368,
			"title": "Diet impacts mortality from cancer: results from the multiethnic cohort study.",
			"journal": "Cancer causes & control : CCC",
			"authorList": [
				"Sharma Sangita",
				"Vik Shelly",
				"Pakseresht Mohammadreza",
				"Shen Lucy",
				"Kolonel Laurence N"
			],
			"DOI": "10.1007/s10552-013-0148-6",
			"date": "2013-09-12",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is the second leading cause of death in the United States and mortality varies by ethnicity. The objective of this study was to examine the association between cancer mortality and dietary intake among a large multiethnic population.",
			"category": 2,
			"name": "Sharma Sangita,2013"
		},
		{
			"PMID": 23324116,
			"title": "Disentangling function from topology to infer the network properties of disease genes.",
			"journal": "BMC systems biology",
			"authorList": [
				"Ghersi Dario",
				"Singh Mona"
			],
			"DOI": "10.1186/1752-0509-7-5",
			"date": "2013-07-08",
			"PMC": "",
			"citation": "",
			"abstract": "The topological features of disease genes within interaction networks are the subject of intense study, as they shed light on common mechanisms of pathology and are useful for uncovering additional disease genes. Computational analyses typically try to uncover whether disease genes exhibit distinct network features, as compared to all genes.",
			"category": 2,
			"name": "Ghersi Dario,2013"
		},
		{
			"PMID": 23318258,
			"title": "Deciphering signatures of mutational processes operative in human cancer.",
			"journal": "Cell reports",
			"authorList": [
				"Alexandrov Ludmil B",
				"Nik-Zainal Serena",
				"Wedge David C",
				"Campbell Peter J",
				"Stratton Michael R"
			],
			"DOI": "10.1016/j.celrep.2012.12.008",
			"date": "2013-07-16",
			"PMC": "",
			"citation": "",
			"abstract": "The genome of a cancer cell carries somatic mutations that are the cumulative consequences of the DNA damage and repair processes operative during the cellular lineage between the fertilized egg and the cancer cell. Remarkably, these mutational processes are poorly characterized. Global sequencing initiatives are yielding catalogs of somatic mutations from thousands of cancers, thus providing the unique opportunity to decipher the signatures of mutational processes operative in human cancer. However, until now there have been no theoretical models describing the signatures of mutational processes operative in cancer genomes and no systematic computational approaches are available to decipher these mutational signatures. Here, by modeling mutational processes as a blind source separation problem, we introduce a computational framework that effectively addresses these questions. Our approach provides a basis for characterizing mutational signatures from cancer-derived somatic mutational catalogs, paving the way to insights into the pathogenetic mechanism underlying all cancers.",
			"category": 2,
			"name": "Alexandrov Ludmil B,2013"
		},
		{
			"PMID": 23314173,
			"title": "Lentiviral vector-based insertional mutagenesis identifies genes associated with liver cancer.",
			"journal": "Nature methods",
			"authorList": [
				"Ranzani Marco",
				"Cesana Daniela",
				"Bartholomae Cynthia C",
				"Sanvito Francesca",
				"Pala Mauro",
				"Benedicenti Fabrizio",
				"Gallina Pierangela",
				"Sergi Lucia Sergi",
				"Merella Stefania",
				"Bulfone Alessandro",
				"Doglioni Claudio",
				"von Kalle Christof",
				"Kim Yoon Jun",
				"Schmidt Manfred",
				"Tonon Giovanni",
				"Naldini Luigi",
				"Montini Eugenio"
			],
			"DOI": "10.1038/nmeth.2331",
			"date": "2013-03-28",
			"PMC": "",
			"citation": "",
			"abstract": "Transposons and \u03b3-retroviruses have been efficiently used as insertional mutagens in different tissues to identify molecular culprits of cancer. However, these systems are characterized by recurring integrations that accumulate in tumor cells and that hamper the identification of early cancer-driving events among bystander and progression-related events. We developed an insertional mutagenesis platform based on lentiviral vectors (LVVs) by which we could efficiently induce hepatocellular carcinoma (HCC) in three different mouse models. By virtue of the LVV's replication-deficient nature and broad genome-wide integration pattern, LVV-based insertional mutagenesis allowed identification of four previously unknown liver cancer-associated genes from a limited number of integrations. We validated the oncogenic potential of all the identified genes in vivo, with different levels of penetrance. The newly identified genes are likely to play a role in human cancer because they are upregulated, amplified and/or deleted in human HCCs and can predict clinical outcomes of patients.",
			"category": 2,
			"name": "Ranzani Marco,2013"
		},
		{
			"PMID": 23307895,
			"title": "Gene copy-number variation in haploid and diploid strains of the yeast Saccharomyces cerevisiae.",
			"journal": "Genetics",
			"authorList": [
				"Zhang Hengshan",
				"Zeidler Ane F B",
				"Song Wei",
				"Puccia Christopher M",
				"Malc Ewa",
				"Greenwell Patricia W",
				"Mieczkowski Piotr A",
				"Petes Thomas D",
				"Argueso Juan Lucas"
			],
			"DOI": "10.1534/genetics.112.146522",
			"date": "2013-08-15",
			"PMC": "",
			"citation": "",
			"abstract": "The increasing ability to sequence and compare multiple individual genomes within a species has highlighted the fact that copy-number variation (CNV) is a substantial and underappreciated source of genetic diversity. Chromosome-scale mutations occur at rates orders of magnitude higher than base substitutions, yet our understanding of the mechanisms leading to CNVs has been lagging. We examined CNV in a region of chromosome 5 (chr5) in haploid and diploid strains of Saccharomyces cerevisiae. We optimized a CNV detection assay based on a reporter cassette containing the SFA1 and CUP1 genes that confer gene dosage-dependent tolerance to formaldehyde and copper, respectively. This optimized reporter allowed the selection of low-order gene amplification events, going from one copy to two copies in haploids and from two to three copies in diploids. In haploid strains, most events involved tandem segmental duplications mediated by nonallelic homologous recombination between flanking direct repeats, primarily Ty1 elements. In diploids, most events involved the formation of a recurrent nonreciprocal translocation between a chr5 Ty1 element and another Ty1 repeat on chr13. In addition to amplification events, a subset of clones displaying elevated resistance to formaldehyde had point mutations within the SFA1 coding sequence. These mutations were all dominant and are proposed to result in hyperactive forms of the formaldehyde dehydrogenase enzyme.",
			"category": 2,
			"name": "Zhang Hengshan,2013"
		},
		{
			"PMID": 23303493,
			"title": "Pathogen chip for respiratory tract infections.",
			"journal": "Journal of clinical microbiology",
			"authorList": [
				"Sim\u00f5es Eric A F",
				"Patel Champa",
				"Sung Wing-Kin",
				"Lee Charlie W H",
				"Loh Kuan Hon",
				"Lucero Marilla",
				"Nohynek Hanna",
				"Nai Geraldine",
				"Thien Pei Ling",
				"Koh Chee Wee",
				"Chan Yang Sun",
				"Ma Jianmin",
				"Maurer-Stroh Sebastian",
				"Carosone-Link Phyllis",
				"Hibberd Martin L",
				"Wong Christopher W",
				"ARIVAC Consortium"
			],
			"DOI": "10.1128/JCM.02317-12",
			"date": "2013-07-29",
			"PMC": "",
			"citation": "",
			"abstract": "Determining the viral etiology of respiratory tract infections (RTI) has been limited for the most part to specific primer PCR-based methods due to their increased sensitivity and specificity compared to other methods, such as tissue culture. However, specific primer approaches have limited the ability to fully understand the diversity of infecting pathogens. A pathogen chip system (PathChip), developed at the Genome Institute of Singapore (GIS), using a random-tagged PCR coupled to a chip with over 170,000 probes, has the potential to recognize all known human viral pathogens. We tested 290 nasal wash specimens from Filipino children <2 years of age with respiratory tract infections using culture and 3 PCR methods-EraGen, Luminex, and the GIS PathChip. The PathChip had good diagnostic accuracy, ranging from 85.9% (95% confidence interval [CI], 81.3 to 89.7%) for rhinovirus/enteroviruses to 98.6% (95% CI, 96.5 to 99.6%) for PIV 2, compared to the other methods and additionally identified a number of viruses not detected by these methods.",
			"category": 2,
			"name": "Sim\u00f5es Eric A F,2013"
		},
		{
			"PMID": 23300022,
			"title": "Ionizing radiation-induced \u03b3-H2AX activity in whole blood culture and the risk of lung cancer.",
			"journal": "Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology",
			"authorList": [
				"He Yonggang",
				"Gong Yilei",
				"Lin Jie",
				"Chang David W",
				"Gu Jian",
				"Roth Jack A",
				"Wu Xifeng"
			],
			"DOI": "10.1158/1055-9965.EPI-12-0794",
			"date": "2013-09-12",
			"PMC": "",
			"citation": "",
			"abstract": "Phenotypic biomarkers of DNA damage repair may enhance cancer risk prediction. The \u03b3-H2AX formed at the sites of double-strand break (DSB) after ionizing radiation is a specific marker of DNA damage.",
			"category": 2,
			"name": "He Yonggang,2013"
		},
		{
			"PMID": 23284693,
			"title": "Estimation of copy number alterations from exome sequencing data.",
			"journal": "PloS one",
			"authorList": [
				"Vald\u00e9s-Mas Rafael",
				"Bea Silvia",
				"Puente Diana A",
				"L\u00f3pez-Ot\u00edn Carlos",
				"Puente Xose S"
			],
			"DOI": "10.1371/journal.pone.0051422",
			"date": "2013-06-17",
			"PMC": "",
			"citation": "",
			"abstract": "Exome sequencing constitutes an important technology for the study of human hereditary diseases and cancer. However, the ability of this approach to identify copy number alterations in primary tumor samples has not been fully addressed. Here we show that somatic copy number alterations can be reliably estimated using exome sequencing data through a strategy that we have termed exome2cnv. Using data from 86 paired normal and primary tumor samples, we identified losses and gains of complete chromosomes or large genomic regions, as well as smaller regions affecting a minimum of one gene. Comparison with high-resolution comparative genomic hybridization (CGH) arrays revealed a high sensitivity and a low number of false positives in the copy number estimation between both approaches. We explore the main factors affecting sensitivity and false positives with real data, and provide a side by side comparison with CGH arrays. Together, these results underscore the utility of exome sequencing to study cancer samples by allowing not only the identification of substitutions and indels, but also the accurate estimation of copy number alterations.",
			"category": 2,
			"name": "Vald\u00e9s-Mas Rafael,2013"
		},
		{
			"PMID": 23279446,
			"title": "Cancer metabolism: key players in metabolic reprogramming.",
			"journal": "Cancer science",
			"authorList": [
				"Soga Tomoyoshi"
			],
			"DOI": "10.1111/cas.12085",
			"date": "2013-04-25",
			"PMC": "",
			"citation": "",
			"abstract": "Over 80 years ago, Warburg discovered that cancer cells generate ATP through the glycolytic pathway, even in the presence of oxygen. The finding of this phenomenon, termed the \"Warburg effect,\" stimulated much research on tumorigenesis, but few explanations were forthcoming to explain the observation. Recently, advanced developments in molecular biology and high-throughput molecular analyses have revealed that many of the signaling pathways altered by gene mutations regulate cell metabolism in cancer. Furthermore, mutations in isocitrate dehydrogenase 1 and 2 were shown to elevate 2-hydroxyglutarate, which led to changes in \u03b1-ketoglutarate-dependent dioxygenase enzyme activity, resulting in an increased risk of malignant tumors. Although these findings led to a renewed interest in cancer metabolism, our knowledge on the specifics of tumor metabolism is still fragmented. This paper reviews recent findings related to key transcription factors and enzymes that play an important role in the regulation of cancer metabolism.",
			"category": 2,
			"name": "Soga Tomoyoshi,2013"
		},
		{
			"PMID": 23268533,
			"title": "Modelling how initiating and transforming oncogenes cooperate to produce a leukaemic cell state.",
			"journal": "Disease models & mechanisms",
			"authorList": [
				"Richardson Simon E"
			],
			"DOI": "10.1242/dmm.011288",
			"date": "2013-06-06",
			"PMC": "",
			"citation": "",
			"abstract": "Summary of and comment on a recent ",
			"category": 2,
			"name": "Richardson Simon E,2013"
		},
		{
			"PMID": 23267056,
			"title": "Biogenesis of RNA polymerases II and III requires the conserved GPN small GTPases in Saccharomyces cerevisiae.",
			"journal": "Genetics",
			"authorList": [
				"Minaker Sean W",
				"Filiatrault Megan C",
				"Ben-Aroya Shay",
				"Hieter Philip",
				"Stirling Peter C"
			],
			"DOI": "10.1534/genetics.112.148726",
			"date": "2013-08-15",
			"PMC": "",
			"citation": "",
			"abstract": "The GPN proteins are a poorly characterized and deeply evolutionarily conserved family of three paralogous small GTPases, Gpn1, 2, and 3. The founding member, GPN1/NPA3/XAB1, is proposed to function in nuclear import of RNA polymerase II along with a recently described protein called Iwr1. Here we show that the previously uncharacterized protein Gpn2 binds both Gpn3 and Npa3/Gpn1 and that temperature-sensitive alleles of Saccharomyces cerevisiae GPN2 and GPN3 exhibit genetic interactions with RNA polymerase II mutants, hypersensitivity to transcription inhibition, and defects in RNA polymerase II nuclear localization. Importantly, we identify previously unrecognized RNA polymerase III localization defects in GPN2, GPN3, and IWR1 mutant backgrounds but find no localization defects of unrelated nuclear proteins or of RNA polymerase I. Previously, it was unclear whether the GPN proteins and Iwr1 had overlapping function in RNA polymerase II assembly or import. In this study, we show that the nuclear import defect of iwr1\u0394, but not the GPN2 or GPN3 mutant defects, is partially suppressed by fusion of a nuclear localization signal to the RNA polymerase II subunit Rpb3. These data, combined with strong genetic interactions between GPN2 and IWR1, suggest that the GPN proteins function upstream of Iwr1 in RNA polymerase II and III biogenesis. We propose that the three GPN proteins execute a common, and likely essential, function in RNA polymerase assembly and transport.",
			"category": 2,
			"name": "Minaker Sean W,2013"
		},
		{
			"PMID": 23260012,
			"title": "Structural analysis of the genome of breast cancer cell line ZR-75-30 identifies twelve expressed fusion genes.",
			"journal": "BMC genomics",
			"authorList": [
				"Schulte Ina",
				"Batty Elizabeth M",
				"Pole Jessica C M",
				"Blood Katherine A",
				"Mo Steven",
				"Cooke Susanna L",
				"Ng Charlotte",
				"Howe Kevin L",
				"Chin Suet-Feung",
				"Brenton James D",
				"Caldas Carlos",
				"Howarth Karen D",
				"Edwards Paul A W"
			],
			"DOI": "10.1186/1471-2164-13-719",
			"date": "2013-06-11",
			"PMC": "",
			"citation": "",
			"abstract": "It has recently emerged that common epithelial cancers such as breast cancers have fusion genes like those in leukaemias. In a representative breast cancer cell line, ZR-75-30, we searched for fusion genes, by analysing genome rearrangements.",
			"category": 2,
			"name": "Schulte Ina,2013"
		},
		{
			"PMID": 23258224,
			"title": "The cancer antigenome.",
			"journal": "The EMBO journal",
			"authorList": [
				"Heemskerk Bianca",
				"Kvistborg Pia",
				"Schumacher Ton N M"
			],
			"DOI": "10.1038/emboj.2012.333",
			"date": "2013-03-26",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer cells deviate from normal body cells in two immunologically important ways. First, tumour cells carry tens to hundreds of protein-changing mutations that are either responsible for cellular transformation or that have accumulated as mere passengers. Second, as a consequence of genetic and epigenetic alterations, tumour cells express a series of proteins that are normally not present or present at lower levels. These changes lead to the presentation of an altered repertoire of MHC class I-associated peptides. Importantly, while there is now strong clinical evidence that cytotoxic T-cell activity against such tumour-associated antigens can lead to cancer regression, at present we fail to understand which tumour-associated antigens form the prime targets in effective immunotherapies. Here, we describe how recent developments in cancer genomics will make it feasible to establish the repertoire of tumour-associated epitopes on a patient-specific basis. The elucidation of this 'cancer antigenome' will be valuable to reveal how clinically successful immunotherapies mediate their effect. Furthermore, the description of the cancer antigenome should form the basis of novel forms of personalized cancer immunotherapy.",
			"category": 2,
			"name": "Heemskerk Bianca,2013"
		},
		{
			"PMID": 23251334,
			"title": "SOX4 transcriptionally regulates multiple SEMA3/plexin family members and promotes tumor growth in pancreatic cancer.",
			"journal": "PloS one",
			"authorList": [
				"Huang Hsin-Yi",
				"Cheng Yu-Yao",
				"Liao Wei-Chih",
				"Tien Yu-Wen",
				"Yang Chih-Hsin James",
				"Hsu Su-Ming",
				"Huang Pei-Hsin"
			],
			"DOI": "10.1371/journal.pone.0048637",
			"date": "2013-06-03",
			"PMC": "",
			"citation": "",
			"abstract": "Semaphorin signaling through Plexin frequently participates in tumorigenesis and malignant progression in various types of cancer. In particular, the role of semaphorin signaling in pancreatic ductal adenocarcinoma (PDAC) remains unexplored, despite a high likelihood of metastasis and mortality. Unlike other epithelial malignancies that often express a small number of specific genes in the Semaphorin/Plexin family, five or more are often expressed in human PDAC. Such concomitant expression of these SEMA3/Plexin family members is not a result of gene amplification, but (at least partially) from increased gene transcription activated by SOX4 de novo expressed in PDAC. Via chromatin-immunoprecipitation, luciferase promoter activity assay and electrophoresis mobility shift assay, SOX4 is demonstrated to bind to the consensus site at the promoter of each SEMA3 and Plexin gene to enhance transcription activity. Conversely, RNAi-knockdown of SOX4 in PDAC cell lines results in decreased expression of SEMA3/Plexin family members and is associated with restricted tumor growth both in vitro and in SCID mice. We further demonstrate that SOX4 levels parallel with the summed expression of SEMA3/Plexin family members (P = 0.033, NPar Kruskal-Wallis one-way analysis), which also correlates with poor survival in human PDAC (P = 0.0409, Kaplan-Meier analysis). Intriguingly, miR-129-2 and miR-335, both of which target SOX4 for degradation, are co-repressed in human PDAC cases associated with up-regulated SOX4 in a statistically significant way. In conclusion, we disclose a miR-129-2(miR-335)/SOX4/Semaphorin-Plexin regulatory axis in the tumorigenesis of pancreatic cancer.",
			"category": 2,
			"name": "Huang Hsin-Yi,2013"
		},
		{
			"PMID": 23249093,
			"title": "Somatic mutagenesis in autoimmunity.",
			"journal": "Autoimmunity",
			"authorList": [
				"Detanico Thiago",
				"St Clair James B",
				"Aviszus Katja",
				"Kirchenbaum Greg",
				"Guo Wenzhong",
				"Wysocki Lawrence J"
			],
			"DOI": "10.3109/08916934.2012.757597",
			"date": "2013-07-23",
			"PMC": "",
			"citation": "",
			"abstract": "Our laboratory investigates systemic autoimmune disease in the context of mouse models of systemic lupus erythematosus (SLE). SLE is associated with high titers of serum autoantibodies of the IgG class that are predominantly directed against nuclear antigens, with pathological manifestations that are considered by many to be characteristic of an immune-complex mediated disease. In this review, we focus on the known and potential roles of somatic mutagenesis in SLE. We will argue that anti-nuclear antibodies (ANA) arise predominantly from nonautoreactive B cells that are transformed into autoreactive cells by the process of somatic hypermutation (SHM), which is normally associated with affinity maturation during the germinal center reaction. We will also discuss the role of SHM in creating antigenic peptides in the V region of the B cell receptor (BCR) and its potential to open an avenue of unregulated T cell help to autoreactive B cells. Finally, we will end this review with new experimental evidence suggesting that spontaneous somatic mutagenesis of genes that regulate B cell survival and activation is a rate-limiting causative factor in the development of ANA.",
			"category": 2,
			"name": "Detanico Thiago,2013"
		},
		{
			"PMID": 23226573,
			"title": "Deciphering Phosphotyrosine-Dependent Signaling Networks in Cancer by SH2 Profiling.",
			"journal": "Genes & cancer",
			"authorList": [
				"Machida Kazuya",
				"Khenkhar Malik",
				"Nollau Peter"
			],
			"DOI": "10.1177/1947601912459048",
			"date": "2012-12-12",
			"PMC": "",
			"citation": "",
			"abstract": "It has been a decade since the introduction of SH2 profiling, a modular domain-based molecular diagnostics tool. This review covers the original concept of SH2 profiling, different analytical platforms, and their applications, from the detailed analysis of single proteins to broad screening in translational research. Illustrated by practical examples, we discuss the uniqueness and advantages of the approach as well as its limitations and challenges. We provide guidance for basic researchers and oncologists who may consider SH2 profiling in their respective cancer research, especially for those focusing on tyrosine phosphoproteomics. SH2 profiling can serve as an alternative phosphoproteomics tool to dissect aberrant tyrosine kinase pathways responsible for individual malignancies, with the goal of facilitating personalized diagnostics for the treatment of cancer.",
			"category": 2,
			"name": "Machida Kazuya,2012"
		},
		{
			"PMID": 23223358,
			"title": "BCR-ABL1 compound mutations in tyrosine kinase inhibitor-resistant CML: frequency and clonal relationships.",
			"journal": "Blood",
			"authorList": [
				"Khorashad Jamshid S",
				"Kelley Todd W",
				"Szankasi Philippe",
				"Mason Clinton C",
				"Soverini Simona",
				"Adrian Lauren T",
				"Eide Christopher A",
				"Zabriskie Matthew S",
				"Lange Thoralf",
				"Estrada Johanna C",
				"Pomicter Anthony D",
				"Eiring Anna M",
				"Kraft Ira L",
				"Anderson David J",
				"Gu Zhimin",
				"Alikian Mary",
				"Reid Alistair G",
				"Foroni Letizia",
				"Marin David",
				"Druker Brian J",
				"O'Hare Thomas",
				"Deininger Michael W"
			],
			"DOI": "10.1182/blood-2012-05-431379",
			"date": "2013-03-12",
			"PMC": "",
			"citation": "",
			"abstract": "BCR-ABL1 compound mutations can confer high-level resistance to imatinib and other ABL1 tyrosine kinase inhibitors (TKIs). The third-generation ABL1 TKI ponatinib is effective against BCR-ABL1 point mutants individually, but remains vulnerable to certain BCR-ABL1 compound mutants. To determine the frequency of compound mutations among chronic myeloid leukemia patients on ABL1 TKI therapy, in the present study, we examined a collection of patient samples (N = 47) with clear evidence of 2 BCR-ABL1 kinase domain mutations by direct sequencing. Using a cloning and sequencing method, we found that 70% (33/47) of double mutations detected by direct sequencing were compound mutations. Sequential, branching, and parallel routes to compound mutations were common. In addition, our approach revealed individual and compound mutations not detectable by direct sequencing. The frequency of clones harboring compound mutations with more than 2 missense mutations was low (10%), whereas the likelihood of silent mutations increased disproportionately with the total number of mutations per clone, suggesting a limited tolerance for BCR-ABL1 kinase domain missense mutations. We conclude that compound mutations are common in patients with sequencing evidence for 2 BCR-ABL1 mutations and frequently reflect a highly complex clonal network, the evolution of which may be limited by the negative impact of missense mutations on kinase function.",
			"category": 2,
			"name": "Khorashad Jamshid S,2013"
		},
		{
			"PMID": 23222956,
			"title": "Recurrent SETBP1 mutations in atypical chronic myeloid leukemia.",
			"journal": "Nature genetics",
			"authorList": [
				"Piazza Rocco",
				"Valletta Simona",
				"Winkelmann Nils",
				"Redaelli Sara",
				"Spinelli Roberta",
				"Pirola Alessandra",
				"Antolini Laura",
				"Mologni Luca",
				"Donadoni Carla",
				"Papaemmanuil Elli",
				"Schnittger Susanne",
				"Kim Dong-Wook",
				"Boultwood Jacqueline",
				"Rossi Fabio",
				"Gaipa Giuseppe",
				"De Martini Greta P",
				"di Celle Paola Francia",
				"Jang Hyun Gyung",
				"Fantin Valeria",
				"Bignell Graham R",
				"Magistroni Vera",
				"Haferlach Torsten",
				"Pogliani Enrico Maria",
				"Campbell Peter J",
				"Chase Andrew J",
				"Tapper William J",
				"Cross Nicholas C P",
				"Gambacorti-Passerini Carlo"
			],
			"DOI": "10.1038/ng.2495",
			"date": "2013-02-22",
			"PMC": "",
			"citation": "",
			"abstract": "Atypical chronic myeloid leukemia (aCML) shares clinical and laboratory features with CML, but it lacks the BCR-ABL1 fusion. We performed exome sequencing of eight aCMLs and identified somatic alterations of SETBP1 (encoding a p.Gly870Ser alteration) in two cases. Targeted resequencing of 70 aCMLs, 574 diverse hematological malignancies and 344 cancer cell lines identified SETBP1 mutations in 24 cases, including 17 of 70 aCMLs (24.3%; 95% confidence interval (CI) = 16-35%). Most mutations (92%) were located between codons 858 and 871 and were identical to changes seen in individuals with Schinzel-Giedion syndrome. Individuals with mutations had higher white blood cell counts (P = 0.008) and worse prognosis (P = 0.01). The p.Gly870Ser alteration abrogated a site for ubiquitination, and cells exogenously expressing this mutant exhibited higher amounts of SETBP1 and SET protein, lower PP2A activity and higher proliferation rates relative to those expressing the wild-type protein. In summary, mutated SETBP1 represents a newly discovered oncogene present in aCML and closely related diseases.",
			"category": 2,
			"name": "Piazza Rocco,2013"
		},
		{
			"PMID": 23221988,
			"title": "On the dynamics of neutral mutations in a mathematical model for a homogeneous stem cell population.",
			"journal": "Journal of the Royal Society, Interface",
			"authorList": [
				"Traulsen Arne",
				"Lenaerts Tom",
				"Pacheco Jorge M",
				"Dingli David"
			],
			"DOI": "10.1098/rsif.2012.0810",
			"date": "2013-05-01",
			"PMC": "",
			"citation": "",
			"abstract": "The theory of the clonal origin of cancer states that a tumour arises from one cell that acquires mutation(s) leading to the malignant phenotype. It is the current belief that many of these mutations give a fitness advantage to the mutant population allowing it to expand, eventually leading to disease. However, mutations that lead to such a clonal expansion need not give a fitness advantage and may in fact be neutral--or almost neutral--with respect to fitness. Such mutant clones can be eliminated or expand stochastically, leading to a malignant phenotype (disease). Mutations in haematopoietic stem cells give rise to diseases such as chronic myeloid leukaemia (CML) and paroxysmal nocturnal haemoglobinuria (PNH). Although neutral drift often leads to clonal extinction, disease is still possible, and in this case, it has important implications both for the incidence of disease and for therapy, as it may be more difficult to eliminate neutral mutations with therapy. We illustrate the consequences of such dynamics, using CML and PNH as examples. These considerations have implications for many other tumours as well.",
			"category": 2,
			"name": "Traulsen Arne,2013"
		},
		{
			"PMID": 23205160,
			"title": "Review of massively parallel DNA sequencing technologies.",
			"journal": "The HUGO journal",
			"authorList": [
				"Moorthie Sowmiya",
				"Mattocks Christopher J",
				"Wright Caroline F"
			],
			"DOI": "10.1007/s11568-011-9156-3",
			"date": "2012-12-04",
			"PMC": "",
			"citation": "",
			"abstract": "Since the development of technologies that can determine the base-pair sequence of DNA, the ability to sequence genes has contributed much to science and medicine. However, it has remained a relatively costly and laborious process, hindering its use as a routine biomedical tool. Recent times are seeing rapid developments in this field, both in the availability of novel sequencing platforms, as well as supporting technologies involved in processes such as targeting and data analysis. This is leading to significant reductions in the cost of sequencing a human genome and the potential for its use as a routine biomedical tool. This review is a snapshot of this rapidly moving field examining the current state of the art, forthcoming developments and some of the issues still to be resolved prior to the use of new sequencing technologies in routine clinical diagnosis.",
			"category": 2,
			"name": "Moorthie Sowmiya,2012"
		},
		{
			"PMID": 23175120,
			"title": "Medulloblastomics: the end of the beginning.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Northcott Paul A",
				"Jones David T W",
				"Kool Marcel",
				"Robinson Giles W",
				"Gilbertson Richard J",
				"Cho Yoon-Jae",
				"Pomeroy Scott L",
				"Korshunov Andrey",
				"Lichter Peter",
				"Taylor Michael D",
				"Pfister Stefan M"
			],
			"DOI": "10.1038/nrc3410",
			"date": "2013-02-04",
			"PMC": "",
			"citation": "",
			"abstract": "The division of medulloblastoma into different subgroups by microarray expression profiling has dramatically changed our perspective of this malignant childhood brain tumour. Now, the availability of next-generation sequencing and complementary high-density genomic technologies has unmasked novel driver mutations in each medulloblastoma subgroup. The implications of these findings for the management of patients are readily apparent, pinpointing previously unappreciated diagnostic and therapeutic targets. In this Review, we summarize the 'explosion' of data emerging from the application of modern genomics to medulloblastoma, and in particular the recurrent targets of mutation in medulloblastoma subgroups. These data are currently making their way into clinical trials as we seek to integrate conventional and molecularly targeted therapies.",
			"category": 2,
			"name": "Northcott Paul A,2013"
		},
		{
			"PMID": 23174106,
			"title": "Next-generation sequencing in the clinic: promises and challenges.",
			"journal": "Cancer letters",
			"authorList": [
				"Xuan Jiekun",
				"Yu Ying",
				"Qing Tao",
				"Guo Lei",
				"Shi Leming"
			],
			"DOI": "10.1016/j.canlet.2012.11.025",
			"date": "2014-01-09",
			"PMC": "",
			"citation": "",
			"abstract": "The advent of next generation sequencing (NGS) technologies has revolutionized the field of genomics, enabling fast and cost-effective generation of genome-scale sequence data with exquisite resolution and accuracy. Over the past years, rapid technological advances led by academic institutions and companies have continued to broaden NGS applications from research to the clinic. A recent crop of discoveries have highlighted the medical impact of NGS technologies on Mendelian and complex diseases, particularly cancer. However, the ever-increasing pace of NGS adoption presents enormous challenges in terms of data processing, storage, management and interpretation as well as sequencing quality control, which hinder the translation from sequence data into clinical practice. In this review, we first summarize the technical characteristics and performance of current NGS platforms. We further highlight advances in the applications of NGS technologies towards the development of clinical diagnostics and therapeutics. Common issues in NGS workflows are also discussed to guide the selection of NGS platforms and pipelines for specific research purposes.",
			"category": 2,
			"name": "Xuan Jiekun,2014"
		},
		{
			"PMID": 23170979,
			"title": "Novel cancerization marker, TP53, and its role in distinguishing normal tissue adjacent to cancerous tissue from normal tissue adjacent to benign tissue.",
			"journal": "World journal of surgical oncology",
			"authorList": [
				"Liu Guo-Yan",
				"Liu Kun-Hong",
				"Li Yin",
				"Pan Chao",
				"Su Ji-Qin",
				"Liao Hong-Feng",
				"Yv Ren-Xiang",
				"Li Zhao-Hui",
				"Yuan Li",
				"Zhang Huan-Jing",
				"Tzeng Chi-Meng",
				"Xiong Bing"
			],
			"DOI": "10.1186/1477-7819-10-252",
			"date": "2013-08-02",
			"PMC": "",
			"citation": "",
			"abstract": "The histopathological and molecular heterogeneity of normal tissue adjacent to cancerous tissue (NTAC) and normal tissue adjacent to benign tissue (NTAB), and the availability of limited specimens make deciphering the mechanisms of carcinogenesis challenging. Our goal was to identify histogenetic biomarkers that could be reliably used to define a transforming fingerprint using RNA in situ hybridization.",
			"category": 2,
			"name": "Liu Guo-Yan,2013"
		},
		{
			"PMID": 23158748,
			"title": "Comprehensive analysis of the genome transcriptome and proteome landscapes of three tumor cell lines.",
			"journal": "Genome medicine",
			"authorList": [
				"Akan Pelin",
				"Alexeyenko Andrey",
				"Costea Paul Igor",
				"Hedberg Lilia",
				"Solnestam Beata Werne",
				"Lundin Sverker",
				"H\u00e4llman Jimmie",
				"Lundberg Emma",
				"Uhl\u00e9n Mathias",
				"Lundeberg Joakim"
			],
			"DOI": "10.1186/gm387",
			"date": "2014-05-20",
			"PMC": "",
			"citation": "",
			"abstract": "We here present a comparative genome, transcriptome and functional network analysis of three human cancer cell lines (A431, U251MG and U2OS), and investigate their relation to protein expression. Gene copy numbers significantly influenced corresponding transcript levels; their effect on protein levels was less pronounced. We focused on genes with altered mRNA and/or protein levels to identify those active in tumor maintenance. We provide comprehensive information for the three genomes and demonstrate the advantage of integrative analysis for identifying tumor-related genes amidst numerous background mutations by relating genomic variation to expression/protein abundance data and use gene networks to reveal implicated pathways.",
			"category": 2,
			"name": "Akan Pelin,2014"
		},
		{
			"PMID": 23138309,
			"title": "Interpreting noncoding genetic variation in complex traits and human disease.",
			"journal": "Nature biotechnology",
			"authorList": [
				"Ward Lucas D",
				"Kellis Manolis"
			],
			"DOI": "10.1038/nbt.2422",
			"date": "2013-03-06",
			"PMC": "",
			"citation": "",
			"abstract": "Association studies provide genome-wide information about the genetic basis of complex disease, but medical research has focused primarily on protein-coding variants, owing to the difficulty of interpreting noncoding mutations. This picture has changed with advances in the systematic annotation of functional noncoding elements. Evolutionary conservation, functional genomics, chromatin state, sequence motifs and molecular quantitative trait loci all provide complementary information about the function of noncoding sequences. These functional maps can help with prioritizing variants on risk haplotypes, filtering mutations encountered in the clinic and performing systems-level analyses to reveal processes underlying disease associations. Advances in predictive modeling can enable data-set integration to reveal pathways shared across loci and alleles, and richer regulatory models can guide the search for epistatic interactions. Lastly, new massively parallel reporter experiments can systematically validate regulatory predictions. Ultimately, advances in regulatory and systems genomics can help unleash the value of whole-genome sequencing for personalized genomic risk assessment, diagnosis and treatment.",
			"category": 2,
			"name": "Ward Lucas D,2013"
		},
		{
			"PMID": 23118487,
			"title": "CellLineNavigator: a workbench for cancer cell line analysis.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Krupp Markus",
				"Itzel Timo",
				"Maass Thorsten",
				"Hildebrandt Andreas",
				"Galle Peter R",
				"Teufel Andreas"
			],
			"DOI": "10.1093/nar/gks1012",
			"date": "2013-05-13",
			"PMC": "",
			"citation": "",
			"abstract": "The CellLineNavigator database, freely available at http://www.medicalgenomics.org/celllinenavigator, is a web-based workbench for large scale comparisons of a large collection of diverse cell lines. It aims to support experimental design in the fields of genomics, systems biology and translational biomedical research. Currently, this compendium holds genome wide expression profiles of 317 different cancer cell lines, categorized into 57 different pathological states and 28 individual tissues. To enlarge the scope of CellLineNavigator, the database was furthermore closely linked to commonly used bioinformatics databases and knowledge repositories. To ensure easy data access and search ability, a simple data and an intuitive querying interface were implemented. It allows the user to explore and filter gene expression, focusing on pathological or physiological conditions. For a more complex search, the advanced query interface may be used to query for (i) differentially expressed genes; (ii) pathological or physiological conditions; or (iii) gene names or functional attributes, such as Kyoto Encyclopaedia of Genes and Genomes pathway maps. These queries may also be combined. Finally, CellLineNavigator allows additional advanced analysis of differentially regulated genes by a direct link to the Database for Annotation, Visualization and Integrated Discovery (DAVID) Bioinformatics Resources.",
			"category": 2,
			"name": "Krupp Markus,2013"
		},
		{
			"PMID": 23110103,
			"title": "COPS: a sensitive and accurate tool for detecting somatic Copy Number Alterations using short-read sequence data from paired samples.",
			"journal": "PloS one",
			"authorList": [
				"Krishnan Neeraja M",
				"Gaur Prakhar",
				"Chaudhary Rakshit",
				"Rao Arjun A",
				"Panda Binay"
			],
			"DOI": "10.1371/journal.pone.0047812",
			"date": "2013-04-11",
			"PMC": "",
			"citation": "",
			"abstract": "Copy Number Alterations (CNAs) such as deletions and duplications; compose a larger percentage of genetic variations than single nucleotide polymorphisms or other structural variations in cancer genomes that undergo major chromosomal re-arrangements. It is, therefore, imperative to identify cancer-specific somatic copy number alterations (SCNAs), with respect to matched normal tissue, in order to understand their association with the disease. We have devised an accurate, sensitive, and easy-to-use tool, COPS, COpy number using Paired Samples, for detecting SCNAs. We rigorously tested the performance of COPS using short sequence simulated reads at various sizes and coverage of SCNAs, read depths, read lengths and also with real tumor:normal paired samples. We found COPS to perform better in comparison to other known SCNA detection tools for all evaluated parameters, namely, sensitivity (detection of true positives), specificity (detection of false positives) and size accuracy. COPS performed well for sequencing reads of all lengths when used with most upstream read alignment tools. Additionally, by incorporating a downstream boundary segmentation detection tool, the accuracy of SCNA boundaries was further improved. Here, we report an accurate, sensitive and easy to use tool in detecting cancer-specific SCNAs using short-read sequence data. In addition to cancer, COPS can be used for any disease as long as sequence reads from both disease and normal samples from the same individual are available. An added boundary segmentation detection module makes COPS detected SCNA boundaries more specific for the samples studied. COPS is available at ftp://115.119.160.213 with username \"cops\" and password \"cops\".",
			"category": 2,
			"name": "Krishnan Neeraja M,2013"
		},
		{
			"PMID": 23109871,
			"title": "Is DNA damage response ready for action anywhere?",
			"journal": "International journal of molecular sciences",
			"authorList": [
				"Terradas Mariona",
				"Mart\u00edn Marta",
				"Hern\u00e1ndez Laia",
				"Tusell Laura",
				"Genesc\u00e0 Anna"
			],
			"DOI": "10.3390/ijms130911569",
			"date": "2015-10-22",
			"PMC": "",
			"citation": "",
			"abstract": "Organisms are continuously exposed to DNA damaging agents, consequently, cells have developed an intricate system known as the DNA damage response (DDR) in order to detect and repair DNA lesions. This response has to be rapid and accurate in order to keep genome integrity. It has been observed that the condensation state of chromatin hinders a proper DDR. However, the condensation state of chromatin is not the only barrier to DDR. In this review, we have collected data regarding the presence of DDR factors on micronuclear DNA lesions that indicate that micronuclei are almost incapable of generating an effective DDR because of defects in their nuclear envelope. Finally, considering the recent observations about the reincorporation of micronuclei to the main bulk of chromosomes, we suggest that, under certain circumstances, micronuclei carrying DNA damage might be a source of chromosome instability.",
			"category": 2,
			"name": "Terradas Mariona,2015"
		},
		{
			"PMID": 23095915,
			"title": "Combined analysis of genome-wide expression and copy number profiles to identify key altered genomic regions in cancer.",
			"journal": "BMC genomics",
			"authorList": [
				"Fontanillo Celia",
				"Aibar Sara",
				"Sanchez-Santos Jose Manuel",
				"De Las Rivas Javier"
			],
			"DOI": "10.1186/1471-2164-13-S5-S5",
			"date": "2013-01-02",
			"PMC": "",
			"citation": "",
			"abstract": "Analysis of DNA copy number alterations and gene expression changes in human samples have been used to find potential target genes in complex diseases. Recent studies have combined these two types of data using different strategies, but focusing on finding gene-based relationships. However, it has been proposed that these data can be used to identify key genomic regions, which may enclose causal genes under the assumption that disease-associated gene expression changes are caused by genomic alterations.",
			"category": 2,
			"name": "Fontanillo Celia,2013"
		},
		{
			"PMID": 23095178,
			"title": "Cancer module genes ranking using kernelized score functions.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"Re Matteo",
				"Valentini Giorgio"
			],
			"DOI": "10.1186/1471-2105-13-S14-S3",
			"date": "2013-05-02",
			"PMC": "",
			"citation": "",
			"abstract": "Co-expression based Cancer Modules (CMs) are sets of genes that act in concert to carry out specific functions in different cancer types, and are constructed by exploiting gene expression profiles related to specific clinical conditions or expression signatures associated to specific processes altered in cancer. Unfortunately, genes involved in cancer are not always detectable using only expression signatures or co-expressed sets of genes, and in principle other types of functional interactions should be exploited to obtain a comprehensive picture of the molecular mechanisms underlying the onset and progression of cancer.",
			"category": 2,
			"name": "Re Matteo,2013"
		},
		{
			"PMID": 23078675,
			"title": "Histotype-specific copy-number alterations in ovarian cancer.",
			"journal": "BMC medical genomics",
			"authorList": [
				"Huang Ruby Yunju",
				"Chen Geng Bo",
				"Matsumura Noriomi",
				"Lai Hung-Cheng",
				"Mori Seiichi",
				"Li Jingjing",
				"Wong Meng Kang",
				"Konishi Ikuo",
				"Thiery Jean-Paul",
				"Goh Liang"
			],
			"DOI": "10.1186/1755-8794-5-47",
			"date": "2013-08-08",
			"PMC": "",
			"citation": "",
			"abstract": "Epithelial ovarian cancer is characterized by multiple genomic alterations; most are passenger alterations which do not confer tumor growth. Like many cancers, it is a heterogeneous disease and can be broadly categorized into 4 main histotypes of clear cell, endometrioid, mucinous, and serous. To date, histotype-specific copy number alterations have been difficult to elucidate. The difficulty lies in having sufficient sample size in each histotype for statistical analyses.",
			"category": 2,
			"name": "Huang Ruby Yunju,2013"
		},
		{
			"PMID": 23070345,
			"title": "Genomic instability at the 13q31 locus and somatic mtDNA mutation in the D-loop site correlate with tumor aggressiveness in sporadic Brazilian breast cancer cases.",
			"journal": "Clinics (Sao Paulo, Brazil)",
			"authorList": [
				"Santos Gilson Costa dos",
				"G\u00f3es Andr\u00e9a Carla de Souza",
				"Vitto Humberto de",
				"Moreira Carla Cristina",
				"Avvad Elizabeth",
				"Rumjanek Franklin David",
				"Moura Gallo Claudia Vitoria de"
			],
			"DOI": "",
			"date": "2013-07-18",
			"PMC": "",
			"citation": "",
			"abstract": "Genomic instability is a hallmark of malignant tissues. In this work, we aimed to characterize nuclear and mitochondrial instabilities by determining short tandem repeats and somatic mitochondrial mutations, respectively, in a cohort of Brazilian sporadic breast cancer cases. Furthermore, we performed an association analysis of the molecular findings and the clinical pathological data.",
			"category": 2,
			"name": "Santos Gilson Costa dos,2013"
		},
		{
			"PMID": 23044540,
			"title": "A novel missense-mutation-related feature extraction scheme for 'driver' mutation identification.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Tan Hua",
				"Bao Jiguang",
				"Zhou Xiaobo"
			],
			"DOI": "10.1093/bioinformatics/bts558",
			"date": "2013-07-29",
			"PMC": "",
			"citation": "",
			"abstract": "It becomes widely accepted that human cancer is a disease involving dynamic changes in the genome and that the missense mutations constitute the bulk of human genetic variations. A multitude of computational algorithms, especially the machine learning-based ones, has consequently been proposed to distinguish missense changes that contribute to the cancer progression ('driver' mutation) from those that do not ('passenger' mutation). However, the existing methods have multifaceted shortcomings, in the sense that they either adopt incomplete feature space or depend on protein structural databases which are usually far from integrated.",
			"category": 2,
			"name": "Tan Hua,2013"
		},
		{
			"PMID": 23014189,
			"title": "Next-generation sequencing in breast cancer: first take home messages.",
			"journal": "Current opinion in oncology",
			"authorList": [
				"Desmedt Christine",
				"Voet Thierry",
				"Sotiriou Christos",
				"Campbell Peter J"
			],
			"DOI": "10.1097/CCO.0b013e328359554e",
			"date": "2013-03-28",
			"PMC": "",
			"citation": "",
			"abstract": "We are currently on the threshold of a revolution in breast cancer research, thanks to the emergence of novel technologies based on next-generation sequencing (NGS). In this review, we will describe the different sequencing technologies and platforms, and summarize the main findings from the latest sequencing articles in breast cancer.",
			"category": 2,
			"name": "Desmedt Christine,2013"
		},
		{
			"PMID": 22981675,
			"title": "Targeted next-generation sequencing of advanced prostate cancer identifies potential therapeutic targets and disease heterogeneity.",
			"journal": "European urology",
			"authorList": [
				"Beltran Himisha",
				"Yelensky Roman",
				"Frampton Garrett M",
				"Park Kyung",
				"Downing Sean R",
				"MacDonald Theresa Y",
				"Jarosz Mirna",
				"Lipson Doron",
				"Tagawa Scott T",
				"Nanus David M",
				"Stephens Philip J",
				"Mosquera Juan Miguel",
				"Cronin Maureen T",
				"Rubin Mark A"
			],
			"DOI": "10.1016/j.eururo.2012.08.053",
			"date": "2013-09-24",
			"PMC": "",
			"citation": "",
			"abstract": "Most personalized cancer care strategies involving DNA sequencing are highly reliant on acquiring sufficient fresh or frozen tissue. It has been challenging to comprehensively evaluate the genome of advanced prostate cancer (PCa) because of limited access to metastatic tissue.",
			"category": 2,
			"name": "Beltran Himisha,2013"
		},
		{
			"PMID": 22965061,
			"title": "Navigating cancer network attractors for tumor-specific therapy.",
			"journal": "Nature biotechnology",
			"authorList": [
				"Creixell Pau",
				"Schoof Erwin M",
				"Erler Janine T",
				"Linding Rune"
			],
			"DOI": "10.1038/nbt.2345",
			"date": "2013-03-29",
			"PMC": "",
			"citation": "",
			"abstract": "Cells employ highly dynamic signaling networks to drive biological decision processes. Perturbations to these signaling networks may attract cells to new malignant signaling and phenotypic states, termed cancer network attractors, that result in cancer development. As different cancer cells reach these malignant states by accumulating different molecular alterations, uncovering these mechanisms represents a grand challenge in cancer biology. Addressing this challenge will require new systems-based strategies that capture the intrinsic properties of cancer signaling networks and provide deeper understanding of the processes by which genetic lesions perturb these networks and lead to disease phenotypes. Network biology will help circumvent fundamental obstacles in cancer treatment, such as drug resistance and metastasis, empowering personalized and tumor-specific cancer therapies.",
			"category": 2,
			"name": "Creixell Pau,2013"
		},
		{
			"PMID": 22954223,
			"title": "Gross chromosomal rearrangement mediated by DNA replication in stressed cells: evidence from Escherichia coli.",
			"journal": "Annals of the New York Academy of Sciences",
			"authorList": [
				"Moore J M",
				"Wimberly Hallie",
				"Thornton P C",
				"Rosenberg Susan M",
				"Hastings P J"
			],
			"DOI": "10.1111/j.1749-6632.2012.06587.x",
			"date": "2012-11-08",
			"PMC": "",
			"citation": "",
			"abstract": "Gross chromosomal rearrangements (GCRs), or changes in chromosome structure, play central roles in evolution and are central to cancer formation and progression. GCRs underlie copy number variation (CNV), and therefore genomic disorders that stem from CNV. We study amplification in Escherichia coli as a model system to understand mechanisms and circumstances of GCR formation. Here, we summarize observations that led us to postulate that GCR occurs by a replicative mechanism as part of activated stress responses. We report that we do not find RecA to be downregulated by stress on a population basis and that constitutive expression of RecA does not inhibit amplification, as would be expected if downregulation of RecA made cells permissive for nonhomologous recombination. Strains deleted for the genes for three proteins that inhibit RecA activity, psiB, dinI, and recX, all show unaltered amplification, suggesting that if they do downregulate RecA indirectly, this activity does not promote amplification.",
			"category": 2,
			"name": "Moore J M,2012"
		},
		{
			"PMID": 22922871,
			"title": "Exome sequencing of hepatitis B virus-associated hepatocellular carcinoma.",
			"journal": "Nature genetics",
			"authorList": [
				"Huang Jian",
				"Deng Qing",
				"Wang Qun",
				"Li Kun-Yu",
				"Dai Ji-Hong",
				"Li Niu",
				"Zhu Zhi-Dong",
				"Zhou Bo",
				"Liu Xiao-Yan",
				"Liu Rui-Fang",
				"Fei Qian-Lan",
				"Chen Hui",
				"Cai Bing",
				"Zhou Boping",
				"Xiao Hua-Sheng",
				"Qin Lun-Xiu",
				"Han Ze-Guang"
			],
			"DOI": "10.1038/ng.2391",
			"date": "2012-12-10",
			"PMC": "",
			"citation": "",
			"abstract": "Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and shows a propensity to metastasize and infiltrate adjacent and more distant tissues. HCC is associated with multiple risk factors, including hepatitis B virus (HBV) infection, which is especially prevalent in China. Here, we used exome sequencing to identify somatic mutations in ten HBV-positive individuals with HCC with portal vein tumor thromboses (PVTTs), intrahepatic metastases. Both C:G>A:T and T:A>A:T transversions were frequently found among the 331 non-silent mutations. Notably, ARID1A, which encodes a component of the SWI/SNF chromatin remodeling complex, was mutated in 14 of 110 (13%) HBV-associated HCC specimens. We used RNA interference to assess the roles of 91 of the confirmed mutated genes in cellular survival. The results suggest that seven of these genes, including VCAM1 and CDK14, may confer growth and infiltration capacity to HCC cells. This study provides a view of the landscape of somatic mutations that may be implicated in advanced HCC.",
			"category": 2,
			"name": "Huang Jian,2012"
		},
		{
			"PMID": 22912832,
			"title": "Frequent amplification of CENPF, GMNN and CDK13 genes in hepatocellular carcinomas.",
			"journal": "PloS one",
			"authorList": [
				"Kim Hye-Eun",
				"Kim Dae-Ghon",
				"Lee Kyung Jin",
				"Son Jang Geun",
				"Song Min-Young",
				"Park Young-Mi",
				"Kim Jae-Jung",
				"Cho Sung-Won",
				"Chi Sung-Gil",
				"Cheong Hyun Sub",
				"Shin Hyoung Doo",
				"Lee Sang-Wook",
				"Lee Jong-Keuk"
			],
			"DOI": "10.1371/journal.pone.0043223",
			"date": "2013-05-01",
			"PMC": "",
			"citation": "",
			"abstract": "Genomic changes frequently occur in cancer cells during tumorigenesis from normal cells. Using the Illumina Human NS-12 single-nucleotide polymorphism (SNP) chip to screen for gene copy number changes in primary hepatocellular carcinomas (HCCs), we initially detected amplification of 35 genes from four genomic regions (1q21-41, 6p21.2-24.1, 7p13 and 8q13-23). By integrated screening of these genes for both DNA copy number and gene expression in HCC and colorectal cancer, we selected CENPF (centromere protein F/mitosin), GMNN (geminin, DNA replication inhibitor), CDK13 (cyclin-dependent kinase 13), and FAM82B (family with sequence similarity 82, member B) as common cancer genes. Each gene exhibited an amplification frequency of ~30% (range, 20-50%) in primary HCC (n = 57) and colorectal cancer (n = 12), as well as in a panel of human cancer cell lines (n = 70). Clonogenic and invasion assays of NIH3T3 cells transfected with each of the four amplified genes showed that CENPF, GMNN, and CDK13 were highly oncogenic whereas FAM82B was not. Interestingly, the oncogenic activity of these genes (excluding FAM82B) was highly correlated with gene-copy numbers in tumor samples (correlation coefficient, r>0.423), indicating that amplifications of CENPF, GMNN, and CDK13 genes are tightly linked and coincident in tumors. Furthermore, we confirmed that CDK13 gene copy number was significantly associated with clinical onset age in patients with HCC (P = 0.0037). Taken together, our results suggest that coincidently amplified CDK13, GMNN, and CENPF genes can play a role as common cancer-driver genes in human cancers.",
			"category": 2,
			"name": "Kim Hye-Eun,2013"
		},
		{
			"PMID": 22911550,
			"title": "Next-generation sequencing reveals the secrets of the chronic lymphocytic leukemia genome.",
			"journal": "Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico",
			"authorList": [
				"Ramsay Andrew J",
				"Mart\u00ednez-Trillos Alejandra",
				"Jares Pedro",
				"Rodr\u00edguez David",
				"Kwarciak Agnieszka",
				"Quesada V\u00edctor"
			],
			"DOI": "10.1007/s12094-012-0922-z",
			"date": "2014-02-05",
			"PMC": "",
			"citation": "",
			"abstract": "The study of the detailed molecular history of cancer development is one of the most promising techniques to understand and fight this diverse and prevalent disease. Unfortunately, this history is as diverse as cancer itself. Therefore, even with next-generation sequencing techniques, it is not easy to distinguish significant (driver) from random (passenger) events. The International Cancer Genome Consortium (ICGC) was formed to solve this fundamental issue by coordinating the sequencing of samples from 50 different cancer types and/or sub-types that are of clinical and societal importance. The contribution of Spain in this consortium has been focused on chronic lymphocytic leukemia (CLL). This approach has unveiled new and unexpected events in the development of CLL. In this review, we introduce the approaches utilized by the consortium for the study of the CLL genome and discuss the recent results and future perspectives of this work.",
			"category": 2,
			"name": "Ramsay Andrew J,2014"
		},
		{
			"PMID": 22901813,
			"title": "Cancer vulnerabilities unveiled by genomic loss.",
			"journal": "Cell",
			"authorList": [
				"Nijhawan Deepak",
				"Zack Travis I",
				"Ren Yin",
				"Strickland Matthew R",
				"Lamothe Rebecca",
				"Schumacher Steven E",
				"Tsherniak Aviad",
				"Besche Henrike C",
				"Rosenbluh Joseph",
				"Shehata Shyemaa",
				"Cowley Glenn S",
				"Weir Barbara A",
				"Goldberg Alfred L",
				"Mesirov Jill P",
				"Root David E",
				"Bhatia Sangeeta N",
				"Beroukhim Rameen",
				"Hahn William C"
			],
			"DOI": "10.1016/j.cell.2012.07.023",
			"date": "2012-10-29",
			"PMC": "",
			"citation": "",
			"abstract": "Due to genome instability, most cancers exhibit loss of regions containing tumor suppressor genes and collateral loss of other genes. To identify cancer-specific vulnerabilities that are the result of copy number losses, we performed integrated analyses of genome-wide copy number and RNAi profiles and identified 56 genes for which gene suppression specifically inhibited the proliferation of cells harboring partial copy number loss of that gene. These CYCLOPS (copy number alterations yielding cancer liabilities owing to partial loss) genes are enriched for spliceosome, proteasome, and ribosome components. One CYCLOPS gene, PSMC2, encodes an essential member of the 19S proteasome. Normal cells express excess PSMC2, which resides in a complex with PSMC1, PSMD2, and PSMD5 and acts as a reservoir protecting cells from PSMC2 suppression. Cells harboring partial PSMC2 copy number loss lack this complex and die after PSMC2 suppression. These observations define a distinct class of cancer-specific liabilities resulting from genome instability.",
			"category": 2,
			"name": "Nijhawan Deepak,2012"
		},
		{
			"PMID": 22895327,
			"title": "Cancer: Exploiting collateral damage.",
			"journal": "Nature",
			"authorList": [
				"Lehner Ben",
				"Park Solip"
			],
			"DOI": "10.1038/488284a",
			"date": "2012-09-24",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Lehner Ben,2012"
		},
		{
			"PMID": 22882894,
			"title": "Chapter 6: Lung cancer in never smokers: epidemiology and risk prediction models.",
			"journal": "Risk analysis : an official publication of the Society for Risk Analysis",
			"authorList": [
				"McCarthy William J",
				"Meza Rafael",
				"Jeon Jihyoun",
				"Moolgavkar Suresh H"
			],
			"DOI": "10.1111/j.1539-6924.2012.01768.x",
			"date": "2013-01-10",
			"PMC": "",
			"citation": "",
			"abstract": "In this chapter we review the epidemiology of lung cancer incidence and mortality among never smokers/nonsmokers and describe the never smoker lung cancer risk models used by the Cancer Intervention and Surveillance Network (CISNET) modelers. Our review focuses on those influences likely to have measurable population impact on never smoker risk, such as secondhand smoke, even though the individual-level impact may be small. Occupational exposures may also contribute importantly to the population attributable risk of lung cancer. We examine the following risk factors in this chapter: age, environmental tobacco smoke, cooking fumes, ionizing radiation including radon gas, inherited genetic susceptibility, selected occupational exposures, preexisting lung disease, and oncogenic viruses. We also compare the prevalence of never smokers between the three CISNET smoking scenarios and present the corresponding lung cancer mortality estimates among never smokers as predicted by a typical CISNET model.",
			"category": 2,
			"name": "McCarthy William J,2013"
		},
		{
			"PMID": 22865120,
			"title": "Mechanisms and impacts of chromosomal translocations in cancers.",
			"journal": "Frontiers of medicine",
			"authorList": [
				"Wang Jing H"
			],
			"DOI": "10.1007/s11684-012-0215-5",
			"date": "2013-02-11",
			"PMC": "",
			"citation": "",
			"abstract": "Chromosomal aberrations have been associated with cancer development since their discovery more than a hundred years ago. Chromosomal translocations, a type of particular structural changes involving heterologous chromosomes, have made a critical impact on diagnosis, prognosis and treatment of cancers. For example, the discovery of translocation between chromosomes 9 and 22 and the subsequent success of targeting the fusion product BCR-ABL transformed the therapy for chronic myelogenous leukemia. In the past few decades, tremendous progress has been achieved towards elucidating the mechanism causing chromosomal translocations. This review focuses on the basic mechanisms underlying the generation of chromosomal translocations. In particular, the contribution of frequency of DNA double strand breaks and spatial proximity of translocating loci is discussed.",
			"category": 2,
			"name": "Wang Jing H,2013"
		},
		{
			"PMID": 22858414,
			"title": "Cancer heterogeneity: origins and implications for genetic association studies.",
			"journal": "Trends in genetics : TIG",
			"authorList": [
				"Urbach Davnah",
				"Lupien Mathieu",
				"Karagas Margaret R",
				"Moore Jason H"
			],
			"DOI": "10.1016/j.tig.2012.07.001",
			"date": "2012-12-21",
			"PMC": "",
			"citation": "",
			"abstract": "Genetic association studies have become standard approaches to characterize the genetic and epigenetic variability associated with cancer development, including predispositions and mutations. However, the bewildering genetic and phenotypic heterogeneity inherent in cancer both magnifies the conceptual and methodological problems associated with these approaches and renders difficult the translation of available genetic information into a knowledge that is both biologically sound and clinically relevant. Here, we elaborate on the underlying causes of this complexity, illustrate why it represents a challenge for genetic association studies, and briefly discuss how it can be reconciled with the ultimate goals of identifying targetable disease pathways and successfully treating individual patients.",
			"category": 2,
			"name": "Urbach Davnah,2012"
		},
		{
			"PMID": 22850751,
			"title": "Overcoming implementation challenges of personalized cancer therapy.",
			"journal": "Nature reviews. Clinical oncology",
			"authorList": [
				"Meric-Bernstam Funda",
				"Mills Gordon B"
			],
			"DOI": "10.1038/nrclinonc.2012.127",
			"date": "2013-01-24",
			"PMC": "",
			"citation": "",
			"abstract": "Personalized cancer therapy is based on the precept that detailed molecular characterization of the patient's tumour and its microenvironment will enable tailored therapies to improve outcomes and decrease toxicity. The goal of personalized therapy is to target aberrations that drive tumour growth and survival, by administering the right drug combination for the right person. This is becoming increasingly achievable with advances in high-throughput technologies to characterize tumours and the expanding repertoire of molecularly targeted therapies. However, there are numerous challenges that need to be surpassed before delivering on the promise of personalized cancer therapy. These include tumour heterogeneity and molecular evolution, costs and potential morbidity of biopsies, lack of effective drugs against most genomic aberrations, technical limitations of molecular tests, and reimbursement and regulatory hurdles. Critically, the 'hype' surrounding personalized cancer therapy must be tempered with realistic expectations, which, today, encompass increased survival times for only a portion of patients.",
			"category": 2,
			"name": "Meric-Bernstam Funda,2013"
		},
		{
			"PMID": 22833821,
			"title": "Whole genome sequencing for lung cancer.",
			"journal": "Journal of thoracic disease",
			"authorList": [
				"Daniels Marissa",
				"Goh Felicia",
				"Wright Casey M",
				"Sriram Krishna B",
				"Relan Vandana",
				"Clarke Belinda E",
				"Duhig Edwina E",
				"Bowman Rayleen V",
				"Yang Ian A",
				"Fong Kwun M"
			],
			"DOI": "10.3978/j.issn.2072-1439.2012.02.01",
			"date": "2012-08-23",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer is a leading cause of cancer related morbidity and mortality globally, and carries a dismal prognosis. Improved understanding of the biology of cancer is required to improve patient outcomes. Next-generation sequencing (NGS) is a powerful tool for whole genome characterisation, enabling comprehensive examination of somatic mutations that drive oncogenesis. Most NGS methods are based on polymerase chain reaction (PCR) amplification of platform-specific DNA fragment libraries, which are then sequenced. These techniques are well suited to high-throughput sequencing and are able to detect the full spectrum of genomic changes present in cancer. However, they require considerable investments in time, laboratory infrastructure, computational analysis and bioinformatic support. Next-generation sequencing has been applied to studies of the whole genome, exome, transcriptome and epigenome, and is changing the paradigm of lung cancer research and patient care. The results of this new technology will transform current knowledge of oncogenic pathways and provide molecular targets of use in the diagnosis and treatment of cancer. Somatic mutations in lung cancer have already been identified by NGS, and large scale genomic studies are underway. Personalised treatment strategies will improve care for those likely to benefit from available therapies, while sparing others the expense and morbidity of futile intervention. Organisational, computational and bioinformatic challenges of NGS are driving technological advances as well as raising ethical issues relating to informed consent and data release. Differentiation between driver and passenger mutations requires careful interpretation of sequencing data. Challenges in the interpretation of results arise from the types of specimens used for DNA extraction, sample processing techniques and tumour content. Tumour heterogeneity can reduce power to detect mutations implicated in oncogenesis. Next-generation sequencing will facilitate investigation of the biological and clinical implications of such variation. These techniques can now be applied to single cells and free circulating DNA, and possibly in the future to DNA obtained from body fluids and from subpopulations of tumour. As costs reduce, and speed and processing accuracy increase, NGS technology will become increasingly accessible to researchers and clinicians, with the ultimate goal of improving the care of patients with lung cancer.",
			"category": 2,
			"name": "Daniels Marissa,2012"
		},
		{
			"PMID": 22809142,
			"title": "Model of translational cancer research in multiple myeloma.",
			"journal": "Cancer science",
			"authorList": [
				"Yasui Hiroshi",
				"Ishida Tadao",
				"Maruyama Reo",
				"Nojima Masanori",
				"Ikeda Hiroshi",
				"Suzuki Hiromu",
				"Hayashi Toshiaki",
				"Shinomura Yasuhisa",
				"Imai Kohzoh"
			],
			"DOI": "10.1111/j.1349-7006.2012.02384.x",
			"date": "2013-03-28",
			"PMC": "",
			"citation": "",
			"abstract": "Recently, intensive laboratory and preclinical studies have identified and validated therapeutic molecular targets in multiple myeloma (MM). The introduction of novel agents such as the proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide, which were rapidly translated from preclinical studies at the Dana-Farber Cancer Institute into clinical trials, has changed the treatment paradigm and markedly extended overall survival; MM has therefore become a remarkable example of translational cancer research in new drug development. In this article, with the aim of determining the key factors underlying success in translational research, we focus on our studies of MM at Dana-Farber Cancer Institute as well as at our institutes. The identification of these key factors will help to promote translational cancer research not only in MM but also in other hematologic malignancies and solid tumors, to develop novel therapies, to overcome drug resistance, and to thereby improve the prognosis of cancer patients.",
			"category": 2,
			"name": "Yasui Hiroshi,2013"
		},
		{
			"PMID": 22806144,
			"title": "Metabolic rewiring drives resistance to targeted cancer therapy.",
			"journal": "Molecular systems biology",
			"authorList": [
				"Locasale Jason W"
			],
			"DOI": "10.1038/msb.2012.30",
			"date": "2013-01-14",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Locasale Jason W,2013"
		},
		{
			"PMID": 22779056,
			"title": "Integrating genome and functional genomics data to reveal perturbed signaling pathways in ovarian cancers.",
			"journal": "AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science",
			"authorList": [
				"Lu Songjian",
				"Lu Xinghua"
			],
			"DOI": "",
			"date": "2012-08-24",
			"PMC": "",
			"citation": "",
			"abstract": "Cancers are genetic diseases, driven by somatic mutations that perturb cellular signaling systems. In this study, we aim to reveal the signal transduction pathways that are perturbed by mutations in ovarian cancer. Our approach searches for genetic mutations that lead to a common cellular response, e.g., differential expression of a set of functional related genes. To this end, we first developed a knowledge mining approach to identify functional expression modules; we then developed a graph-based data mining approach to identify mutations that are highly related to the functional modules, as a means to re-constitute signal pathways. Our results indicate that unification of knowledge mining with data mining significantly enhance identification of potential signaling pathways in ovarian cancers.",
			"category": 2,
			"name": "Lu Songjian,2012"
		},
		{
			"PMID": 22759651,
			"title": "Prioritization of pathogenic mutations in the protein kinase superfamily.",
			"journal": "BMC genomics",
			"authorList": [
				"Izarzugaza Jose M G",
				"del Pozo Angela",
				"Vazquez Miguel",
				"Valencia Alfonso"
			],
			"DOI": "10.1186/1471-2164-13-S4-S3",
			"date": "2012-10-31",
			"PMC": "",
			"citation": "",
			"abstract": "Most of the many mutations described in human protein kinases are tolerated without significant disruption of the corresponding structures or molecular functions, while some of them have been associated to a variety of human diseases, including cancer. In the last decade, a plethora of computational methods to predict the effect of missense single-nucleotide variants (SNVs) have been developed. Still, current high-throughput sequencing efforts and the concomitant need for massive interpretation of protein sequence variants will demand for more efficient and/or accurate computational methods in the forthcoming years.",
			"category": 2,
			"name": "Izarzugaza Jose M G,2012"
		},
		{
			"PMID": 22759592,
			"title": "Emerging frontiers in pancreatic cancer research: elaboration of key genes, cells and the extracellular milieu.",
			"journal": "Current opinion in gastroenterology",
			"authorList": [
				"Kumar-Sinha Chandan",
				"Wei Iris",
				"Simeone Diane M"
			],
			"DOI": "10.1097/MOG.0b013e3283567f69",
			"date": "2013-02-06",
			"PMC": "",
			"citation": "",
			"abstract": "We review recent literature with a view to forge an integrative understanding of the molecular, cellular and extracellular milieu of pancreatic cancer, and discuss them in the context of development of novel, personalized therapeutic options.",
			"category": 2,
			"name": "Kumar-Sinha Chandan,2013"
		},
		{
			"PMID": 22739340,
			"title": "RNA-Seq and human complex diseases: recent accomplishments and future perspectives.",
			"journal": "European journal of human genetics : EJHG",
			"authorList": [
				"Costa Valerio",
				"Aprile Marianna",
				"Esposito Roberta",
				"Ciccodicola Alfredo"
			],
			"DOI": "10.1038/ejhg.2012.129",
			"date": "2013-06-19",
			"PMC": "",
			"citation": "",
			"abstract": "The availability of the human genome sequence has allowed identification of disease-causing mutations in many Mendelian disorders, and detection of significant associations of nucleotide polymorphisms to complex diseases and traits. Despite these progresses, finding the causative variations for most of the common diseases remains a complex task. Several studies have shown gene expression analyses provide a quite unbiased way to investigate complex traits and common disorders' pathogenesis. Therefore, whole-transcriptome analysis is increasingly acquiring a key role in the knowledge of mechanisms responsible for complex diseases. Hybridization- and tag-based technologies have elucidated the involvement of multiple genes and pathways in pathological conditions, providing insights into the expression of thousand of coding and noncoding RNAs, such as microRNAs. However, the introduction of Next-Generation Sequencing, particularly of RNA-Seq, has overcome some drawbacks of previously used technologies. Identifying, in a single experiment, potentially novel genes/exons and splice isoforms, RNA editing, fusion transcripts and allele-specific expression are some of its advantages. RNA-Seq has been fruitfully applied to study cancer and host-pathogens interactions, and it is taking first steps for studying neurodegenerative diseases (ND) as well as neuropsychiatric diseases. In addition, it is emerging as a very powerful tool to study quantitative trait loci associated with gene expression in complex diseases. This paper provides an overview on gene expression profiling of complex diseases, with emphasis on RNA-Seq, its advantages over conventional technologies for studying cancer and ND, and for linking nucleotide variations to gene expression changes, also discussing its limitations.",
			"category": 2,
			"name": "Costa Valerio,2013"
		},
		{
			"PMID": 22728587,
			"title": "A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects.",
			"journal": "Nature reviews. Microbiology",
			"authorList": [
				"Tjalsma Harold",
				"Boleij Annemarie",
				"Marchesi Julian R",
				"Dutilh Bas E"
			],
			"DOI": "10.1038/nrmicro2819",
			"date": "2012-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer has long been considered a genetic disease. However, accumulating evidence supports the involvement of infectious agents in the development of cancer, especially in those organs that are continuously exposed to microorganisms, such as the large intestine. Recent next-generation sequencing studies of the intestinal microbiota now offer an unprecedented view of the aetiology of sporadic colorectal cancer and have revealed that the microbiota associated with colorectal cancer contains bacterial species that differ in their temporal associations with developing tumours. Here, we propose a bacterial driver-passenger model for microbial involvement in the development of colorectal cancer and suggest that this model be incorporated into the genetic paradigm of cancer progression.",
			"category": 2,
			"name": "Tjalsma Harold,2012"
		},
		{
			"PMID": 22724047,
			"title": "Transcriptional output in a prospective design conditionally on follow-up and exposure: the multistage model of cancer.",
			"journal": "International journal of molecular epidemiology and genetics",
			"authorList": [
				"Lund Eiliv",
				"Plancade Sandra"
			],
			"DOI": "",
			"date": "2012-08-02",
			"PMC": "",
			"citation": "",
			"abstract": "Transcriptomics as the analysis of mRNA and microRNA could be implemented in prospective studies both in peripheral blood and tissues. Its application in cancer epidemiology could provide a new understanding of the functional changes underlying the multistage model of carcinogenesis, as well as the relationship between these changes and exposure to carcinogens. Transcriptomics is not merely another -omics technology for risk assessment in traditional prospective studies. Instead, this novel approach has the potential to estimate the distribution of gene expression conditionally on different exposures, and to study the length of the different stages of carcinogenesis. If it proves to be a valid approach, transcriptomics could be an opportunity to make meaningful advances in our understanding of the carcinogenic process.",
			"category": 2,
			"name": "Lund Eiliv,2012"
		},
		{
			"PMID": 22722201,
			"title": "The landscape of cancer genes and mutational processes in breast cancer.",
			"journal": "Nature",
			"authorList": [
				"Stephens Philip J",
				"Tarpey Patrick S",
				"Davies Helen",
				"Van Loo Peter",
				"Greenman Chris",
				"Wedge David C",
				"Nik-Zainal Serena",
				"Martin Sancha",
				"Varela Ignacio",
				"Bignell Graham R",
				"Yates Lucy R",
				"Papaemmanuil Elli",
				"Beare David",
				"Butler Adam",
				"Cheverton Angela",
				"Gamble John",
				"Hinton Jonathan",
				"Jia Mingming",
				"Jayakumar Alagu",
				"Jones David",
				"Latimer Calli",
				"Lau King Wai",
				"McLaren Stuart",
				"McBride David J",
				"Menzies Andrew",
				"Mudie Laura",
				"Raine Keiran",
				"Rad Roland",
				"Chapman Michael Spencer",
				"Teague Jon",
				"Easton Douglas",
				"Langer\u00f8d Anita",
				"Oslo Breast Cancer Consortium (OSBREAC)",
				"Lee Ming Ta Michael",
				"Shen Chen-Yang",
				"Tee Benita Tan Kiat",
				"Huimin Bernice Wong",
				"Broeks Annegien",
				"Vargas Ana Cristina",
				"Turashvili Gulisa",
				"Martens John",
				"Fatima Aquila",
				"Miron Penelope",
				"Chin Suet-Feung",
				"Thomas Gilles",
				"Boyault Sandrine",
				"Mariani Odette",
				"Lakhani Sunil R",
				"van de Vijver Marc",
				"van 't Veer Laura",
				"Foekens John",
				"Desmedt Christine",
				"Sotiriou Christos",
				"Tutt Andrew",
				"Caldas Carlos",
				"Reis-Filho Jorge S",
				"Aparicio Samuel A J R",
				"Salomon Anne Vincent",
				"B\u00f8rresen-Dale Anne-Lise",
				"Richardson Andrea L",
				"Campbell Peter J",
				"Futreal P Andrew",
				"Stratton Michael R"
			],
			"DOI": "10.1038/nature11017",
			"date": "2012-08-14",
			"PMC": "",
			"citation": "",
			"abstract": "All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease.",
			"category": 2,
			"name": "Stephens Philip J,2012"
		},
		{
			"PMID": 22699861,
			"title": "Transcriptional and metabolic data integration and modeling for identification of active pathways.",
			"journal": "Biostatistics (Oxford, England)",
			"authorList": [
				"Jauhiainen Alexandra",
				"Nerman Olle",
				"Michailidis George",
				"J\u00f6rnsten Rebecka"
			],
			"DOI": "10.1093/biostatistics/kxs016",
			"date": "2013-02-21",
			"PMC": "",
			"citation": "",
			"abstract": "With the growing availability of omics data generated to describe different cells and tissues, the modeling and interpretation of such data has become increasingly important. Pathways are sets of reactions involving genes, metabolites, and proteins highlighting functional modules in the cell. Therefore, to discover activated or perturbed pathways when comparing two conditions, for example two different tissues, it is beneficial to use several types of omics data. We present a model that integrates transcriptomic and metabolomic data in order to make an informed pathway-level decision. Since metabolites can be seen as end-points of perturbations happening at the gene level, the gene expression data constitute the explanatory variables in a sparse regression model for the metabolite data. Sophisticated model selection procedures are developed to determine an appropriate model. We demonstrate that the transcript profiles can be used to informatively explain the metabolite data from cancer cell lines. Simulation studies further show that the proposed model offers a better performance in identifying active pathways than, for example, enrichment methods performed separately on the transcript and metabolite data.",
			"category": 2,
			"name": "Jauhiainen Alexandra,2013"
		},
		{
			"PMID": 22691569,
			"title": "Cancer core modules identification through genomic and transcriptomic changes correlation detection at network level.",
			"journal": "BMC systems biology",
			"authorList": [
				"Li Wenting",
				"Wang Rui",
				"Bai Linfu",
				"Yan Zhangming",
				"Sun Zhirong"
			],
			"DOI": "10.1186/1752-0509-6-64",
			"date": "2012-12-13",
			"PMC": "",
			"citation": "",
			"abstract": "Identification of driver mutations among numerous genomic alternations remains a critical challenge to the elucidation of the underlying mechanisms of cancer. Because driver mutations by definition are associated with a greater number of cancer phenotypes compared to other mutations, we hypothesized that driver mutations could more easily be identified once the genotype-phenotype correlations are detected across tumor samples.",
			"category": 2,
			"name": "Li Wenting,2012"
		},
		{
			"PMID": 22666660,
			"title": "Genomics of acute myeloid leukemia: the next generation.",
			"journal": "Frontiers in oncology",
			"authorList": [
				"Riva Laura",
				"Luzi Lucilla",
				"Pelicci Pier Giuseppe"
			],
			"DOI": "10.3389/fonc.2012.00040",
			"date": "2012-08-23",
			"PMC": "",
			"citation": "",
			"abstract": "Acute myeloid leukemia (AML) is, as other types of cancer, a genetic disorder of somatic cells. The detection of somatic molecular abnormalities that may cause and maintain AML is crucial for patient stratification. The development of mutation-specific therapeutic interventions will hopefully increase cure rates and improve patients' quality of life. This review illustrates how next generation sequencing technologies are changing the study of cancer genomics of adult AML patients.",
			"category": 2,
			"name": "Riva Laura,2012"
		},
		{
			"PMID": 22637570,
			"title": "Integrative analysis of genome-wide loss of heterozygosity and monoallelic expression at nucleotide resolution reveals disrupted pathways in triple-negative breast cancer.",
			"journal": "Genome research",
			"authorList": [
				"Ha Gavin",
				"Roth Andrew",
				"Lai Daniel",
				"Bashashati Ali",
				"Ding Jiarui",
				"Goya Rodrigo",
				"Giuliany Ryan",
				"Rosner Jamie",
				"Oloumi Arusha",
				"Shumansky Karey",
				"Chin Suet-Feung",
				"Turashvili Gulisa",
				"Hirst Martin",
				"Caldas Carlos",
				"Marra Marco A",
				"Aparicio Samuel",
				"Shah Sohrab P"
			],
			"DOI": "10.1101/gr.137570.112",
			"date": "2013-02-19",
			"PMC": "",
			"citation": "",
			"abstract": "Loss of heterozygosity (LOH) and copy number alteration (CNA) feature prominently in the somatic genomic landscape of tumors. As such, karyotypic aberrations in cancer genomes have been studied extensively to discover novel oncogenes and tumor-suppressor genes. Advances in sequencing technology have enabled the cost-effective detection of tumor genome and transcriptome mutation events at single-base-pair resolution; however, computational methods for predicting segmental regions of LOH in this context are not yet fully explored. Consequently, whole transcriptome, nucleotide-level resolution analysis of monoallelic expression patterns associated with LOH has not yet been undertaken in cancer. We developed a novel approach for inference of LOH from paired tumor/normal sequence data and applied it to a cohort of 23 triple-negative breast cancer (TNBC) genomes. Following extensive benchmarking experiments, we describe the nucleotide-resolution landscape of LOH in TNBC and assess the consequent effect of LOH on the transcriptomes of these tumors using RNA-seq-derived measurements of allele-specific expression. We show that the majority of monoallelic expression in the transcriptomes of triple-negative breast cancer can be explained by genomic regions of LOH and establish an upper bound for monoallelic expression that may be explained by other tumor-specific modifications such as epigenetics or mutations. Monoallelically expressed genes associated with LOH reveal that cell cycle, homologous recombination and actin-cytoskeletal functions are putatively disrupted by LOH in TNBC. Finally, we show how inference of LOH can be used to interpret allele frequencies of somatic mutations and postulate on temporal ordering of mutations in the evolutionary history of these tumors.",
			"category": 2,
			"name": "Ha Gavin,2013"
		},
		{
			"PMID": 22628656,
			"title": "Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation.",
			"journal": "Science (New York, N.Y.)",
			"authorList": [
				"Jain Mohit",
				"Nilsson Roland",
				"Sharma Sonia",
				"Madhusudhan Nikhil",
				"Kitami Toshimori",
				"Souza Amanda L",
				"Kafri Ran",
				"Kirschner Marc W",
				"Clish Clary B",
				"Mootha Vamsi K"
			],
			"DOI": "10.1126/science.1218595",
			"date": "2012-06-08",
			"PMC": "",
			"citation": "",
			"abstract": "Metabolic reprogramming has been proposed to be a hallmark of cancer, yet a systematic characterization of the metabolic pathways active in transformed cells is currently lacking. Using mass spectrometry, we measured the consumption and release (CORE) profiles of 219 metabolites from media across the NCI-60 cancer cell lines, and integrated these data with a preexisting atlas of gene expression. This analysis identified glycine consumption and expression of the mitochondrial glycine biosynthetic pathway as strongly correlated with rates of proliferation across cancer cells. Antagonizing glycine uptake and its mitochondrial biosynthesis preferentially impaired rapidly proliferating cells. Moreover, higher expression of this pathway was associated with greater mortality in breast cancer patients. Increased reliance on glycine may represent a metabolic vulnerability for selectively targeting rapid cancer cell proliferation.",
			"category": 2,
			"name": "Jain Mohit,2012"
		},
		{
			"PMID": 22608084,
			"title": "Mutational processes molding the genomes of 21 breast cancers.",
			"journal": "Cell",
			"authorList": [
				"Nik-Zainal Serena",
				"Alexandrov Ludmil B",
				"Wedge David C",
				"Van Loo Peter",
				"Greenman Christopher D",
				"Raine Keiran",
				"Jones David",
				"Hinton Jonathan",
				"Marshall John",
				"Stebbings Lucy A",
				"Menzies Andrew",
				"Martin Sancha",
				"Leung Kenric",
				"Chen Lina",
				"Leroy Catherine",
				"Ramakrishna Manasa",
				"Rance Richard",
				"Lau King Wai",
				"Mudie Laura J",
				"Varela Ignacio",
				"McBride David J",
				"Bignell Graham R",
				"Cooke Susanna L",
				"Shlien Adam",
				"Gamble John",
				"Whitmore Ian",
				"Maddison Mark",
				"Tarpey Patrick S",
				"Davies Helen R",
				"Papaemmanuil Elli",
				"Stephens Philip J",
				"McLaren Stuart",
				"Butler Adam P",
				"Teague Jon W",
				"J\u00f6nsson G\u00f6ran",
				"Garber Judy E",
				"Silver Daniel",
				"Miron Penelope",
				"Fatima Aquila",
				"Boyault Sandrine",
				"Langer\u00f8d Anita",
				"Tutt Andrew",
				"Martens John W M",
				"Aparicio Samuel A J R",
				"Borg \u00c5ke",
				"Salomon Anne Vincent",
				"Thomas Gilles",
				"B\u00f8rresen-Dale Anne-Lise",
				"Richardson Andrea L",
				"Neuberger Michael S",
				"Futreal P Andrew",
				"Campbell Peter J",
				"Stratton Michael R",
				"Breast Cancer Working Group of the International Cancer Genome Consortium"
			],
			"DOI": "10.1016/j.cell.2012.04.024",
			"date": "2012-07-30",
			"PMC": "",
			"citation": "",
			"abstract": "All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed \"kataegis,\" was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed.",
			"category": 2,
			"name": "Nik-Zainal Serena,2012"
		},
		{
			"PMID": 22608083,
			"title": "The life history of 21 breast cancers.",
			"journal": "Cell",
			"authorList": [
				"Nik-Zainal Serena",
				"Van Loo Peter",
				"Wedge David C",
				"Alexandrov Ludmil B",
				"Greenman Christopher D",
				"Lau King Wai",
				"Raine Keiran",
				"Jones David",
				"Marshall John",
				"Ramakrishna Manasa",
				"Shlien Adam",
				"Cooke Susanna L",
				"Hinton Jonathan",
				"Menzies Andrew",
				"Stebbings Lucy A",
				"Leroy Catherine",
				"Jia Mingming",
				"Rance Richard",
				"Mudie Laura J",
				"Gamble Stephen J",
				"Stephens Philip J",
				"McLaren Stuart",
				"Tarpey Patrick S",
				"Papaemmanuil Elli",
				"Davies Helen R",
				"Varela Ignacio",
				"McBride David J",
				"Bignell Graham R",
				"Leung Kenric",
				"Butler Adam P",
				"Teague Jon W",
				"Martin Sancha",
				"J\u00f6nsson Goran",
				"Mariani Odette",
				"Boyault Sandrine",
				"Miron Penelope",
				"Fatima Aquila",
				"Langer\u00f8d Anita",
				"Aparicio Samuel A J R",
				"Tutt Andrew",
				"Sieuwerts Anieta M",
				"Borg \u00c5ke",
				"Thomas Gilles",
				"Salomon Anne Vincent",
				"Richardson Andrea L",
				"B\u00f8rresen-Dale Anne-Lise",
				"Futreal P Andrew",
				"Stratton Michael R",
				"Campbell Peter J",
				"Breast Cancer Working Group of the International Cancer Genome Consortium"
			],
			"DOI": "10.1016/j.cell.2012.04.023",
			"date": "2012-07-30",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer evolves dynamically as clonal expansions supersede one another driven by shifting selective pressures, mutational processes, and disrupted cancer genes. These processes mark the genome, such that a cancer's life history is encrypted in the somatic mutations present. We developed algorithms to decipher this narrative and applied them to 21 breast cancers. Mutational processes evolve across a cancer's lifespan, with many emerging late but contributing extensive genetic variation. Subclonal diversification is prominent, and most mutations are found in just a fraction of tumor cells. Every tumor has a dominant subclonal lineage, representing more than 50% of tumor cells. Minimal expansion of these subclones occurs until many hundreds to thousands of mutations have accumulated, implying the existence of long-lived, quiescent cell lineages capable of substantial proliferation upon acquisition of enabling genomic changes. Expansion of the dominant subclone to an appreciable mass may therefore represent the final rate-limiting step in a breast cancer's development, triggering diagnosis.",
			"category": 2,
			"name": "Nik-Zainal Serena,2012"
		},
		{
			"PMID": 22590557,
			"title": "Differential pathogenesis of lung adenocarcinoma subtypes involving sequence mutations, copy number, chromosomal instability, and methylation.",
			"journal": "PloS one",
			"authorList": [
				"Wilkerson Matthew D",
				"Yin Xiaoying",
				"Walter Vonn",
				"Zhao Ni",
				"Cabanski Christopher R",
				"Hayward Michele C",
				"Miller C Ryan",
				"Socinski Mark A",
				"Parsons Alden M",
				"Thorne Leigh B",
				"Haithcock Benjamin E",
				"Veeramachaneni Nirmal K",
				"Funkhouser William K",
				"Randell Scott H",
				"Bernard Philip S",
				"Perou Charles M",
				"Hayes D Neil"
			],
			"DOI": "10.1371/journal.pone.0036530",
			"date": "2012-09-19",
			"PMC": "",
			"citation": "",
			"abstract": "Lung adenocarcinoma (LAD) has extreme genetic variation among patients, which is currently not well understood, limiting progress in therapy development and research. LAD intrinsic molecular subtypes are a validated stratification of naturally-occurring gene expression patterns and encompass different functional pathways and patient outcomes. Patients may have incurred different mutations and alterations that led to the different subtypes. We hypothesized that the LAD molecular subtypes co-occur with distinct mutations and alterations in patient tumors.",
			"category": 2,
			"name": "Wilkerson Matthew D,2012"
		},
		{
			"PMID": 22586510,
			"title": "The use of molecular profiling for diagnosis and research in non-Hodgkin's lymphoma.",
			"journal": "Hematology reports",
			"authorList": [
				"Piris Miguel Angel"
			],
			"DOI": "10.4081/hr.2011.s3.e2",
			"date": "2012-10-02",
			"PMC": "",
			"citation": "",
			"abstract": "Molecular profiling facilitates the understanding of the genetic processes underlying the development of cancer, and makes it possible to use specific signatures to prognosticate clinical outcome and to predict response to specific treatments. There has been a great increase in the availability of tools for exploring genetic abnormalities in cancer cells, which have allowed a more comprehensive characterization of the mutations, translocations, and copy-number variations that may affect the development of cancer or therapy response. An improved understanding of the molecular basis of cancer is helping also in the identification of new molecular targets for therapy.",
			"category": 2,
			"name": "Piris Miguel Angel,2012"
		},
		{
			"PMID": 22585170,
			"title": "High-throughput detection of actionable genomic alterations in clinical tumor samples by targeted, massively parallel sequencing.",
			"journal": "Cancer discovery",
			"authorList": [
				"Wagle Nikhil",
				"Berger Michael F",
				"Davis Matthew J",
				"Blumenstiel Brendan",
				"Defelice Matthew",
				"Pochanard Panisa",
				"Ducar Matthew",
				"Van Hummelen Paul",
				"Macconaill Laura E",
				"Hahn William C",
				"Meyerson Matthew",
				"Gabriel Stacey B",
				"Garraway Levi A"
			],
			"DOI": "10.1158/2159-8290.CD-11-0184",
			"date": "2013-01-15",
			"PMC": "",
			"citation": "",
			"abstract": "Knowledge of \"actionable\" somatic genomic alterations present in each tumor (e.g., point mutations, small insertions/deletions, and copy-number alterations that direct therapeutic options) should facilitate individualized approaches to cancer treatment. However, clinical implementation of systematic genomic profiling has rarely been achieved beyond limited numbers of oncogene point mutations. To address this challenge, we utilized a targeted, massively parallel sequencing approach to detect tumor genomic alterations in formalin-fixed, paraffin-embedded (FFPE) tumor samples. Nearly 400-fold mean sequence coverage was achieved, and single-nucleotide sequence variants, small insertions/deletions, and chromosomal copynumber alterations were detected simultaneously with high accuracy compared with other methods in clinical use. Putatively actionable genomic alterations, including those that predict sensitivity or resistance to established and experimental therapies, were detected in each tumor sample tested. Thus, targeted deep sequencing of clinical tumor material may enable mutation-driven clinical trials and, ultimately, \"personalized\" cancer treatment.",
			"category": 2,
			"name": "Wagle Nikhil,2013"
		},
		{
			"PMID": 22582146,
			"title": "Developing genetically engineered mouse models to study tumor suppression.",
			"journal": "Current protocols in mouse biology",
			"authorList": [
				"Xiong Shunbin",
				"Parker-Thornburg Jan",
				"Lozano Guillermina"
			],
			"DOI": "10.1002/9780470942390.mo110159",
			"date": "2022-10-05",
			"PMC": "",
			"citation": "",
			"abstract": "Since the late 1980s, the tools to generate mice with deletions of tumor suppressors have made it possible to study such deletions in the context of a whole animal. Deletion of some tumor suppressors results in viable mice while deletion of others yield embryo lethal phenotypes cementing the concept that genes that often go awry in cancer are also of developmental importance. More sophisticated mouse models were subsequently developed to delete a gene in a specific cell type at a specific time point. Additionally, incorporation of point mutations in a specific gene as observed in human tumors has also revealed their contributions to tumorigenesis. On the other hand, some models never develop cancer unless combined with other deletions suggesting a modifying role in tumorigenesis. This review will describe the technical aspects of generating these mice and provide examples of the outcomes obtained from alterations of different tumor suppressors.",
			"category": 2,
			"name": "Xiong Shunbin,2022"
		},
		{
			"PMID": 22567329,
			"title": "Recent advances in molecular technologies and their application in pathogen detection in foods with particular reference to yersinia.",
			"journal": "Journal of pathogens",
			"authorList": [
				"Gui Jin",
				"Patel Isha R"
			],
			"DOI": "10.4061/2011/310135",
			"date": "2012-08-23",
			"PMC": "",
			"citation": "",
			"abstract": "Yersinia enterocolitica is an important zoonotic pathogen that can cause yersiniosis in humans and animals. Food has been suggested to be the main source of yersiniosis. It is critical for the researchers to be able to detect Yersinia or any other foodborne pathogen with increased sensitivity and specificity, as well as in real-time, in the case of a foodborne disease outbreak. Conventional detection methods are known to be labor intensive, time consuming, or expensive. On the other hand, more sensitive molecular-based detection methods like next generation sequencing, microarray, and many others are capable of providing faster results. DNA testing is now possible on a single molecule, and high-throughput analysis allows multiple detection reactions to be performed at once, thus allowing a range of characteristics to be rapidly and simultaneously determined. Despite better detection efficiencies, results derived using molecular biology methods can be affected by the various food matrixes. With the improvements in sample preparation, data analysis, and testing procedures, molecular detection techniques will likely continue to simplify and increase the speed of detection while simultaneously improving the sensitivity and specificity for tracking pathogens in food matrices.",
			"category": 2,
			"name": "Gui Jin,2012"
		},
		{
			"PMID": 22550129,
			"title": "Next generation sequencing and a new era of medicine.",
			"journal": "Gut",
			"authorList": [
				"Casey Graham",
				"Conti David",
				"Haile Robert",
				"Duggan David"
			],
			"DOI": "10.1136/gutjnl-2011-301935",
			"date": "2013-07-02",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Casey Graham,2013"
		},
		{
			"PMID": 22549840,
			"title": "Reliable detection of subclonal single-nucleotide variants in tumour cell populations.",
			"journal": "Nature communications",
			"authorList": [
				"Gerstung Moritz",
				"Beisel Christian",
				"Rechsteiner Markus",
				"Wild Peter",
				"Schraml Peter",
				"Moch Holger",
				"Beerenwinkel Niko"
			],
			"DOI": "10.1038/ncomms1814",
			"date": "2012-07-26",
			"PMC": "",
			"citation": "",
			"abstract": "According to the clonal evolution model, tumour growth is driven by competing subclones in somatically evolving cancer cell populations, which gives rise to genetically heterogeneous tumours. Here we present a comparative targeted deep-sequencing approach combined with a customised statistical algorithm, called deepSNV, for detecting and quantifying subclonal single-nucleotide variants in mixed populations. We show in a rigorous experimental assessment that our approach is capable of detecting variants with frequencies as low as 1/10,000 alleles. In selected genomic loci of the TP53 and VHL genes isolated from matched tumour and normal samples of four renal cell carcinoma patients, we detect 24 variants at allele frequencies ranging from 0.0002 to 0.34. Moreover, we demonstrate how the allele frequencies of known single-nucleotide polymorphisms can be exploited to detect loss of heterozygosity. Our findings demonstrate that genomic diversity is common in renal cell carcinomas and provide quantitative evidence for the clonal evolution model.",
			"category": 2,
			"name": "Gerstung Moritz,2012"
		},
		{
			"PMID": 22539962,
			"title": "Integrative subtype discovery in glioblastoma using iCluster.",
			"journal": "PloS one",
			"authorList": [
				"Shen Ronglai",
				"Mo Qianxing",
				"Schultz Nikolaus",
				"Seshan Venkatraman E",
				"Olshen Adam B",
				"Huse Jason",
				"Ladanyi Marc",
				"Sander Chris"
			],
			"DOI": "10.1371/journal.pone.0035236",
			"date": "2012-09-10",
			"PMC": "",
			"citation": "",
			"abstract": "Large-scale cancer genome projects, such as the Cancer Genome Atlas (TCGA) project, are comprehensive molecular characterization efforts to accelerate our understanding of cancer biology and the discovery of new therapeutic targets. The accumulating wealth of multidimensional data provides a new paradigm for important research problems including cancer subtype discovery. The current standard approach relies on separate clustering analyses followed by manual integration. Results can be highly data type dependent, restricting the ability to discover new insights from multidimensional data. In this study, we present an integrative subtype analysis of the TCGA glioblastoma (GBM) data set. Our analysis revealed new insights through integrated subtype characterization. We found three distinct integrated tumor subtypes. Subtype 1 lacks the classical GBM events of chr 7 gain and chr 10 loss. This subclass is enriched for the G-CIMP phenotype and shows hypermethylation of genes involved in brain development and neuronal differentiation. The tumors in this subclass display a Proneural expression profile. Subtype 2 is characterized by a near complete association with EGFR amplification, overrepresentation of promoter methylation of homeobox and G-protein signaling genes, and a Classical expression profile. Subtype 3 is characterized by NF1 and PTEN alterations and exhibits a Mesenchymal-like expression profile. The data analysis workflow we propose provides a unified and computationally scalable framework to harness the full potential of large-scale integrated cancer genomic data for integrative subtype discovery.",
			"category": 2,
			"name": "Shen Ronglai,2012"
		},
		{
			"PMID": 22535522,
			"title": "Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response.",
			"journal": "Molecular biology of the cell",
			"authorList": [
				"Tang Ho Lam",
				"Tang Ho Man",
				"Mak Keng Hou",
				"Hu Shaomin",
				"Wang Shan Shan",
				"Wong Kit Man",
				"Wong Chung Sing Timothy",
				"Wu Hoi Yan",
				"Law Hiu Tung",
				"Liu Kan",
				"Talbot C Conover",
				"Lau Wan Keung",
				"Montell Denise J",
				"Fung Ming Chiu"
			],
			"DOI": "10.1091/mbc.E11-11-0926",
			"date": "2012-10-10",
			"PMC": "",
			"citation": "",
			"abstract": "Apoptosis serves as a protective mechanism by eliminating damaged cells through programmed cell death. After apoptotic cells pass critical checkpoints, including mitochondrial fragmentation, executioner caspase activation, and DNA damage, it is assumed that cell death inevitably follows. However, this assumption has not been tested directly. Here we report an unexpected reversal of late-stage apoptosis in primary liver and heart cells, macrophages, NIH 3T3 fibroblasts, cervical cancer HeLa cells, and brain cells. After exposure to an inducer of apoptosis, cells exhibited multiple morphological and biochemical hallmarks of late-stage apoptosis, including mitochondrial fragmentation, caspase-3 activation, and DNA damage. Surprisingly, the vast majority of dying cells arrested the apoptotic process and recovered when the inducer was washed away. Of importance, some cells acquired permanent genetic changes and underwent oncogenic transformation at a higher frequency than controls. Global gene expression analysis identified a molecular signature of the reversal process. We propose that reversal of apoptosis is an unanticipated mechanism to rescue cells from crisis and propose to name this mechanism \"anastasis\" (Greek for \"rising to life\"). Whereas carcinogenesis represents a harmful side effect, potential benefits of anastasis could include preservation of cells that are difficult to replace and stress-induced genetic diversity.",
			"category": 2,
			"name": "Tang Ho Lam,2012"
		},
		{
			"PMID": 22516585,
			"title": "Molecular pathology.",
			"journal": "Molecular oncology",
			"authorList": [
				"Hamilton Stanley R"
			],
			"DOI": "10.1016/j.molonc.2012.02.007",
			"date": "2012-08-23",
			"PMC": "",
			"citation": "",
			"abstract": "Molecular pathology as applied to neoplasia is a rapidly expanding component of the discipline of pathology that uses molecular biology tools in addition to conventional morphologic, immunohistochemical and chemical analyses of abnormalities in tissues and cells to understand the etiology and pathogenesis of tumors, establish their diagnosis, and contribute to prognostication and therapeutic decisions for cancer patient care. Biomarkers are a fundamental component of personalized cancer care, and the discipline of molecular pathology therefore contributes throughout the continuum from biomarker research to use in standard-of-care personalized cancer therapy. This brief review addresses some of the specific roles of molecular pathology in that continuum.",
			"category": 2,
			"name": "Hamilton Stanley R,2012"
		},
		{
			"PMID": 22508724,
			"title": "Emerging insights into the molecular and cellular basis of glioblastoma.",
			"journal": "Genes & development",
			"authorList": [
				"Dunn Gavin P",
				"Rinne Mikael L",
				"Wykosky Jill",
				"Genovese Giannicola",
				"Quayle Steven N",
				"Dunn Ian F",
				"Agarwalla Pankaj K",
				"Chheda Milan G",
				"Campos Benito",
				"Wang Alan",
				"Brennan Cameron",
				"Ligon Keith L",
				"Furnari Frank",
				"Cavenee Webster K",
				"Depinho Ronald A",
				"Chin Lynda",
				"Hahn William C"
			],
			"DOI": "10.1101/gad.187922.112",
			"date": "2012-06-15",
			"PMC": "",
			"citation": "",
			"abstract": "Glioblastoma is both the most common and lethal primary malignant brain tumor. Extensive multiplatform genomic characterization has provided a higher-resolution picture of the molecular alterations underlying this disease. These studies provide the emerging view that \"glioblastoma\" represents several histologically similar yet molecularly heterogeneous diseases, which influences taxonomic classification systems, prognosis, and therapeutic decisions.",
			"category": 2,
			"name": "Dunn Gavin P,2012"
		},
		{
			"PMID": 22504875,
			"title": "Nuclear morphometry, nucleomics and prostate cancer progression.",
			"journal": "Asian journal of andrology",
			"authorList": [
				"Veltri Robert W",
				"Christudass Christhunesa S",
				"Isharwal Sumit"
			],
			"DOI": "10.1038/aja.2011.148",
			"date": "2012-09-20",
			"PMC": "",
			"citation": "",
			"abstract": "Prostate cancer (PCa) results from a multistep process. This process includes initiation, which occurs through various aging events and multiple insults (such as chronic infection, inflammation and genetic instability through reactive oxygen species causing DNA double-strand breaks), followed by a multistep process of progression. These steps include several genetic and epigenetic alterations, as well as alterations to the chromatin structure, which occur in response to the carcinogenic stress-related events that sustain proliferative signaling. Events such as evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis are readily observed. In addition, in conjunction with these critical drivers of carcinogenesis, other factors related to the etiopathogenesis of PCa, involving energy metabolism and evasion of the immune surveillance system, appear to be involved. In addition, when cancer spread and metastasis occur, the 'tumor microenvironment' in the bone of PCa patients may provide a way to sustain dormancy or senescence and eventually establish a 'seed and soil' site where PCa proliferation and growth may occur over time. When PCa is initiated and progression ensues, significant alterations in nuclear size, shape and heterochromatin (DNA transcription) organization are found, and key nuclear transcriptional and structural proteins, as well as multiple nuclear bodies can lead to precancerous and malignant changes. These series of cellular and tissue-related malignancy-associated events can be quantified to assess disease progression and management.",
			"category": 2,
			"name": "Veltri Robert W,2012"
		},
		{
			"PMID": 22494239,
			"title": "Multiple cellular mechanisms prevent chromosomal rearrangements involving repetitive DNA.",
			"journal": "Critical reviews in biochemistry and molecular biology",
			"authorList": [
				"George Carolyn M",
				"Alani Eric"
			],
			"DOI": "10.3109/10409238.2012.675644",
			"date": "2012-08-13",
			"PMC": "",
			"citation": "",
			"abstract": "Repetitive DNA is present in the eukaryotic genome in the form of segmental duplications, tandem and interspersed repeats, and satellites. Repetitive sequences can be beneficial by serving specific cellular functions (e.g. centromeric and telomeric DNA) and by providing a rapid means for adaptive evolution. However, such elements are also substrates for deleterious chromosomal rearrangements that affect fitness and promote human disease. Recent studies analyzing the role of nuclear organization in DNA repair and factors that suppress non-allelic homologous recombination (NAHR) have provided insights into how genome stability is maintained in eukaryotes. In this review, we outline the types of repetitive sequences seen in eukaryotic genomes and how recombination mechanisms are regulated at the DNA sequence, cell organization, chromatin structure, and cell cycle control levels to prevent chromosomal rearrangements involving these sequences.",
			"category": 2,
			"name": "George Carolyn M,2012"
		},
		{
			"PMID": 22492711,
			"title": "An analysis of substitution, deletion and insertion mutations in cancer genes.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Iengar Prathima"
			],
			"DOI": "10.1093/nar/gks290",
			"date": "2012-11-05",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer-associated mutations in cancer genes constitute a diverse set of mutations associated with the disease. To gain insight into features of the set, substitution, deletion and insertion mutations were analysed at the nucleotide level, from the COSMIC database. The most frequent substitutions were c \u2192 t, g \u2192 a, g \u2192 t, and the most frequent codon changes were to termination codons. Deletions more than insertions, FS (frameshift) indels more than I-F (in-frame) ones, and single-nucleotide indels, were frequent. FS indels cause loss of significant fractions of proteins. The 5'-cut in FS deletions, and 5'-ligation in FS insertions, often occur between pairs of identical bases. Interestingly, the cut-site and 3'-ligation in insertions, and 3'-cut and join-pair in deletions, were each found to be the same significantly often (p < 0.001). It is suggested that these features aid the incorporation of indel mutations. Tumor suppressors undergo larger numbers of mutations, especially disruptive ones, over the entire protein length, to inactivate two alleles. Proto-oncogenes undergo fewer, less-disruptive mutations, in selected protein regions, to activate a single allele. Finally, catalogues, in ranked order, of genes mutated in each cancer, and cancers in which each gene is mutated, were created. The study highlights the nucleotide level preferences and disruptive nature of cancer mutations.",
			"category": 2,
			"name": "Iengar Prathima,2012"
		},
		{
			"PMID": 22489325,
			"title": "Perspectives on personalized cancer care.",
			"journal": "Urologic oncology",
			"authorList": [
				"Dancika Garrett M",
				"Theodorescu Dan"
			],
			"DOI": "",
			"date": "2012-06-26",
			"PMC": "",
			"citation": "",
			"abstract": "Sir William Osler has been quoted as saying \u201c",
			"category": 2,
			"name": "Dancika Garrett M,2012"
		},
		{
			"PMID": 22451720,
			"title": "Targeting of KRAS mutant tumors by HSP90 inhibitors involves degradation of STK33.",
			"journal": "The Journal of experimental medicine",
			"authorList": [
				"Azoitei Ninel",
				"Hoffmann Christopher M",
				"Ellegast Jana M",
				"Ball Claudia R",
				"Obermayer Kerstin",
				"G\u00f6\u00dfele Ulrike",
				"Koch Britta",
				"Faber Katrin",
				"Genze Felicitas",
				"Schrader Mark",
				"Kestler Hans A",
				"D\u00f6hner Hartmut",
				"Chiosis Gabriela",
				"Glimm Hanno",
				"Fr\u00f6hling Stefan",
				"Scholl Claudia"
			],
			"DOI": "10.1084/jem.20111910",
			"date": "2012-06-04",
			"PMC": "",
			"citation": "",
			"abstract": "Previous efforts to develop drugs that directly inhibit the activity of mutant KRAS, the most commonly mutated human oncogene, have not been successful. Cancer cells driven by mutant KRAS require expression of the serine/threonine kinase STK33 for their viability and proliferation, identifying STK33 as a context-dependent therapeutic target. However, specific strategies for interfering with the critical functions of STK33 are not yet available. Here, using a mass spectrometry-based screen for STK33 protein interaction partners, we report that the HSP90/CDC37 chaperone complex binds to and stabilizes STK33 in human cancer cells. Pharmacologic inhibition of HSP90, using structurally divergent small molecules currently in clinical development, induced proteasome-mediated degradation of STK33 in human cancer cells of various tissue origin in vitro and in vivo, and triggered apoptosis preferentially in KRAS mutant cells in an STK33-dependent manner. Furthermore, HSP90 inhibitor treatment impaired sphere formation and viability of primary human colon tumor-initiating cells harboring mutant KRAS. These findings provide mechanistic insight into the activity of HSP90 inhibitors in KRAS mutant cancer cells, indicate that the enhanced requirement for STK33 can be exploited to target mutant KRAS-driven tumors, and identify STK33 depletion through HSP90 inhibition as a biomarker-guided therapeutic strategy with immediate translational potential.",
			"category": 2,
			"name": "Azoitei Ninel,2012"
		},
		{
			"PMID": 22441987,
			"title": "Loss of giant obscurins promotes breast epithelial cell survival through apoptotic resistance.",
			"journal": "FASEB journal : official publication of the Federation of American Societies for Experimental Biology",
			"authorList": [
				"Perry Nicole A",
				"Shriver Marey",
				"Mameza Marie G",
				"Grabias Bryan",
				"Balzer Eric",
				"Kontrogianni-Konstantopoulos Aikaterini"
			],
			"DOI": "10.1096/fj.12-205419",
			"date": "2012-09-20",
			"PMC": "",
			"citation": "",
			"abstract": "Obscurins (\u223c70 - 870 kDa), encoded by the single OBSCN gene, are cytoskeletal proteins originally identified in striated muscles with structural and regulatory roles. Recently, analysis of 13,023 genes in breast and colorectal cancers identified OBSCN as one of the most frequently mutated genes, implicating it in cancer formation. Herein we studied the expression profile of obscurins in breast, colon, and skin cancer cell lines and their involvement in cell survival. Immunoblot analysis demonstrated significant reduction of obscurin proteins [corrected] in cancer cells, resulting from decreased mRNA levels and/or the presence of mutant transcripts. In normal epithelium, obscurins localize in cytoplasmic puncta, the cell membrane, and the nucleus. Accordingly, subcellular fractionation demonstrated the presence of 2 novel nuclear isoforms of \u223c110 and \u223c120 kDa. Nontumorigenic MCF10A breast epithelial cells stably transduced with shRNAs targeting giant obscurins exhibited increased viability (\u223c30%) and reduced apoptosis (\u223c20%) following exposure to the DNA-damaging agent etoposide. Quantitative RT-PCR further indicated that the antiapoptotic genes BAG4 and HAX1 were up-regulated (1.5- and 1.4-fold, respectively), whereas initiator caspase-9 and death caspase-3 transcripts were down-regulated (0.8- and 0.6-fold, respectively). Our findings are the first to pinpoint critical roles for obscurins in cancer development by contributing to the regulation of cell survival.",
			"category": 2,
			"name": "Perry Nicole A,2012"
		},
		{
			"PMID": 22370636,
			"title": "Conditional activation of Pik3ca(H1047R) in a knock-in mouse model promotes mammary tumorigenesis and emergence of mutations.",
			"journal": "Oncogene",
			"authorList": [
				"Yuan W",
				"Stawiski E",
				"Janakiraman V",
				"Chan E",
				"Durinck S",
				"Edgar K A",
				"Kljavin N M",
				"Rivers C S",
				"Gnad F",
				"Roose-Girma M",
				"Haverty P M",
				"Fedorowicz G",
				"Heldens S",
				"Soriano R H",
				"Zhang Z",
				"Wallin J J",
				"Johnson L",
				"Merchant M",
				"Modrusan Z",
				"Stern H M",
				"Seshagiri S"
			],
			"DOI": "10.1038/onc.2012.53",
			"date": "2013-03-11",
			"PMC": "",
			"citation": "",
			"abstract": "Oncogenic mutations in PIK3CA, which encodes the phosphoinositide-3-kinase (PI3K) catalytic subunit p110\u03b1, occur in \u223c25% of human breast cancers. In this study, we report the development of a knock-in mouse model for breast cancer where the endogenous Pik3ca allele was modified to allow tissue-specific conditional expression of a frequently found Pik3ca(H1047R) (Pik3ca(e20H1047R)) mutant allele. We found that activation of the latent Pik3ca(H1047R) allele resulted in breast tumors with multiple histological types. Whole-exome analysis of the Pik3ca(H1047R)-driven mammary tumors identified multiple mutations, including Trp53 mutations that appeared spontaneously during the development of adenocarinoma and spindle cell tumors. Further, we used this model to test the efficacy of GDC-0941, a PI3K inhibitor, in clinical development, and showed that the tumors respond to PI3K inhibition.",
			"category": 2,
			"name": "Yuan W,2013"
		},
		{
			"PMID": 22355534,
			"title": "A novel potent tumour promoter aberrantly overexpressed in most human cancers.",
			"journal": "Scientific reports",
			"authorList": [
				"Takahashi Atsushi",
				"Tokita Hisashi",
				"Takahashi Kenzo",
				"Takeoka Tomoharu",
				"Murayama Kosho",
				"Tomotsune Daihachiro",
				"Ohira Miki",
				"Iwamatsu Akihiro",
				"Ohara Kazuaki",
				"Yazaki Kazufumi",
				"Koda Tadayuki",
				"Nakagawara Akira",
				"Tani Kenzaburo"
			],
			"DOI": "10.1038/srep00015",
			"date": "2013-08-28",
			"PMC": "",
			"citation": "",
			"abstract": "The complexity and heterogeneity of tumours have hindered efforts to identify commonalities among different cancers. Furthermore, because we have limited information on the prevalence and nature of ubiquitous molecular events that occur in neoplasms, it is unfeasible to implement molecular-targeted cancer screening and prevention. Here, we found that the FEAT protein is overexpressed in most human cancers, but weakly expressed in normal tissues including the testis, brain, and liver. Transgenic mice that ectopically expressed FEAT in the thymus, spleen, liver, and lung spontaneously developed invasive malignant lymphoma (48%, 19/40) and lung-metastasizing liver cancer (hepatocellular carcinoma) (35%, 14/40) that models human hepatocarcinogenesis, indicating the FEAT protein potently drives tumorigenesis in vivo. Gene expression profiling suggested that FEAT drives receptor tyrosine kinase and hedgehog signalling pathways. These findings demonstrate that integrated efforts to identify FEAT-like ubiquitous oncoproteins are useful and may provide promising approaches for cost-effective cancer screening and prevention.",
			"category": 2,
			"name": "Takahashi Atsushi,2013"
		},
		{
			"PMID": 22349821,
			"title": "Clonal evolution of acute leukemia genomes.",
			"journal": "Oncogene",
			"authorList": [
				"Jan M",
				"Majeti R"
			],
			"DOI": "10.1038/onc.2012.48",
			"date": "2013-03-05",
			"PMC": "",
			"citation": "",
			"abstract": "In large part, cancer results from the accumulation of multiple mutations in a single cell lineage that are sequentially acquired and subject to an evolutionary process where selection drives the expansion of more fit subclones. Owing to the technical challenge of distinguishing and isolating distinct cancer subclones, many aspects of this clonal evolution are poorly understood, including the diversity of different subclones in an individual cancer, the nature of the subclones contributing to relapse, and the identity of pre-cancerous mutations. These issues are not just important to our understanding of cancer biology, but are also clinically important given the need to understand the nature of subclones responsible for the refractory and relapsed disease that cause significant morbidity and mortality in patients. Recently, advanced genomic techniques have been used to investigate clonal diversity and evolution in acute leukemia. Studies of pediatric acute lymphoblastic leukemia (ALL) demonstrated that in individual patients there are multiple genetic subclones of leukemia-initiating cells, with a complex clonal architecture. Separate studies also investigating pediatric ALL determined that the clonal basis of relapse was variable and complex, with relapse often evolving from a clone ancestral to the predominant de novo leukemia clone. Additional studies in both ALL and acute myeloid leukemia have identified pre-leukemic mutations in some individual cases. This review will highlight these recent reports investigating the clonal evolution of acute leukemia genomes and discuss the implications for clinical therapy.",
			"category": 2,
			"name": "Jan M,2013"
		},
		{
			"PMID": 22342219,
			"title": "Exploiting genetic complexity in cancer to improve therapeutic strategies.",
			"journal": "Drug discovery today",
			"authorList": [
				"Garnett Mathew J",
				"McDermott Ultan"
			],
			"DOI": "10.1016/j.drudis.2012.01.025",
			"date": "2012-06-28",
			"PMC": "",
			"citation": "",
			"abstract": "Advances in genome sequencing technologies are enabling researchers to make rapid progress in defining the entire repertoire of causal genetic changes in cancer. The response of patients with cancer to therapy is often highly variable and there is an increasing number of examples where mutations in cancer genomes have been shown to have a profound effect on the clinical effectiveness of drugs. An urgent challenge for the research and clinical communities is how to translate these genomic data sets into new and improved therapeutic strategies for the treatment of patients. The use of large-scale cell line-based drug screens to identify genomic 'biomarkers' of drug response for the stratification of patients has the potential to transform how patients with cancer are treated.",
			"category": 2,
			"name": "Garnett Mathew J,2012"
		},
		{
			"PMID": 22341455,
			"title": "Telomerase reactivation following telomere dysfunction yields murine prostate tumors with bone metastases.",
			"journal": "Cell",
			"authorList": [
				"Ding Zhihu",
				"Wu Chang-Jiun",
				"Jaskelioff Mariela",
				"Ivanova Elena",
				"Kost-Alimova Maria",
				"Protopopov Alexei",
				"Chu Gerald C",
				"Wang Guocan",
				"Lu Xin",
				"Labrot Emma S",
				"Hu Jian",
				"Wang Wei",
				"Xiao Yonghong",
				"Zhang Hailei",
				"Zhang Jianhua",
				"Zhang Jingfang",
				"Gan Boyi",
				"Perry Samuel R",
				"Jiang Shan",
				"Li Liren",
				"Horner James W",
				"Wang Y Alan",
				"Chin Lynda",
				"DePinho Ronald A"
			],
			"DOI": "10.1016/j.cell.2012.01.039",
			"date": "2012-04-20",
			"PMC": "",
			"citation": "",
			"abstract": "To determine the role of telomere dysfunction and telomerase reactivation in generating pro-oncogenic genomic events and in carcinoma progression, an inducible telomerase reverse transcriptase (mTert) allele was crossed onto a prostate cancer-prone mouse model null for Pten and p53 tumor suppressors. Constitutive telomerase deficiency and associated telomere dysfunction constrained cancer progression. In contrast, telomerase reactivation in the setting of telomere dysfunction alleviated intratumoral DNA-damage signaling and generated aggressive cancers with rearranged genomes and new tumor biological properties (bone metastases). Comparative oncogenomic analysis revealed numerous recurrent amplifications and deletions of relevance to human prostate cancer. Murine tumors show enrichment of the TGF-\u03b2/SMAD4 network, and genetic validation studies confirmed the cooperative roles of Pten, p53, and Smad4 deficiencies in prostate cancer progression, including skeletal metastases. Thus, telomerase reactivation in tumor cells experiencing telomere dysfunction enables full malignant progression and provides a mechanism for acquisition of cancer-relevant genomic events endowing new tumor biological capabilities.",
			"category": 2,
			"name": "Ding Zhihu,2012"
		},
		{
			"PMID": 22303399,
			"title": "When one and one gives more than two: challenges and opportunities of integrative omics.",
			"journal": "Frontiers in genetics",
			"authorList": [
				"Choi Hyungwon",
				"Pavelka Norman"
			],
			"DOI": "10.3389/fgene.2011.00105",
			"date": "2012-10-02",
			"PMC": "",
			"citation": "",
			"abstract": "Since the dawn of the post-genomic era a myriad of novel high-throughput technologies have been developed that are capable of measuring thousands of biological molecules at once, giving rise to various \"omics\" platforms. These advances offer the unique opportunity to study how individual parts of a biological system work together to produce emerging phenotypes. Today, many research laboratories are moving toward applying multiple omics platforms to analyze the same biological samples. In addition, network information of interacting molecules is being incorporated more and more into the analysis and interpretation of these multiple omics datasets, which provides novel ways to integrate multiple layers of heterogeneous biological information into a single coherent picture. Here, we provide a perspective on how such recent \"integrative omics\" efforts are likely going to shift biological paradigms once again, and what challenges lie ahead.",
			"category": 2,
			"name": "Choi Hyungwon,2012"
		},
		{
			"PMID": 22302147,
			"title": "cn.MOPS: mixture of Poissons for discovering copy number variations in next-generation sequencing data with a low false discovery rate.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Klambauer G\u00fcnter",
				"Schwarzbauer Karin",
				"Mayr Andreas",
				"Clevert Djork-Arn\u00e9",
				"Mitterecker Andreas",
				"Bodenhofer Ulrich",
				"Hochreiter Sepp"
			],
			"DOI": "10.1093/nar/gks003",
			"date": "2012-07-17",
			"PMC": "",
			"citation": "",
			"abstract": "Quantitative analyses of next-generation sequencing (NGS) data, such as the detection of copy number variations (CNVs), remain challenging. Current methods detect CNVs as changes in the depth of coverage along chromosomes. Technological or genomic variations in the depth of coverage thus lead to a high false discovery rate (FDR), even upon correction for GC content. In the context of association studies between CNVs and disease, a high FDR means many false CNVs, thereby decreasing the discovery power of the study after correction for multiple testing. We propose 'Copy Number estimation by a Mixture Of PoissonS' (cn.MOPS), a data processing pipeline for CNV detection in NGS data. In contrast to previous approaches, cn.MOPS incorporates modeling of depths of coverage across samples at each genomic position. Therefore, cn.MOPS is not affected by read count variations along chromosomes. Using a Bayesian approach, cn.MOPS decomposes variations in the depth of coverage across samples into integer copy numbers and noise by means of its mixture components and Poisson distributions, respectively. The noise estimate allows for reducing the FDR by filtering out detections having high noise that are likely to be false detections. We compared cn.MOPS with the five most popular methods for CNV detection in NGS data using four benchmark datasets: (i) simulated data, (ii) NGS data from a male HapMap individual with implanted CNVs from the X chromosome, (iii) data from HapMap individuals with known CNVs, (iv) high coverage data from the 1000 Genomes Project. cn.MOPS outperformed its five competitors in terms of precision (1-FDR) and recall for both gains and losses in all benchmark data sets. The software cn.MOPS is publicly available as an R package at http://www.bioinf.jku.at/software/cnmops/ and at Bioconductor.",
			"category": 2,
			"name": "Klambauer G\u00fcnter,2012"
		},
		{
			"PMID": 22269275,
			"title": "Applications of targeted gene capture and next-generation sequencing technologies in studies of human deafness and other genetic disabilities.",
			"journal": "Hearing research",
			"authorList": [
				"Lin Xi",
				"Tang Wenxue",
				"Ahmad Shoeb",
				"Lu Jingqiao",
				"Colby Candice C",
				"Zhu Jason",
				"Yu Qing"
			],
			"DOI": "10.1016/j.heares.2012.01.004",
			"date": "2012-10-10",
			"PMC": "",
			"citation": "",
			"abstract": "The goal of sequencing the entire human genome for $1000 is almost in sight. However, the total costs including DNA sequencing, data management, and analysis to yield a clear data interpretation are unlikely to be lowered significantly any time soon to make studies on a population scale and daily clinical uses feasible. Alternatively, the targeted enrichment of specific groups of disease and biological pathway-focused genes and the capture of up to an entire human exome (~1% of the genome) allowing an unbiased investigation of the complete protein-coding regions in the genome are now routine. Targeted gene capture followed by sequencing with massively parallel next-generation sequencing (NGS) has the advantages of 1) significant cost saving, 2) higher sequencing accuracy because of deeper achievable coverage, 3) a significantly shorter turnaround time, and 4) a more feasible data set for a bioinformatic analysis outcome that is functionally interpretable. Gene capture combined with NGS has allowed a much greater number of samples to be examined than is currently practical with whole-genome sequencing. Such an approach promises to bring a paradigm shift to biomedical research of Mendelian disorders and their clinical diagnoses, ultimately enabling personalized medicine based on one's genetic profile. In this review, we describe major methodologies currently used for gene capture and detection of genetic variations by NGS. We will highlight applications of this technology in studies of genetic disorders and discuss issues pertaining to applications of this powerful technology in genetic screening and the discovery of genes implicated in syndromic and non-syndromic hearing loss.",
			"category": 2,
			"name": "Lin Xi,2012"
		},
		{
			"PMID": 22262869,
			"title": "Gene signatures revisited.",
			"journal": "Journal of the National Cancer Institute",
			"authorList": [
				"Baker Stuart G"
			],
			"DOI": "10.1093/jnci/djr557",
			"date": "2012-04-12",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Baker Stuart G,2012"
		},
		{
			"PMID": 22262772,
			"title": "Microscale functional cytomics for studying hematologic cancers.",
			"journal": "Blood",
			"authorList": [
				"Young Edmond W K",
				"Pak Chorom",
				"Kahl Brad S",
				"Yang David T",
				"Callander Natalie S",
				"Miyamoto Shigeki",
				"Beebe David J"
			],
			"DOI": "10.1182/blood-2011-10-384347",
			"date": "2012-05-21",
			"PMC": "",
			"citation": "",
			"abstract": "An important problem in translational cancer research is our limited ability to functionally characterize behaviors of primary patient cancer cells and associated stromal cell types, and relate mechanistic understanding to therapy selection. Functional analyses of primary samples face at least 3 major challenges: limited availability of primary samples for testing, paucity of functional information extracted from samples, and lack of functional methods accessible to many researchers. We developed a microscale cell culture platform that overcomes these limitations, especially for hematologic cancers. A key feature of the platform is the ability to compartmentalize small populations of adherent and nonadherent cells in controlled microenvironments that can better reflect physiological conditions and enable cell-cell interaction studies. Custom image analysis was developed to measure cell viability and protein subcellular localizations in single cells to provide insights into heterogeneity of cellular responses. We validated our platform by assessing viability and nuclear translocations of NF-\u03baB and STAT3 in multiple myeloma cells exposed to different conditions, including cocultured bone marrow stromal cells. We further assessed its utility by analyzing NF-\u03baB activation in a primary chronic lymphocytic leukemia patient sample. Our platform can be applied to myriad biological questions, enabling high-content functional cytomics of primary hematologic malignancies.",
			"category": 2,
			"name": "Young Edmond W K,2012"
		},
		{
			"PMID": 22262009,
			"title": "Microarray analysis of copy number variation in single cells.",
			"journal": "Nature protocols",
			"authorList": [
				"Konings Peter",
				"Vanneste Evelyne",
				"Jackmaert Sigrun",
				"Ampe Mich\u00e8le",
				"Verbeke Geert",
				"Moreau Yves",
				"Vermeesch Joris Robert",
				"Voet Thierry"
			],
			"DOI": "10.1038/nprot.2011.426",
			"date": "2012-11-13",
			"PMC": "",
			"citation": "",
			"abstract": "We present a protocol for reliably detecting DNA copy number aberrations in a single human cell. Multiple displacement-amplified DNAs of a cell are hybridized to a 3,000-bacterial artificial chromosome (BAC) array and to an Affymetrix 250,000 (250K)-SNP array. Subsequent copy number calling is based on the integration of BAC probe-specific copy number probabilities that are estimated by comparing probe intensities with a single-cell whole-genome amplification (WGA) reference model for diploid chromosomes, as well as SNP copy number and loss-of-heterozygosity states estimated by hidden Markov models (HMM). All methods for detecting DNA copy number aberrations in single human cells have difficulty in confidently discriminating WGA artifacts from true genetic variants. Furthermore, some methods lack thorough validation for segmental DNA imbalance detection. Our protocol minimizes false-positive variant calling and enables uniparental isodisomy detection in single cells. Additionally, it provides quality assessment, allowing the exclusion of uninterpretable single-cell WGA samples. The protocol takes 5-7 d.",
			"category": 2,
			"name": "Konings Peter,2012"
		},
		{
			"PMID": 22258401,
			"title": "Quantification of subclonal distributions of recurrent genomic aberrations in paired pre-treatment and relapse samples from patients with B-cell chronic lymphocytic leukemia.",
			"journal": "Leukemia",
			"authorList": [
				"Knight S J L",
				"Yau C",
				"Clifford R",
				"Timbs A T",
				"Sadighi Akha E",
				"Dr\u00e9au H M",
				"Burns A",
				"Ciria C",
				"Oscier D G",
				"Pettitt A R",
				"Dutton S",
				"Holmes C C",
				"Taylor J",
				"Cazier J-B",
				"Schuh A"
			],
			"DOI": "10.1038/leu.2012.13",
			"date": "2012-10-09",
			"PMC": "",
			"citation": "",
			"abstract": "Genome-wide array approaches and sequencing analyses are powerful tools for identifying genetic aberrations in cancers, including leukemias and lymphomas. However, the clinical and biological significance of such aberrations and their subclonal distribution are poorly understood. Here, we present the first genome-wide array based study of pre-treatment and relapse samples from patients with B-cell chronic lymphocytic leukemia (B-CLL) that uses the computational statistical tool OncoSNP. We show that quantification of the proportion of copy number alterations (CNAs) and copy neutral loss of heterozygosity regions (cnLOHs) in each sample is feasible. Furthermore, we (i) reveal complex changes in the subclonal architecture of paired samples at relapse compared with pre-treatment, (ii) provide evidence supporting an association between increased genomic complexity and poor clinical outcome (iii) report previously undefined, recurrent CNA/cnLOH regions that expand or newly occur at relapse and therefore might harbor candidate driver genes of relapse and/or chemotherapy resistance. Our findings are likely to impact on future therapeutic strategies aimed towards selecting effective and individually tailored targeted therapies.",
			"category": 2,
			"name": "Knight S J L,2012"
		},
		{
			"PMID": 22234187,
			"title": "Endogenous DNA replication stress results in expansion of dNTP pools and a mutator phenotype.",
			"journal": "The EMBO journal",
			"authorList": [
				"Davidson Marta B",
				"Katou Yuki",
				"Keszthelyi Andrea",
				"Sing Tina L",
				"Xia Tian",
				"Ou Jiongwen",
				"Vaisica Jessica A",
				"Thevakumaran Neroshan",
				"Marjavaara Lisette",
				"Myers Chad L",
				"Chabes Andrei",
				"Shirahige Katsuhiko",
				"Brown Grant W"
			],
			"DOI": "10.1038/emboj.2011.485",
			"date": "2012-04-11",
			"PMC": "",
			"citation": "",
			"abstract": "The integrity of the genome depends on diverse pathways that regulate DNA metabolism. Defects in these pathways result in genome instability, a hallmark of cancer. Deletion of ELG1 in budding yeast, when combined with hypomorphic alleles of PCNA results in spontaneous DNA damage during S phase that elicits upregulation of ribonucleotide reductase (RNR) activity. Increased RNR activity leads to a dramatic expansion of deoxyribonucleotide (dNTP) pools in G1 that allows cells to synthesize significant fractions of the genome in the presence of hydroxyurea in the subsequent S phase. Consistent with the recognized correlation between dNTP levels and spontaneous mutation, compromising ELG1 and PCNA results in a significant increase in mutation rates. Deletion of distinct genome stability genes RAD54, RAD55, and TSA1 also results in increased dNTP levels and mutagenesis, suggesting that this is a general phenomenon. Together, our data point to a vicious circle in which mutations in gatekeeper genes give rise to genomic instability during S phase, inducing expansion of the dNTP pool, which in turn results in high levels of spontaneous mutagenesis.",
			"category": 2,
			"name": "Davidson Marta B,2012"
		},
		{
			"PMID": 22200771,
			"title": "Spliceosome mutations in hematopoietic malignancies.",
			"journal": "Nature genetics",
			"authorList": [
				"Hahn Christopher N",
				"Scott Hamish S"
			],
			"DOI": "10.1038/ng.1045",
			"date": "2012-02-27",
			"PMC": "",
			"citation": "",
			"abstract": "Recent studies, including two in this issue, report heterozygous missense mutations in the U2AF1 and SF3B1 genes that encode spliceosome subunits. U2AF1 is frequently mutated in myeloid hematopoietic malignancies, especially in myelodysplastic syndrome (MDS), and SF3B1 is frequently mutated in both MDS and chronic lymphocytic leukemia (CLL).",
			"category": 2,
			"name": "Hahn Christopher N,2012"
		},
		{
			"PMID": 22198145,
			"title": "Mutability and mutational spectrum of chromosome transmission fidelity genes.",
			"journal": "Chromosoma",
			"authorList": [
				"Stirling Peter C",
				"Crisp Matthew J",
				"Basrai Munira A",
				"Tucker Cheryl M",
				"Dunham Maitreya J",
				"Spencer Forrest A",
				"Hieter Philip"
			],
			"DOI": "10.1007/s00412-011-0356-3",
			"date": "2012-09-05",
			"PMC": "",
			"citation": "",
			"abstract": "It has been more than two decades since the original chromosome transmission fidelity (Ctf) screen of Saccharomyces cerevisiae was published. Since that time the spectrum of mutations known to cause Ctf and, more generally, chromosome instability (CIN) has expanded dramatically as a result of systematic screens across yeast mutant arrays. Here we describe a comprehensive summary of the original Ctf genetic screen and the cloning of the remaining complementation groups as efforts to expand our knowledge of the CIN gene repertoire and its mutability in a model eukaryote. At the time of the original screen, it was impossible to predict either the genes and processes that would be overrepresented in a pool of random mutants displaying a Ctf phenotype or what the entire set of genes potentially mutable to Ctf would be. We show that in a collection of 136 randomly selected Ctf mutants, >65% of mutants map to 13 genes, 12 of which are involved in sister chromatid cohesion and/or kinetochore function. Extensive screening of systematic mutant collections has shown that ~350 genes with functions as diverse as RNA processing and proteasomal activity mutate to cause a Ctf phenotype and at least 692 genes are required for faithful chromosome segregation. The enrichment of random Ctf alleles in only 13 of ~350 possible Ctf genes suggests that these genes are more easily mutable to cause genome instability than the others. These observations inform our understanding of recurring CIN mutations in human cancers where presumably random mutations are responsible for initiating the frequently observed CIN phenotype of tumors.",
			"category": 2,
			"name": "Stirling Peter C,2012"
		},
		{
			"PMID": 22180681,
			"title": "Methods, challenges, and promise of next-generation sequencing in cancer biology.",
			"journal": "The Yale journal of biology and medicine",
			"authorList": [
				"Haimovich Adrian D"
			],
			"DOI": "",
			"date": "2012-04-16",
			"PMC": "",
			"citation": "",
			"abstract": "It is generally accepted that cancers result from the aggregation of somatic mutations. The emergence of next-generation sequencing (NGS) technologies during the past half-decade has enabled studies of cancer genomes with high sensitivity and resolution through whole-genome and whole-exome sequencing approaches, among others. This saltatory advance introduces the possibility of assembling multiple cancer genomes for analysis in a cost-effective manner. Analytical approaches are now applied to the detection of a number of somatic genome alterations, including nucleotide substitutions, insertions/deletions, copy number variations, and chromosomal rearrangements. This review provides a thorough introduction to the cancer genomics pipeline as well as a case study of these methods put into practice.",
			"category": 2,
			"name": "Haimovich Adrian D,2012"
		},
		{
			"PMID": 22174824,
			"title": "Identification of tumor suppressors and oncogenes from genomic and epigenetic features in ovarian cancer.",
			"journal": "PloS one",
			"authorList": [
				"Wrzeszczynski Kazimierz O",
				"Varadan Vinay",
				"Byrnes James",
				"Lum Elena",
				"Kamalakaran Sitharthan",
				"Levine Douglas A",
				"Dimitrova Nevenka",
				"Zhang Michael Q",
				"Lucito Robert"
			],
			"DOI": "10.1371/journal.pone.0028503",
			"date": "2012-04-23",
			"PMC": "",
			"citation": "",
			"abstract": "The identification of genetic and epigenetic alterations from primary tumor cells has become a common method to identify genes critical to the development and progression of cancer. We seek to identify those genetic and epigenetic aberrations that have the most impact on gene function within the tumor. First, we perform a bioinformatic analysis of copy number variation (CNV) and DNA methylation covering the genetic landscape of ovarian cancer tumor cells. We separately examined CNV and DNA methylation for 42 primary serous ovarian cancer samples using MOMA-ROMA assays and 379 tumor samples analyzed by The Cancer Genome Atlas. We have identified 346 genes with significant deletions or amplifications among the tumor samples. Utilizing associated gene expression data we predict 156 genes with altered copy number and correlated changes in expression. Among these genes CCNE1, POP4, UQCRB, PHF20L1 and C19orf2 were identified within both data sets. We were specifically interested in copy number variation as our base genomic property in the prediction of tumor suppressors and oncogenes in the altered ovarian tumor. We therefore identify changes in DNA methylation and expression for all amplified and deleted genes. We statistically define tumor suppressor and oncogenic features for these modalities and perform a correlation analysis with expression. We predicted 611 potential oncogenes and tumor suppressors candidates by integrating these data types. Genes with a strong correlation for methylation dependent expression changes exhibited at varying copy number aberrations include CDCA8, ATAD2, CDKN2A, RAB25, AURKA, BOP1 and EIF2C3. We provide copy number variation and DNA methylation analysis for over 11,500 individual genes covering the genetic landscape of ovarian cancer tumors. We show the extent of genomic and epigenetic alterations for known tumor suppressors and oncogenes and also use these defined features to identify potential ovarian cancer gene candidates.",
			"category": 2,
			"name": "Wrzeszczynski Kazimierz O,2012"
		},
		{
			"PMID": 22156295,
			"title": "Whole-exome sequencing of human pancreatic cancers and characterization of genomic instability caused by MLH1 haploinsufficiency and complete deficiency.",
			"journal": "Genome research",
			"authorList": [
				"Wang Linghua",
				"Tsutsumi Shuichi",
				"Kawaguchi Tokuichi",
				"Nagasaki Koichi",
				"Tatsuno Kenji",
				"Yamamoto Shogo",
				"Sang Fei",
				"Sonoda Kohtaro",
				"Sugawara Minoru",
				"Saiura Akio",
				"Hirono Seiko",
				"Yamaue Hiroki",
				"Miki Yoshio",
				"Isomura Minoru",
				"Totoki Yasushi",
				"Nagae Genta",
				"Isagawa Takayuki",
				"Ueda Hiroki",
				"Murayama-Hosokawa Satsuki",
				"Shibata Tatsuhiro",
				"Sakamoto Hiromi",
				"Kanai Yae",
				"Kaneda Atsushi",
				"Noda Tetsuo",
				"Aburatani Hiroyuki"
			],
			"DOI": "10.1101/gr.123109.111",
			"date": "2012-06-13",
			"PMC": "",
			"citation": "",
			"abstract": "Whole-exome sequencing (Exome-seq) has been successfully applied in several recent studies. We here sequenced the exomes of 15 pancreatic tumor cell lines and their matched normal samples. We captured 162,073 exons of 16,954 genes and sequenced the targeted regions to a mean coverage of 56-fold. This study identified a total of 1517 somatic mutations and validated 934 mutations by transcriptome sequencing. We detected recurrent mutations in 56 genes. Among them, 41 have not been described. The mutation rates varied widely among cell lines. The diversity of the mutation rates was significantly correlated with the distinct MLH1 copy-number status. Exome-seq revealed intensive genomic instability in a cell line with MLH1 homozygous deletion, indicated by a dramatically elevated rate of somatic substitutions, small insertions/deletions (indels), as well as indels in microsatellites. Notably, we found that MLH1 expression was decreased by nearly half in cell lines with an allelic loss of MLH1. While these cell lines were negative in conventional microsatellite instability assay, they showed a 10.5-fold increase in the rate of somatic indels, e.g., truncating indels in TP53 and TGFBR2, indicating MLH1 haploinsufficiency in the correction of DNA indel errors. We further analyzed the exomes of 15 renal cell carcinomas and confirmed MLH1 haploinsufficiency. We observed a much higher rate of indel mutations in the affected cases and identified recurrent truncating indels in several cancer genes such as VHL, PBRM1, and JARID1C. Together, our data suggest that MLH1 hemizygous deletion, through increasing the rate of indel mutations, could drive the development and progression of sporadic cancers.",
			"category": 2,
			"name": "Wang Linghua,2012"
		},
		{
			"PMID": 22155605,
			"title": "Human genetics and genomics a decade after the release of the draft sequence of the human genome.",
			"journal": "Human genomics",
			"authorList": [
				"Naidoo Nasheen",
				"Pawitan Yudi",
				"Soong Richie",
				"Cooper David N",
				"Ku Chee-Seng"
			],
			"DOI": "",
			"date": "2012-05-08",
			"PMC": "",
			"citation": "",
			"abstract": "Substantial progress has been made in human genetics and genomics research over the past ten years since the publication of the draft sequence of the human genome in 2001. Findings emanating directly from the Human Genome Project, together with those from follow-on studies, have had an enormous impact on our understanding of the architecture and function of the human genome. Major developments have been made in cataloguing genetic variation, the International HapMap Project, and with respect to advances in genotyping technologies. These developments are vital for the emergence of genome-wide association studies in the investigation of complex diseases and traits. In parallel, the advent of high-throughput sequencing technologies has ushered in the 'personal genome sequencing' era for both normal and cancer genomes, and made possible large-scale genome sequencing studies such as the 1000 Genomes Project and the International Cancer Genome Consortium. The high-throughput sequencing and sequence-capture technologies are also providing new opportunities to study Mendelian disorders through exome sequencing and whole-genome sequencing. This paper reviews these major developments in human genetics and genomics over the past decade.",
			"category": 2,
			"name": "Naidoo Nasheen,2012"
		},
		{
			"PMID": 22147895,
			"title": "Loss-of-function germline GATA2 mutations in patients with MDS/AML or MonoMAC syndrome and primary lymphedema reveal a key role for GATA2 in the lymphatic vasculature.",
			"journal": "Blood",
			"authorList": [
				"Kazenwadel Jan",
				"Secker Genevieve A",
				"Liu Yajuan J",
				"Rosenfeld Jill A",
				"Wildin Robert S",
				"Cuellar-Rodriguez Jennifer",
				"Hsu Amy P",
				"Dyack Sarah",
				"Fernandez Conrad V",
				"Chong Chan-Eng",
				"Babic Milena",
				"Bardy Peter G",
				"Shimamura Akiko",
				"Zhang Michael Y",
				"Walsh Tom",
				"Holland Steven M",
				"Hickstein Dennis D",
				"Horwitz Marshall S",
				"Hahn Christopher N",
				"Scott Hamish S",
				"Harvey Natasha L"
			],
			"DOI": "10.1182/blood-2011-08-374363",
			"date": "2012-04-05",
			"PMC": "",
			"citation": "",
			"abstract": "Recent work has established that heterozygous germline GATA2 mutations predispose carriers to familial myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), \"MonoMAC\" syndrome, and DCML deficiency. Here, we describe a previously unreported MDS family carrying a missense GATA2 mutation (p.Thr354Met), one patient with MDS/AML carrying a frameshift GATA2 mutation (p.Leu332Thrfs*53), another with MDS harboring a GATA2 splice site mutation, and 3 patients exhibiting MDS or MDS/AML who have large deletions encompassing the GATA2 locus. Intriguingly, 2 MDS/AML or \"MonoMAC\" syndrome patients with GATA2 deletions and one with a frameshift mutation also have primary lymphedema. Primary lymphedema occurs as a result of aberrations in the development and/or function of lymphatic vessels, spurring us to investigate whether GATA2 plays a role in the lymphatic vasculature. We demonstrate here that GATA2 protein is present at high levels in lymphatic vessel valves and that GATA2 controls the expression of genes important for programming lymphatic valve development. Our data expand the phenotypes associated with germline GATA2 mutations to include predisposition to primary lymphedema and suggest that complete haploinsufficiency or loss of function of GATA2, rather than missense mutations, is the key predisposing factor for lymphedema onset. Moreover, we reveal a crucial role for GATA2 in lymphatic vascular development.",
			"category": 2,
			"name": "Kazenwadel Jan,2012"
		},
		{
			"PMID": 22133722,
			"title": "Personalized oncology through integrative high-throughput sequencing: a pilot study.",
			"journal": "Science translational medicine",
			"authorList": [
				"Roychowdhury Sameek",
				"Iyer Matthew K",
				"Robinson Dan R",
				"Lonigro Robert J",
				"Wu Yi-Mi",
				"Cao Xuhong",
				"Kalyana-Sundaram Shanker",
				"Sam Lee",
				"Balbin O Alejandro",
				"Quist Michael J",
				"Barrette Terrence",
				"Everett Jessica",
				"Siddiqui Javed",
				"Kunju Lakshmi P",
				"Navone Nora",
				"Araujo John C",
				"Troncoso Patricia",
				"Logothetis Christopher J",
				"Innis Jeffrey W",
				"Smith David C",
				"Lao Christopher D",
				"Kim Scott Y",
				"Roberts J Scott",
				"Gruber Stephen B",
				"Pienta Kenneth J",
				"Talpaz Moshe",
				"Chinnaiyan Arul M"
			],
			"DOI": "10.1126/scitranslmed.3003161",
			"date": "2012-07-12",
			"PMC": "",
			"citation": "",
			"abstract": "Individual cancers harbor a set of genetic aberrations that can be informative for identifying rational therapies currently available or in clinical trials. We implemented a pilot study to explore the practical challenges of applying high-throughput sequencing in clinical oncology. We enrolled patients with advanced or refractory cancer who were eligible for clinical trials. For each patient, we performed whole-genome sequencing of the tumor, targeted whole-exome sequencing of tumor and normal DNA, and transcriptome sequencing (RNA-Seq) of the tumor to identify potentially informative mutations in a clinically relevant time frame of 3 to 4 weeks. With this approach, we detected several classes of cancer mutations including structural rearrangements, copy number alterations, point mutations, and gene expression alterations. A multidisciplinary Sequencing Tumor Board (STB) deliberated on the clinical interpretation of the sequencing results obtained. We tested our sequencing strategy on human prostate cancer xenografts. Next, we enrolled two patients into the clinical protocol and were able to review the results at our STB within 24 days of biopsy. The first patient had metastatic colorectal cancer in which we identified somatic point mutations in NRAS, TP53, AURKA, FAS, and MYH11, plus amplification and overexpression of cyclin-dependent kinase 8 (CDK8). The second patient had malignant melanoma, in which we identified a somatic point mutation in HRAS and a structural rearrangement affecting CDKN2C. The STB identified the CDK8 amplification and Ras mutation as providing a rationale for clinical trials with CDK inhibitors or MEK (mitogen-activated or extracellular signal-regulated protein kinase kinase) and PI3K (phosphatidylinositol 3-kinase) inhibitors, respectively. Integrative high-throughput sequencing of patients with advanced cancer generates a comprehensive, individual mutational landscape to facilitate biomarker-driven clinical trials in oncology.",
			"category": 2,
			"name": "Roychowdhury Sameek,2012"
		},
		{
			"PMID": 22132062,
			"title": "Current status and future potential of somatic mutation testing from circulating free DNA in patients with solid tumours.",
			"journal": "The HUGO journal",
			"authorList": [
				"Aung K L",
				"Board R E",
				"Ellison G",
				"Donald E",
				"Ward T",
				"Clack G",
				"Ranson M",
				"Hughes A",
				"Newman W",
				"Dive C"
			],
			"DOI": "10.1007/s11568-011-9149-2",
			"date": "2012-08-23",
			"PMC": "",
			"citation": "",
			"abstract": "Genetic alterations can determine the natural history of cancer and its treatment response. With further advances in DNA sequencing technology, multiple novel genetic alterations will be discovered which could be exploited as prognostic, predictive and pharmacodynamic biomarkers in the development and use of cancer therapeutics. As such, the importance in clinical practice of efficient and robust somatic mutation testing in solid tumours cannot be overemphasized in the current era of personalized medicine. However, significant challenges remain regarding the testing of genetic biomarkers in clinical practice. Reliance on archived formalin fixed, paraffin embedded tumour, obtained from diagnostic biopsies, for testing somatic genetic alterations could restrict the scientific community in asking relevant questions about a patient's cancer biology. Problems inherent with using formalin fixed, archival tissue are well recognized and difficult to resolve. It could be argued that to achieve rapid and efficient incorporation of genetic biomarkers into clinical practice, somatic mutation testing in cancer patients should be simpler, less invasive using a readily available clinical sample, whilst maintaining robustness and reproducibility. In this regard, use of circulating free DNA (cfDNA) from plasma or serum as an alternative and/or additional source of DNA to test cancer specific genetic alterations is an attractive proposition. In light of encouraging results from recent studies, this mini review will discuss the current role and future potential of somatic mutation testing from circulating or cell free DNA derived from the blood of patients with solid tumours.",
			"category": 2,
			"name": "Aung K L,2012"
		},
		{
			"PMID": 22112486,
			"title": "Preneoplasia of lung cancer.",
			"journal": "Cancer biomarkers : section A of Disease markers",
			"authorList": [
				"Gazdar Adi F",
				"Brambilla Elisabeth"
			],
			"DOI": "10.3233/CBM-2011-0166",
			"date": "2012-07-12",
			"PMC": "",
			"citation": "",
			"abstract": "As with other epithelial cancers, lung cancer develops over a period of several years or decades via a series of progressive morphological changes accompanied by molecular alterations that commence in histologically normal epithelium. However the development of lung cancer presents certain unique features that complicates this evaluation. Anatomically the respiratory tree may be divided into central and peripheral compartments having different gross and histological anatomies as well as different functions. In addition, there are three major forms of lung cancer and many minor forms. Many of these forms arise predominantly in either the central or peripheral compartments. Squamous cell and small cell carcinomas predominantly arise in the central compartment, while adenocarcinomas predominantly arise peripherally. Large cell carcinomas are not a single entity but consist of poorly differentiated forms of the other types and, possibly, some truly undifferentiated \"stem cell like\" tumors. The multistage origin of squamous cell carcinomas, because of their central location, can be followed more closely than the peripherally arising adenocarcinomas. Squamous cell carcinomas arise after a series of reactive, metaplastic, premalignant and preinvasive changes. However, long term observations indicate that not all tumors follow a defined histologic course, and the clinical course, especially of early lesions, is difficult to predict. Peripheral adenocarcinomas are believed to arise from precursor lesions known as atypical adenomatous hyperplasias and may have extensive in situ growth before becoming invasive. Small cell carcinomas are believed to arise from severely molecularly damaged epithelium without going through recognizable preneoplastic changes. The molecular changes that occur prior to the onset on invasive cancers are extensive. As documented in this chapter, they encompass all of the six classic Hallmarks of Cancer other than invasion and metastasis, which by definition occur beyond preneoplasia. A study of preinvasive lung cancer has yielded much valuable biologic information that impacts on clinical management.",
			"category": 2,
			"name": "Gazdar Adi F,2012"
		},
		{
			"PMID": 22101486,
			"title": "High order chromatin architecture shapes the landscape of chromosomal alterations in cancer.",
			"journal": "Nature biotechnology",
			"authorList": [
				"Fudenberg Geoff",
				"Getz Gad",
				"Meyerson Matthew",
				"Mirny Leonid A"
			],
			"DOI": "10.1038/nbt.2049",
			"date": "2012-06-15",
			"PMC": "",
			"citation": "",
			"abstract": "The accumulation of data on structural variation in cancer genomes provides an opportunity to better understand the mechanisms of genomic alterations and the forces of selection that act upon these alterations in cancer. Here we test evidence supporting the influence of two major forces, spatial chromosome structure and purifying (or negative) selection, on the landscape of somatic copy-number alterations (SCNAs) in cancer. Using a maximum likelihood approach, we compare SCNA maps and three-dimensional genome architecture as determined by genome-wide chromosome conformation capture (HiC) and described by the proposed fractal-globule model. This analysis suggests that the distribution of chromosomal alterations in cancer is spatially related to three-dimensional genomic architecture and that purifying selection, as well as positive selection, influences SCNAs during somatic evolution of cancer cells.",
			"category": 2,
			"name": "Fudenberg Geoff,2012"
		},
		{
			"PMID": 22080562,
			"title": "Network of Cancer Genes (NCG 3.0): integration and analysis of genetic and network properties of cancer genes.",
			"journal": "Nucleic acids research",
			"authorList": [
				"D'Antonio Matteo",
				"Pendino Vera",
				"Sinha Shruti",
				"Ciccarelli Francesca D"
			],
			"DOI": "10.1093/nar/gkr952",
			"date": "2012-07-05",
			"PMC": "",
			"citation": "",
			"abstract": "The identification of a constantly increasing number of genes whose mutations are causally implicated in tumor initiation and progression (cancer genes) requires the development of tools to store and analyze them. The Network of Cancer Genes (NCG 3.0) collects information on 1494 cancer genes that have been found mutated in 16 different cancer types. These genes were collected from the Cancer Gene Census as well as from 18 whole exome and 11 whole-genome screenings of cancer samples. For each cancer gene, NCG 3.0 provides a summary of the gene features and the cross-reference to other databases. In addition, it describes duplicability, evolutionary origin, orthology, network properties, interaction partners, microRNA regulation and functional roles of cancer genes and of all genes that are related to them. This integrated network of information can be used to better characterize cancer genes in the context of the system in which they act. The data can also be used to identify novel candidates that share the same properties of known cancer genes and may therefore play a similar role in cancer. NCG 3.0 is freely available at http://bio.ifom-ieo-campus.it/ncg.",
			"category": 2,
			"name": "D'Antonio Matteo,2012"
		},
		{
			"PMID": 22057237,
			"title": "Insertional mutagenesis identifies multiple networks of cooperating genes driving intestinal tumorigenesis.",
			"journal": "Nature genetics",
			"authorList": [
				"March H Nikki",
				"Rust Alistair G",
				"Wright Nicholas A",
				"ten Hoeve Jelle",
				"de Ridder Jeroen",
				"Eldridge Matthew",
				"van der Weyden Louise",
				"Berns Anton",
				"Gadiot Jules",
				"Uren Anthony",
				"Kemp Richard",
				"Arends Mark J",
				"Wessels Lodewyk F A",
				"Winton Douglas J",
				"Adams David J"
			],
			"DOI": "10.1038/ng.990",
			"date": "2012-01-20",
			"PMC": "",
			"citation": "",
			"abstract": "The evolution of colorectal cancer suggests the involvement of many genes. To identify new drivers of intestinal cancer, we performed insertional mutagenesis using the Sleeping Beauty transposon system in mice carrying germline or somatic Apc mutations. By analyzing common insertion sites (CISs) isolated from 446 tumors, we identified many hundreds of candidate cancer drivers. Comparison to human data sets suggested that 234 CIS-targeted genes are also dysregulated in human colorectal cancers. In addition, we found 183 CIS-containing genes that are candidate Wnt targets and showed that 20 CISs-containing genes are newly discovered modifiers of canonical Wnt signaling. We also identified mutations associated with a subset of tumors containing an expanded number of Paneth cells, a hallmark of deregulated Wnt signaling, and genes associated with more severe dysplasia included those encoding members of the FGF signaling cascade. Some 70 genes had co-occurrence of CIS pairs, clustering into 38 sub-networks that may regulate tumor development.",
			"category": 2,
			"name": "March H Nikki,2012"
		},
		{
			"PMID": 22052464,
			"title": "Finding a Panacea among combination cancer therapies.",
			"journal": "Cancer research",
			"authorList": [
				"Yamaguchi Ryuji",
				"Perkins Guy"
			],
			"DOI": "10.1158/0008-5472.CAN-11-3091",
			"date": "2012-02-21",
			"PMC": "",
			"citation": "",
			"abstract": "Because each cancer is a heterogeneous mix of cancer cells at different stages of development, we are faced with trying to treat many different diseased cells all at once. An authentic approach is to build a genomic and proteomic profile of a patient, identify the target oncogenes, and prescribe the combination of targeted drugs tailored for that patient. However, there are many practical problems with this personalized medicine approach: (i) cancers often generate treatment-resistant phenotypes, (ii) the treatment could be enormously expensive, and (iii) most of the targeted drugs have not been developed yet. We propose a different approach: therapies that combine 2-deoxyglucose (2DG) with Bcl-2 antagonist such as ABT-263/737 (ABT). Proapoptotic protein Bak is normally sequestered by Mcl-1 and Bcl-xL. Only when Bak is released from both Mcl-1 and Bcl-xL can it induce apoptosis. 2DG can prime highly glycolytic cells by dissociating Bak-Mcl-1 complex. Some brain cells and most cancer cells are primed by 2DG. ABT can bind to Bcl-xL, dissociating Bak-Bcl-xL complex, freeing Bak and inducing apoptosis. Because ABT cannot cross blood-brain barrier, the only cells exposed to both agents are highly glycolytic cancer cells located outside the brain. Because ABT directly triggers apoptosis at the step very near the terminal point of apoptosis, 2DG-ABT combination therapies are applicable to many types of cancer at all stages of development, with little side effect.",
			"category": 2,
			"name": "Yamaguchi Ryuji,2012"
		},
		{
			"PMID": 22002595,
			"title": "Genomic profiling of glioblastoma: convergence of fundamental biologic tenets and novel insights.",
			"journal": "Journal of neuro-oncology",
			"authorList": [
				"Ng Kimberly",
				"Kim Ryan",
				"Kesari Santosh",
				"Carter Bob",
				"Chen Clark C"
			],
			"DOI": "10.1007/s11060-011-0714-2",
			"date": "2012-06-01",
			"PMC": "",
			"citation": "",
			"abstract": "With advances in genomic profiling and sequencing technology, we are beginning to understand the landscape of the genetic events that accumulated during the neoplastic process. The insights gleamed from these genomic profiling studies with regards to glioblastoma etiology has been particularly satisfying because it cemented the clinical pertinence of major concepts in cancer biology-concepts developed over the past three decades. This article will review how the glioblastoma genomic data set serves as an illustrative platform for the concepts put forward by Hanahan and Weinberg on the cancer phenotype. The picture emerging suggests that most glioblastomas evolve along a multitude of pathways rather than a single defined pathway. In this context, the article will further provide a discussion of the subtypes of glioblastoma as they relate to key principles of developmental neurobiology.",
			"category": 2,
			"name": "Ng Kimberly,2012"
		},
		{
			"PMID": 21998737,
			"title": "Age-specific incidence data indicate four mutations are required for human testicular cancers.",
			"journal": "PloS one",
			"authorList": [
				"Brody James P"
			],
			"DOI": "10.1371/journal.pone.0025978",
			"date": "2012-02-13",
			"PMC": "",
			"citation": "",
			"abstract": "Normal human cells require a series of genetic alterations to undergo malignant transformation. Direct sequencing of human tumors has identified hundreds of mutations in tumors, but many of these are thought to be unnecessary and a result of, rather than a cause of, the tumor. The exact number of mutations to transform a normal human cell into a tumor cell is unknown. Here I show that male gonadal germ cell tumors, the most common form of testicular cancers, occur after four mutations. I infer this by constructing a mathematical model based upon the multi-hit hypothesis and comparing it to the age-specific incidence data. This result is consistent with the multi-hit hypothesis, and implies that these cancers are genetically or epigenetically predetermined at birth or an early age.",
			"category": 2,
			"name": "Brody James P,2012"
		},
		{
			"PMID": 21989305,
			"title": "Urothelial carcinoma of the bladder: definition, treatment and future efforts.",
			"journal": "Nature reviews. Urology",
			"authorList": [
				"Prasad Sandip M",
				"Decastro G Joel",
				"Steinberg Gary D",
				"Medscape"
			],
			"DOI": "10.1038/nrurol.2011.144",
			"date": "2012-08-16",
			"PMC": "",
			"citation": "",
			"abstract": "The identification of patients with high-risk bladder cancer is important for the timely and appropriate treatment of this lethal disease. The understanding of the natural history of bladder cancer has improved; however, the criteria used to define high-risk disease and the relevant treatment strategies have remained the same for the past several decades, despite multiple large, randomized, prospective clinical trials that have evaluated the use of intravesical, surgical and systemic therapies. The genetic signature of high-risk bladder cancer has been a focus of investigation and has led to the discovery of potential molecular targets for disease identification, risk stratification and therapy. These advances, combined with a comprehensive risk assessment profile that incorporates available pathological and clinical characteristics, might improve the diagnosis and treatment of patients with bladder cancer.",
			"category": 2,
			"name": "Prasad Sandip M,2012"
		},
		{
			"PMID": 21989071,
			"title": "Personalized cancer medicine--advances and socio-economic challenges.",
			"journal": "Nature reviews. Clinical oncology",
			"authorList": [
				"Jackson David B",
				"Sood Anil K"
			],
			"DOI": "10.1038/nrclinonc.2011.151",
			"date": "2012-03-22",
			"PMC": "",
			"citation": "",
			"abstract": "It was Hippocrates, the father of Western medicine, who first emphasized the patient as the most important determinant of therapeutic efficacy. Although the principle of adjusting treatment to specific patient characteristics has since been the strategy of physicians, this is undermined by a population-biased approach to drug development. Therefore, it is generally true to say that our current evidential approach to cancer treatment is driven more by drug-regulation requirements and market considerations than the specific needs of an individual patient. But, with cancer drug costs now spiraling out of control and the modest efficacy typically seen in patients, the community is again turning to Hippocrates' ancient paradigm--this time with emphasis on molecular considerations. Rapidly evolving technologies are empowering us to describe the molecular 'nature' of a patient and/or tumor and with this has come the beginning of truly personalized medicine, with maximized efficacy, cost effectiveness and hopefully improved survival for the patient.",
			"category": 2,
			"name": "Jackson David B,2012"
		},
		{
			"PMID": 21985575,
			"title": "Prioritizing cancer-related genes with aberrant methylation based on a weighted protein-protein interaction network.",
			"journal": "BMC systems biology",
			"authorList": [
				"Liu Hui",
				"Su Jianzhong",
				"Li Junhua",
				"Liu Hongbo",
				"Lv Jie",
				"Li Boyan",
				"Qiao Hong",
				"Zhang Yan"
			],
			"DOI": "10.1186/1752-0509-5-158",
			"date": "2012-05-18",
			"PMC": "",
			"citation": "",
			"abstract": "As an important epigenetic modification, DNA methylation plays a crucial role in the development of mammals and in the occurrence of complex diseases. Genes that interact directly or indirectly may have the same or similar functions in the biological processes in which they are involved and together contribute to the related disease phenotypes. The complicated relations between genes can be clearly represented using network theory. A protein-protein interaction (PPI) network offers a platform from which to systematically identify disease-related genes from the relations between genes with similar functions.",
			"category": 2,
			"name": "Liu Hui,2012"
		},
		{
			"PMID": 21969829,
			"title": "The Amazing Power of Cancer Cells to Recapitulate Extraembryonic Functions: The Cuckoo's Tricks.",
			"journal": "Journal of oncology",
			"authorList": [
				"Arias Jose-Ignacio",
				"Aller Maria-Angeles",
				"Prieto Isabel",
				"Arias Ana",
				"de Julian Zoe",
				"Yang Heping",
				"Arias Jaime"
			],
			"DOI": "10.1155/2012/521284",
			"date": "2011-11-10",
			"PMC": "",
			"citation": "",
			"abstract": "Inflammation is implicated in tumor development, invasion, and metastasis. Hence, it has been suggested that common cellular and molecular mechanisms are activated in wound repair and in cancer development. In addition, it has been previously proposed that the inflammatory response, which is associated with the wound healing process, could recapitulate ontogeny through the reexpression of the extraembryonic, that is, amniotic and vitelline, functions in the interstitial space of the injured tissue. If so, the use of inflammation by the cancer-initiating cell can also be supported in the ability to reacquire extraembryonic functional axes for tumor development, invasion, and metastasis. Thus, the diverse components of the tumor microenvironment could represent the overlapping reexpression of amniotic and vitelline functions. These functions would favor a gastrulation-like process, that is, the creation of a reactive stroma in which fibrogenesis and angiogenesis stand out.",
			"category": 2,
			"name": "Arias Jose-Ignacio,2011"
		},
		{
			"PMID": 21966543,
			"title": "What can ecology teach us about cancer?",
			"journal": "Translational oncology",
			"authorList": [
				"Kareva Irina"
			],
			"DOI": "",
			"date": "2011-11-10",
			"PMC": "",
			"citation": "",
			"abstract": "In 2008, Pienta et al. (Transl Oncol. 2008;1:158-164) introduced the term ecological therapy for cancer treatment and, in particular, emphasized that destruction of the tumor microenvironment would be more effective than just killing the cells that inhabit it. Proposed here is an expansion on the idea of ecological therapy of cancer, incorporating 1) literature on species invasion, i.e., a right cancerous clone needs to be at the right place at the right time to actually invade its environment, and 2) the literature on niche construction, that is, the idea that once a tumor is formed, cancer cells they modify their microenvironment (niche construction) by changing pH through glycolysis, secreting growth factors and recruiting tumor-associated macrophages to promote cell growth, activating fibroblasts, evading predation from immune system, making the cancer that much more difficult to eradicate. Paleontological literature suggests that the largestmass extinctions occurred when environmental stress that would weaken the population was coupled with some pulse destructive event that caused extensive mortality. To have the same effect on cells in the tumor, rather than, or at least in addition to, killing the cells, one would also need to target the niche that they created for themselves.",
			"category": 2,
			"name": "Kareva Irina,2011"
		},
		{
			"PMID": 21964605,
			"title": "Mutation of the Nrf2 gene in non-small cell lung cancer.",
			"journal": "Molecular biology reports",
			"authorList": [
				"Hu Yi",
				"Ju Yanfang",
				"Lin Dongmei",
				"Wang Zhikuan",
				"Huang Yurong",
				"Zhang Sujie",
				"Wu Chao",
				"Jiao Shunchang"
			],
			"DOI": "10.1007/s11033-011-1266-4",
			"date": "2012-06-28",
			"PMC": "",
			"citation": "",
			"abstract": "Nrf2 (NFE2L2) is a transcription factor belonging to the Cap'N'Collar subfamily of basic-leucine zipper (bZIP) family of transcription factors, which plays a significant role in adaptive responses to oxidative stress. To investigate the relationship of between the mutation of Nrf2 gene and non-small cell lung cancer (NSCLC), in this study, we sequenced the Nrf2 gene from a total of 103 patients with NSCLC and corresponding blood samples. It is found that there is a discordance of Nrf2 mutations between NSCLC and corresponding blood samples. These differences may indicate that the variants in the Nrf2 gene are associated with an increased risk for lung cancer. In addition, the factor of smoking status is observed to play important roles in triggering the occurrence of the disorder.",
			"category": 2,
			"name": "Hu Yi,2012"
		},
		{
			"PMID": 21962511,
			"title": "Genome-wide translocation sequencing reveals mechanisms of chromosome breaks and rearrangements in B cells.",
			"journal": "Cell",
			"authorList": [
				"Chiarle Roberto",
				"Zhang Yu",
				"Frock Richard L",
				"Lewis Susanna M",
				"Molinie Benoit",
				"Ho Yu-Jui",
				"Myers Darienne R",
				"Choi Vivian W",
				"Compagno Mara",
				"Malkin Daniel J",
				"Neuberg Donna",
				"Monti Stefano",
				"Giallourakis Cosmas C",
				"Gostissa Monica",
				"Alt Frederick W"
			],
			"DOI": "10.1016/j.cell.2011.07.049",
			"date": "2011-11-30",
			"PMC": "",
			"citation": "",
			"abstract": "Whereas chromosomal translocations are common pathogenetic events in cancer, mechanisms that promote them are poorly understood. To elucidate translocation mechanisms in mammalian cells, we developed high-throughput, genome-wide translocation sequencing (HTGTS). We employed HTGTS to identify tens of thousands of independent translocation junctions involving fixed I-SceI meganuclease-generated DNA double-strand breaks (DSBs) within the c-myc oncogene or IgH locus of B lymphocytes induced for activation-induced cytidine deaminase (AID)-dependent IgH class switching. DSBs translocated widely across the genome but were preferentially targeted to transcribed chromosomal regions. Additionally, numerous AID-dependent and AID-independent hot spots were targeted, with the latter comprising mainly cryptic I-SceI targets. Comparison of translocation junctions with genome-wide nuclear run-ons revealed a marked association between transcription start sites and translocation targeting. The majority of translocation junctions were formed via end-joining with short microhomologies. Our findings have implications for diverse fields, including gene therapy and cancer genomics.",
			"category": 2,
			"name": "Chiarle Roberto,2011"
		},
		{
			"PMID": 21955857,
			"title": "Comprehensive comparison of three commercial human whole-exome capture platforms.",
			"journal": "Genome biology",
			"authorList": [
				"Xu Yu",
				"Jiang Hui",
				"Tyler-Smith Chris",
				"Xue Yali",
				"Jiang Tao",
				"Wang Jiawei",
				"Wu Mingzhi",
				"Liu Xiao",
				"Tian Geng",
				"Wang Jun",
				"Wang Jian",
				"Yang Huangming",
				"Zhang Xiuqing"
			],
			"DOI": "10.1186/gb-2011-12-9-r95",
			"date": "2012-08-23",
			"PMC": "",
			"citation": "",
			"abstract": "Exome sequencing, which allows the global analysis of protein coding sequences in the human genome, has become an effective and affordable approach to detecting causative genetic mutations in diseases. Currently, there are several commercial human exome capture platforms; however, the relative performances of these have not been characterized sufficiently to know which is best for a particular study.",
			"category": 2,
			"name": "Xu Yu,2012"
		},
		{
			"PMID": 21953712,
			"title": "Oncogene addiction as a foundational rationale for targeted anti-cancer therapy: promises and perils.",
			"journal": "EMBO molecular medicine",
			"authorList": [
				"Torti Davide",
				"Trusolino Livio"
			],
			"DOI": "10.1002/emmm.201100176",
			"date": "2012-02-20",
			"PMC": "",
			"citation": "",
			"abstract": "A decade has elapsed since the concept of oncogene addiction was first proposed. It postulates that - despite the diverse array of genetic lesions typical of cancer - some tumours rely on one single dominant oncogene for growth and survival, so that inhibition of this specific oncogene is sufficient to halt the neoplastic phenotype. A large amount of evidence has proven the pervasive power of this notion, both in basic research and in therapeutic applications. However, in the face of such a considerable body of knowledge, the intimate molecular mechanisms mediating this phenomenon remain elusive. At the clinical level, successful translation of the oncogene addiction model into the rational and effective design of targeted therapeutics against individual oncoproteins still faces major obstacles, mainly due to the emergence of escape mechanisms and drug resistance. Here, we offer an overview of the relevant literature, encompassing both biological aspects and recent clinical insights. We discuss the key advantages and pitfalls of this concept and reconsider it as an illustrative principle to guide post-genomic cancer research and drug development.",
			"category": 2,
			"name": "Torti Davide,2012"
		},
		{
			"PMID": 21949692,
			"title": "Efficient elimination of cancer cells by deoxyglucose-ABT-263/737 combination therapy.",
			"journal": "PloS one",
			"authorList": [
				"Yamaguchi Ryuji",
				"Janssen Edith",
				"Perkins Guy",
				"Ellisman Mark",
				"Kitada Shinichi",
				"Reed John C"
			],
			"DOI": "10.1371/journal.pone.0024102",
			"date": "2012-03-01",
			"PMC": "",
			"citation": "",
			"abstract": "As single agents, ABT-263 and ABT-737 (ABT), molecular antagonists of the Bcl-2 family, bind tightly to Bcl-2, Bcl-xL and Bcl-w, but not to Mcl-1, and induce apoptosis only in limited cell types. The compound 2-deoxyglucose (2DG), in contrast, partially blocks glycolysis, slowing cell growth but rarely causing cell death. Injected into an animal, 2DG accumulates predominantly in tumors but does not harm other tissues. However, when cells that were highly resistant to ABT were pre-treated with 2DG for 3 hours, ABT became a potent inducer of apoptosis, rapidly releasing cytochrome c from the mitochondria and activating caspases at submicromolar concentrations in a Bak/Bax-dependent manner. Bak is normally sequestered in complexes with Mcl-1 and Bcl-xL. 2DG primes cells by interfering with Bak-Mcl-1 association, making it easier for ABT to dissociate Bak from Bcl-xL, freeing Bak to induce apoptosis. A highly active glucose transporter and Bid, as an agent of the mitochondrial apoptotic signal amplification loop, are necessary for efficient apoptosis induction in this system. This combination treatment of cancer-bearing mice was very effective against tumor xenograft from hormone-independent highly metastasized chemo-resistant human prostate cancer cells, suggesting that the combination treatment may provide a safe and effective alternative to genotoxin-based cancer therapies.",
			"category": 2,
			"name": "Yamaguchi Ryuji,2012"
		},
		{
			"PMID": 21936522,
			"title": "Data-independent proteomic screen identifies novel tamoxifen agonist that mediates drug resistance.",
			"journal": "Journal of proteome research",
			"authorList": [
				"Hengel Shawna Mae",
				"Murray Euan",
				"Langdon Simon",
				"Hayward Larry",
				"O'Donoghue Jean",
				"Panchaud Alexandre",
				"Hupp Ted",
				"Goodlett David R"
			],
			"DOI": "10.1021/pr2004117",
			"date": "2011-12-16",
			"PMC": "",
			"citation": "",
			"abstract": "A label-free quantitative variation of the recently developed data-independent shotgun proteomic method precursor acquisition independent from ion count (PAcIFIC) was used to identify novel proteins implicated in cancer progression and resistance. Specifically, this screen identified the pro-metastatic protein anterior gradient 2 (AGR2) as significantly up-regulated in tamoxifen-treated cells. Highlighting the need for direct proteome profiling methods like PAcIFIC, neither data-dependent gas-phase fractionation nor a transcriptomic screen detected AGR2 protein/transcript at significantly up-regulated levels. Further cell-based experiments using human cancer cell lines and in vivo xenografts confirmed the PAcIFIC hypothesis that AGR2 is up-regulated in MCF-7 cells post tamoxifen treatment and that it is implicated in drug resistance mediation.",
			"category": 2,
			"name": "Hengel Shawna Mae,2011"
		},
		{
			"PMID": 21935468,
			"title": "CDinFusion--submission-ready, on-line integration of sequence and contextual data.",
			"journal": "PloS one",
			"authorList": [
				"Hankeln Wolfgang",
				"Wendel Norma Johanna",
				"Gerken Jan",
				"Waldmann Jost",
				"Buttigieg Pier Luigi",
				"Kostadinov Ivaylo",
				"Kottmann Renzo",
				"Yilmaz Pelin",
				"Gl\u00f6ckner Frank Oliver"
			],
			"DOI": "10.1371/journal.pone.0024797",
			"date": "2012-02-28",
			"PMC": "",
			"citation": "",
			"abstract": "State of the art (DNA) sequencing methods applied in \"Omics\" studies grant insight into the 'blueprints' of organisms from all domains of life. Sequencing is carried out around the globe and the data is submitted to the public repositories of the International Nucleotide Sequence Database Collaboration. However, the context in which these studies are conducted often gets lost, because experimental data, as well as information about the environment are rarely submitted along with the sequence data. If these contextual or metadata are missing, key opportunities of comparison and analysis across studies and habitats are hampered or even impossible. To address this problem, the Genomic Standards Consortium (GSC) promotes checklists and standards to better describe our sequence data collection and to promote the capturing, exchange and integration of sequence data with contextual data. In a recent community effort the GSC has developed a series of recommendations for contextual data that should be submitted along with sequence data. To support the scientific community to significantly enhance the quality and quantity of contextual data in the public sequence data repositories, specialized software tools are needed. In this work we present CDinFusion, a web-based tool to integrate contextual and sequence data in (Multi)FASTA format prior to submission. The tool is open source and available under the Lesser GNU Public License 3. A public installation is hosted and maintained at the Max Planck Institute for Marine Microbiology at http://www.megx.net/cdinfusion. The tool may also be installed locally using the open source code available at http://code.google.com/p/cdinfusion.",
			"category": 2,
			"name": "Hankeln Wolfgang,2012"
		},
		{
			"PMID": 21908773,
			"title": "Mutual exclusivity analysis identifies oncogenic network modules.",
			"journal": "Genome research",
			"authorList": [
				"Ciriello Giovanni",
				"Cerami Ethan",
				"Sander Chris",
				"Schultz Nikolaus"
			],
			"DOI": "10.1101/gr.125567.111",
			"date": "2012-06-13",
			"PMC": "",
			"citation": "",
			"abstract": "Although individual tumors of the same clinical type have surprisingly diverse genomic alterations, these events tend to occur in a limited number of pathways, and alterations that affect the same pathway tend to not co-occur in the same patient. While pathway analysis has been a powerful tool in cancer genomics, our knowledge of oncogenic pathway modules is incomplete. To systematically identify such modules, we have developed a novel method, Mutual Exclusivity Modules in cancer (MEMo). The method uses correlation analysis and statistical tests to identify network modules by three criteria: (1) Member genes are recurrently altered across a set of tumor samples; (2) member genes are known to or are likely to participate in the same biological process; and (3) alteration events within the modules are mutually exclusive. Applied to data from the Cancer Genome Atlas (TCGA), the method identifies the principal known altered modules in glioblastoma (GBM) and highlights the striking mutual exclusivity of genomic alterations in the PI(3)K, p53, and Rb pathways. In serous ovarian cancer, we make the novel observation that inactivation of BRCA1 and BRCA2 is mutually exclusive of amplification of CCNE1 and inactivation of RB1, suggesting distinct alternative causes of genomic instability in this cancer type; and, we identify RBBP8 as a candidate oncogene involved in Rb-mediated cell cycle control. When applied to any cancer genomics data set, the algorithm can nominate oncogenic alterations that have a particularly strong selective effect and may also be useful in the design of therapeutic combinations in cases where mutual exclusivity reflects synthetic lethality.",
			"category": 2,
			"name": "Ciriello Giovanni,2012"
		},
		{
			"PMID": 21900272,
			"title": "Distinguishing driver and passenger mutations in an evolutionary history categorized by interference.",
			"journal": "Genetics",
			"authorList": [
				"Illingworth Christopher J R",
				"Mustonen Ville"
			],
			"DOI": "10.1534/genetics.111.133975",
			"date": "2012-03-01",
			"PMC": "",
			"citation": "",
			"abstract": "In many biological scenarios, from the development of drug resistance in pathogens to the progression of healthy cells toward cancer, quantifying the selection acting on observed mutations is a central question. One difficulty in answering this question is the complexity of the background upon which mutations can arise, with multiple potential interactions between genetic loci. We here present a method for discerning selection from a population history that accounts for interference between mutations. Given sequences sampled from multiple time points in the history of a population, we infer selection at each locus by maximizing a likelihood function derived from a multilocus evolution model. We apply the method to the question of distinguishing between loci where new mutations are under positive selection (drivers) and loci that emit neutral mutations (passengers) in a Wright-Fisher model of evolution. Relative to an otherwise equivalent method in which the genetic background of mutations was ignored, our method inferred selection coefficients more accurately for both driver mutations evolving under clonal interference and passenger mutations reaching fixation in the population through genetic drift or hitchhiking. In a population history recorded by 750 sets of sequences of 100 individuals taken at intervals of 100 generations, a set of 50 loci were divided into drivers and passengers with a mean accuracy of >0.95 across a range of numbers of driver loci. The potential application of our model, either in full or in part, to a range of biological systems, is discussed.",
			"category": 2,
			"name": "Illingworth Christopher J R,2012"
		},
		{
			"PMID": 21892964,
			"title": "Does market exclusivity hinder the development of Follow-on Orphan Medicinal Products in Europe?",
			"journal": "Orphanet journal of rare diseases",
			"authorList": [
				"Brabers Anne E M",
				"Moors Ellen H M",
				"van Weely Sonja",
				"de Vrueh Remco L A"
			],
			"DOI": "10.1186/1750-1172-6-59",
			"date": "2012-02-29",
			"PMC": "",
			"citation": "",
			"abstract": "We determined whether the market exclusivity incentive of the European Orphan Drug Regulation results in a market monopoly or that absence of another Orphan Medicinal Product (OMP) for the same rare disorder, a so-called follow-on OMP, is a matter of time or market size. In the interest of rare disorder patients better understanding of the effect of the market exclusivity incentive on follow-on OMP development is warranted.",
			"category": 2,
			"name": "Brabers Anne E M,2012"
		},
		{
			"PMID": 21882037,
			"title": "Mammalian NADH:ubiquinone oxidoreductase (Complex I) and nicotinamide nucleotide transhydrogenase (Nnt) together regulate the mitochondrial production of H\u2082O\u2082--implications for their role in disease, especially cancer.",
			"journal": "Journal of bioenergetics and biomembranes",
			"authorList": [
				"Albracht Simon P J",
				"Meijer Alfred J",
				"Rydstr\u00f6m Jan"
			],
			"DOI": "10.1007/s10863-011-9381-4",
			"date": "2012-01-10",
			"PMC": "",
			"citation": "",
			"abstract": "Mammalian NADH:ubiquinone oxidoreductase (Complex I) in the mitochondrial inner membrane catalyzes the oxidation of NADH in the matrix. Excess NADH reduces nine of the ten prosthetic groups of the enzyme in bovine-heart submitochondrial particles with a rate of at least 3,300 s\u207b\u00b9. This results in an overall NADH\u2192O\u2082 rate of ca. 150 s\u207b\u00b9. It has long been known that the bovine enzyme also has a specific reaction site for NADPH. At neutral pH excess NADPH reduces only three to four of the prosthetic groups in Complex I with a rate of 40 s\u207b\u00b9 at 22 \u00b0C. The reducing equivalents remain essentially locked in the enzyme because the overall NADPH\u2192O\u2082 rate (1.4 s\u207b\u00b9) is negligible. The physiological significance of the reaction with NADPH is still unclear. A number of recent developments has revived our thinking about this enigma. We hypothesize that Complex I and the \u0394p-driven nicotinamide nucleotide transhydrogenase (Nnt) co-operate in an energy-dependent attenuation of the hydrogen-peroxide generation by Complex I. This co-operation is thought to be mediated by the NADPH/NADP\u207a ratio in the vicinity of the NADPH site of Complex I. It is proposed that the specific H\u2082O\u2082 production by Complex I, and the attenuation of it, is of importance for apoptosis, autophagy and the survival mechanism of a number of cancers. Verification of this hypothesis may contribute to a better understanding of the regulation of these processes.",
			"category": 2,
			"name": "Albracht Simon P J,2012"
		},
		{
			"PMID": 21850037,
			"title": "What does physics have to do with cancer?",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Michor Franziska",
				"Liphardt Jan",
				"Ferrari Mauro",
				"Widom Jonathan"
			],
			"DOI": "10.1038/nrc3092",
			"date": "2011-10-24",
			"PMC": "",
			"citation": "",
			"abstract": "Large-scale cancer genomics, proteomics and RNA-sequencing efforts are currently mapping in fine detail the genetic and biochemical alterations that occur in cancer. However, it is becoming clear that it is difficult to integrate and interpret these data and to translate them into treatments. This difficulty is compounded by the recognition that cancer cells evolve, and that initiation, progression and metastasis are influenced by a wide variety of factors. To help tackle this challenge, the US National Cancer Institute Physical Sciences-Oncology Centers initiative is bringing together physicists, cancer biologists, chemists, mathematicians and engineers. How are we beginning to address cancer from the perspective of the physical sciences?",
			"category": 2,
			"name": "Michor Franziska,2011"
		},
		{
			"PMID": 21807965,
			"title": "Progressive genomic instability in the FVB/Kras(LA2) mouse model of lung cancer.",
			"journal": "Molecular cancer research : MCR",
			"authorList": [
				"To Minh D",
				"Quigley David A",
				"Mao Jian-Hua",
				"Del Rosario Reyno",
				"Hsu Jeff",
				"Hodgson Graeme",
				"Jacks Tyler",
				"Balmain Allan"
			],
			"DOI": "10.1158/1541-7786.MCR-11-0219",
			"date": "2012-04-16",
			"PMC": "",
			"citation": "",
			"abstract": "Alterations in DNA copy number contribute to the development and progression of cancers and are common in epithelial tumors. We have used array Comparative Genomic Hybridization (aCGH) to visualize DNA copy number alterations across the genomes of lung tumors in the Kras(LA2) model of lung cancer. Copy number gain involving the Kras locus, as focal amplification or whole chromosome gain, is the most common alteration in these tumors and with a prevalence that increased significantly with increasing tumor size. Furthermore, Kras amplification was the only major genomic event among the smallest lung tumors, suggesting that this alteration occurs early during the development of mutant Kras-driven lung cancers. Recurring gains and deletions of other chromosomes occur progressively more frequently among larger tumors. These results are in contrast to a previous aCGH analysis of lung tumors from Kras(LA2) mice on a mixed genetic background, in which relatively few DNA copy number alterations were observed regardless of tumor size. Our model features the Kras(LA2) allele on the inbred FVB/N mouse strain, and in this genetic background, there is a highly statistically significant increase in level of genomic instability with increasing tumor size. These data suggest that recurring DNA copy alterations are important for tumor progression in the Kras(LA2) model of lung cancer and that the requirement for these alterations may be dependent on the genetic background of the mouse strain.",
			"category": 2,
			"name": "To Minh D,2012"
		},
		{
			"PMID": 21806811,
			"title": "Inferring causal genomic alterations in breast cancer using gene expression data.",
			"journal": "BMC systems biology",
			"authorList": [
				"Tran Linh M",
				"Zhang Bin",
				"Zhang Zhan",
				"Zhang Chunsheng",
				"Xie Tao",
				"Lamb John R",
				"Dai Hongyue",
				"Schadt Eric E",
				"Zhu Jun"
			],
			"DOI": "10.1186/1752-0509-5-121",
			"date": "2011-12-19",
			"PMC": "",
			"citation": "",
			"abstract": "One of the primary objectives in cancer research is to identify causal genomic alterations, such as somatic copy number variation (CNV) and somatic mutations, during tumor development. Many valuable studies lack genomic data to detect CNV; therefore, methods that are able to infer CNVs from gene expression data would help maximize the value of these studies.",
			"category": 2,
			"name": "Tran Linh M,2011"
		},
		{
			"PMID": 21802130,
			"title": "A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language?",
			"journal": "Cell",
			"authorList": [
				"Salmena Leonardo",
				"Poliseno Laura",
				"Tay Yvonne",
				"Kats Lev",
				"Pandolfi Pier Paolo"
			],
			"DOI": "10.1016/j.cell.2011.07.014",
			"date": "2011-09-29",
			"PMC": "",
			"citation": "",
			"abstract": "Here, we present a unifying hypothesis about how messenger RNAs, transcribed pseudogenes, and long noncoding RNAs \"talk\" to each other using microRNA response elements (MREs) as letters of a new language. We propose that this \"competing endogenous RNA\" (ceRNA) activity forms a large-scale regulatory network across the transcriptome, greatly expanding the functional genetic information in the human genome and playing important roles in pathological conditions, such as cancer.",
			"category": 2,
			"name": "Salmena Leonardo,2011"
		},
		{
			"PMID": 21779452,
			"title": "Evolutionary dynamics of chronic myeloid leukemia.",
			"journal": "Genes & cancer",
			"authorList": [
				"Dingli David",
				"Traulsen Arne",
				"Lenaerts Tom",
				"Pacheco Jorge M"
			],
			"DOI": "10.1177/1947601910371122",
			"date": "2011-11-10",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is an evolutionary process that arises due to mutations and expands through the selection of clones with higher reproductive success that will outcompete their peers. Most tumors require many mutations to explain the cancer phenotype, making it difficult to identify the gene(s) that confer the reproductive fitness to the clone. Moreover, the impact of any oncogene is context dependent: it can increase the fitness of particular stages of cell differentiation but not other stages. In addition, the fitness advantage of an oncogene is not irreversible: sometimes it can be reversed with targeted therapy, for example. The understanding of these dynamical processes and their consequences may be greatly simplified when addressed from an evolutionary perspective. Using the dynamics of chronic myeloid leukemia-perhaps the best understood human neoplasm-as an example, we show how three fundamental evolutionary behaviors provide insights into the dynamics of this disease: (1) BCR-ABL does not affect the reproductive success of any cell within the stem cell pool (resulting therefore in neutral drift), (2) BCR-ABL expression gives a fitness (selective) advantage to progenitor cells, and (3) imatinib therapy reduces the fitness of progenitor cells expressing the oncogene (selective disadvantage) and consequently leads to significant reductions in disease burden. These three different evolutionary dynamics scenarios based on the interpretation of mutation and gene expression as potentially leading to a fitness imbalance of cell populations clearly explain the course of the disease, providing as such a better grasp of cancer dynamics and the role of related therapies.",
			"category": 2,
			"name": "Dingli David,2011"
		},
		{
			"PMID": 21772280,
			"title": "Inflammation meets cancer, with NF-\u03baB as the matchmaker.",
			"journal": "Nature immunology",
			"authorList": [
				"Ben-Neriah Yinon",
				"Karin Michael"
			],
			"DOI": "10.1038/ni.2060",
			"date": "2011-10-07",
			"PMC": "",
			"citation": "",
			"abstract": "Inflammation is a fundamental protective response that sometimes goes awry and becomes a major cofactor in the pathogenesis of many chronic human diseases, including cancer. Here we review the evolutionary relationship and opposing functions of the transcription factor NF-\u03baB in inflammation and cancer. Although it seems to fulfill a distinctly tumor-promoting role in many types of cancer, NF-\u03baB has a confounding role in certain tumors. Understanding the activity and function of NF-\u03baB in the context of tumorigenesis is critical for its successful taming, an important challenge for modern cancer biology.",
			"category": 2,
			"name": "Ben-Neriah Yinon,2011"
		},
		{
			"PMID": 21771309,
			"title": "Qualitative thematic analysis of consent forms used in cancer genome sequencing.",
			"journal": "BMC medical ethics",
			"authorList": [
				"Allen Clarissa",
				"Foulkes William D"
			],
			"DOI": "10.1186/1472-6939-12-14",
			"date": "2011-11-15",
			"PMC": "",
			"citation": "",
			"abstract": "Large-scale whole genome sequencing (WGS) studies promise to revolutionize cancer research by identifying targets for therapy and by discovering molecular biomarkers to aid early diagnosis, to better determine prognosis and to improve treatment response prediction. Such projects raise a number of ethical, legal, and social (ELS) issues that should be considered. In this study, we set out to discover how these issues are being handled across different jurisdictions.",
			"category": 2,
			"name": "Allen Clarissa,2011"
		},
		{
			"PMID": 21765995,
			"title": "The role of epigenetic alterations in papillary thyroid carcinogenesis.",
			"journal": "Journal of thyroid research",
			"authorList": [
				"Eze Ogechukwu P",
				"Starker Lee F",
				"Carling Tobias"
			],
			"DOI": "10.4061/2011/895470",
			"date": "2011-11-10",
			"PMC": "",
			"citation": "",
			"abstract": "Papillary thyroid carcinoma (PTC) accounts for over 80% of all thyroid malignancies. The molecular pathogenesis remains incompletely clarified although activation of the RET fusion oncogenes, and RAS and BRAF oncogenes, has been well characterized. Novel technologies using genome-wide approaches to study tumor genomes and epigenomes have provided great insights into tumor development. Growing evidence shows that acquired epigenetic abnormalities participate with genetic alterations to cause altered patterns of gene expression/function. It has been established beyond doubt that promoter cytosine methylation in CpG islands, and the subsequent gene silencing, is intimately involved in cancer development. These epigenetic events very likely contribute to significant variation in gene expression profiling, phenotypic features, and biologic characteristics seen in PTC. Hypermethylation of promoter regions has also been analyzed in PTC, and most studies have focused on individual genes or a small cohort of genes implicated in tumorigenesis.",
			"category": 2,
			"name": "Eze Ogechukwu P,2011"
		},
		{
			"PMID": 21763698,
			"title": "Structural and functional impact of cancer-related missense somatic mutations.",
			"journal": "Journal of molecular biology",
			"authorList": [
				"Shi Zhen",
				"Moult John"
			],
			"DOI": "10.1016/j.jmb.2011.06.046",
			"date": "2011-12-07",
			"PMC": "",
			"citation": "",
			"abstract": "A number of large-scale cancer somatic genome sequencing projects are now identifying genetic alterations in cancers. Evaluation of the effects of these mutations is essential for understanding their contribution to tumorigenesis. We have used SNPs3D, a software suite originally developed for analyzing nonsynonymous germ-line variants, to identify single-base mutations with a high impact on protein structure and function. Two machine learning methods are used: one identifying mutations that destabilize protein three-dimensional structure and the other utilizing sequence conservation and detecting all types of effects on in vivo protein function. Incorporation of detailed structure information into the analysis allows detailed interpretation of the functional effects of mutations in specific cases.\u00a0 Data from a set of breast and colorectal tumors were analyzed. In known cancer genes, mutations approaching 100% of mutations are found to impact protein function, supporting the view that these methods are appropriate for identifying driver mutations. Overall, 50-60% of all somatic missense mutations are predicted to have a high impact on structural stability or to more generally affect the function of the corresponding proteins. This value is similar to the fraction of all possible missense mutations that have a high impact and is much higher than the corresponding one for human population single-nucleotide polymorphisms, at about 30%. The majority of mutations in tumor suppressors destabilize protein structure, while mutations in oncogenes operate in more varied ways, including destabilization of less active conformational states. The set of high-impact mutations encompasses the possible drivers.",
			"category": 2,
			"name": "Shi Zhen,2011"
		},
		{
			"PMID": 21738155,
			"title": "A viral strategy to ambush tumors.",
			"journal": "Nature medicine",
			"authorList": [
				"Alvarez-Breckenridge Christopher",
				"Chiocca E Antonio"
			],
			"DOI": "10.1038/nm0711-784",
			"date": "2011-09-20",
			"PMC": "",
			"citation": "",
			"abstract": "A new combinatorial approach harnesses the power of immuno- and virotherapy in a vesicular stomatitis virus (VSV) vector carrying a cDNA library that expresses normal human prostate antigens, thus providing proof of principle that this vaccine can induce prostate tumor rejection in mice (pages 854\u2013859). This strategy might bypass many of the issues associated with conventional cancer immuno- or virotherapy.",
			"category": 2,
			"name": "Alvarez-Breckenridge Christopher,2011"
		},
		{
			"PMID": 21725294,
			"title": "DNA secondary structures and epigenetic determinants of cancer genome evolution.",
			"journal": "Nature structural & molecular biology",
			"authorList": [
				"De Subhajyoti",
				"Michor Franziska"
			],
			"DOI": "10.1038/nsmb.2089",
			"date": "2011-11-28",
			"PMC": "",
			"citation": "",
			"abstract": "An unstable genome is a hallmark of many cancers. It is unclear, however, whether some mutagenic features driving somatic alterations in cancer are encoded in the genome sequence and whether they can operate in a tissue-specific manner. We performed a genome-wide analysis of 663,446 DNA breakpoints associated with somatic copy-number alterations (SCNAs) from 2,792 cancer samples classified into 26 cancer types. Many SCNA breakpoints are spatially clustered in cancer genomes. We observed a significant enrichment for G-quadruplex sequences (G4s) in the vicinity of SCNA breakpoints and established that SCNAs show a strand bias consistent with G4-mediated structural alterations. Notably, abnormal hypomethylation near G4s-rich regions is a common signature for many SCNA breakpoint hotspots. We propose a mechanistic hypothesis that abnormal hypomethylation in genomic regions enriched for G4s acts as a mutagenic factor driving tissue-specific mutational landscapes in cancer.",
			"category": 2,
			"name": "De Subhajyoti,2011"
		},
		{
			"PMID": 21709698,
			"title": "Challenging issues in pediatric oncology.",
			"journal": "Nature reviews. Clinical oncology",
			"authorList": [
				"Pui Ching-Hon",
				"Gajjar Amar J",
				"Kane Javier R",
				"Qaddoumi Ibrahim A",
				"Pappo Alberto S"
			],
			"DOI": "10.1038/nrclinonc.2011.95",
			"date": "2011-12-22",
			"PMC": "",
			"citation": "",
			"abstract": "Improvements in protocol-driven clinical trials and supportive care for children and adolescents with cancer have reduced mortality rates by more than 50% over the past three decades. Overall, the 5-year survival rate for patients with pediatric cancer has increased to approximately 80%. Recognition of the biological heterogeneity within specific subtypes of cancer, the discovery of genetic lesions that drive malignant transformation and cancer progression, and improved understanding of the basis of drug resistance will undoubtedly catalyze further advances in risk-directed treatments and the development of targeted therapies, boosting the cure rates further. Emerging new treatments include novel formulations of existing chemotherapeutic agents, monoclonal antibodies against cancer-associated antigens, and molecular therapies that target genetic lesions and their associated signaling pathways. Recent findings that link pharmacogenomic variations with drug exposure, adverse effects, and efficacy should accelerate efforts to develop personalized therapy for individual patients. Finally, palliative care should be included as an essential part of cancer management to prevent and relieve the suffering and to improve the quality of life of patients and their families.",
			"category": 2,
			"name": "Pui Ching-Hon,2011"
		},
		{
			"PMID": 21695222,
			"title": "Microfabricated physical spatial gradients for investigating cell migration and invasion dynamics.",
			"journal": "PloS one",
			"authorList": [
				"Mak Michael",
				"Reinhart-King Cynthia A",
				"Erickson David"
			],
			"DOI": "10.1371/journal.pone.0020825",
			"date": "2011-11-02",
			"PMC": "",
			"citation": "",
			"abstract": "We devise a novel assay that introduces micro-architectures into highly confining microchannels to probe the decision making processes of migrating cells. The conditions are meant to mimic the tight spaces in the physiological environment that cancer cells encounter during metastasis within the matrix dense stroma and during intravasation and extravasation through the vascular wall. In this study we use the assay to investigate the relative probabilities of a cell 1) permeating and 2) repolarizing (turning around) when it migrates into a spatially confining region. We observe the existence of both states even within a single cell line, indicating phenotypic heterogeneity in cell migration invasiveness and persistence. We also show that varying the spatial gradient of the taper can induce behavioral changes in cells, and different cell types respond differently to spatial changes. Particularly, for bovine aortic endothelial cells (BAECs), higher spatial gradients induce more cells to permeate (60%) than lower gradients (12%). Furthermore, highly metastatic breast cancer cells (MDA-MB-231) demonstrate a more invasive and permeative nature (87%) than non-metastatic breast epithelial cells (MCF-10A) (25%). We examine the migration dynamics of cells in the tapered region and derive characteristic constants that quantify this transition process. Our data indicate that cell response to physical spatial gradients is both cell-type specific and heterogeneous within a cell population, analogous to the behaviors reported to occur during tumor progression. Incorporation of micro-architectures in confined channels enables the probing of migration behaviors specific to defined geometries that mimic in vivo microenvironments.",
			"category": 2,
			"name": "Mak Michael,2011"
		},
		{
			"PMID": 21691773,
			"title": "Integrative computational biology for cancer research.",
			"journal": "Human genetics",
			"authorList": [
				"Fortney Kristen",
				"Jurisica Igor"
			],
			"DOI": "10.1007/s00439-011-0983-z",
			"date": "2011-11-14",
			"PMC": "",
			"citation": "",
			"abstract": "Over the past two decades, high-throughput (HTP) technologies such as microarrays and mass spectrometry have fundamentally changed clinical cancer research. They have revealed novel molecular markers of cancer subtypes, metastasis, and drug sensitivity and resistance. Some have been translated into the clinic as tools for early disease diagnosis, prognosis, and individualized treatment and response monitoring. Despite these successes, many challenges remain: HTP platforms are often noisy and suffer from false positives and false negatives; optimal analysis and successful validation require complex workflows; and great volumes of data are accumulating at a rapid pace. Here we discuss these challenges, and show how integrative computational biology can help diminish them by creating new software tools, analytical methods, and data standards.",
			"category": 2,
			"name": "Fortney Kristen,2011"
		},
		{
			"PMID": 21685067,
			"title": "Uncover disease genes by maximizing information flow in the phenome-interactome network.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Chen Yong",
				"Jiang Tao",
				"Jiang Rui"
			],
			"DOI": "10.1093/bioinformatics/btr213",
			"date": "2011-10-27",
			"PMC": "",
			"citation": "",
			"abstract": "Pinpointing genes that underlie human inherited diseases among candidate genes in susceptibility genetic regions is the primary step towards the understanding of pathogenesis of diseases. Although several probabilistic models have been proposed to prioritize candidate genes using phenotype similarities and protein-protein interactions, no combinatorial approaches have been proposed in the literature.",
			"category": 2,
			"name": "Chen Yong,2011"
		},
		{
			"PMID": 21643984,
			"title": "Somatic variation and cancer: therapies lost in the mix.",
			"journal": "Human genetics",
			"authorList": [
				"Biankin Andrew V",
				"Hudson Thomas J"
			],
			"DOI": "10.1007/s00439-011-1010-0",
			"date": "2011-08-23",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer arises as a consequence of mutations in genomes of cancer cells, which over time allow them to proliferate and spread to distant sites. Large-scale sequencing of cancer genomes is revealing an increasing number of potential driver mutations that may allow specific targeting of cancer genes, proteins, and pathways. Comprehensive views of cancer genomes are also revealing enormous heterogeneity of mutation profiles, even among tumours derived from the same organs and having similar pathological characteristics. There are now many examples where mutation profiles observed in tumours have been shown to correlate with clinical features of disease, drug response, and patient outcomes. When ignored, molecular heterogeneity can lead to failures in drug development, as drugs that may have efficacy in subgroups of patients with specific molecular phenotypes may show marginal response when tested in large groups of unselected patients. This article explores issues relevant to the clinical translation of sequence-based mutation profiles in the clinical development of targeted therapies and in the future management of cancer patients.",
			"category": 2,
			"name": "Biankin Andrew V,2011"
		},
		{
			"PMID": 21620140,
			"title": "Analysis of the human endogenous coregulator complexome.",
			"journal": "Cell",
			"authorList": [
				"Malovannaya Anna",
				"Lanz Rainer B",
				"Jung Sung Yun",
				"Bulynko Yaroslava",
				"Le Nguyen T",
				"Chan Doug W",
				"Ding Chen",
				"Shi Yi",
				"Yucer Nur",
				"Krenciute Giedre",
				"Kim Beom-Jun",
				"Li Chunshu",
				"Chen Rui",
				"Li Wei",
				"Wang Yi",
				"O'Malley Bert W",
				"Qin Jun"
			],
			"DOI": "10.1016/j.cell.2011.05.006",
			"date": "2011-08-01",
			"PMC": "",
			"citation": "",
			"abstract": "Elucidation of endogenous cellular protein-protein interactions and their networks is most desirable for biological studies. Here we report our study of endogenous human coregulator protein complex networks obtained from integrative mass spectrometry-based analysis of 3290 affinity purifications. By preserving weak protein interactions during complex isolation and utilizing high levels of reciprocity in the large dataset, we identified many unreported protein associations, such as a transcriptional network formed by ZMYND8, ZNF687, and ZNF592. Furthermore, our work revealed a tiered interplay within networks that share common proteins, providing a conceptual organization of a cellular proteome composed of minimal endogenous modules (MEMOs), complex isoforms (uniCOREs), and regulatory complex-complex interaction networks (CCIs). This resource will effectively fill a void in linking correlative genomic studies with an understanding of transcriptional regulatory protein functions within the proteome for formulation and testing of future hypotheses.",
			"category": 2,
			"name": "Malovannaya Anna,2011"
		},
		{
			"PMID": 21603310,
			"title": "Eagles report: Developing cancer biomarkers from genome-wide DNA methylation analyses.",
			"journal": "World journal of clinical oncology",
			"authorList": [
				"Schulz Wolfgang A",
				"Goering Wolfgang"
			],
			"DOI": "10.5306/wjco.v2.i1.1",
			"date": "2011-07-14",
			"PMC": "",
			"citation": "",
			"abstract": "Analyses of DNA methylation in human cancers have identified hypermethylation of individual genes and diminished methylation at repeat elements as common alterations, and have thereby provided important mechanistic insights into cancer biology as well as biomarkers for cancer detection, prognosis and prediction of therapy responses. The techniques available in the past were best suited for investigations of individual candidate genes and sequences, whereas recently developed high-throughput techniques promise to generate unbiased and comprehensive surveys of DNA methylation states across entire genomes. In this minireview we give a short overview of established and novel techniques and outline some major questions that can now be addressed to develop further cancer biomarkers and therapies based on DNA methylation.",
			"category": 2,
			"name": "Schulz Wolfgang A,2011"
		},
		{
			"PMID": 21586118,
			"title": "The Roche Cancer Genome Database 2.0.",
			"journal": "BMC medical genomics",
			"authorList": [
				"K\u00fcntzer Jan",
				"Maisel Daniela",
				"Lenhof Hans-Peter",
				"Klostermann Stefan",
				"Burtscher Helmut"
			],
			"DOI": "10.1186/1755-8794-4-43",
			"date": "2011-09-09",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is a disease of genome alterations that arise through the acquisition of multiple somatic DNA sequence mutations. Some of these mutations can be critical for the development of a tumor and can be useful to characterize tumor types or predict outcome.",
			"category": 2,
			"name": "K\u00fcntzer Jan,2011"
		},
		{
			"PMID": 21575252,
			"title": "Germ-line mutations in epidermal growth factor receptor (EGFR) are rare but may contribute to oncogenesis: a novel germ-line mutation in EGFR detected in a patient with lung adenocarcinoma.",
			"journal": "BMC cancer",
			"authorList": [
				"Centeno Irene",
				"Blay Pilar",
				"Santamar\u00eda I\u00f1igo",
				"Astudillo Aurora",
				"Pitiot Ana S",
				"Osorio Fernando G",
				"Gonz\u00e1lez-Arriaga Patricia",
				"Iglesias Fernando",
				"Men\u00e9ndez Primitiva",
				"Tard\u00f3n Adonina",
				"Freije Jose M",
				"Balb\u00edn Milagros"
			],
			"DOI": "10.1186/1471-2407-11-172",
			"date": "2011-09-16",
			"PMC": "",
			"citation": "",
			"abstract": "A subset of lung cancer patients harbour EGFR somatic mutations in their tumours and are candidates for treatment with EGFR tyrosine kinase inhibitors. In a few cases EGFR mutations have also been found in the germ line, suggesting a role in lung carcinogenesis. Objetives of this study were: 1) To analyze the EGFR gene mutations in a population diagnosed with lung adenocarcinoma from Northern Spain. 2) To determine the frequency of a new germ-line mutation found in our laboratory as well as the frequency in our population of three other EGFR germ-line mutations detected by other authors. 3) To determine whether the novel mutation detected may have a functional effect on the EGFR protein.",
			"category": 2,
			"name": "Centeno Irene,2011"
		},
		{
			"PMID": 21547123,
			"title": "Targeting the cell cycle in esophageal adenocarcinoma: an adjunct to anticancer treatment.",
			"journal": "World journal of gastroenterology",
			"authorList": [
				"Dibb Martyn",
				"Ang Yeng S"
			],
			"DOI": "10.3748/wjg.v17.i16.2063",
			"date": "2011-08-15",
			"PMC": "",
			"citation": "",
			"abstract": "Esophageal adenocarcinoma is a major cause of cancer death in men in the developed world. Continuing poor outcomes with conventional therapies that predominantly target apoptosis pathways have lead to increasing interest in treatments that target the cell cycle. A large international effort has led to the development of a large number of inhibitors, which target cell cycle kinases, including cyclin-dependent kinases, Aurora kinases and polo-like kinase. Initial phase\u2005I/II trials in solid tumors have often demonstrated only modest clinical benefits of monotherapy. This may relate in part to a failure to identify the patient populations that will gain the most clinical benefit. Newer compounds lacking the side effect profile of first-generation compounds may show utility as adjunctive treatments targeted to an individual's predicted response to treatment.",
			"category": 2,
			"name": "Dibb Martyn,2011"
		},
		{
			"PMID": 21537385,
			"title": "Towards a more functional concept of causality in cancer research.",
			"journal": "International journal of molecular epidemiology and genetics",
			"authorList": [
				"Lund Eiliv",
				"Dumeaux Vanessa"
			],
			"DOI": "",
			"date": "2011-07-14",
			"PMC": "",
			"citation": "",
			"abstract": "Advances in molecular technologies challenge the different concepts of causality in biology, epidemiology and multistage mathematical models. The lack of integration of the different aspects of causality into a common framework could postpone our attempts to build a human causal model of carcinogenesis. We present here some aspects of differences in methodology, terminology and traditions between the scientific disciplines and propose a research strategy using functional analyses of the transcriptome and epigenetics to illuminate causality in complex biological systems. Overcoming the challenges of biological material collection suitable for such analyses into a prospective design, this could give unique opportunities for verification of mechanistic information from basic biological research in a human model system. The ultimate goal is to obtain a dynamic causal description of the different carcinogenesis stages. The success of this novel approach depends on the biological relationship between the gene expression of the somatic driver mutations or co-expressed genes in tumours and the gene expressions mirrored in peripheral blood along the different stages of carcinogenesis. The use of gene expression profiles and epigenetics could produce a functional concept of causality to explain the human multistage carcinogenic process.",
			"category": 2,
			"name": "Lund Eiliv,2011"
		},
		{
			"PMID": 21535262,
			"title": "A model for random genetic damage directing selection of diploid or aneuploid tumours.",
			"journal": "Cell proliferation",
			"authorList": [
				"Bazeley P S",
				"Nestor Kalinoski A L",
				"Ways J A",
				"Liu S-T",
				"Ramdath R S",
				"Matsui S-i",
				"Allison D C"
			],
			"DOI": "10.1111/j.1365-2184.2011.00746.x",
			"date": "2011-07-12",
			"PMC": "",
			"citation": "",
			"abstract": "To test whether genetic instability may determine whether tumours become aneuploid or diploid.",
			"category": 2,
			"name": "Bazeley P S,2011"
		},
		{
			"PMID": 21527027,
			"title": "GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers.",
			"journal": "Genome biology",
			"authorList": [
				"Mermel Craig H",
				"Schumacher Steven E",
				"Hill Barbara",
				"Meyerson Matthew L",
				"Beroukhim Rameen",
				"Getz Gad"
			],
			"DOI": "10.1186/gb-2011-12-4-r41",
			"date": "2012-02-14",
			"PMC": "",
			"citation": "",
			"abstract": "We describe methods with enhanced power and specificity to identify genes targeted by somatic copy-number alterations (SCNAs) that drive cancer growth. By separating SCNA profiles into underlying arm-level and focal alterations, we improve the estimation of background rates for each category. We additionally describe a probabilistic method for defining the boundaries of selected-for SCNA regions with user-defined confidence. Here we detail this revised computational approach, GISTIC2.0, and validate its performance in real and simulated datasets.",
			"category": 2,
			"name": "Mermel Craig H,2012"
		},
		{
			"PMID": 21525943,
			"title": "Warheads and avoiding Star Wars.",
			"journal": "EMBO reports",
			"authorList": [
				"Colaco Camilo"
			],
			"DOI": "10.1038/embor.2011.67",
			"date": "2011-08-22",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Colaco Camilo,2011"
		},
		{
			"PMID": 21503935,
			"title": "The tissue organization field theory of cancer: a testable replacement for the somatic mutation theory.",
			"journal": "BioEssays : news and reviews in molecular, cellular and developmental biology",
			"authorList": [
				"Soto Ana M",
				"Sonnenschein Carlos"
			],
			"DOI": "10.1002/bies.201100025",
			"date": "2011-09-23",
			"PMC": "",
			"citation": "",
			"abstract": "The somatic mutation theory (SMT) of cancer has been and remains the prevalent theory attempting to explain how neoplasms arise and progress. This theory proposes that cancer is a clonal, cell-based disease, and implicitly assumes that quiescence is the default state of cells in multicellular organisms. The SMT has not been rigorously tested, and several lines of evidence raise questions that are not addressed by this theory. Herein, we propose experimental strategies that may validate the SMT. We also call attention to an alternative theory of carcinogenesis, the tissue organization field theory (TOFT), which posits that cancer is a tissue-based disease and that proliferation is the default state of all cells. Based on epistemological and experimental evidence, we argue that the TOFT compellingly explains carcinogenesis, while placing it within an evolutionarily relevant context.",
			"category": 2,
			"name": "Soto Ana M,2011"
		},
		{
			"PMID": 21489208,
			"title": "Somatic mutations in cancer development.",
			"journal": "Environmental health : a global access science source",
			"authorList": [
				"Luzzatto Lucio"
			],
			"DOI": "10.1186/1476-069X-10-S1-S12",
			"date": "2011-08-31",
			"PMC": "",
			"citation": "",
			"abstract": "The transformation of a normal cell into a cancer cell takes place through a sequence of a small number of discrete genetic events, somatic mutations: thus, cancer can be regarded properly as a genetic disease of somatic cells. The analogy between evolution of organisms and evolution of cell populations is compelling: in both cases what drives change is mutation, but it is Darwinian selection that enables clones that have a growth advantage to expand, thus providing a larger target size for the next mutation to hit. The search for molecular lesions in tumors has taken on a new dimension thanks to two powerful technologies: the micro-arrays for quantitative analysis of global gene expresssion (the transcriptome); and 'deep' sequencing for the global analysis of the entire genome (or at least the exome). The former offers the most complete phenotypic characterization of a tumor we could ever hope for--we could call this the ultimate phenotype; the latter can identify all the somatic mutations in an individual tumor--we could call this the somatic genotype. However, there is definitely the risk that while we are 'drowned by data, we remain thirsty for knowledge'. If we want to heed the teachings of Lorenzo Tomatis, I think the message is clear: we ought to take advantage of the new powerful technologies--not by becoming their slaves, but remaining their masters. Identifying somatic mutations in a tumor is important not because it qualifies for 'oncogenomics', but because through a deeper understanding of the nature of that particular tumor it can help us to optimize therapy or to design new therapeutic approaches.",
			"category": 2,
			"name": "Luzzatto Lucio,2011"
		},
		{
			"PMID": 21483478,
			"title": "CAERUS: predicting CAncER oUtcomeS using relationship between protein structural information, protein networks, gene expression data, and mutation data.",
			"journal": "PLoS computational biology",
			"authorList": [
				"Zhang Kelvin Xi",
				"Ouellette B F Francis"
			],
			"DOI": "10.1371/journal.pcbi.1001114",
			"date": "2011-07-22",
			"PMC": "",
			"citation": "",
			"abstract": "Carcinogenesis is a complex process with multiple genetic and environmental factors contributing to the development of one or more tumors. Understanding the underlying mechanism of this process and identifying related markers to assess the outcome of this process would lead to more directed treatment and thus significantly reduce the mortality rate of cancers. Recently, molecular diagnostics and prognostics based on the identification of patterns within gene expression profiles in the context of protein interaction networks were reported. However, the predictive performances of these approaches were limited. In this study we propose a novel integrated approach, named CAERUS, for the identification of gene signatures to predict cancer outcomes based on the domain interaction network in human proteome. We first developed a model to score each protein by quantifying the domain connections to its interacting partners and the somatic mutations present in the domain. We then defined proteins as gene signatures if their scores were above a preset threshold. Next, for each gene signature, we quantified the correlation of the expression levels between this gene signature and its neighboring proteins. The results of the quantification in each patient were then used to predict cancer outcome by a modified na\u00efve Bayes classifier. In this study we achieved a favorable accuracy of 88.3%, sensitivity of 87.2%, and specificity of 88.9% on a set of well-documented gene expression profiles of 253 consecutive breast cancer patients with different outcomes. We also compiled a list of cancer-associated gene signatures and domains, which provided testable hypotheses for further experimental investigation. Our approach proved successful on different independent breast cancer data sets as well as an ovarian cancer data set. This study constitutes the first predictive method to classify cancer outcomes based on the relationship between the domain organization and protein network.",
			"category": 2,
			"name": "Zhang Kelvin Xi,2011"
		},
		{
			"PMID": 21470959,
			"title": "High-throughput analysis of the mutagenic and cytotoxic properties of DNA lesions by next-generation sequencing.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Yuan Bifeng",
				"Wang Jianshuang",
				"Cao Huachuan",
				"Sun Ruobai",
				"Wang Yinsheng"
			],
			"DOI": "10.1093/nar/gkr159",
			"date": "2011-10-17",
			"PMC": "",
			"citation": "",
			"abstract": "Human cells are constantly exposed to environmental and endogenous agents which can induce damage to DNA. Understanding the implications of these DNA modifications in the etiology of human diseases requires the examination about how these DNA lesions block DNA replication and induce mutations in cells. All previously reported shuttle vector-based methods for investigating the cytotoxic and mutagenic properties of DNA lesions in cells have low-throughput, where plasmids containing individual lesions are transfected into cells one lesion at a time and the products from the replication of individual lesions are analyzed separately. The advent of next-generation sequencing (NGS) technology has facilitated investigators to design scientific approaches that were previously not technically feasible or affordable. In this study, we developed a new method employing NGS, together with shuttle vector technology, to have a multiplexed and quantitative assessment of how DNA lesions perturb the efficiency and accuracy of DNA replication in cells. By using this method, we examined the replication of four carboxymethylated DNA lesions and two oxidatively induced bulky DNA lesions including (5'S) diastereomers of 8,5'-cyclo-2'-deoxyguanosine (cyclo-dG) and 8,5'-cyclo-2'-deoxyadenosine (cyclo-dA) in five different strains of Escherichia coli cells. We further validated the results obtained from NGS using previously established methods. Taken together, the newly developed method provided a high-throughput and readily affordable method for assessing quantitatively how DNA lesions compromise the efficiency and fidelity of DNA replication in cells.",
			"category": 2,
			"name": "Yuan Bifeng,2011"
		},
		{
			"PMID": 21441214,
			"title": "Germline fitness-based scoring of cancer mutations.",
			"journal": "Genetics",
			"authorList": [
				"Fischer Andrej",
				"Greenman Chris",
				"Mustonen Ville"
			],
			"DOI": "10.1534/genetics.111.127480",
			"date": "2011-10-20",
			"PMC": "",
			"citation": "",
			"abstract": "A key goal in cancer research is to find the genomic alterations that underlie malignant cells. Genomics has proved successful in identifying somatic variants at a large scale. However, it has become evident that a typical cancer exhibits a heterogenous mutation pattern across samples. Cases where the same alteration is observed repeatedly seem to be the exception rather than the norm. Thus, pinpointing the key alterations (driver mutations) from a background of variations with no direct causal link to cancer (passenger mutations) is difficult. Here we analyze somatic missense mutations from cancer samples and their healthy tissue counterparts (germline mutations) from the viewpoint of germline fitness. We calibrate a scoring system from protein domain alignments to score mutations and their target loci. We show first that this score predicts to a good degree the rate of polymorphism of the observed germline variation. The scoring is then applied to somatic mutations. We show that candidate cancer genes prone to copy number loss harbor mutations with germline fitness effects that are significantly more deleterious than expected by chance. This suggests that missense mutations play a driving role in tumor suppressor genes. Furthermore, these mutations fall preferably onto loci in sequence neighborhoods that are high scoring in terms of germline fitness. In contrast, for somatic mutations in candidate onco genes we do not observe a statistically significant effect. These results help to inform how to exploit germline fitness predictions in discovering new genes and mutations responsible for cancer.",
			"category": 2,
			"name": "Fischer Andrej,2011"
		},
		{
			"PMID": 21415896,
			"title": "Targeted deep resequencing of the human cancer genome using next-generation technologies.",
			"journal": "Biotechnology & genetic engineering reviews",
			"authorList": [
				"Myllykangas Samuel",
				"Ji Hanlee P"
			],
			"DOI": "",
			"date": "2011-04-07",
			"PMC": "",
			"citation": "",
			"abstract": "Next-generation sequencing technologies have revolutionized our ability to identify genetic variants, either germline or somatic point mutations, that occur in cancer. Parallelization and miniaturization of DNA sequencing enables massive data throughput and for the first time, large-scale, nucleotide resolution views of cancer genomes can be achieved. Systematic, large-scale sequencing surveys have revealed that the genetic spectrum of mutations in cancers appears to be highly complex with numerous low frequency bystander somatic variations, and a limited number of common, frequently mutated genes. Large sample sizes and deeper resequencing are much needed in resolving clinical and biological relevance of the mutations as well as in detecting somatic variants in heterogeneous samples and cancer cell sub-populations. However, even with the next-generation sequencing technologies, the overwhelming size of the human genome and need for very high fold coverage represents a major challenge for up-scaling cancer genome sequencing projects. Assays to target, capture, enrich or partition disease-specific regions of the genome offer immediate solutions for reducing the complexity of the sequencing libraries. Integration of targeted DNA capture assays and next-generation deep resequencing improves the ability to identify clinically and biologically relevant mutations.",
			"category": 2,
			"name": "Myllykangas Samuel,2011"
		},
		{
			"PMID": 21414488,
			"title": "Interactome networks and human disease.",
			"journal": "Cell",
			"authorList": [
				"Vidal Marc",
				"Cusick Michael E",
				"Barab\u00e1si Albert-L\u00e1szl\u00f3"
			],
			"DOI": "10.1016/j.cell.2011.02.016",
			"date": "2011-06-06",
			"PMC": "",
			"citation": "",
			"abstract": "Complex biological systems and cellular networks may underlie most genotype to phenotype relationships. Here, we review basic concepts in network biology, discussing different types of interactome networks and the insights that can come from analyzing them. We elaborate on why interactome networks are important to consider in biology, how they can be mapped and integrated with each other, what global properties are starting to emerge from interactome network models, and how these properties may relate to human disease.",
			"category": 2,
			"name": "Vidal Marc,2011"
		},
		{
			"PMID": 21406553,
			"title": "Making sense of cancer genomic data.",
			"journal": "Genes & development",
			"authorList": [
				"Chin Lynda",
				"Hahn William C",
				"Getz Gad",
				"Meyerson Matthew"
			],
			"DOI": "10.1101/gad.2017311",
			"date": "2011-05-05",
			"PMC": "",
			"citation": "",
			"abstract": "High-throughput tools for nucleic acid characterization now provide the means to conduct comprehensive analyses of all somatic alterations in the cancer genomes. Both large-scale and focused efforts have identified new targets of translational potential. The deluge of information that emerges from these genome-scale investigations has stimulated a parallel development of new analytical frameworks and tools. The complexity of somatic genomic alterations in cancer genomes also requires the development of robust methods for the interrogation of the function of genes identified by these genomics efforts. Here we provide an overview of the current state of cancer genomics, appraise the current portals and tools for accessing and analyzing cancer genomic data, and discuss emerging approaches to exploring the functions of somatically altered genes in cancer.",
			"category": 2,
			"name": "Chin Lynda,2011"
		},
		{
			"PMID": 21399634,
			"title": "Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia.",
			"journal": "Nature genetics",
			"authorList": [
				"Yan Xiao-Jing",
				"Xu Jie",
				"Gu Zhao-Hui",
				"Pan Chun-Ming",
				"Lu Gang",
				"Shen Yang",
				"Shi Jing-Yi",
				"Zhu Yong-Mei",
				"Tang Lin",
				"Zhang Xiao-Wei",
				"Liang Wen-Xue",
				"Mi Jian-Qing",
				"Song Huai-Dong",
				"Li Ke-Qin",
				"Chen Zhu",
				"Chen Sai-Juan"
			],
			"DOI": "10.1038/ng.788",
			"date": "2011-05-09",
			"PMC": "",
			"citation": "",
			"abstract": "Abnormal epigenetic regulation has been implicated in oncogenesis. We report here the identification of somatic mutations by exome sequencing in acute monocytic leukemia, the M5 subtype of acute myeloid leukemia (AML-M5). We discovered mutations in DNMT3A (encoding DNA methyltransferase 3A) in 23 of 112 (20.5%) cases. The DNMT3A mutants showed reduced enzymatic activity or aberrant affinity to histone H3 in vitro. Notably, there were alterations of DNA methylation patterns and/or gene expression profiles (such as HOXB genes) in samples with DNMT3A mutations as compared with those without such changes. Leukemias with DNMT3A mutations constituted a group of poor prognosis with elderly disease onset and of promonocytic as well as monocytic predominance among AML-M5 individuals. Screening other leukemia subtypes showed Arg882 alterations in 13.6% of acute myelomonocytic leukemia (AML-M4) cases. Our work suggests a contribution of aberrant DNA methyltransferase activity to the pathogenesis of acute monocytic leukemia and provides a useful new biomarker for relevant cases.",
			"category": 2,
			"name": "Yan Xiao-Jing,2011"
		},
		{
			"PMID": 21393386,
			"title": "RAF gene fusion breakpoints in pediatric brain tumors are characterized by significant enrichment of sequence microhomology.",
			"journal": "Genome research",
			"authorList": [
				"Lawson Andrew R J",
				"Hindley Guy F L",
				"Forshew Tim",
				"Tatevossian Ruth G",
				"Jamie Gabriel A",
				"Kelly Gavin P",
				"Neale Geoffrey A",
				"Ma Jing",
				"Jones Tania A",
				"Ellison David W",
				"Sheer Denise"
			],
			"DOI": "10.1101/gr.115782.110",
			"date": "2011-07-13",
			"PMC": "",
			"citation": "",
			"abstract": "Gene fusions involving members of the RAF family of protein kinases have recently been identified as characteristic aberrations of low-grade astrocytomas, the most common tumors of the central nervous system in children. While it has been shown that these fusions cause constitutive activation of the ERK/MAPK pathway, very little is known about their formation. Here, we present a detailed analysis of RAF gene fusion breakpoints from a well-characterized cohort of 43 low-grade astrocytomas. Our findings show that the rearrangements that generate these RAF gene fusions may be simple or complex and that both inserted nucleotides and microhomology are common at the DNA breakpoints. Furthermore, we identify novel enrichment of microhomologous sequences in the regions immediately flanking the breakpoints. We thus provide evidence that the tandem duplications responsible for these fusions are generated by microhomology-mediated break-induced replication (MMBIR). Although MMBIR has previously been implicated in the pathogenesis of other diseases and the evolution of eukaryotic genomes, we demonstrate here that the proposed details of MMBIR are consistent with a recurrent rearrangement in cancer. Our analysis of repetitive elements, Z-DNA and sequence motifs in the fusion partners identified significant enrichment of the human minisatellite conserved sequence/\u03c7-like element at one side of the breakpoint. Therefore, in addition to furthering our understanding of low-grade astrocytomas, this study provides insights into the molecular mechanistic details of MMBIR and the sequence of events that occur in the formation of genomic rearrangements.",
			"category": 2,
			"name": "Lawson Andrew R J,2011"
		},
		{
			"PMID": 21379385,
			"title": "Functional characterization of human cancer-derived TRKB mutations.",
			"journal": "PloS one",
			"authorList": [
				"Geiger Thomas R",
				"Song Ji-Ying",
				"Rosado Aranzazu",
				"Peeper Daniel S"
			],
			"DOI": "10.1371/journal.pone.0016871",
			"date": "2011-09-01",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer originates from cells that have acquired mutations in genes critical for controlling cell proliferation, survival and differentiation. Often, tumors continue to depend on these so-called driver mutations, providing the rationale for targeted anticancer therapies. To date, large-scale sequencing analyses have revealed hundreds of mutations in human tumors. However, without their functional validation it remains unclear which mutations correspond to driver, or rather bystander, mutations and, therefore, whether the mutated gene represents a target for therapeutic intervention. In human colorectal tumors, the neurotrophic receptor TRKB has been found mutated on two different sites in its kinase domain (TRKB(T695I) and TRKB(D751N)). Another site, in the extracellular part of TRKB, is mutated in a human lung adenocarcinoma cell line (TRKB(L138F)). Lastly, our own analysis has identified one additional TRKB point mutation proximal to the kinase domain (TRKB(P507L)) in a human melanoma cell line. The functional consequences of all these point mutations, however, have so far remained elusive. Previously, we have shown that TRKB is a potent suppressor of anoikis and that TRKB-expressing cells form highly invasive and metastatic tumors in nude mice. To assess the functional consequences of these four TRKB mutations, we determined their potential to suppress anoikis and to form tumors in nude mice. Unexpectedly, both colon cancer-derived mutants, TRKB(T695I) and TRKB(D751N), displayed reduced activity compared to that of wild-type TRKB. Consistently, upon stimulation with the TRKB ligand BDNF, these mutants were impaired in activating TRKB and its downstream effectors AKT and ERK. The two mutants derived from human tumor cell lines (TRKB(L138F) and TRKB(P507L)) were functionally indistinguishable from wild-type TRKB in both in-vitro and in-vivo assays. In conclusion, we fail to detect any gain-of-function of four cancer-derived TRKB point mutations.",
			"category": 2,
			"name": "Geiger Thomas R,2011"
		},
		{
			"PMID": 21371302,
			"title": "CDCOCA: a statistical method to define complexity dependence of co-occuring chromosomal aberrations.",
			"journal": "BMC medical genomics",
			"authorList": [
				"Kumar Nitin",
				"Rehrauer Hubert",
				"Cai Haoyang",
				"Baudis Michael"
			],
			"DOI": "10.1186/1755-8794-4-21",
			"date": "2011-06-20",
			"PMC": "",
			"citation": "",
			"abstract": "Copy number alterations (CNA) play a key role in cancer development and progression. Since more than one CNA can be detected in most tumors, frequently co-occurring genetic CNA may point to cooperating cancer related genes. Existing methods for co-occurrence evaluation so far have not considered the overall heterogeneity of CNA per tumor, resulting in a preferential detection of frequent changes with limited specificity for each association due to the high genetic instability of many samples.",
			"category": 2,
			"name": "Kumar Nitin,2011"
		},
		{
			"PMID": 21360066,
			"title": "Tumour-associated antigens: considerations for their use in tumour immunotherapy.",
			"journal": "International journal of hematology",
			"authorList": [
				"Linley Adam J",
				"Ahmad Murrium",
				"Rees Robert C"
			],
			"DOI": "10.1007/s12185-011-0783-1",
			"date": "2011-06-30",
			"PMC": "",
			"citation": "",
			"abstract": "Since their discovery, tumour-associated antigens (TAA) have provided highly inviting targets for cancer therapy, especially immunotherapy. Evidence now points to their involvement in the malignant phenotype of transformed cells and heightens their importance for being targeted by different treatments. TAA vary in their nature and pattern of expression and this influences the way therapy is directed towards them. While large numbers of these antigens have been isolated from solid tumours, fewer are linked with haematological malignancies. Those TAA found in this latter group of cancers, referred to as leukaemia-associated antigens (LAA), also appear to have significant potential for promoting the malignant phenotype and have been described in detail in terms of expression and therapy. Interestingly, the action of some of LAA in blood cancers, which are stem cell derived, could act as model for solid tumours, which are increasingly thought to be also derived from a cancer stem cell origin. In this review, TAA and their use in immunotherapy will be discussed. The nature and expression of these antigens will be described together with the events that provide tumours, including haematological cancers, with the ability to avoid immune deletion.",
			"category": 2,
			"name": "Linley Adam J,2011"
		},
		{
			"PMID": 21350479,
			"title": "Cancer: When catastrophe strikes a cell.",
			"journal": "Nature",
			"authorList": [
				"Tubio Jose M C",
				"Estivill Xavier"
			],
			"DOI": "10.1038/470476a",
			"date": "2011-03-11",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Tubio Jose M C,2011"
		},
		{
			"PMID": 21278161,
			"title": "CHILD: a new tool for detecting low-abundance insertions and deletions in standard sequence traces.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Zhidkov Ilia",
				"Cohen Raphael",
				"Geifman Nophar",
				"Mishmar Dan",
				"Rubin Eitan"
			],
			"DOI": "10.1093/nar/gkq1354",
			"date": "2011-07-04",
			"PMC": "",
			"citation": "",
			"abstract": "Several methods have been proposed for detecting insertion/deletions (indels) from chromatograms generated by Sanger sequencing. However, most such methods are unsuitable when the mutated and normal variants occur at unequal ratios, such as is expected to be the case in cancer, with organellar DNA or with alternatively spliced RNAs. In addition, the current methods do not provide robust estimates of the statistical confidence of their results, and the sensitivity of this approach has not been rigorously evaluated. Here, we present CHILD, a tool specifically designed for indel detection in mixtures where one variant is rare. CHILD makes use of standard sequence alignment statistics to evaluate the significance of the results. The sensitivity of CHILD was tested by sequencing controlled mixtures of deleted and undeleted plasmids at various ratios. Our results indicate that CHILD can identify deleted molecules present as just 5% of the mixture. Notably, the results were plasmid/primer-specific; for some primers and/or plasmids, the deleted molecule was only detected when it comprised 10% or more of the mixture. The false positive rate was estimated to be lower than 0.4%. CHILD was implemented as a user-oriented web site, providing a sensitive and experimentally validated method for the detection of rare indel-carrying molecules in common Sanger sequence reads.",
			"category": 2,
			"name": "Zhidkov Ilia,2011"
		},
		{
			"PMID": 21272445,
			"title": "Protein folding, protein homeostasis, and cancer.",
			"journal": "Chinese journal of cancer",
			"authorList": [
				"Van Drie John H"
			],
			"DOI": "",
			"date": "2012-08-24",
			"PMC": "",
			"citation": "",
			"abstract": "Proteins fold into their functional 3-dimensional structures from a linear amino acid sequence. In vitro this process is spontaneous; while in vivo it is orchestrated by a specialized set of proteins, called chaperones. Protein folding is an ongoing cellular process, as cellular proteins constantly undergo synthesis and degradation. Here emerging links between this process and cancer are reviewed. This perspective both yields insights into the current struggle to develop novel cancer chemotherapeutics and has implications for future chemotherapy discovery.",
			"category": 2,
			"name": "Van Drie John H,2012"
		},
		{
			"PMID": 21272156,
			"title": "Tumor hypoxia and genetic alterations in sporadic cancers.",
			"journal": "The journal of obstetrics and gynaecology research",
			"authorList": [
				"Koi Minoru",
				"Boland Clement R"
			],
			"DOI": "10.1111/j.1447-0756.2010.01377.x",
			"date": "2011-08-01",
			"PMC": "",
			"citation": "",
			"abstract": "The cancer genome contains many gene alterations. How cancer cells acquire these alterations is a matter for discussion. One hypothesis is that cancer cells obtain mutations in genome stability genes at an early stage of tumor development, which results in genetic instability and generates a gene pool that enhances cellular proliferation and survival. Another hypothesis puts its emphasis on the natural selection of gene mutations for fitness. Recent data for systematic cancer genome sequencing shows that mutations in stability genes are rare in human sporadic cancers. Instead, many \u201cpassenger\u201d mutations that do not drive the carcinogenesis process have been found in the cancer genome. Both the hypotheses mentioned above fall short in explaining recent data. Recently, many studies demonstrate the role of the tumor microenvironment, especially hypoxia and reoxygenation, in genetic instability. In this review, literature will be presented which supports a third hypothesis, i.e. that hypoxia/re-oxygenation induces genetic instability.",
			"category": 2,
			"name": "Koi Minoru,2011"
		},
		{
			"PMID": 21261984,
			"title": "Deep RNA sequencing analysis of readthrough gene fusions in human prostate adenocarcinoma and reference samples.",
			"journal": "BMC medical genomics",
			"authorList": [
				"Nacu Serban",
				"Yuan Wenlin",
				"Kan Zhengyan",
				"Bhatt Deepali",
				"Rivers Celina Sanchez",
				"Stinson Jeremy",
				"Peters Brock A",
				"Modrusan Zora",
				"Jung Kenneth",
				"Seshagiri Somasekar",
				"Wu Thomas D"
			],
			"DOI": "10.1186/1755-8794-4-11",
			"date": "2011-04-19",
			"PMC": "",
			"citation": "",
			"abstract": "Readthrough fusions across adjacent genes in the genome, or transcription-induced chimeras (TICs), have been estimated using expressed sequence tag (EST) libraries to involve 4-6% of all genes. Deep transcriptional sequencing (RNA-Seq) now makes it possible to study the occurrence and expression levels of TICs in individual samples across the genome.",
			"category": 2,
			"name": "Nacu Serban,2011"
		},
		{
			"PMID": 21258394,
			"title": "Regulation of cancer cell metabolism.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Cairns Rob A",
				"Harris Isaac S",
				"Mak Tak W"
			],
			"DOI": "10.1038/nrc2981",
			"date": "2011-03-08",
			"PMC": "",
			"citation": "",
			"abstract": "Interest in the topic of tumour metabolism has waxed and waned over the past century of cancer research. The early observations of Warburg and his contemporaries established that there are fundamental differences in the central metabolic pathways operating in malignant tissue. However, the initial hypotheses that were based on these observations proved inadequate to explain tumorigenesis, and the oncogene revolution pushed tumour metabolism to the margins of cancer research. In recent years, interest has been renewed as it has become clear that many of the signalling pathways that are affected by genetic mutations and the tumour microenvironment have a profound effect on core metabolism, making this topic once again one of the most intense areas of research in cancer biology.",
			"category": 2,
			"name": "Cairns Rob A,2011"
		},
		{
			"PMID": 21253829,
			"title": "Alterations of the retinoblastoma gene in metastatic breast cancer.",
			"journal": "Clinical & experimental metastasis",
			"authorList": [
				"Berge Elisabet Ognedal",
				"Knappskog Stian",
				"Lillehaug Johan Richard",
				"L\u00f8nning Per Eystein"
			],
			"DOI": "10.1007/s10585-011-9375-y",
			"date": "2011-04-05",
			"PMC": "",
			"citation": "",
			"abstract": "Germline mutations affecting the retinoblastoma gene (RB1) predispose to inherited retinoblastomas but also other malignancies, including breast cancer. While somatic RB1 mutations have been detected in different malignancies, information about the potential role of RB1 mutations in breast cancer is limited. Recently, we discovered RB1 mutations to be associated with resistance to anthracyclines/mitomycin in primary breast cancer. The present work is the first report evaluating RB1 mutation and epigenetic status in metastatic breast cancer. Among 148 breast cancer samples analyzed by MLPA, four samples harbored intragenic deletions/duplications: Thus, exons 1-2 were deleted in two tumors and exons 21-23 in one tumor, while one sample harbored duplication of exons 18-23. The entire RB1 gene was duplicated in two tumors and multiple amplifications were revealed in one sample. Reduced copy number was observed in 17 samples (11.5%). No point mutation or promoter hypermethylation was discovered (n = 38 and 114 tumors analyzed, respectively). Interestingly, among seven tumors expressing lack of response to epirubicin, two samples harbored alterations in RB1, contrasting none out of 16 tumors with stable disease or an objective response (P = 0.08). In summary, the frequency of RB1 alterations in metastatic lesions was not increased when compared to primary breast cancer, indicating that RB1 alterations do not play a major role in metastatic development. While a non-significant association suggesting RB1 alterations to be linked to therapy resistance was observed, our data do not suggest a major role for RB1 alterations explaining acquired drug resistance.",
			"category": 2,
			"name": "Berge Elisabet Ognedal,2011"
		},
		{
			"PMID": 21248225,
			"title": "Mutant proteins as cancer-specific biomarkers.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Wang Qing",
				"Chaerkady Raghothama",
				"Wu Jian",
				"Hwang Hee Jung",
				"Papadopoulos Nick",
				"Kopelovich Levy",
				"Maitra Anirban",
				"Matthaei Hanno",
				"Eshleman James R",
				"Hruban Ralph H",
				"Kinzler Kenneth W",
				"Pandey Akhilesh",
				"Vogelstein Bert"
			],
			"DOI": "10.1073/pnas.1019203108",
			"date": "2011-03-30",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer biomarkers are currently the subject of intense research because of their potential utility for diagnosis, prognosis, and targeted therapy. In theory, the gene products resulting from somatic mutations are the ultimate protein biomarkers, being not simply associated with tumors but actually responsible for tumorigenesis. We show here that the altered protein products resulting from somatic mutations can be identified directly and quantified by mass spectrometry. The peptides expressed from normal and mutant alleles were detected by selected reaction monitoring (SRM) of their product ions using a triple-quadrupole mass spectrometer. As a prototypical example of this approach, we demonstrated that it is possible to quantify the number and fraction of mutant Ras protein present in cancer cell lines. There were an average of 1.3 million molecules of Ras protein per cell, and the ratio of mutant to normal Ras proteins ranged from 0.49 to 5.6. Similarly, we found that mutant Ras proteins could be detected and quantified in clinical specimens such as colorectal and pancreatic tumor tissues as well as in premalignant pancreatic cyst fluids. In addition to answering basic questions about the relative levels of genetically abnormal proteins in tumors, this approach could prove useful for diagnostic applications.",
			"category": 2,
			"name": "Wang Qing,2011"
		},
		{
			"PMID": 21246315,
			"title": "The pharmacokinetic/pharmacodynamic pipeline: translating anticancer drug pharmacology to the clinic.",
			"journal": "The AAPS journal",
			"authorList": [
				"Zhou Qingyu",
				"Gallo James M"
			],
			"DOI": "10.1208/s12248-011-9253-1",
			"date": "2011-05-19",
			"PMC": "",
			"citation": "",
			"abstract": "Progress in an understanding of the genetic basis of cancer coupled to molecular pharmacology of potential new anticancer drugs calls for new approaches that are able to address key issues in the drug development process, including pharmacokinetic (PK) and pharmacodynamic (PD) relationships. The incorporation of predictive preclinical PK/PD models into rationally designed early-stage clinical trials offers a promising way to relieve a significant bottleneck in the drug discovery pipeline. The aim of the current review is to discuss some considerations for how quantitative PK and PD analyses for anticancer drugs may be conducted and integrated into a global translational effort, and the importance of examining drug disposition and dynamics in target tissues to support the development of preclinical PK/PD models that can be subsequently extrapolated to predict pharmacologic characteristics in patients. In this article, we describe three different physiologically based (PB) PK modeling approaches, i.e., the whole-body PBPK model, the hybrid PBPK model, and the two-pore model for macromolecules, as well as their applications. General conclusions are that greater effort should be made to generate more clinical data that could validate scaled preclinical PB-PK/PD tumor-based models and, thus, stimulate a framework for preclinical to clinical translation. Finally, given the innovative techniques to measure tissue drug concentrations and associated biomarkers of drug responses, development of predictive PK/PD models will become a standard approach for drug discovery and development.",
			"category": 2,
			"name": "Zhou Qingyu,2011"
		},
		{
			"PMID": 21215367,
			"title": "Massive genomic rearrangement acquired in a single catastrophic event during cancer development.",
			"journal": "Cell",
			"authorList": [
				"Stephens Philip J",
				"Greenman Chris D",
				"Fu Beiyuan",
				"Yang Fengtang",
				"Bignell Graham R",
				"Mudie Laura J",
				"Pleasance Erin D",
				"Lau King Wai",
				"Beare David",
				"Stebbings Lucy A",
				"McLaren Stuart",
				"Lin Meng-Lay",
				"McBride David J",
				"Varela Ignacio",
				"Nik-Zainal Serena",
				"Leroy Catherine",
				"Jia Mingming",
				"Menzies Andrew",
				"Butler Adam P",
				"Teague Jon W",
				"Quail Michael A",
				"Burton John",
				"Swerdlow Harold",
				"Carter Nigel P",
				"Morsberger Laura A",
				"Iacobuzio-Donahue Christine",
				"Follows George A",
				"Green Anthony R",
				"Flanagan Adrienne M",
				"Stratton Michael R",
				"Futreal P Andrew",
				"Campbell Peter J"
			],
			"DOI": "10.1016/j.cell.2010.11.055",
			"date": "2011-01-27",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in \u223c25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer.",
			"category": 2,
			"name": "Stephens Philip J,2011"
		},
		{
			"PMID": 21212237,
			"title": "Comparison of constitutional and replication stress-induced genome structural variation by SNP array and mate-pair sequencing.",
			"journal": "Genetics",
			"authorList": [
				"Arlt Martin F",
				"Ozdemir Alev Cagla",
				"Birkeland Shanda R",
				"Lyons Robert H",
				"Glover Thomas W",
				"Wilson Thomas E"
			],
			"DOI": "10.1534/genetics.110.124776",
			"date": "2011-07-12",
			"PMC": "",
			"citation": "",
			"abstract": "Copy-number variants (CNVs) are a major source of genetic variation in human health and disease. Previous studies have implicated replication stress as a causative factor in CNV formation. However, existing data are technically limited in the quality of comparisons that can be made between human CNVs and experimentally induced variants. Here, we used two high-resolution strategies-single nucleotide polymorphism (SNP) arrays and mate-pair sequencing-to compare CNVs that occur constitutionally to those that arise following aphidicolin-induced DNA replication stress in the same human cells. Although the optimized methods provided complementary information, sequencing was more sensitive to small variants and provided superior structural descriptions. The majority of constitutional and all aphidicolin-induced CNVs appear to be formed via homology-independent mechanisms, while aphidicolin-induced CNVs were of a larger median size than constitutional events even when mate-pair data were considered. Aphidicolin thus appears to stimulate formation of CNVs that closely resemble human pathogenic CNVs and the subset of larger nonhomologous constitutional CNVs.",
			"category": 2,
			"name": "Arlt Martin F,2011"
		},
		{
			"PMID": 21189224,
			"title": "Systems approaches to molecular cancer diagnostics.",
			"journal": "Discovery medicine",
			"authorList": [
				"Ma Shuyi",
				"Funk Cory C",
				"Price Nathan D"
			],
			"DOI": "",
			"date": "2011-04-29",
			"PMC": "",
			"citation": "",
			"abstract": "The search for improved molecular cancer diagnostics is a challenge for which systems approaches show great promise. As is becoming increasingly clear, cancer is a perpetually-evolving, highly multi-factorial disease. With next generation sequencing providing an ever-increasing amount of high-throughput data, the need for analytical tools that can provide meaningful context is critical. Systems approaches have demonstrated an ability to separate meaningful signal from noise that arises from population heterogeneity, heterogeneity within and across tumors, and multiple sources of technical variation when sufficient sample sizes are obtained and standardized measurement technologies are used. The ability to develop clinically useful molecular cancer diagnostics will be predicated on advancements on two major fronts: 1) more comprehensive and accurate measurements of multiple endpoints, and 2) more sophisticated analytical tools that synthesize high-throughput data into meaningful reflections of cellular states. To this end, systems approaches that have integrated transcriptomic data onto biomolecular networks have shown promise in their ability to classify tumor subtypes, predict clinical progression, and inform treatment options. Ultimately, the success of systems approaches will be measured by their ability to develop molecular cancer diagnostics through distilling complex, systems-wide information into actionable information in the clinic.",
			"category": 2,
			"name": "Ma Shuyi,2011"
		},
		{
			"PMID": 21184075,
			"title": "Histological and immediate postoperative outcome after preoperative cetuximab: case-matched control study.",
			"journal": "World journal of surgery",
			"authorList": [
				"Spiliotis John",
				"Zoras Odysseas"
			],
			"DOI": "10.1007/s00268-010-0915-4",
			"date": "2011-08-23",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Spiliotis John,2011"
		},
		{
			"PMID": 21172086,
			"title": "Are current development programs realising the full potential of new agents?",
			"journal": "Breast cancer research : BCR",
			"authorList": [
				"L\u00f8nning Per Eystein"
			],
			"DOI": "10.1186/bcr2752",
			"date": "2011-07-13",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "L\u00f8nning Per Eystein,2011"
		},
		{
			"PMID": 21135245,
			"title": "Hepatocyte-specific deletion of DDB1 induces liver regeneration and tumorigenesis.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Yamaji Sachie",
				"Zhang Mingjun",
				"Zhang Jing",
				"Endo Yoko",
				"Bibikova Elena",
				"Goff Stephen P",
				"Cang Yong"
			],
			"DOI": "10.1073/pnas.1015793108",
			"date": "2011-02-02",
			"PMC": "",
			"citation": "",
			"abstract": "Etiologic risk factors for hepatocellular carcinoma can be involved in the transformation process by directly targeting intracellular signaling pathways or by indirectly stimulating chronic cycles of hepatocyte destruction and regeneration. However, the contribution of these two routes to hepatocarcinogenesis has not been determined, partly because of the difficulty in distinguishing damaged and regenerated hepatocytes. Here we report that induced deletion of the damaged DNA binding protein 1 (DDB1) abrogates the self-renewing capacity of hepatocytes, resulting in compensatory proliferation of DDB1-expressing hepatocytes. Constitutive stimulation of this regeneration process leads to development of hepatocellular carcinoma, which surprisingly contains no disruption of the DDB1 gene, indicating a cell-nonautonomous role of DDB1 inactivation in tumor initiation. Our results suggest that viruses and hepatoxins may cause liver tumors by simply driving hepatocyte turnover without directly targeting cancer cells.",
			"category": 2,
			"name": "Yamaji Sachie,2011"
		},
		{
			"PMID": 21129771,
			"title": "An integrated approach to uncover drivers of cancer.",
			"journal": "Cell",
			"authorList": [
				"Akavia Uri David",
				"Litvin Oren",
				"Kim Jessica",
				"Sanchez-Garcia Felix",
				"Kotliar Dylan",
				"Causton Helen C",
				"Pochanard Panisa",
				"Mozes Eyal",
				"Garraway Levi A",
				"Pe'er Dana"
			],
			"DOI": "10.1016/j.cell.2010.11.013",
			"date": "2011-01-18",
			"PMC": "",
			"citation": "",
			"abstract": "Systematic characterization of cancer genomes has revealed a staggering number of diverse aberrations that differ among individuals, such that the functional importance and physiological impact of most tumor genetic alterations remain poorly defined. We developed a computational framework that integrates chromosomal copy number and gene expression data for detecting aberrations that promote cancer progression. We demonstrate the utility of this framework using a melanoma data set. Our analysis correctly identified known drivers of melanoma and predicted multiple tumor dependencies. Two dependencies, TBC1D16 and RAB27A, confirmed empirically, suggest that abnormal regulation of protein trafficking contributes to proliferation in melanoma. Together, these results demonstrate the ability of integrative Bayesian approaches to identify candidate drivers with biological, and possibly therapeutic, importance in cancer.",
			"category": 2,
			"name": "Akavia Uri David,2011"
		},
		{
			"PMID": 21124932,
			"title": "Exploring the link between germline and somatic genetic alterations in breast carcinogenesis.",
			"journal": "PloS one",
			"authorList": [
				"Bonifaci N\u00faria",
				"G\u00f3rski Bohdan",
				"Masoj\u0107 Bartlomiej",
				"Woko\u0142orczyk Dominika",
				"Jakubowska Anna",
				"D\u0119bniak Tadeusz",
				"Berenguer Antoni",
				"Serra Musach Jordi",
				"Brunet Joan",
				"Dopazo Joaqu\u00edn",
				"Narod Steven A",
				"Lubi\u0144ski Jan",
				"L\u00e1zaro Conxi",
				"Cybulski Cezary",
				"Pujana Miguel Angel"
			],
			"DOI": "10.1371/journal.pone.0014078",
			"date": "2011-04-27",
			"PMC": "",
			"citation": "",
			"abstract": "Recent genome-wide association studies (GWASs) have identified candidate genes contributing to cancer risk through low-penetrance mutations. Many of these genes were unexpected and, intriguingly, included well-known players in carcinogenesis at the somatic level. To assess the hypothesis of a germline-somatic link in carcinogenesis, we evaluated the distribution of somatic gene labels within the ordered results of a breast cancer risk GWAS. This analysis suggested frequent influence on risk of genetic variation in loci encoding for \"driver kinases\" (i.e., kinases encoded by genes that showed higher somatic mutation rates than expected by chance and, therefore, whose deregulation may contribute to cancer development and/or progression). Assessment of these predictions using a population-based case-control study in Poland replicated the association for rs3732568 in EPHB1 (odds ratio (OR)\u200a=\u200a0.79; 95% confidence interval (CI): 0.63-0.98; P(trend)\u200a=\u200a0.031). Analyses by early age at diagnosis and by estrogen receptor \u03b1 (ER\u03b1) tumor status indicated potential associations for rs6852678 in CDKL2 (OR\u200a=\u200a0.32, 95% CI: 0.10-1.00; P(recessive)\u200a=\u200a0.044) and rs10878640 in DYRK2 (OR\u200a=\u200a2.39, 95% CI: 1.32-4.30; P(dominant)\u200a=\u200a0.003), and for rs12765929, rs9836340, rs4707795 in BMPR1A, EPHA3 and EPHA7, respectively (ER\u03b1 tumor status P(interaction)<0.05). The identification of three novel candidates as EPH receptor genes might indicate a link between perturbed compartmentalization of early neoplastic lesions and breast cancer risk and progression. Together, these data may lay the foundations for replication in additional populations and could potentially increase our knowledge of the underlying molecular mechanisms of breast carcinogenesis.",
			"category": 2,
			"name": "Bonifaci N\u00faria,2011"
		},
		{
			"PMID": 21116761,
			"title": "Somatic mutations of the mixed-lineage leukemia 3 (MLL3) gene in primary breast cancers.",
			"journal": "Pathology oncology research : POR",
			"authorList": [
				"Wang Xin-Xin",
				"Fu Liya",
				"Li Xuan",
				"Wu Xiao",
				"Zhu Zhengmao",
				"Fu Li",
				"Dong Jin-Tang"
			],
			"DOI": "10.1007/s12253-010-9316-0",
			"date": "2011-09-27",
			"PMC": "",
			"citation": "",
			"abstract": "The mixed-lineage leukemia 3 (MLL3) gene, which encodes an important component of a histone H3 lysine 4 methyltransferase complex named the ASC-2- and Mll3-containing complex (ASCOM), has been implicated as a tumor suppressor gene due to its frequent mutations in multiple types of human tumors as well as tumor induction upon targeted inactivation of the gene in mice. The role of MLL3 in breast cancer, however, remains unknown. In this study, we sequenced all 59 exons of MLL3 (14.7 Kb coding sequence) in 38 breast cancers from Chinese women, and found three somatic mutations in two of the cases, including one frameshift mutation (c.2687 ins A) that truncates the majority of the MLL3 protein, and two synonymous mutations. In addition to 24 known single nucleotide polymorphisms (SNPs), 5 novel SNPs were also detected in the 38 women; and interestingly, all the 5 novel SNPs alter amino acid sequences of MLL3 thus could have functional consequences. We also examined the expression of MLL3 mRNA in 30 breast tumors and their matched normal breast tissues. While no associations were found between expression change and clinicopathologic parameters, 40% of the samples showed reduced expression in cancer tissues. These results suggest that mutation of MLL3 plays a role in the development of breast cancer.",
			"category": 2,
			"name": "Wang Xin-Xin,2011"
		},
		{
			"PMID": 21113414,
			"title": "Integrated genomic analyses identify ERRFI1 and TACC3 as glioblastoma-targeted genes.",
			"journal": "Oncotarget",
			"authorList": [
				"Duncan Christopher G",
				"Killela Patrick J",
				"Payne Cathy A",
				"Lampson Benjamin",
				"Chen William C",
				"Liu Jeff",
				"Solomon David",
				"Waldman Todd",
				"Towers Aaron J",
				"Gregory Simon G",
				"McDonald Kerrie L",
				"McLendon Roger E",
				"Bigner Darell D",
				"Yan Hai"
			],
			"DOI": "",
			"date": "2011-08-24",
			"PMC": "",
			"citation": "",
			"abstract": "The glioblastoma genome displays remarkable chromosomal aberrations, which harbor critical glioblastoma-specific genes contributing to several oncogenetic pathways. To identify glioblastoma-targeted genes, we completed a multifaceted genome-wide analysis to characterize the most significant aberrations of DNA content occurring in glioblastomas. We performed copy number analysis of 111 glioblastomas by Digital Karyotyping and Illumina BeadChip assays and validated our findings using data from the TCGA (The Cancer Genome Atlas) glioblastoma project. From this study, we identified recurrent focal copy number alterations in 1p36.23 and 4p16.3. Expression analyses of genes located in the two regions revealed genes which are dysregulated in glioblastomas. Specifically, we identify EGFR negative regulator, ERRFI1, within the minimal region of deletion in 1p36.23. In glioblastoma cells with a focal deletion of the ERRFI1 locus, restoration of ERRFI1 expression slowed cell migration. Furthermore, we demonstrate that TACC3, an Aurora-A kinase substrate, on 4p16.3, displays gain of copy number, is overexpressed in a glioma-grade-specific pattern, and correlates with Aurora kinase overexpression in glioblastomas. Our multifaceted genomic evaluation of glioblastoma establishes ERRFI1 as a potential candidate tumor suppressor gene and TACC3 as a potential oncogene, and provides insight on targets for oncogenic pathway-based therapy.",
			"category": 2,
			"name": "Duncan Christopher G,2011"
		},
		{
			"PMID": 21108813,
			"title": "Tumor heterogeneity in neoplasms of breast, colon, and skin.",
			"journal": "BMC research notes",
			"authorList": [
				"Li Jian",
				"Wang Kai",
				"Jensen Thomas Dyrs\u00f8",
				"Li Shengting",
				"Bolund Lars",
				"Wiuf Carsten"
			],
			"DOI": "10.1186/1756-0500-3-321",
			"date": "2011-07-14",
			"PMC": "",
			"citation": "",
			"abstract": "Different cell subpopulations in a single tumor may show diverse capacities for growth, differentiation, metastasis formation, and sensitivity to treatments. Thus, heterogeneity is an important feature of tumors. However, due to limitations in experimental and analytical techniques, tumor heterogeneity has rarely been studied in detail.",
			"category": 2,
			"name": "Li Jian,2011"
		},
		{
			"PMID": 21102459,
			"title": "Invasive three-dimensional organotypic neoplasia from multiple normal human epithelia.",
			"journal": "Nature medicine",
			"authorList": [
				"Ridky Todd W",
				"Chow Jennifer M",
				"Wong David J",
				"Khavari Paul A"
			],
			"DOI": "10.1038/nm.2265",
			"date": "2011-01-24",
			"PMC": "",
			"citation": "",
			"abstract": "Refined cancer models are required if researchers are to assess the burgeoning number of potential targets for cancer therapeutics in a clinically relevant context that allows a fast turnaround. Here we use tumor-associated genetic pathways to transform primary human epithelial cells from the epidermis, oropharynx, esophagus and cervix into genetically defined tumors in a human three-dimensional (3D) tissue environment that incorporates cell-populated stroma and intact basement membrane. These engineered organotypic tissues recapitulated natural features of tumor progression, including epithelial invasion through basement membrane, a complex process that is necessary for biological malignancy in 90% of human cancers. Invasion was rapid and was potentiated by stromal cells. Oncogenic signals in 3D tissue, but not 2D culture, resembled gene expression profiles from spontaneous human cancers. We screened 3D organotypic neoplasia with well-characterized signaling pathway inhibitors to distill a clinically faithful cancer gene signature. Multitissue 3D human tissue cancer models may provide an efficient and relevant complement to current approaches to characterizing cancer progression.",
			"category": 2,
			"name": "Ridky Todd W,2011"
		},
		{
			"PMID": 21061422,
			"title": "The critical protein interactions and structures that elicit growth deregulation in cancer and viral replication.",
			"journal": "Wiley interdisciplinary reviews. Systems biology and medicine",
			"authorList": [
				"Ou Horng D",
				"May Andrew P",
				"O'Shea Clodagh C"
			],
			"DOI": "10.1002/wsbm.88",
			"date": "2011-03-31",
			"PMC": "",
			"citation": "",
			"abstract": "One of the greatest challenges in biomedicine is to define the critical targets and network interactions that are subverted to elicit growth deregulation in human cells. Understanding and developing rational treatments for cancer requires a definition of the key molecular targets and how they interact to elicit the complex growth deregulation phenotype. Viral proteins provide discerning and powerful probes to understand both how cells work and how they can be manipulated using a minimal number of components. The small DNA viruses have evolved to target inherent weaknesses in cellular protein interaction networks to hijack the cellular DNA and protein replication machinery. In the battle to escape the inevitability of senescence and programmed cell death, cancers have converged on similar mechanisms, through the acquisition and selection of somatic mutations that drive unchecked cellular replication in tumors. Understanding the dynamic mechanisms through which a minimal number of viral proteins promote host cells to undergo unscheduled and pathological replication is a powerful strategy to identify critical targets that are also disrupted in cancer. Viruses can therefore be used as tools to probe the system-wide protein-protein interactions and structures that drive growth deregulation in human cells. Ultimately this can provide a path for developing system context-dependent therapeutics. This review will describe ongoing experimental approaches using viruses to study pathways deregulated in cancer, with a particular focus on viral cellular protein-protein interactions and structures.",
			"category": 2,
			"name": "Ou Horng D,2011"
		},
		{
			"PMID": 21059271,
			"title": "Multi-level reproducibility of signature hubs in human interactome for breast cancer metastasis.",
			"journal": "BMC systems biology",
			"authorList": [
				"Yao Chen",
				"Li Hongdong",
				"Zhou Chenggui",
				"Zhang Lin",
				"Zou Jinfeng",
				"Guo Zheng"
			],
			"DOI": "10.1186/1752-0509-4-151",
			"date": "2011-02-15",
			"PMC": "",
			"citation": "",
			"abstract": "It has been suggested that, in the human protein-protein interaction network, changes of co-expression between highly connected proteins (\"hub\") and their interaction neighbours might have important roles in cancer metastasis and be predictive disease signatures for patient outcome. However, for a cancer, such disease signatures identified from different studies have little overlap.",
			"category": 2,
			"name": "Yao Chen,2011"
		},
		{
			"PMID": 21048000,
			"title": "Translating tumor antigens into cancer vaccines.",
			"journal": "Clinical and vaccine immunology : CVI",
			"authorList": [
				"Buonaguro Luigi",
				"Petrizzo Annacarmen",
				"Tornesello Maria Lina",
				"Buonaguro Franco M"
			],
			"DOI": "10.1128/CVI.00286-10",
			"date": "2011-04-21",
			"PMC": "",
			"citation": "",
			"abstract": "Vaccines represent a strategic successful tool used to prevent or contain diseases with high morbidity and/or mortality. However, while vaccines have proven to be effective in combating pathogenic microorganisms, based on the immune recognition of these foreign antigens, vaccines aimed at inducing effective antitumor activity are still unsatisfactory. Nevertheless, the effectiveness of the two licensed cancer-preventive vaccines targeting tumor-associated viral agents (anti-HBV [hepatitis B virus], to prevent HBV-associated hepatocellular carcinoma, and anti-HPV [human papillomavirus], to prevent HPV-associated cervical carcinoma), along with the recent FDA approval of sipuleucel-T (for the therapeutic treatment of prostate cancer), represents a significant advancement in the field of cancer vaccines and a boost for new studies in the field. Specific active immunotherapies based on anticancer vaccines represent, indeed, a field in continuous evolution and expansion. Significant improvements may result from the selection of the appropriate tumor-specific target antigen (to overcome the peripheral immune tolerance) and/or the development of immunization strategies effective at inducing a protective immune response. This review aims to describe the vast spectrum of tumor antigens and strategies to develop cancer vaccines.",
			"category": 2,
			"name": "Buonaguro Luigi,2011"
		},
		{
			"PMID": 21036922,
			"title": "Discovery of non-ETS gene fusions in human prostate cancer using next-generation RNA sequencing.",
			"journal": "Genome research",
			"authorList": [
				"Pflueger Dorothee",
				"Terry St\u00e9phane",
				"Sboner Andrea",
				"Habegger Lukas",
				"Esgueva Raquel",
				"Lin Pei-Chun",
				"Svensson Maria A",
				"Kitabayashi Naoki",
				"Moss Benjamin J",
				"MacDonald Theresa Y",
				"Cao Xuhong",
				"Barrette Terrence",
				"Tewari Ashutosh K",
				"Chee Mark S",
				"Chinnaiyan Arul M",
				"Rickman David S",
				"Demichelis Francesca",
				"Gerstein Mark B",
				"Rubin Mark A"
			],
			"DOI": "10.1101/gr.110684.110",
			"date": "2011-04-21",
			"PMC": "",
			"citation": "",
			"abstract": "Half of prostate cancers harbor gene fusions between TMPRSS2 and members of the ETS transcription factor family. To date, little is known about the presence of non-ETS fusion events in prostate cancer. We used next-generation transcriptome sequencing (RNA-seq) in order to explore the whole transcriptome of 25 human prostate cancer samples for the presence of chimeric fusion transcripts. We generated more than 1 billion sequence reads and used a novel computational approach (FusionSeq) in order to identify novel gene fusion candidates with high confidence. In total, we discovered and characterized seven new cancer-specific gene fusions, two involving the ETS genes ETV1 and ERG, and four involving non-ETS genes such as CDKN1A (p21), CD9, and IKBKB (IKK-beta), genes known to exhibit key biological roles in cellular homeostasis or assumed to be critical in tumorigenesis of other tumor entities, as well as the oncogene PIGU and the tumor suppressor gene RSRC2. The novel gene fusions are found to be of low frequency, but, interestingly, the non-ETS fusions were all present in prostate cancer harboring the TMPRSS2-ERG gene fusion. Future work will focus on determining if the ETS rearrangements in prostate cancer are associated or directly predispose to a rearrangement-prone phenotype.",
			"category": 2,
			"name": "Pflueger Dorothee,2011"
		},
		{
			"PMID": 20975993,
			"title": "Identification of Piwil2-like (PL2L) proteins that promote tumorigenesis.",
			"journal": "PloS one",
			"authorList": [
				"Ye Yin",
				"Yin De-Tao",
				"Chen Li",
				"Zhou Quansheng",
				"Shen Rulong",
				"He Gang",
				"Yan Qingtao",
				"Tong Zhenyu",
				"Issekutz Andrew C",
				"Shapiro Charles L",
				"Barsky Sanford H",
				"Lin Haifan",
				"Li Jian-Jian",
				"Gao Jian-Xin"
			],
			"DOI": "10.1371/journal.pone.0013406",
			"date": "2011-03-07",
			"PMC": "",
			"citation": "",
			"abstract": "PIWIL2, a member of PIWI/AGO gene family, is expressed in the germline stem cells (GSCs) of testis for gametogenesis but not in adult somatic and stem cells. It has been implicated to play an important role in tumor development. We have previously reported that precancerous stem cells (pCSCs) constitutively express Piwil2 transcripts to promote their proliferation. Here we show that these transcripts de facto represent Piwil2-like (PL2L) proteins. We have identified several PL2L proteins including PL2L80, PL2L60, PL2L50 and PL2L40, using combined methods of Gene-Exon-Mapping Reverse Transcription Polymerase Chain Reaction (GEM RT-PCR), bioinformatics and a group of novel monoclonal antibodies. Among them, PL2L60 rather than Piwil2 and other PL2L proteins is predominantly expressed in various types of human and mouse tumor cells. It promotes tumor cell survival and proliferation in vitro through up-regulation of Stat3 and Bcl2 gene expressions, the cell cycle entry from G(0/1) into S-phase, and the nuclear expression of NF-\u03baB, which contribute to the tumorigenicity of tumor cells in vivo. Consistently, PL2L proteins rather than Piwil2 are predominantly expressed in the cytoplasm or cytoplasm and nucleus of euchromatin-enriched tumor cells in human primary and metastatic cancers, such as breast and cervical cancers. Moreover, nuclear PL2L proteins are always co-expressed with nuclear NF-\u03baB. These results reveal that PL2L60 can coordinate with NF-\u03baB to promote tumorigenesis and might mediate a common pathway for tumor development without tissue restriction. The identification of PL2L proteins provides a novel insight into the mechanisms of cancer development as well as a novel bridge linking cancer diagnostics and anticancer drug development.",
			"category": 2,
			"name": "Ye Yin,2011"
		},
		{
			"PMID": 20847746,
			"title": "Advances in understanding cancer genomes through second-generation sequencing.",
			"journal": "Nature reviews. Genetics",
			"authorList": [
				"Meyerson Matthew",
				"Gabriel Stacey",
				"Getz Gad"
			],
			"DOI": "10.1038/nrg2841",
			"date": "2010-10-29",
			"PMC": "",
			"citation": "",
			"abstract": "Cancers are caused by the accumulation of genomic alterations. Therefore, analyses of cancer genome sequences and structures provide insights for understanding cancer biology, diagnosis and therapy. The application of second-generation DNA sequencing technologies (also known as next-generation sequencing) - through whole-genome, whole-exome and whole-transcriptome approaches - is allowing substantial advances in cancer genomics. These methods are facilitating an increase in the efficiency and resolution of detection of each of the principal types of somatic cancer genome alterations, including nucleotide substitutions, small insertions and deletions, copy number alterations, chromosomal rearrangements and microbial infections. This Review focuses on the methodological considerations for characterizing somatic genome alterations in cancer and the future prospects for these approaches.",
			"category": 2,
			"name": "Meyerson Matthew,2010"
		},
		{
			"PMID": 20847737,
			"title": "Mutated genes, pathways and processes in tumours.",
			"journal": "EMBO reports",
			"authorList": [
				"Baudot Ana\u00efs",
				"de la Torre Victor",
				"Valencia Alfonso"
			],
			"DOI": "10.1038/embor.2010.133",
			"date": "2011-01-04",
			"PMC": "",
			"citation": "",
			"abstract": "Integration of the many available sources of cancer gene information--such as large-scale tumour-resequencing studies--identifies the 'usual suspect' genes, mutated in many tumour types, as well as different sets of mutated genes according to the specific tumour type. Scaling-up the analysis reveals that this large collection of mutated genes cluster into a smaller number of signalling pathways and processes. From this, we draw a map of the altered processes, and their combinations, in more than 10 tumours types. Literature searches identify pathways and processes that are covered sparsely in the literature, and invite the proposal of new hypotheses to investigate cancer initiation and progression.",
			"category": 2,
			"name": "Baudot Ana\u00efs,2011"
		},
		{
			"PMID": 20837533,
			"title": "Allele-specific copy number analysis of tumors.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Van Loo Peter",
				"Nordgard Silje H",
				"Lingj\u00e6rde Ole Christian",
				"Russnes Hege G",
				"Rye Inga H",
				"Sun Wei",
				"Weigman Victor J",
				"Marynen Peter",
				"Zetterberg Anders",
				"Naume Bj\u00f8rn",
				"Perou Charles M",
				"B\u00f8rresen-Dale Anne-Lise",
				"Kristensen Vessela N"
			],
			"DOI": "10.1073/pnas.1009843107",
			"date": "2010-10-28",
			"PMC": "",
			"citation": "",
			"abstract": "We present an allele-specific copy number analysis of the in vivo breast cancer genome. We describe a unique bioinformatics approach, ASCAT (allele-specific copy number analysis of tumors), to accurately dissect the allele-specific copy number of solid tumors, simultaneously estimating and adjusting for both tumor ploidy and nonaberrant cell admixture. This allows calculation of \"ASCAT profiles\" (genome-wide allele-specific copy-number profiles) from which gains, losses, copy number-neutral events, and loss of heterozygosity (LOH) can accurately be determined. In an early-stage breast carcinoma series, we observe aneuploidy (>2.7n) in 45% of the cases and an average nonaberrant cell admixture of 49%. By aggregation of ASCAT profiles across our series, we obtain genomic frequency distributions of gains and losses, as well as genome-wide views of LOH and copy number-neutral events in breast cancer. In addition, the ASCAT profiles reveal differences in aberrant tumor cell fraction, ploidy, gains, losses, LOH, and copy number-neutral events between the five previously identified molecular breast cancer subtypes. Basal-like breast carcinomas have a significantly higher frequency of LOH compared with other subtypes, and their ASCAT profiles show large-scale loss of genomic material during tumor development, followed by a whole-genome duplication, resulting in near-triploid genomes. Finally, from the ASCAT profiles, we construct a genome-wide map of allelic skewness in breast cancer, indicating loci where one allele is preferentially lost, whereas the other allele is preferentially gained. We hypothesize that these alternative alleles have a different influence on breast carcinoma development.",
			"category": 2,
			"name": "Van Loo Peter,2010"
		},
		{
			"PMID": 20807447,
			"title": "Important role of indels in somatic mutations of human cancer genes.",
			"journal": "BMC medical genetics",
			"authorList": [
				"Yang Haiwang",
				"Zhong Yan",
				"Peng Cheng",
				"Chen Jian-Qun",
				"Tian Dacheng"
			],
			"DOI": "10.1186/1471-2350-11-128",
			"date": "2010-10-07",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is clonal proliferation that arises owing to mutations in a subset of genes that confer growth advantage. More and more cancer related genes are found to have accumulated somatic mutations. However, little has been reported about mutational patterns of insertions/deletions (indels) in these genes.",
			"category": 2,
			"name": "Yang Haiwang,2010"
		},
		{
			"PMID": 20739953,
			"title": "High frequencies of leukemia stem cells in poor-outcome childhood precursor-B acute lymphoblastic leukemias.",
			"journal": "Leukemia",
			"authorList": [
				"Morisot S",
				"Wayne A S",
				"Bohana-Kashtan O",
				"Kaplan I M",
				"Gocke C D",
				"Hildreth R",
				"Stetler-Stevenson M",
				"Walker R L",
				"Davis S",
				"Meltzer P S",
				"Wheelan S J",
				"Brown P",
				"Jones R J",
				"Shultz L D",
				"Civin C I"
			],
			"DOI": "10.1038/leu.2010.184",
			"date": "2010-12-22",
			"PMC": "",
			"citation": "",
			"abstract": "In order to develop a xenograft model to determine the efficacy of new therapies against primary human precursor-B acute lymphoblastic leukemia (ALL) stem cells (LSCs), we used the highly immunodeficient non-obese diabetic (NOD).Cg-Prkdc(scid)IL2rg(tmlWjl)/SzJ (NOD-severe combined immune deficient (scid) IL2rg(-/-)) mouse strain. Intravenous transplantation of 2 of 2 ALL cell lines and 9 of 14 primary ALL cases generated leukemia-like proliferations in recipient mice by 1-7 months after transplant. Leukemias were retransplantable, and the immunophenotypes, gene rearrangements and expression profiles were identical or similar to those of the original primary samples. NOD-scid mice transplanted with the same primary samples developed similar leukemias with only a slightly longer latency than did NOD-scid-IL2Rg(-/-) mice. In this highly sensitive NOD-scid-IL2Rg(-/-)-based assay, 1-100 unsorted primary human ALL cells from five of five tested patients, four of whom eventually experienced leukemia relapse, generated leukemias in recipient mice. This very high frequency of LSCs suggests that a hierarchical LSC model is not valuable for poor-outcome ALL.",
			"category": 2,
			"name": "Morisot S,2010"
		},
		{
			"PMID": 20728025,
			"title": "The role of mechanistic factors in promoting chromosomal translocations found in lymphoid and other cancers.",
			"journal": "Advances in immunology",
			"authorList": [
				"Zhang Yu",
				"Gostissa Monica",
				"Hildebrand Dominic G",
				"Becker Michael S",
				"Boboila Cristian",
				"Chiarle Roberto",
				"Lewis Susanna",
				"Alt Frederick W"
			],
			"DOI": "10.1016/S0065-2776(10)06004-9",
			"date": "2010-11-04",
			"PMC": "",
			"citation": "",
			"abstract": "Recurrent chromosomal abnormalities, especially chromosomal translocations, are strongly associated with certain subtypes of leukemia, lymphoma and solid tumors. The appearance of particular translocations or associated genomic alterations can be important indicators of disease prognosis, and in some cases, certain translocations may indicate appropriate therapy protocols. To date, most of our knowledge about chromosomal translocations has derived from characterization of the highly selected recurrent translocations found in certain cancers. Until recently, mechanisms that promote or suppress chromosomal translocations, in particular, those responsible for their initiation, have not been addressed. For translocations to occur, two distinct chromosomal loci must be broken, brought together (synapsed) and joined. Here, we discuss recent findings on processes and pathways that influence the initiation of chromosomal translocations, including the generation fo DNA double strand breaks (DSBs) by general factors or in the context of the Lymphocyte-specific V(D)J and IgH class-switch recombination processes. We also discuss the role of spatial proximity of DSBs in the interphase nucleus with respect to how DSBs on different chromosomes are justaposed for joining. In addition, we discuss the DNA DSB response and its role in recognizing and tethering chromosomal DSBs to prevent translocations, as well as potential roles of the classical and alternative DSB end-joining pathways in suppressing or promoting translocations. Finally, we discuss the potential roles of long range regulatory elements, such as the 3'IgH enhancer complex, in promoting the expression of certain translocations that are frequent in lymphomas and, thereby, contributing to their frequent appearance in tumors.",
			"category": 2,
			"name": "Zhang Yu,2010"
		},
		{
			"PMID": 20725990,
			"title": "Use of cancer-specific genomic rearrangements to quantify disease burden in plasma from patients with solid tumors.",
			"journal": "Genes, chromosomes & cancer",
			"authorList": [
				"McBride David J",
				"Orpana Arto K",
				"Sotiriou Christos",
				"Joensuu Heikki",
				"Stephens Philip J",
				"Mudie Laura J",
				"H\u00e4m\u00e4l\u00e4inen Eija",
				"Stebbings Lucy A",
				"Andersson Leif C",
				"Flanagan Adrienne M",
				"Durbecq Virginie",
				"Ignatiadis Michail",
				"Kallioniemi Olli",
				"Heckman Caroline A",
				"Alitalo Kari",
				"Edgren Henrik",
				"Futreal P Andrew",
				"Stratton Michael R",
				"Campbell Peter J"
			],
			"DOI": "10.1002/gcc.20815",
			"date": "2011-01-13",
			"PMC": "",
			"citation": "",
			"abstract": "Detection of recurrent somatic rearrangements routinely allows monitoring of residual disease burden in leukemias, but is not used for most solid tumors. However, next-generation sequencing now allows rapid identification of patient-specific rearrangements in solid tumors. We mapped genomic rearrangements in three cancers and showed that PCR assays for rearrangements could detect a single copy of the tumor genome in plasma without false positives. Disease status, drug responsiveness, and incipient relapse could be serially assessed. In future, this strategy could be readily established in diagnostic laboratories, with major impact on monitoring of disease status and personalizing treatment of solid tumors.",
			"category": 2,
			"name": "McBride David J,2011"
		},
		{
			"PMID": 20705338,
			"title": "The expansion of T-cells and hematopoietic progenitors as a result of overexpression of the lymphoblastic leukemia gene, Lyl1 can support leukemia formation.",
			"journal": "Leukemia research",
			"authorList": [
				"Lukov Georgi L",
				"Rossi Lara",
				"Souroullas George P",
				"Mao Rui",
				"Goodell Margaret A"
			],
			"DOI": "10.1016/j.leukres.2010.07.023",
			"date": "2011-05-17",
			"PMC": "",
			"citation": "",
			"abstract": "This study investigates the function of the lymphoblastic leukemia gene, Lyl1 in the hematopoietic system and its oncogenic potential in the development of leukemia. Overexpression of Lyl1 in mouse bone marrow cells caused T-cell increase in the peripheral blood and expansion of the hematopoietic progenitors in culture and in the bone marrow. These observations were the result of increased proliferation and suppressed apoptosis of the progenitor cells caused by the Lyl1-overexpression. Our studies present substantial evidence supporting the secondary, pro-leukemic effect of Lyl1 in early hematopoietic progenitors with the potential to cause expansion of malignant cells with a stem/early progenitor-like phenotype.",
			"category": 2,
			"name": "Lukov Georgi L,2011"
		},
		{
			"PMID": 20703099,
			"title": "Genes essential for cell viability that are linked to tumor suppressor genes play a role in cancer susceptibility.",
			"journal": "Cell cycle (Georgetown, Tex.)",
			"authorList": [
				"Wang Yuxun",
				"Huang Bin",
				"Edelmann Lisa",
				"Kolodner Richard D",
				"Edelmann Winfried"
			],
			"DOI": "10.4161/cc.9.16.12951",
			"date": "2011-01-18",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Wang Yuxun,2011"
		},
		{
			"PMID": 20696777,
			"title": "Heterogeneous and complex rearrangements of chromosome arm 6q in chondromyxoid fibroma: delineation of breakpoints and analysis of candidate target genes.",
			"journal": "The American journal of pathology",
			"authorList": [
				"Romeo Salvatore",
				"Duim Ronald A J",
				"Bridge Julia A",
				"Mertens Fredrik",
				"de Jong Danielle",
				"Dal Cin Paola",
				"Wijers-Koster Pauline M",
				"Debiec-Rychter Maria",
				"Sciot Raf",
				"Rosenberg Andrew E",
				"Szuhai Karoly",
				"Hogendoorn Pancras C W"
			],
			"DOI": "10.2353/ajpath.2010.091277",
			"date": "2010-12-13",
			"PMC": "",
			"citation": "",
			"abstract": "Chondromyxoid fibroma (CMF) is an uncommon benign cartilaginous tumor of bone usually occurring during the second decade of life. CMF is associated with recurrent rearrangements of chromosome bands 6p23-25, 6q12-15, and 6q23-27. To delineate further the role and frequency of the involvement of three candidate regions (6q13, 6q23.3 and 6q24) in the pathogenesis of CMF, we studied a group of 43 cases using a molecular cytogenetic approach. Fluorescence in situ hybridization with probe sets bracketing the putative breakpoint regions was performed in 30 cases. The expression level of nearby candidate genes was studied by immunohistochemistry and quantitative RT-PCR in 24 and 23 cases, respectively. Whole-genome copy number screening was performed by array comparative genomic hybridization in 16 cases. Balanced and unbalanced rearrangements of 6q13 and 6q23.3 occurred in six and five cases, respectively, and a hemizygous deletion in 6q24 was found in five cases. Two known tumor suppressor genes map to the latter region: PLAGL1 and UTRN. However, neither of these two genes nor BCLAF1 and COL12A1, respectively located in 6q23.3 and 6q13, showed altered expression. Therefore, although rearrangements of chromosomal regions 6q13, 6q23.3, and 6q24 are common in CMF, the complexity of the changes precludes the use of a single fluorescence in situ hybridization probe set as an adjunct diagnostic tool. These data indicate that the genetic alterations in CMF are heterogeneous and are likely a result of a cryptic rearrangement beyond the resolution level of combined binary ratio fluorescence in situ hybridization or a point mutation.",
			"category": 2,
			"name": "Romeo Salvatore,2010"
		},
		{
			"PMID": 20679594,
			"title": "Lung cancer cell lines as tools for biomedical discovery and research.",
			"journal": "Journal of the National Cancer Institute",
			"authorList": [
				"Gazdar Adi F",
				"Girard Luc",
				"Lockwood William W",
				"Lam Wan L",
				"Minna John D"
			],
			"DOI": "10.1093/jnci/djq279",
			"date": "2010-09-28",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer cell lines have made a substantial contribution to lung cancer translational research and biomedical discovery. A systematic approach to initiating and characterizing cell lines from small cell and non-small cell lung carcinomas has led to the current collection of more than 200 lung cancer cell lines, a number that exceeds those for other common epithelial cancers combined. The ready availability and widespread dissemination of the lines to investigators worldwide have resulted in more than 9000 citations, including multiple examples of important biomedical discoveries. The high (but not perfect) genomic similarities between lung cancer cell lines and the lung tumor type from which they were derived provide evidence of the relevance of their use. However, major problems including misidentification or cell line contamination remain. Ongoing studies and new approaches are expected to reveal the full potential of the lung cancer cell line panel.",
			"category": 2,
			"name": "Gazdar Adi F,2010"
		},
		{
			"PMID": 20670437,
			"title": "Personalized therapies in the cancer \"omics\" era.",
			"journal": "Molecular cancer",
			"authorList": [
				"Oca\u00f1a Alberto",
				"Pandiella Atanasio"
			],
			"DOI": "10.1186/1476-4598-9-202",
			"date": "2010-12-06",
			"PMC": "",
			"citation": "",
			"abstract": "A molecular hallmark of cancer is the presence of genetic alterations in the tumoral DNA. Understanding how these alterations translate into the malignant phenotype is critical for the adequate treatment of oncologic diseases. Several cancer genome sequencing reports have uncovered the number and identity of proteins and pathways frequently altered in cancer. In this article we discuss how integration of these genomic data with other biological and proteomic studies may help in designing anticancer therapies \"a la carte\". An important conclusion is that next generation treatment of neoplasias must be based on rational drug combinations that target various pathways and cellular entities that sustain the survival of cancer cells.",
			"category": 2,
			"name": "Oca\u00f1a Alberto,2010"
		},
		{
			"PMID": 20639550,
			"title": "Human variation databases.",
			"journal": "Database : the journal of biological databases and curation",
			"authorList": [
				"K\u00fcntzer Jan",
				"Eggle Daniela",
				"Klostermann Stefan",
				"Burtscher Helmut"
			],
			"DOI": "10.1093/database/baq015",
			"date": "2010-12-06",
			"PMC": "",
			"citation": "",
			"abstract": "More than 100,000 human genetic variations have been described in various genes that are associated with a wide variety of diseases. Such data provides invaluable information for both clinical medicine and basic science. A number of locus-specific databases have been developed to exploit this huge amount of data. However, the scope, format and content of these databases differ strongly and as no standard for variation databases has yet been adopted, the way data is presented varies enormously. This review aims to give an overview of current resources for human variation data in public and commercial resources.",
			"category": 2,
			"name": "K\u00fcntzer Jan,2010"
		},
		{
			"PMID": 20609406,
			"title": "Probing the probes: fitness factors for small molecule tools.",
			"journal": "Chemistry & biology",
			"authorList": [
				"Workman Paul",
				"Collins Ian"
			],
			"DOI": "10.1016/j.chembiol.2010.05.013",
			"date": "2010-10-07",
			"PMC": "",
			"citation": "",
			"abstract": "Chemical probes for interrogating biological processes are of considerable current interest. Cell permeable small molecule tools have a major role in facilitating the functional annotation of the human genome, understanding both physiological and pathological processes, and validating new molecular targets. To be valuable, chemical tools must satisfy necessary criteria and recent publications have suggested objective guidelines for what makes a useful chemical probe. Although recognizing that such guidelines may be valuable, we caution against overly restrictive rules that may stifle innovation in favor of a \"fit-for-purpose\" approach. Reviewing the literature and providing examples from the cancer field, we recommend a series of \"fitness factors\" to be considered when assessing chemical probes. We hope this will encourage innovative chemical biology research while minimizing the generation of poor quality and misleading biological data, thus increasing understanding of the particular biological area, to the benefit of basic research and drug discovery.",
			"category": 2,
			"name": "Workman Paul,2010"
		},
		{
			"PMID": 20569696,
			"title": "Wilms tumor chromatin profiles highlight stem cell properties and a renal developmental network.",
			"journal": "Cell stem cell",
			"authorList": [
				"Aiden Aviva Presser",
				"Rivera Miguel N",
				"Rheinbay Esther",
				"Ku Manching",
				"Coffman Erik J",
				"Truong Thanh T",
				"Vargas Sara O",
				"Lander Eric S",
				"Haber Daniel A",
				"Bernstein Bradley E"
			],
			"DOI": "10.1016/j.stem.2010.03.016",
			"date": "2010-11-24",
			"PMC": "",
			"citation": "",
			"abstract": "Wilms tumor is the most common pediatric kidney cancer. To identify transcriptional and epigenetic mechanisms that drive this disease, we compared genome-wide chromatin profiles of Wilms tumors, embryonic stem cells (ESCs), and normal kidney. Wilms tumors prominently exhibit large active chromatin domains previously observed in ESCs. In the cancer, these domains frequently correspond to genes that are critical for kidney development and expressed in the renal stem cell compartment. Wilms cells also express \"embryonic\" chromatin regulators and maintain stem cell-like p16 silencing. Finally, Wilms and ESCs both exhibit \"bivalent\" chromatin modifications at silent promoters that may be poised for activation. In Wilms tumor, bivalent promoters correlate to genes expressed in specific kidney compartments and point to a kidney-specific differentiation program arrested at an early-progenitor stage. We suggest that Wilms cells share a transcriptional and epigenetic landscape with a normal renal stem cell, which is inherently susceptible to transformation and may represent a cell of origin for this disease.",
			"category": 2,
			"name": "Aiden Aviva Presser,2010"
		},
		{
			"PMID": 20552370,
			"title": "Comparative-effectiveness research and good clinical practice for laparoscopic rectal surgery after neoadjuvant treatment.",
			"journal": "Surgical endoscopy",
			"authorList": [
				"Hottenrott C"
			],
			"DOI": "10.1007/s00464-010-1154-3",
			"date": "2011-05-03",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Hottenrott C,2011"
		},
		{
			"PMID": 20547997,
			"title": "Research on early-stage carcinogenesis: are we approaching paradigm instability?",
			"journal": "Journal of clinical oncology : official journal of the American Society of Clinical Oncology",
			"authorList": [
				"Baker Stuart G",
				"Cappuccio Antonio",
				"Potter John D"
			],
			"DOI": "10.1200/JCO.2010.28.5460",
			"date": "2010-07-20",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Baker Stuart G,2010"
		},
		{
			"PMID": 20535131,
			"title": "Envisioning the future of early anticancer drug development.",
			"journal": "Nature reviews. Cancer",
			"authorList": [
				"Yap Timothy A",
				"Sandhu Shahneen K",
				"Workman Paul",
				"de Bono Johann S"
			],
			"DOI": "10.1038/nrc2870",
			"date": "2010-07-27",
			"PMC": "",
			"citation": "",
			"abstract": "The development of novel molecularly targeted cancer therapeutics remains slow and expensive with many late-stage failures. There is an urgent need to accelerate this process by improving early clinical anticancer drug evaluation through modern and rational trial designs that incorporate predictive, pharmacokinetic, pharmacodynamic, pharmacogenomic and intermediate end-point biomarkers. In this article, we discuss current approaches and propose strategies that will potentially maximize benefit to patients and expedite the regulatory approvals of new anticancer drugs.",
			"category": 2,
			"name": "Yap Timothy A,2010"
		},
		{
			"PMID": 20505728,
			"title": "The mutation spectrum revealed by paired genome sequences from a lung cancer patient.",
			"journal": "Nature",
			"authorList": [
				"Lee William",
				"Jiang Zhaoshi",
				"Liu Jinfeng",
				"Haverty Peter M",
				"Guan Yinghui",
				"Stinson Jeremy",
				"Yue Peng",
				"Zhang Yan",
				"Pant Krishna P",
				"Bhatt Deepali",
				"Ha Connie",
				"Johnson Stephanie",
				"Kennemer Michael I",
				"Mohan Sankar",
				"Nazarenko Igor",
				"Watanabe Colin",
				"Sparks Andrew B",
				"Shames David S",
				"Gentleman Robert",
				"de Sauvage Frederic J",
				"Stern Howard",
				"Pandita Ajay",
				"Ballinger Dennis G",
				"Drmanac Radoje",
				"Modrusan Zora",
				"Seshagiri Somasekar",
				"Zhang Zemin"
			],
			"DOI": "10.1038/nature09004",
			"date": "2010-07-02",
			"PMC": "",
			"citation": "",
			"abstract": "Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small-cell lung carcinomas in smokers being the predominant form of the disease. Although previous studies have identified important common somatic mutations in lung cancers, they have primarily focused on a limited set of genes and have thus provided a constrained view of the mutational spectrum. Recent cancer sequencing efforts have used next-generation sequencing technologies to provide a genome-wide view of mutations in leukaemia, breast cancer and cancer cell lines. Here we present the complete sequences of a primary lung tumour (60x coverage) and adjacent normal tissue (46x). Comparing the two genomes, we identify a wide variety of somatic variations, including >50,000 high-confidence single nucleotide variants. We validated 530 somatic single nucleotide variants in this tumour, including one in the KRAS proto-oncogene and 391 others in coding regions, as well as 43 large-scale structural variations. These constitute a large set of new somatic mutations and yield an estimated 17.7 per megabase genome-wide somatic mutation rate. Notably, we observe a distinct pattern of selection against mutations within expressed genes compared to non-expressed genes and in promoter regions up to 5 kilobases upstream of all protein-coding genes. Furthermore, we observe a higher rate of amino acid-changing mutations in kinase genes. We present a comprehensive view of somatic alterations in a single lung tumour, and provide the first evidence, to our knowledge, of distinct selective pressures present within the tumour environment.",
			"category": 2,
			"name": "Lee William,2010"
		},
		{
			"PMID": 20502460,
			"title": "Guidelines for the welfare and use of animals in cancer research.",
			"journal": "British journal of cancer",
			"authorList": [
				"Workman P",
				"Aboagye E O",
				"Balkwill F",
				"Balmain A",
				"Bruder G",
				"Chaplin D J",
				"Double J A",
				"Everitt J",
				"Farningham D A H",
				"Glennie M J",
				"Kelland L R",
				"Robinson V",
				"Stratford I J",
				"Tozer G M",
				"Watson S",
				"Wedge S R",
				"Eccles S A",
				"Committee of the National Cancer Research Institute"
			],
			"DOI": "10.1038/sj.bjc.6605642",
			"date": "2010-06-17",
			"PMC": "",
			"citation": "",
			"abstract": "Animal experiments remain essential to understand the fundamental mechanisms underpinning malignancy and to discover improved methods to prevent, diagnose and treat cancer. Excellent standards of animal care are fully consistent with the conduct of high quality cancer research. Here we provide updated guidelines on the welfare and use of animals in cancer research. All experiments should incorporate the 3Rs: replacement, reduction and refinement. Focusing on animal welfare, we present recommendations on all aspects of cancer research, including: study design, statistics and pilot studies; choice of tumour models (e.g., genetically engineered, orthotopic and metastatic); therapy (including drugs and radiation); imaging (covering techniques, anaesthesia and restraint); humane endpoints (including tumour burden and site); and publication of best practice.",
			"category": 2,
			"name": "Workman P,2010"
		},
		{
			"PMID": 20492640,
			"title": "Phylostratigraphic tracking of cancer genes suggests a link to the emergence of multicellularity in metazoa.",
			"journal": "BMC biology",
			"authorList": [
				"Domazet-Loso Tomislav",
				"Tautz Diethard"
			],
			"DOI": "10.1186/1741-7007-8-66",
			"date": "2010-09-22",
			"PMC": "",
			"citation": "",
			"abstract": "Phylostratigraphy is a method used to correlate the evolutionary origin of founder genes (that is, functional founder protein domains) of gene families with particular macroevolutionary transitions. It is based on a model of genome evolution that suggests that the origin of complex phenotypic innovations will be accompanied by the emergence of such founder genes, the descendants of which can still be traced in extant organisms. The origin of multicellularity can be considered to be a macroevolutionary transition, for which new gene functions would have been required. Cancer should be tightly connected to multicellular life since it can be viewed as a malfunction of interaction between cells in a multicellular organism. A phylostratigraphic tracking of the origin of cancer genes should, therefore, also provide insights into the origin of multicellularity.",
			"category": 2,
			"name": "Domazet-Loso Tomislav,2010"
		},
		{
			"PMID": 20467480,
			"title": "Genes with relevance for early to late progression of colon carcinoma based on combined genomic and transcriptomic information from the same patients.",
			"journal": "Cancer informatics",
			"authorList": [
				"Lagerstedt Kristina K",
				"Kristiansson Erik",
				"L\u00f6nnroth Christina",
				"Andersson Marianne",
				"Iresj\u00f6 Britt-Marie",
				"Gustafsson Annika",
				"Hansson Elisabeth",
				"Kressner Ulf",
				"Nordgren Svante",
				"Enlund Fredrik",
				"Lundholm Kent"
			],
			"DOI": "",
			"date": "2010-06-09",
			"PMC": "",
			"citation": "",
			"abstract": "Genetic and epigenetic alterations in colorectal cancer are numerous. However, it is difficult to judge whether such changes are primary or secondary to the appearance and progression of tumors. Therefore, the aim of the present study was to identify altered DNA regions with significant covariation to transcription alterations along colon cancer progression.",
			"category": 2,
			"name": "Lagerstedt Kristina K,2010"
		},
		{
			"PMID": 20466604,
			"title": "Molecular basis for therapy resistance.",
			"journal": "Molecular oncology",
			"authorList": [
				"L\u00f8nning Per E"
			],
			"DOI": "10.1016/j.molonc.2010.04.005",
			"date": "2010-10-08",
			"PMC": "",
			"citation": "",
			"abstract": "Chemoresistance remains the main reason for therapeutic failure in breast cancer as well as most other solid tumours. While gene expression profiles related to prognosis have been developed, so far use of such signatures as well as single markers has been of limited value predicting drug resistance. Novel technologies, in particular with regard to high through-put sequencing holds great promises for future identification of the key \"driver\" mechanisms guiding chemosensitivity versus resistance in breast cancer as well as other malignant conditions.",
			"category": 2,
			"name": "L\u00f8nning Per E,2010"
		},
		{
			"PMID": 20442418,
			"title": "In vivo identification of regulators of cell invasion across basement membranes.",
			"journal": "Science signaling",
			"authorList": [
				"Matus David Q",
				"Li Xiao-Yan",
				"Durbin Sarah",
				"Agarwal Daniel",
				"Chi Qiuyi",
				"Weiss Stephen J",
				"Sherwood David R"
			],
			"DOI": "10.1126/scisignal.2000654",
			"date": "2010-07-26",
			"PMC": "",
			"citation": "",
			"abstract": "Cell invasion through basement membranes during development, immune surveillance, and metastasis remains poorly understood. To gain further insight into this key cellular behavior, we performed an in vivo screen for regulators of cell invasion through basement membranes, using the simple model of Caenorhabditis elegans anchor cell invasion, and identified 99 genes that promote invasion, including the genes encoding the chaperonin complex cct. Notably, most of these genes have not been previously implicated in invasive cell behavior. We characterized members of the cct complex and 11 other gene products, determining the distinct aspects of the invasive cascade that they regulate, including formation of a specialized invasive cell membrane and its ability to breach the basement membrane. RNA interference-mediated knockdown of the human orthologs of cct-5 and lit-1, which had not previously been implicated in cell invasion, reduced the invasiveness of metastatic carcinoma cells, suggesting that a conserved genetic program underlies cell invasion. These results increase our understanding of the genetic underpinnings of cell invasion and also provide new potential therapeutic targets to limit this behavior.",
			"category": 2,
			"name": "Matus David Q,2010"
		},
		{
			"PMID": 20430953,
			"title": "Roles for growth factors in cancer progression.",
			"journal": "Physiology (Bethesda, Md.)",
			"authorList": [
				"Witsch Esther",
				"Sela Michael",
				"Yarden Yosef"
			],
			"DOI": "10.1152/physiol.00045.2009",
			"date": "2010-07-21",
			"PMC": "",
			"citation": "",
			"abstract": "Under physiological conditions, cells receive fate-determining signals from their tissue surroundings, primarily in the form of polypeptide growth factors. Integration of these extracellular signals underlies tissue homeostasis. Although departure from homeostasis and tumor initiation are instigated by oncogenic mutations rather than by growth factors, the latter are the major regulators of all subsequent steps of tumor progression, namely clonal expansion, invasion across tissue barriers, angiogenesis, and colonization of distant niches. Here, we discuss the relevant growth factor families, their roles in tumor biology, as well as the respective downstream signaling pathways. Importantly, cancer-associated activating mutations that impinge on these pathways often relieve, in part, the reliance of tumors on growth factors. On the other hand, growth factors are frequently involved in evolvement of resistance to therapeutic regimens, which extends the roles for polypeptide factors to very late phases of tumor progression and offers opportunities for cancer therapy.",
			"category": 2,
			"name": "Witsch Esther,2010"
		},
		{
			"PMID": 20414679,
			"title": "Monitoring and assessing the intraabdominal therapeutic response for gastric cancer: is second-look laparoscopy the solution?",
			"journal": "Surgical endoscopy",
			"authorList": [
				"Zoras Odysseas",
				"Spiliotis John"
			],
			"DOI": "10.1007/s00464-010-0958-5",
			"date": "2011-02-03",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Zoras Odysseas,2011"
		},
		{
			"PMID": 20407605,
			"title": "Piwil2 expressed in various stages of cervical neoplasia is a potential complementary marker for p16.",
			"journal": "American journal of translational research",
			"authorList": [
				"He Gang",
				"Chen Li",
				"Ye Yin",
				"Xiao Yi",
				"Hua Keding",
				"Jarjoura David",
				"Nakano Toru",
				"Barsky Sanford H",
				"Shen Rulong",
				"Gao Jian-Xin"
			],
			"DOI": "",
			"date": "2011-07-14",
			"PMC": "",
			"citation": "",
			"abstract": "Generally, cancers may undergo the developmental stages of benign proliferation, precancer and invasive cancer. Identification of biomarkers that are expressed throughout the developmental stages will facilitate detection, prevention and therapy of cancer. Piwil2, a member of AGO/PIWI family of proteins, has been suggested to be associated with tumor development. Here we reported that piwil2 can be detected by immunohistochemistry (IHC) in various stages of human cervical squamous cell carcinomas and adenocarcinomas. Interestingly, piwil2 was also detected in some metaplastic epithelial cells as well as histologically \"normal\" appearing tissues adjacent to malignant lesions. While all the premalignant and malignant lesions expressed varying levels of piwil2, p16(INK4a) (p16), a surrogate indicator of high-risk human papillomavirus (HR-HPV) infection, was detected in only 84.62% of the specimens. In Papanicolaou (Pap) test, piwil2 was also detected in atypical glandular cells (AGC), low-grade (LSIL) and high-grade squamous intraepithelial lesions (HSIL), whereas p16 was not always concomitantly detected in the same specimens. The results suggest that piwil2 might play important roles throughout the process of cervical cancer development and have the potential to be used as a complementary marker for p16(INK4a). It is worth further study to improve the sensitivity and specificity of current screening methods for cervical cancers.",
			"category": 2,
			"name": "He Gang,2011"
		},
		{
			"PMID": 20399812,
			"title": "A cancer-derived mutation in the PSTAIRE helix of cyclin-dependent kinase 2 alters the stability of cyclin binding.",
			"journal": "Biochimica et biophysica acta",
			"authorList": [
				"Child Emma S",
				"Hendrychov\u00e1 Tereza",
				"McCague Karen",
				"Futreal Andy",
				"Otyepka Michal",
				"Mann David J"
			],
			"DOI": "10.1016/j.bbamcr.2010.04.004",
			"date": "2010-07-27",
			"PMC": "",
			"citation": "",
			"abstract": "Cyclin-dependent kinase 2 (cdk2) is a central regulator of the mammalian cell cycle. Here we describe the properties of a mutant form of cdk2 identified during large-scale sequencing of protein kinases from cancerous tissue. The mutation substituted a leucine for a proline in the PSTAIRE helix, the central motif in the interaction of the cdk with its regulatory cyclin subunit. We demonstrate that whilst the mutant cdk2 is considerably impaired in stable cyclin association, it is still able to generate an active kinase that can functionally complement defective cdks in vivo. Molecular dynamic simulations and biophysical measurements indicate that the observed biochemical properties likely stem from increased flexibility within the cyclin-binding helix.",
			"category": 2,
			"name": "Child Emma S,2010"
		},
		{
			"PMID": 20398334,
			"title": "Integrative analysis of gene expression and copy number alterations using canonical correlation analysis.",
			"journal": "BMC bioinformatics",
			"authorList": [
				"Soneson Charlotte",
				"Lilljebj\u00f6rn Henrik",
				"Fioretos Thoas",
				"Fontes Magnus"
			],
			"DOI": "10.1186/1471-2105-11-191",
			"date": "2010-06-09",
			"PMC": "",
			"citation": "",
			"abstract": "With the rapid development of new genetic measurement methods, several types of genetic alterations can be quantified in a high-throughput manner. While the initial focus has been on investigating each data set separately, there is an increasing interest in studying the correlation structure between two or more data sets. Multivariate methods based on Canonical Correlation Analysis (CCA) have been proposed for integrating paired genetic data sets. The high dimensionality of microarray data imposes computational difficulties, which have been addressed for instance by studying the covariance structure of the data, or by reducing the number of variables prior to applying the CCA. In this work, we propose a new method for analyzing high-dimensional paired genetic data sets, which mainly emphasizes the correlation structure and still permits efficient application to very large data sets. The method is implemented by translating a regularized CCA to its dual form, where the computational complexity depends mainly on the number of samples instead of the number of variables. The optimal regularization parameters are chosen by cross-validation. We apply the regularized dual CCA, as well as a classical CCA preceded by a dimension-reducing Principal Components Analysis (PCA), to a paired data set of gene expression changes and copy number alterations in leukemia.",
			"category": 2,
			"name": "Soneson Charlotte,2010"
		},
		{
			"PMID": 20393554,
			"title": "International network of cancer genome projects.",
			"journal": "Nature",
			"authorList": [
				"International Cancer Genome Consortium",
				"Hudson Thomas J",
				"Anderson Warwick",
				"Artez Axel",
				"Barker Anna D",
				"Bell Cindy",
				"Bernab\u00e9 Rosa R",
				"Bhan M K",
				"Calvo Fabien",
				"Eerola Iiro",
				"Gerhard Daniela S",
				"Guttmacher Alan",
				"Guyer Mark",
				"Hemsley Fiona M",
				"Jennings Jennifer L",
				"Kerr David",
				"Klatt Peter",
				"Kolar Patrik",
				"Kusada Jun",
				"Lane David P",
				"Laplace Frank",
				"Youyong Lu",
				"Nettekoven Gerd",
				"Ozenberger Brad",
				"Peterson Jane",
				"Rao T S",
				"Remacle Jacques",
				"Schafer Alan J",
				"Shibata Tatsuhiro",
				"Stratton Michael R",
				"Vockley Joseph G",
				"Watanabe Koichi",
				"Yang Huanming",
				"Yuen Matthew M F",
				"Knoppers Bartha M",
				"Bobrow Martin",
				"Cambon-Thomsen Anne",
				"Dressler Lynn G",
				"Dyke Stephanie O M",
				"Joly Yann",
				"Kato Kazuto",
				"Kennedy Karen L",
				"Nicol\u00e1s Pilar",
				"Parker Michael J",
				"Rial-Sebbag Emmanuelle",
				"Romeo-Casabona Carlos M",
				"Shaw Kenna M",
				"Wallace Susan",
				"Wiesner Georgia L",
				"Zeps Nikolajs",
				"Lichter Peter",
				"Biankin Andrew V",
				"Chabannon Christian",
				"Chin Lynda",
				"Cl\u00e9ment Bruno",
				"de Alava Enrique",
				"Degos Fran\u00e7oise",
				"Ferguson Martin L",
				"Geary Peter",
				"Hayes D Neil",
				"Hudson Thomas J",
				"Johns Amber L",
				"Kasprzyk Arek",
				"Nakagawa Hidewaki",
				"Penny Robert",
				"Piris Miguel A",
				"Sarin Rajiv",
				"Scarpa Aldo",
				"Shibata Tatsuhiro",
				"van de Vijver Marc",
				"Futreal P Andrew",
				"Aburatani Hiroyuki",
				"Bay\u00e9s M\u00f3nica",
				"Botwell David D L",
				"Campbell Peter J",
				"Estivill Xavier",
				"Gerhard Daniela S",
				"Grimmond Sean M",
				"Gut Ivo",
				"Hirst Martin",
				"L\u00f3pez-Ot\u00edn Carlos",
				"Majumder Partha",
				"Marra Marco",
				"McPherson John D",
				"Nakagawa Hidewaki",
				"Ning Zemin",
				"Puente Xose S",
				"Ruan Yijun",
				"Shibata Tatsuhiro",
				"Stratton Michael R",
				"Stunnenberg Hendrik G",
				"Swerdlow Harold",
				"Velculescu Victor E",
				"Wilson Richard K",
				"Xue Hong H",
				"Yang Liu",
				"Spellman Paul T",
				"Bader Gary D",
				"Boutros Paul C",
				"Campbell Peter J",
				"Flicek Paul",
				"Getz Gad",
				"Guig\u00f3 Roderic",
				"Guo Guangwu",
				"Haussler David",
				"Heath Simon",
				"Hubbard Tim J",
				"Jiang Tao",
				"Jones Steven M",
				"Li Qibin",
				"L\u00f3pez-Bigas Nuria",
				"Luo Ruibang",
				"Muthuswamy Lakshmi",
				"Ouellette B F Francis",
				"Pearson John V",
				"Puente Xose S",
				"Quesada Victor",
				"Raphael Benjamin J",
				"Sander Chris",
				"Shibata Tatsuhiro",
				"Speed Terence P",
				"Stein Lincoln D",
				"Stuart Joshua M",
				"Teague Jon W",
				"Totoki Yasushi",
				"Tsunoda Tatsuhiko",
				"Valencia Alfonso",
				"Wheeler David A",
				"Wu Honglong",
				"Zhao Shancen",
				"Zhou Guangyu",
				"Stein Lincoln D",
				"Guig\u00f3 Roderic",
				"Hubbard Tim J",
				"Joly Yann",
				"Jones Steven M",
				"Kasprzyk Arek",
				"Lathrop Mark",
				"L\u00f3pez-Bigas Nuria",
				"Ouellette B F Francis",
				"Spellman Paul T",
				"Teague Jon W",
				"Thomas Gilles",
				"Valencia Alfonso",
				"Yoshida Teruhiko",
				"Kennedy Karen L",
				"Axton Myles",
				"Dyke Stephanie O M",
				"Futreal P Andrew",
				"Gerhard Daniela S",
				"Gunter Chris",
				"Guyer Mark",
				"Hudson Thomas J",
				"McPherson John D",
				"Miller Linda J",
				"Ozenberger Brad",
				"Shaw Kenna M",
				"Kasprzyk Arek",
				"Stein Lincoln D",
				"Zhang Junjun",
				"Haider Syed A",
				"Wang Jianxin",
				"Yung Christina K",
				"Cros Anthony",
				"Liang Yong",
				"Gnaneshan Saravanamuttu",
				"Guberman Jonathan",
				"Hsu Jack",
				"Bobrow Martin",
				"Chalmers Don R C",
				"Hasel Karl W",
				"Joly Yann",
				"Kaan Terry S H",
				"Kennedy Karen L",
				"Knoppers Bartha M",
				"Lowrance William W",
				"Masui Tohru",
				"Nicol\u00e1s Pilar",
				"Rial-Sebbag Emmanuelle",
				"Rodriguez Laura Lyman",
				"Vergely Catherine",
				"Yoshida Teruhiko",
				"Grimmond Sean M",
				"Biankin Andrew V",
				"Bowtell David D L",
				"Cloonan Nicole",
				"deFazio Anna",
				"Eshleman James R",
				"Etemadmoghadam Dariush",
				"Gardiner Brooke B",
				"Kench James G",
				"Scarpa Aldo",
				"Sutherland Robert L",
				"Tempero Margaret A",
				"Waddell Nicola J",
				"Wilson Peter J",
				"McPherson John D",
				"Gallinger Steve",
				"Tsao Ming-Sound",
				"Shaw Patricia A",
				"Petersen Gloria M",
				"Mukhopadhyay Debabrata",
				"Chin Lynda",
				"DePinho Ronald A",
				"Thayer Sarah",
				"Muthuswamy Lakshmi",
				"Shazand Kamran",
				"Beck Timothy",
				"Sam Michelle",
				"Timms Lee",
				"Ballin Vanessa",
				"Lu Youyong",
				"Ji Jiafu",
				"Zhang Xiuqing",
				"Chen Feng",
				"Hu Xueda",
				"Zhou Guangyu",
				"Yang Qi",
				"Tian Geng",
				"Zhang Lianhai",
				"Xing Xiaofang",
				"Li Xianghong",
				"Zhu Zhenggang",
				"Yu Yingyan",
				"Yu Jun",
				"Yang Huanming",
				"Lathrop Mark",
				"Tost J\u00f6rg",
				"Brennan Paul",
				"Holcatova Ivana",
				"Zaridze David",
				"Brazma Alvis",
				"Egevard Lars",
				"Prokhortchouk Egor",
				"Banks Rosamonde Elizabeth",
				"Uhl\u00e9n Mathias",
				"Cambon-Thomsen Anne",
				"Viksna Juris",
				"Ponten Fredrik",
				"Skryabin Konstantin",
				"Stratton Michael R",
				"Futreal P Andrew",
				"Birney Ewan",
				"Borg Ake",
				"B\u00f8rresen-Dale Anne-Lise",
				"Caldas Carlos",
				"Foekens John A",
				"Martin Sancha",
				"Reis-Filho Jorge S",
				"Richardson Andrea L",
				"Sotiriou Christos",
				"Stunnenberg Hendrik G",
				"Thoms Giles",
				"van de Vijver Marc",
				"van't Veer Laura",
				"Calvo Fabien",
				"Birnbaum Daniel",
				"Blanche H\u00e9l\u00e8ne",
				"Boucher Pascal",
				"Boyault Sandrine",
				"Chabannon Christian",
				"Gut Ivo",
				"Masson-Jacquemier Jocelyne D",
				"Lathrop Mark",
				"Pauport\u00e9 Iris",
				"Pivot Xavier",
				"Vincent-Salomon Anne",
				"Tabone Eric",
				"Theillet Charles",
				"Thomas Gilles",
				"Tost J\u00f6rg",
				"Treilleux Isabelle",
				"Calvo Fabien",
				"Bioulac-Sage Paulette",
				"Cl\u00e9ment Bruno",
				"Decaens Thomas",
				"Degos Fran\u00e7oise",
				"Franco Dominique",
				"Gut Ivo",
				"Gut Marta",
				"Heath Simon",
				"Lathrop Mark",
				"Samuel Didier",
				"Thomas Gilles",
				"Zucman-Rossi Jessica",
				"Lichter Peter",
				"Eils Roland",
				"Brors Benedikt",
				"Korbel Jan O",
				"Korshunov Andrey",
				"Landgraf Pablo",
				"Lehrach Hans",
				"Pfister Stefan",
				"Radlwimmer Bernhard",
				"Reifenberger Guido",
				"Taylor Michael D",
				"von Kalle Christof",
				"Majumder Partha P",
				"Sarin Rajiv",
				"Rao T S",
				"Bhan M K",
				"Scarpa Aldo",
				"Pederzoli Paolo",
				"Lawlor Rita A",
				"Delledonne Massimo",
				"Bardelli Alberto",
				"Biankin Andrew V",
				"Grimmond Sean M",
				"Gress Thomas",
				"Klimstra David",
				"Zamboni Giuseppe",
				"Shibata Tatsuhiro",
				"Nakamura Yusuke",
				"Nakagawa Hidewaki",
				"Kusada Jun",
				"Tsunoda Tatsuhiko",
				"Miyano Satoru",
				"Aburatani Hiroyuki",
				"Kato Kazuto",
				"Fujimoto Akihiro",
				"Yoshida Teruhiko",
				"Campo Elias",
				"L\u00f3pez-Ot\u00edn Carlos",
				"Estivill Xavier",
				"Guig\u00f3 Roderic",
				"de Sanjos\u00e9 Silvia",
				"Piris Miguel A",
				"Montserrat Emili",
				"Gonz\u00e1lez-D\u00edaz Marcos",
				"Puente Xose S",
				"Jares Pedro",
				"Valencia Alfonso",
				"Himmelbauer Heinz",
				"Quesada Victor",
				"Bea Silvia",
				"Stratton Michael R",
				"Futreal P Andrew",
				"Campbell Peter J",
				"Vincent-Salomon Anne",
				"Richardson Andrea L",
				"Reis-Filho Jorge S",
				"van de Vijver Marc",
				"Thomas Gilles",
				"Masson-Jacquemier Jocelyne D",
				"Aparicio Samuel",
				"Borg Ake",
				"B\u00f8rresen-Dale Anne-Lise",
				"Caldas Carlos",
				"Foekens John A",
				"Stunnenberg Hendrik G",
				"van't Veer Laura",
				"Easton Douglas F",
				"Spellman Paul T",
				"Martin Sancha",
				"Barker Anna D",
				"Chin Lynda",
				"Collins Francis S",
				"Compton Carolyn C",
				"Ferguson Martin L",
				"Gerhard Daniela S",
				"Getz Gad",
				"Gunter Chris",
				"Guttmacher Alan",
				"Guyer Mark",
				"Hayes D Neil",
				"Lander Eric S",
				"Ozenberger Brad",
				"Penny Robert",
				"Peterson Jane",
				"Sander Chris",
				"Shaw Kenna M",
				"Speed Terence P",
				"Spellman Paul T",
				"Vockley Joseph G",
				"Wheeler David A",
				"Wilson Richard K",
				"Hudson Thomas J",
				"Chin Lynda",
				"Knoppers Bartha M",
				"Lander Eric S",
				"Lichter Peter",
				"Stein Lincoln D",
				"Stratton Michael R",
				"Anderson Warwick",
				"Barker Anna D",
				"Bell Cindy",
				"Bobrow Martin",
				"Burke Wylie",
				"Collins Francis S",
				"Compton Carolyn C",
				"DePinho Ronald A",
				"Easton Douglas F",
				"Futreal P Andrew",
				"Gerhard Daniela S",
				"Green Anthony R",
				"Guyer Mark",
				"Hamilton Stanley R",
				"Hubbard Tim J",
				"Kallioniemi Olli P",
				"Kennedy Karen L",
				"Ley Timothy J",
				"Liu Edison T",
				"Lu Youyong",
				"Majumder Partha",
				"Marra Marco",
				"Ozenberger Brad",
				"Peterson Jane",
				"Schafer Alan J",
				"Spellman Paul T",
				"Stunnenberg Hendrik G",
				"Wainwright Brandon J",
				"Wilson Richard K",
				"Yang Huanming"
			],
			"DOI": "10.1038/nature08987",
			"date": "2010-06-02",
			"PMC": "",
			"citation": "",
			"abstract": "The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.",
			"category": 2,
			"name": "International Cancer Genome Consortium,2010"
		},
		{
			"PMID": 20376142,
			"title": "Cancer: drug-tolerant insurgents.",
			"journal": "Nature",
			"authorList": [
				"Workman Paul",
				"Travers Jon"
			],
			"DOI": "10.1038/464844a",
			"date": "2010-05-17",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Workman Paul,2010"
		},
		{
			"PMID": 20372935,
			"title": "New technology-based innovation changes surgical practice and research direction in solid cancers.",
			"journal": "Surgical endoscopy",
			"authorList": [
				"Katsios Christos",
				"Baltogiannis Georgios",
				"Roukos Dimitrios H"
			],
			"DOI": "10.1007/s00464-010-1020-3",
			"date": "2011-02-01",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Katsios Christos,2011"
		},
		{
			"PMID": 20354872,
			"title": "Hope from Japan for esophagogastric cancers: esophagectomy and endoscopic submucosal dissection for gastric tube cancer.",
			"journal": "Surgical endoscopy",
			"authorList": [
				"Katsios Christos",
				"Roukos Dimitrios H",
				"Baltogiannis Georgios"
			],
			"DOI": "10.1007/s00464-010-1024-z",
			"date": "2011-02-01",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Katsios Christos,2011"
		},
		{
			"PMID": 20351699,
			"title": "The molecular pathology of cancer.",
			"journal": "Nature reviews. Clinical oncology",
			"authorList": [
				"Harris Timothy J R",
				"McCormick Frank"
			],
			"DOI": "10.1038/nrclinonc.2010.41",
			"date": "2010-07-27",
			"PMC": "",
			"citation": "",
			"abstract": "Rapid technical advances in DNA sequencing and genome-wide association studies are driving the discovery of the germline and somatic mutations that are present in different cancers. Mutations in genes involved in cellular signaling are common, and often shared by tumors that arise in distinct anatomical locations. Here we review the most important molecular changes in different cancers from the perspective of what should be analyzed on a routine basis in the clinic. The paradigms are EGFR mutations in adenocarcinoma of the lung that can be treated with gefitinib, KRAS mutations in colon cancer with respect to treatment with EGFR antibodies, and the use of gene-expression analysis for ER-positive, node-negative breast cancer patients with respect to chemotherapy options. Several other examples in both solid and hematological cancers are also provided. We focus on how disease subtypes can influence therapy and discuss the implications of the impending molecular diagnostic revolution from the point of view of the patients, clinicians, and the diagnostic and pharmaceutical companies. This paradigm shift is occurring first in cancer patient management and is likely to promote the application of these technologies to other diseases.",
			"category": 2,
			"name": "Harris Timothy J R,2010"
		},
		{
			"PMID": 20304806,
			"title": "SNP array analysis in hematologic malignancies: avoiding false discoveries.",
			"journal": "Blood",
			"authorList": [
				"Heinrichs Stefan",
				"Li Cheng",
				"Look A Thomas"
			],
			"DOI": "10.1182/blood-2009-11-203182",
			"date": "2010-06-17",
			"PMC": "",
			"citation": "",
			"abstract": "Comprehensive analysis of the cancer genome has become a standard approach to identifying new disease loci, and ultimately will guide therapeutic decisions. A key technology in this effort, single nucleotide polymorphism arrays, has been applied in hematologic malignancies to detect deletions, amplifications, and loss of heterozygosity (LOH) at high resolution. An inherent challenge of such studies lies in correctly distinguishing somatically acquired, cancer-specific lesions from patient-specific inherited copy number variations or segments of homozygosity. Failure to include appropriate normal DNA reference samples for each patient in retrospective or prospective studies makes it difficult to identify small somatic deletions not evident by standard cytogenetic analysis. In addition, the lack of proper controls can also lead to vastly overestimated frequencies of LOH without accompanying loss of DNA copies, so-called copy-neutral LOH. Here we use examples from patients with myeloid malignancies to demonstrate the superiority of matched tumor and normal DNA samples (paired studies) over multiple unpaired samples with respect to reducing false discovery rates in high-resolution single nucleotide polymorphism array analysis. Comparisons between matched tumor and normal samples will continue to be critical as the field moves from high resolution array analysis to deep sequencing to detect abnormalities in the cancer genome.",
			"category": 2,
			"name": "Heinrichs Stefan,2010"
		},
		{
			"PMID": 20299530,
			"title": "Progressive 3q amplification consistently targets SOX2 in preinvasive squamous lung cancer.",
			"journal": "American journal of respiratory and critical care medicine",
			"authorList": [
				"McCaughan Frank",
				"Pole Jessica C M",
				"Bankier Alan T",
				"Konfortov Bernard A",
				"Carroll Bernadette",
				"Falzon Mary",
				"Rabbitts Terence H",
				"George P Jeremy",
				"Dear Paul H",
				"Rabbitts Pamela H"
			],
			"DOI": "10.1164/rccm.201001-0005OC",
			"date": "2010-08-02",
			"PMC": "",
			"citation": "",
			"abstract": "Amplification of distal 3q is the most common genomic aberration in squamous lung cancer (SQC). SQC develops in a multistage progression from normal bronchial epithelium through dysplasia to invasive disease. Identifying the key driver events in the early pathogenesis of SQC will facilitate the search for predictive molecular biomarkers and the identification of novel molecular targets for chemoprevention and therapeutic strategies. For technical reasons, previous attempts to analyze 3q amplification in preinvasive lesions have focused on small numbers of predetermined candidate loci rather than an unbiased survey of copy-number variation.",
			"category": 2,
			"name": "McCaughan Frank,2010"
		},
		{
			"PMID": 20236477,
			"title": "High-throughput analysis of chromosome translocations and other genome rearrangements in epithelial cancers.",
			"journal": "Genome medicine",
			"authorList": [
				"Newman Scott",
				"Edwards Paul Aw"
			],
			"DOI": "10.1186/gm140",
			"date": "2011-07-14",
			"PMC": "",
			"citation": "",
			"abstract": "Genes that are broken or fused by structural changes to the genome are an important class of mutation in the leukemias and sarcomas but have been largely overlooked in the common epithelial cancers. Large-scale sequencing is changing our perceptions of the cancer genome, and it is now being applied to structural changes, using the 'paired end' strategy. This reveals more clearly than before the extent to which many cancer genomes are rearranged and how much these rearrangements contribute to the mutational burden of epithelial tumors. In particular, there are probably many fusion genes, analogous to those found in leukemias, to be found in common cancers, such as breast carcinoma, and some of these will prove to be important in cancer diagnosis and treatment.",
			"category": 2,
			"name": "Newman Scott,2011"
		},
		{
			"PMID": 20208995,
			"title": "Increasing alternative promoter repertories is positively associated with differential expression and disease susceptibility.",
			"journal": "PloS one",
			"authorList": [
				"Liu Song"
			],
			"DOI": "10.1371/journal.pone.0009482",
			"date": "2011-01-11",
			"PMC": "",
			"citation": "",
			"abstract": "Alternative Promoter (AP) usages have been shown to enable diversified transcriptional regulation of individual gene in a context-specific (e.g., pathway, cell lineage, tissue type, and development stage et. ac.) way. Aberrant uses of APs have been directly linked to mechanism of certain human diseases. However, whether or not there exists a general link between a gene's AP repertoire and its expression diversity is currently unknown. The general relation between a gene's AP repertoire and its disease susceptibility also remains largely unexplored.",
			"category": 2,
			"name": "Liu Song,2011"
		},
		{
			"PMID": 20194951,
			"title": "An effective model for natural selection in promoters.",
			"journal": "Genome research",
			"authorList": [
				"Hoffman Michael M",
				"Birney Ewan"
			],
			"DOI": "10.1101/gr.096719.109",
			"date": "2010-08-23",
			"PMC": "",
			"citation": "",
			"abstract": "We have produced an evolutionary model for promoters, analogous to the commonly used synonymous/nonsynonymous mutation models for protein-coding sequences. Although our model, called Sunflower, relies on some simple assumptions, it captures enough of the biology of transcription factor action to show clear correlation with other biological features. Sunflower predicts a binding profile of transcription factors to DNA sequences, in which different factors compete for the same potential binding sites. The parametrized model simultaneously estimates a continuous measurement of binding occupancy across the genomic sequence for each factor. We can then introduce a localized mutation, rerun the binding model, and record the difference in binding profiles. A single mutation can alter interactions both upstream and downstream of its position due to potential overlapping binding sites, and our statistic captures this domino effect. Over evolutionary time, we observe a clear excess of low-scoring mutations fixed in promoters, consistent with most changes being neutral. However, this is not consistent across all promoters, and some promoters show more rapid divergence. This divergence often occurs in the presence of relatively constant protein-coding divergence. Interestingly, different classes of promoters show different sensitivity to mutations, with phosphorylation-related genes having promoters inherently more sensitive to mutations than immune genes. Although there have previously been a number of models attempting to handle transcription factor binding, Sunflower provides a richer biological model, incorporating weak binding sites and the possibility of competition. The results show the first clear correlations between such a model and evolutionary processes.",
			"category": 2,
			"name": "Hoffman Michael M,2010"
		},
		{
			"PMID": 20182602,
			"title": "TP53 mutations in human cancers: origins, consequences, and clinical use.",
			"journal": "Cold Spring Harbor perspectives in biology",
			"authorList": [
				"Olivier Magali",
				"Hollstein Monica",
				"Hainaut Pierre"
			],
			"DOI": "10.1101/cshperspect.a001008",
			"date": "2010-09-29",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic mutations in the TP53 gene are one of the most frequent alterations in human cancers, and germline mutations are the underlying cause of Li-Fraumeni syndrome, which predisposes to a wide spectrum of early-onset cancers. Most mutations are single-base substitutions distributed throughout the coding sequence. Their diverse types and positions may inform on the nature of mutagenic mechanisms involved in cancer etiology. TP53 mutations are also potential prognostic and predictive markers, as well as targets for pharmacological intervention. All mutations found in human cancers are compiled in the IARC TP53 Database (http://www-p53.iarc.fr/). A human TP53 knockin mouse model (Hupki mouse) provides an experimental model to study mutagenesis in the context of a human TP53 sequence. Here, we summarize current knowledge on TP53 gene variations observed in human cancers and populations, and current clinical applications derived from this knowledge.",
			"category": 2,
			"name": "Olivier Magali,2010"
		},
		{
			"PMID": 20179022,
			"title": "Integrative analysis of the melanoma transcriptome.",
			"journal": "Genome research",
			"authorList": [
				"Berger Michael F",
				"Levin Joshua Z",
				"Vijayendran Krishna",
				"Sivachenko Andrey",
				"Adiconis Xian",
				"Maguire Jared",
				"Johnson Laura A",
				"Robinson James",
				"Verhaak Roel G",
				"Sougnez Carrie",
				"Onofrio Robert C",
				"Ziaugra Liuda",
				"Cibulskis Kristian",
				"Laine Elisabeth",
				"Barretina Jordi",
				"Winckler Wendy",
				"Fisher David E",
				"Getz Gad",
				"Meyerson Matthew",
				"Jaffe David B",
				"Gabriel Stacey B",
				"Lander Eric S",
				"Dummer Reinhard",
				"Gnirke Andreas",
				"Nusbaum Chad",
				"Garraway Levi A"
			],
			"DOI": "10.1101/gr.103697.109",
			"date": "2010-08-06",
			"PMC": "",
			"citation": "",
			"abstract": "Global studies of transcript structure and abundance in cancer cells enable the systematic discovery of aberrations that contribute to carcinogenesis, including gene fusions, alternative splice isoforms, and somatic mutations. We developed a systematic approach to characterize the spectrum of cancer-associated mRNA alterations through integration of transcriptomic and structural genomic data, and we applied this approach to generate new insights into melanoma biology. Using paired-end massively parallel sequencing of cDNA (RNA-seq) together with analyses of high-resolution chromosomal copy number data, we identified 11 novel melanoma gene fusions produced by underlying genomic rearrangements, as well as 12 novel readthrough transcripts. We mapped these chimeric transcripts to base-pair resolution and traced them to their genomic origins using matched chromosomal copy number information. We also used these data to discover and validate base-pair mutations that accumulated in these melanomas, revealing a surprisingly high rate of somatic mutation and lending support to the notion that point mutations constitute the major driver of melanoma progression. Taken together, these results may indicate new avenues for target discovery in melanoma, while also providing a template for large-scale transcriptome studies across many tumor types.",
			"category": 2,
			"name": "Berger Michael F,2010"
		},
		{
			"PMID": 20177914,
			"title": "Double endoscopic intraluminal surgery: superior to ESD for early gastric cancer?",
			"journal": "Surgical endoscopy",
			"authorList": [
				"Fatourou E",
				"Papaziogas B"
			],
			"DOI": "10.1007/s00464-010-0957-6",
			"date": "2011-02-03",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Fatourou E,2011"
		},
		{
			"PMID": 20174472,
			"title": "Tumor transcriptome sequencing reveals allelic expression imbalances associated with copy number alterations.",
			"journal": "PloS one",
			"authorList": [
				"Tuch Brian B",
				"Laborde Rebecca R",
				"Xu Xing",
				"Gu Jian",
				"Chung Christina B",
				"Monighetti Cinna K",
				"Stanley Sarah J",
				"Olsen Kerry D",
				"Kasperbauer Jan L",
				"Moore Eric J",
				"Broomer Adam J",
				"Tan Ruoying",
				"Brzoska Pius M",
				"Muller Matthew W",
				"Siddiqui Asim S",
				"Asmann Yan W",
				"Sun Yongming",
				"Kuersten Scott",
				"Barker Melissa A",
				"De La Vega Francisco M",
				"Smith David I"
			],
			"DOI": "10.1371/journal.pone.0009317",
			"date": "2010-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "Due to growing throughput and shrinking cost, massively parallel sequencing is rapidly becoming an attractive alternative to microarrays for the genome-wide study of gene expression and copy number alterations in primary tumors. The sequencing of transcripts (RNA-Seq) should offer several advantages over microarray-based methods, including the ability to detect somatic mutations and accurately measure allele-specific expression. To investigate these advantages we have applied a novel, strand-specific RNA-Seq method to tumors and matched normal tissue from three patients with oral squamous cell carcinomas. Additionally, to better understand the genomic determinants of the gene expression changes observed, we have sequenced the tumor and normal genomes of one of these patients. We demonstrate here that our RNA-Seq method accurately measures allelic imbalance and that measurement on the genome-wide scale yields novel insights into cancer etiology. As expected, the set of genes differentially expressed in the tumors is enriched for cell adhesion and differentiation functions, but, unexpectedly, the set of allelically imbalanced genes is also enriched for these same cancer-related functions. By comparing the transcriptomic perturbations observed in one patient to his underlying normal and tumor genomes, we find that allelic imbalance in the tumor is associated with copy number mutations and that copy number mutations are, in turn, strongly associated with changes in transcript abundance. These results support a model in which allele-specific deletions and duplications drive allele-specific changes in gene expression in the developing tumor.",
			"category": 2,
			"name": "Tuch Brian B,2010"
		},
		{
			"PMID": 20169195,
			"title": "Automated network analysis identifies core pathways in glioblastoma.",
			"journal": "PloS one",
			"authorList": [
				"Cerami Ethan",
				"Demir Emek",
				"Schultz Nikolaus",
				"Taylor Barry S",
				"Sander Chris"
			],
			"DOI": "10.1371/journal.pone.0008918",
			"date": "2010-09-30",
			"PMC": "",
			"citation": "",
			"abstract": "Glioblastoma multiforme (GBM) is the most common and aggressive type of brain tumor in humans and the first cancer with comprehensive genomic profiles mapped by The Cancer Genome Atlas (TCGA) project. A central challenge in large-scale genome projects, such as the TCGA GBM project, is the ability to distinguish cancer-causing \"driver\" mutations from passively selected \"passenger\" mutations.",
			"category": 2,
			"name": "Cerami Ethan,2010"
		},
		{
			"PMID": 20164920,
			"title": "The landscape of somatic copy-number alteration across human cancers.",
			"journal": "Nature",
			"authorList": [
				"Beroukhim Rameen",
				"Mermel Craig H",
				"Porter Dale",
				"Wei Guo",
				"Raychaudhuri Soumya",
				"Donovan Jerry",
				"Barretina Jordi",
				"Boehm Jesse S",
				"Dobson Jennifer",
				"Urashima Mitsuyoshi",
				"Mc Henry Kevin T",
				"Pinchback Reid M",
				"Ligon Azra H",
				"Cho Yoon-Jae",
				"Haery Leila",
				"Greulich Heidi",
				"Reich Michael",
				"Winckler Wendy",
				"Lawrence Michael S",
				"Weir Barbara A",
				"Tanaka Kumiko E",
				"Chiang Derek Y",
				"Bass Adam J",
				"Loo Alice",
				"Hoffman Carter",
				"Prensner John",
				"Liefeld Ted",
				"Gao Qing",
				"Yecies Derek",
				"Signoretti Sabina",
				"Maher Elizabeth",
				"Kaye Frederic J",
				"Sasaki Hidefumi",
				"Tepper Joel E",
				"Fletcher Jonathan A",
				"Tabernero Josep",
				"Baselga Jos\u00e9",
				"Tsao Ming-Sound",
				"Demichelis Francesca",
				"Rubin Mark A",
				"Janne Pasi A",
				"Daly Mark J",
				"Nucera Carmelo",
				"Levine Ross L",
				"Ebert Benjamin L",
				"Gabriel Stacey",
				"Rustgi Anil K",
				"Antonescu Cristina R",
				"Ladanyi Marc",
				"Letai Anthony",
				"Garraway Levi A",
				"Loda Massimo",
				"Beer David G",
				"True Lawrence D",
				"Okamoto Aikou",
				"Pomeroy Scott L",
				"Singer Samuel",
				"Golub Todd R",
				"Lander Eric S",
				"Getz Gad",
				"Sellers William R",
				"Meyerson Matthew"
			],
			"DOI": "10.1038/nature08822",
			"date": "2010-03-29",
			"PMC": "",
			"citation": "",
			"abstract": "A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-kappaBeta pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types.",
			"category": 2,
			"name": "Beroukhim Rameen,2010"
		},
		{
			"PMID": 20164919,
			"title": "Signatures of mutation and selection in the cancer genome.",
			"journal": "Nature",
			"authorList": [
				"Bignell Graham R",
				"Greenman Chris D",
				"Davies Helen",
				"Butler Adam P",
				"Edkins Sarah",
				"Andrews Jenny M",
				"Buck Gemma",
				"Chen Lina",
				"Beare David",
				"Latimer Calli",
				"Widaa Sara",
				"Hinton Jonathon",
				"Fahey Ciara",
				"Fu Beiyuan",
				"Swamy Sajani",
				"Dalgliesh Gillian L",
				"Teh Bin T",
				"Deloukas Panos",
				"Yang Fengtang",
				"Campbell Peter J",
				"Futreal P Andrew",
				"Stratton Michael R"
			],
			"DOI": "10.1038/nature08768",
			"date": "2010-03-29",
			"PMC": "",
			"citation": "",
			"abstract": "The cancer genome is moulded by the dual processes of somatic mutation and selection. Homozygous deletions in cancer genomes occur over recessive cancer genes, where they can confer selective growth advantage, and over fragile sites, where they are thought to reflect an increased local rate of DNA breakage. However, most homozygous deletions in cancer genomes are unexplained. Here we identified 2,428 somatic homozygous deletions in 746 cancer cell lines. These overlie 11% of protein-coding genes that, therefore, are not mandatory for survival of human cells. We derived structural signatures that distinguish between homozygous deletions over recessive cancer genes and fragile sites. Application to clusters of unexplained homozygous deletions suggests that many are in regions of inherent fragility, whereas a small subset overlies recessive cancer genes. The results illustrate how structural signatures can be used to distinguish between the influences of mutation and selection in cancer genomes. The extensive copy number, genotyping, sequence and expression data available for this large series of publicly available cancer cell lines renders them informative reagents for future studies of cancer biology and drug discovery.",
			"category": 2,
			"name": "Bignell Graham R,2010"
		},
		{
			"PMID": 20161678,
			"title": "Next-generation sequencing of cancer genomes: back to the future.",
			"journal": "Personalized medicine",
			"authorList": [
				"Walter Matthew J",
				"Graubert Timothy A",
				"Dipersio John F",
				"Mardis Elaine R",
				"Wilson Richard K",
				"Ley Timothy J"
			],
			"DOI": "",
			"date": "2024-04-19",
			"PMC": "",
			"citation": "",
			"abstract": "The systematic karyotyping of bone marrow cells was the first genomic approach used to personalize therapy for patients with leukemia. The paradigm established by cytogenetic studies in leukemia (from gene discovery to therapeutic intervention) now has the potential to be rapidly extended with the use of whole-genome sequencing approaches for cancer, which are now possible. We are now entering a period of exponential growth in cancer gene discovery that will provide many novel therapeutic targets for a large number of cancer types. Establishing the pathogenetic relevance of individual mutations is a major challenge that must be solved. However, after thousands of cancer genomes have been sequenced, the genetic rules of cancer will become known and new approaches for diagnosis, risk stratification and individualized treatment of cancer patients will surely follow.",
			"category": 2,
			"name": "Walter Matthew J,2024"
		},
		{
			"PMID": 20130864,
			"title": "Letter to the editor: Breast cancer in young women in Africa: are there genetic and clinical differences with European ancestry patients?",
			"journal": "World journal of surgery",
			"authorList": [
				"Baltogiannis Georgios",
				"Roukos D H"
			],
			"DOI": "10.1007/s00268-010-0436-1",
			"date": "2010-11-01",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Baltogiannis Georgios,2010"
		},
		{
			"PMID": 20130035,
			"title": "SNVMix: predicting single nucleotide variants from next-generation sequencing of tumors.",
			"journal": "Bioinformatics (Oxford, England)",
			"authorList": [
				"Goya Rodrigo",
				"Sun Mark G F",
				"Morin Ryan D",
				"Leung Gillian",
				"Ha Gavin",
				"Wiegand Kimberley C",
				"Senz Janine",
				"Crisan Anamaria",
				"Marra Marco A",
				"Hirst Martin",
				"Huntsman David",
				"Murphy Kevin P",
				"Aparicio Sam",
				"Shah Sohrab P"
			],
			"DOI": "10.1093/bioinformatics/btq040",
			"date": "2010-06-21",
			"PMC": "",
			"citation": "",
			"abstract": "Next-generation sequencing (NGS) has enabled whole genome and transcriptome single nucleotide variant (SNV) discovery in cancer. NGS produces millions of short sequence reads that, once aligned to a reference genome sequence, can be interpreted for the presence of SNVs. Although tools exist for SNV discovery from NGS data, none are specifically suited to work with data from tumors, where altered ploidy and tumor cellularity impact the statistical expectations of SNV discovery.",
			"category": 2,
			"name": "Goya Rodrigo,2010"
		},
		{
			"PMID": 20108112,
			"title": "Integrating the multiple dimensions of genomic and epigenomic landscapes of cancer.",
			"journal": "Cancer metastasis reviews",
			"authorList": [
				"Chari Raj",
				"Thu Kelsie L",
				"Wilson Ian M",
				"Lockwood William W",
				"Lonergan Kim M",
				"Coe Bradley P",
				"Malloff Chad A",
				"Gazdar Adi F",
				"Lam Stephen",
				"Garnis Cathie",
				"MacAulay Calum E",
				"Alvarez Carlos E",
				"Lam Wan L"
			],
			"DOI": "10.1007/s10555-010-9199-2",
			"date": "2010-04-27",
			"PMC": "",
			"citation": "",
			"abstract": "Advances in high-throughput, genome-wide profiling technologies have allowed for an unprecedented view of the cancer genome landscape. Specifically, high-density microarrays and sequencing-based strategies have been widely utilized to identify genetic (such as gene dosage, allelic status, and mutations in gene sequence) and epigenetic (such as DNA methylation, histone modification, and microRNA) aberrations in cancer. Although the application of these profiling technologies in unidimensional analyses has been instrumental in cancer gene discovery, genes affected by low-frequency events are often overlooked. The integrative approach of analyzing parallel dimensions has enabled the identification of (a) genes that are often disrupted by multiple mechanisms but at low frequencies by any one mechanism and (b) pathways that are often disrupted at multiple components but at low frequencies at individual components. These benefits of using an integrative approach illustrate the concept that the whole is greater than the sum of its parts. As efforts have now turned toward parallel and integrative multidimensional approaches for studying the cancer genome landscape in hopes of obtaining a more insightful understanding of the key genes and pathways driving cancer cells, this review describes key findings disseminating from such high-throughput, integrative analyses, including contributions to our understanding of causative genetic events in cancer cell biology.",
			"category": 2,
			"name": "Chari Raj,2010"
		},
		{
			"PMID": 20079948,
			"title": "Lung cancer cell lines: Useless artifacts or invaluable tools for medical science?",
			"journal": "Lung cancer (Amsterdam, Netherlands)",
			"authorList": [
				"Gazdar Adi F",
				"Gao Boning",
				"Minna John D"
			],
			"DOI": "10.1016/j.lungcan.2009.12.005",
			"date": "2010-09-21",
			"PMC": "",
			"citation": "",
			"abstract": "Multiple cell lines (estimated at 300-400) have been established from human small cell (SCLC) and non-small cell lung cancers (NSCLC). These cell lines have been widely dispersed to and used by the scientific community worldwide, with over 8000 citations resulting from their study. However, there remains considerable skepticism on the part of the scientific community as to the validity of research resulting from their use. These questions center around the genomic instability of cultured cells, lack of differentiation of cultured cells and absence of stromal-vascular-inflammatory cell compartments. In this report we discuss the advantages and disadvantages of the use of cell lines, address the issues of instability and lack of differentiation. Perhaps the most important finding is that every important, recurrent genetic and epigenetic change including gene mutations, deletions, amplifications, translocations and methylation-induced gene silencing found in tumors has been identified in cell lines and vice versa. These \"driver mutations\" represented in cell lines offer opportunities for biological characterization and application to translational research. Another potential shortcoming of cell lines is the difficulty of studying multistage pathogenesis in vitro. To overcome this problem, we have developed cultures from central and peripheral airways that serve as models for the multistage pathogenesis of tumors arising in these two very different compartments. Finally the issue of cell line contamination must be addressed and safeguarded against. A full understanding of the advantages and shortcomings of cell lines is required for the investigator to derive the maximum benefit from their use.",
			"category": 2,
			"name": "Gazdar Adi F,2010"
		},
		{
			"PMID": 20072650,
			"title": "Genetic and epigenetic inactivation of Kruppel-like factor 4 in medulloblastoma.",
			"journal": "Neoplasia (New York, N.Y.)",
			"authorList": [
				"Nakahara Yukiko",
				"Northcott Paul A",
				"Li Meihua",
				"Kongkham Paul N",
				"Smith Christian",
				"Yan Hai",
				"Croul Sidney",
				"Ra Young-Shin",
				"Eberhart Charles",
				"Huang Annie",
				"Bigner Darell",
				"Grajkowska Wesia",
				"Van Meter Timothy",
				"Rutka James T",
				"Taylor Michael D"
			],
			"DOI": "",
			"date": "2010-05-10",
			"PMC": "",
			"citation": "",
			"abstract": "Although medulloblastoma is the most common pediatric malignant brain tumor, its molecular underpinnings are largely unknown. We have identified rare, recurrent homozygous deletions of Kruppel-like Factor 4 (KLF4) in medulloblastoma using high-resolution single nucleotide polymorphism arrays, digital karyotyping, and genomic real-time polymerase chain reaction (PCR). Furthermore, we show that there is loss of physiological KLF4 expression in more than 40% of primary medulloblastomas both at the RNA and protein levels. Medulloblastoma cell lines drastically increase the expression of KLF4 in response to the demethylating agent 5-azacytidine and demonstrate dense methylation of the promoter CpG island by bisulfite sequencing. Methylation-specific PCR targeting the KLF4 promoter demonstrates CpG methylation in approximately 16% of primary medulloblastomas. Reexpression of KLF4 in the D283 medulloblastoma cell line results in significant growth suppression both in vitro and in vivo. We conclude that KLF4 is inactivated by either genetic or epigenetic mechanisms in a large subset of medulloblastomas and that it likely functions as a tumor suppressor gene in the pathogenesis of medulloblastoma.",
			"category": 2,
			"name": "Nakahara Yukiko,2010"
		},
		{
			"PMID": 20068150,
			"title": "Insertional mutagenesis in mice deficient for p15Ink4b, p16Ink4a, p21Cip1, and p27Kip1 reveals cancer gene interactions and correlations with tumor phenotypes.",
			"journal": "Cancer research",
			"authorList": [
				"Kool Jaap",
				"Uren Anthony G",
				"Martins Carla P",
				"Sie Daoud",
				"de Ridder Jeroen",
				"Turner Geoffrey",
				"van Uitert Miranda",
				"Matentzoglu Konstantin",
				"Lagcher Wendy",
				"Krimpenfort Paul",
				"Gadiot Jules",
				"Pritchard Colin",
				"Lenz Jack",
				"Lund Anders H",
				"Jonkers Jos",
				"Rogers Jane",
				"Adams David J",
				"Wessels Lodewyk",
				"Berns Anton",
				"van Lohuizen Maarten"
			],
			"DOI": "10.1158/0008-5472.CAN-09-2736",
			"date": "2010-03-09",
			"PMC": "",
			"citation": "",
			"abstract": "The cyclin dependent kinase (CDK) inhibitors p15, p16, p21, and p27 are frequently deleted, silenced, or downregulated in many malignancies. Inactivation of CDK inhibitors predisposes mice to tumor development, showing that these genes function as tumor suppressors. Here, we describe high-throughput murine leukemia virus insertional mutagenesis screens in mice that are deficient for one or two CDK inhibitors. We retrieved 9,117 retroviral insertions from 476 lymphomas to define hundreds of loci that are mutated more frequently than expected by chance. Many of these loci are skewed toward a specific genetic context of predisposing germline and somatic mutations. We also found associations between these loci with gender, age of tumor onset, and lymphocyte lineage (B or T cell). Comparison of retroviral insertion sites with single nucleotide polymorphisms associated with chronic lymphocytic leukemia revealed a significant overlap between the datasets. Together, our findings highlight the importance of genetic context within large-scale mutation detection studies, and they show a novel use for insertional mutagenesis data in prioritizing disease-associated genes that emerge from genome-wide association studies.",
			"category": 2,
			"name": "Kool Jaap,2010"
		},
		{
			"PMID": 20065079,
			"title": "Genetic lesions in chronic lymphocytic leukemia: what's ready for prime time use?",
			"journal": "Haematologica",
			"authorList": [
				"Moreno Carol",
				"Montserrat Emili"
			],
			"DOI": "10.3324/haematol.2009.016873",
			"date": "2011-08-05",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Moreno Carol,2011"
		},
		{
			"PMID": 20051673,
			"title": "Translational research in cancer genetics: the road less traveled.",
			"journal": "Public health genomics",
			"authorList": [
				"Schully S D",
				"Benedicto C B",
				"Gillanders E M",
				"Wang S S",
				"Khoury M J"
			],
			"DOI": "10.1159/000272897",
			"date": "2011-04-19",
			"PMC": "",
			"citation": "",
			"abstract": "Gene discoveries in cancer have the potential for clinical and public health applications. To take advantage of such discoveries, a translational research agenda is needed to take discoveries from the bench to population health impact. To assess the current status of translational research in cancer genetics, we analyzed the extramural grant portfolio of the National Cancer Institute (NCI) from Fiscal Year 2007, as well as the cancer genetic research articles published in 2007. We classified both funded grants and publications as follows: T0 as discovery research; T1 as research to develop a candidate health application (e.g., test or therapy); T2 as research that evaluates a candidate application and develops evidence-based recommendations; T3 as research that assesses how to integrate an evidence-based recommendation into cancer care and prevention; and T4 as research that assesses health outcomes and population impact. We found that 1.8% of the grant portfolio and 0.6% of the published literature was T2 research or beyond. In addition to discovery research in cancer genetics, a translational research infrastructure is urgently needed to methodically evaluate and translate gene discoveries for cancer care and prevention.",
			"category": 2,
			"name": "Schully S D,2011"
		},
		{
			"PMID": 20043280,
			"title": "Decoding the evolution of a breast cancer genome.",
			"journal": "EMBO molecular medicine",
			"authorList": [
				"Bedard Philippe L",
				"Sotiriou Christos"
			],
			"DOI": "10.1002/emmm.200900054",
			"date": "2010-03-10",
			"PMC": "",
			"citation": "",
			"abstract": "Shah et al have recently reported the first successful sequencing of the entire genome of a solid tumour (Shah et al, 2009). Philippe Bedard and Christos Sotiriou analyse their findings as well as the challenges of applying the study of cancer genomes to clinical cancer care.",
			"category": 2,
			"name": "Bedard Philippe L,2010"
		},
		{
			"PMID": 20033038,
			"title": "Complex landscapes of somatic rearrangement in human breast cancer genomes.",
			"journal": "Nature",
			"authorList": [
				"Stephens Philip J",
				"McBride David J",
				"Lin Meng-Lay",
				"Varela Ignacio",
				"Pleasance Erin D",
				"Simpson Jared T",
				"Stebbings Lucy A",
				"Leroy Catherine",
				"Edkins Sarah",
				"Mudie Laura J",
				"Greenman Chris D",
				"Jia Mingming",
				"Latimer Calli",
				"Teague Jon W",
				"Lau King Wai",
				"Burton John",
				"Quail Michael A",
				"Swerdlow Harold",
				"Churcher Carol",
				"Natrajan Rachael",
				"Sieuwerts Anieta M",
				"Martens John W M",
				"Silver Daniel P",
				"Langer\u00f8d Anita",
				"Russnes Hege E G",
				"Foekens John A",
				"Reis-Filho Jorge S",
				"van 't Veer Laura",
				"Richardson Andrea L",
				"B\u00f8rresen-Dale Anne-Lise",
				"Campbell Peter J",
				"Futreal P Andrew",
				"Stratton Michael R"
			],
			"DOI": "10.1038/nature08645",
			"date": "2010-01-04",
			"PMC": "",
			"citation": "",
			"abstract": "Multiple somatic rearrangements are often found in cancer genomes; however, the underlying processes of rearrangement and their contribution to cancer development are poorly characterized. Here we use a paired-end sequencing strategy to identify somatic rearrangements in breast cancer genomes. There are more rearrangements in some breast cancers than previously appreciated. Rearrangements are more frequent over gene footprints and most are intrachromosomal. Multiple rearrangement architectures are present, but tandem duplications are particularly common in some cancers, perhaps reflecting a specific defect in DNA maintenance. Short overlapping sequences at most rearrangement junctions indicate that these have been mediated by non-homologous end-joining DNA repair, although varying sequence patterns indicate that multiple processes of this type are operative. Several expressed in-frame fusion genes were identified but none was recurrent. The study provides a new perspective on cancer genomes, highlighting the diversity of somatic rearrangements and their potential contribution to cancer development.",
			"category": 2,
			"name": "Stephens Philip J,2010"
		},
		{
			"PMID": 20030863,
			"title": "Next-generation sequencing.",
			"journal": "Breast cancer research : BCR",
			"authorList": [
				"Reis-Filho Jorge S"
			],
			"DOI": "10.1186/bcr2431",
			"date": "2010-05-03",
			"PMC": "",
			"citation": "",
			"abstract": "Next-generation sequencing (also known as massively parallel sequencing) technologies are revolutionising our ability to characterise cancers at the genomic, transcriptomic and epigenetic levels. Cataloguing all mutations, copy number aberrations and somatic rearrangements in an entire cancer genome at base pair resolution can now be performed in a matter of weeks. Furthermore, massively parallel sequencing can be used as a means for unbiased transcriptomic analysis of mRNAs, small RNAs and noncoding RNAs, genome-wide methylation assays and high-throughput chromatin immunoprecipitation assays. Here, I discuss the potential impact of this technology on breast cancer research and the challenges that come with this technological breakthrough.",
			"category": 2,
			"name": "Reis-Filho Jorge S,2010"
		},
		{
			"PMID": 20016488,
			"title": "A small-cell lung cancer genome with complex signatures of tobacco exposure.",
			"journal": "Nature",
			"authorList": [
				"Pleasance Erin D",
				"Stephens Philip J",
				"O'Meara Sarah",
				"McBride David J",
				"Meynert Alison",
				"Jones David",
				"Lin Meng-Lay",
				"Beare David",
				"Lau King Wai",
				"Greenman Chris",
				"Varela Ignacio",
				"Nik-Zainal Serena",
				"Davies Helen R",
				"Ordo\u00f1ez Gonzalo R",
				"Mudie Laura J",
				"Latimer Calli",
				"Edkins Sarah",
				"Stebbings Lucy",
				"Chen Lina",
				"Jia Mingming",
				"Leroy Catherine",
				"Marshall John",
				"Menzies Andrew",
				"Butler Adam",
				"Teague Jon W",
				"Mangion Jonathon",
				"Sun Yongming A",
				"McLaughlin Stephen F",
				"Peckham Heather E",
				"Tsung Eric F",
				"Costa Gina L",
				"Lee Clarence C",
				"Minna John D",
				"Gazdar Adi",
				"Birney Ewan",
				"Rhodes Michael D",
				"McKernan Kevin J",
				"Stratton Michael R",
				"Futreal P Andrew",
				"Campbell Peter J"
			],
			"DOI": "10.1038/nature08629",
			"date": "2010-02-24",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer is driven by mutation. Worldwide, tobacco smoking is the principal lifestyle exposure that causes cancer, exerting carcinogenicity through >60 chemicals that bind and mutate DNA. Using massively parallel sequencing technology, we sequenced a small-cell lung cancer cell line, NCI-H209, to explore the mutational burden associated with tobacco smoking. A total of 22,910 somatic substitutions were identified, including 134 in coding exons. Multiple mutation signatures testify to the cocktail of carcinogens in tobacco smoke and their proclivities for particular bases and surrounding sequence context. Effects of transcription-coupled repair and a second, more general, expression-linked repair pathway were evident. We identified a tandem duplication that duplicates exons 3-8 of CHD7 in frame, and another two lines carrying PVT1-CHD7 fusion genes, indicating that CHD7 may be recurrently rearranged in this disease. These findings illustrate the potential for next-generation sequencing to provide unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer.",
			"category": 2,
			"name": "Pleasance Erin D,2010"
		},
		{
			"PMID": 20016485,
			"title": "A comprehensive catalogue of somatic mutations from a human cancer genome.",
			"journal": "Nature",
			"authorList": [
				"Pleasance Erin D",
				"Cheetham R Keira",
				"Stephens Philip J",
				"McBride David J",
				"Humphray Sean J",
				"Greenman Chris D",
				"Varela Ignacio",
				"Lin Meng-Lay",
				"Ord\u00f3\u00f1ez Gonzalo R",
				"Bignell Graham R",
				"Ye Kai",
				"Alipaz Julie",
				"Bauer Markus J",
				"Beare David",
				"Butler Adam",
				"Carter Richard J",
				"Chen Lina",
				"Cox Anthony J",
				"Edkins Sarah",
				"Kokko-Gonzales Paula I",
				"Gormley Niall A",
				"Grocock Russell J",
				"Haudenschild Christian D",
				"Hims Matthew M",
				"James Terena",
				"Jia Mingming",
				"Kingsbury Zoya",
				"Leroy Catherine",
				"Marshall John",
				"Menzies Andrew",
				"Mudie Laura J",
				"Ning Zemin",
				"Royce Tom",
				"Schulz-Trieglaff Ole B",
				"Spiridou Anastassia",
				"Stebbings Lucy A",
				"Szajkowski Lukasz",
				"Teague Jon",
				"Williamson David",
				"Chin Lynda",
				"Ross Mark T",
				"Campbell Peter J",
				"Bentley David R",
				"Futreal P Andrew",
				"Stratton Michael R"
			],
			"DOI": "10.1038/nature08658",
			"date": "2010-02-24",
			"PMC": "",
			"citation": "",
			"abstract": "All cancers carry somatic mutations. A subset of these somatic alterations, termed driver mutations, confer selective growth advantage and are implicated in cancer development, whereas the remainder are passengers. Here we have sequenced the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The catalogue provides remarkable insights into the forces that have shaped this cancer genome. The dominant mutational signature reflects DNA damage due to ultraviolet light exposure, a known risk factor for malignant melanoma, whereas the uneven distribution of mutations across the genome, with a lower prevalence in gene footprints, indicates that DNA repair has been preferentially deployed towards transcribed regions. The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic.",
			"category": 2,
			"name": "Pleasance Erin D,2010"
		},
		{
			"PMID": 20012171,
			"title": "Biology of urothelial tumorigenesis: insights from genetically engineered mice.",
			"journal": "Cancer metastasis reviews",
			"authorList": [
				"Wu Xue-Ru"
			],
			"DOI": "10.1007/s10555-009-9189-4",
			"date": "2010-03-26",
			"PMC": "",
			"citation": "",
			"abstract": "Urothelium, one of the slowest cycling epithelia in the body, embodies a unique biological context for cellular transformation. Introduction of oncogenes into or removing tumor suppressor genes from the urothelial cells or a combination of both using the transgenic and/or knockout mouse approaches has provided useful insights into the molecular mechanisms of urothelial transformation and tumorigenesis. It is becoming increasingly clear that over-activation of the receptor tyrosine kinase (RTK) pathway, as exemplified by the constitutively activated Ha-ras oncogene, is both necessary and sufficient to initiate the low-grade, non-invasive urothelial carcinomas. Dosage of the mutated Ha-ras, but not concurrent inactivation of pro-senescence molecules p16Ink4a and p19Arf, dictates whether and when the low-grade urothelial carcinomas arise. Inactivation of both p53 and pRb, a prevailing paradigm previously proposed for muscle-invasive urothelial tumorigenesis, is found to be necessary but insufficient to initiate this urothelial carcinoma variant. Instead, downregulation in p53/pRb co-deficient urothelial cells of p107, a pRb family member, is associated with the genesis of the muscle-invasive bladder cancers. p53 deficiency also seems to be capable of cooperating with that of PTEN in eliciting invasive urothelial carcinomas. The genetically engineered mice have improved the molecular definition of the divergent pathways of urothelial tumorigenesis and progression, helped delineate the intricate crosstalk among different genetic alterations within a urothelium-specific context, identified new prognostic markers and novel therapeutic targets potentially applicable for clinical intervention, and provided in vivo platforms for testing preventive strategies of bladder cancer.",
			"category": 2,
			"name": "Wu Xue-Ru,2010"
		},
		{
			"PMID": 19966129,
			"title": "An alternative approach to medical genetics based on modern evolutionary biology. Part 5: epigenetics and genomics.",
			"journal": "Journal of the Royal Society of Medicine",
			"authorList": [
				"Ryan Frank P"
			],
			"DOI": "10.1258/jrsm.2009.090365",
			"date": "2010-01-28",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Ryan Frank P,2010"
		},
		{
			"PMID": 19906700,
			"title": "Network of Cancer Genes: a web resource to analyze duplicability, orthology and network properties of cancer genes.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Syed Adnan S",
				"D'Antonio Matteo",
				"Ciccarelli Francesca D"
			],
			"DOI": "10.1093/nar/gkp957",
			"date": "2010-02-01",
			"PMC": "",
			"citation": "",
			"abstract": "The Network of Cancer Genes (NCG) collects and integrates data on 736 human genes that are mutated in various types of cancer. For each gene, NCG provides information on duplicability, orthology, evolutionary appearance and topological properties of the encoded protein in a comprehensive version of the human protein-protein interaction network. NCG also stores information on all primary interactors of cancer proteins, thus providing a complete overview of 5357 proteins that constitute direct and indirect determinants of human cancer. With the constant delivery of results from the mutational screenings of cancer genomes, NCG represents a versatile resource for retrieving detailed information on particular cancer genes, as well as for identifying common properties of precompiled lists of cancer genes. NCG is freely available at: http://bio.ifom-ieo-campus.it/ncg.",
			"category": 2,
			"name": "Syed Adnan S,2010"
		},
		{
			"PMID": 19903760,
			"title": "Inferring tumor progression from genomic heterogeneity.",
			"journal": "Genome research",
			"authorList": [
				"Navin Nicholas",
				"Krasnitz Alexander",
				"Rodgers Linda",
				"Cook Kerry",
				"Meth Jennifer",
				"Kendall Jude",
				"Riggs Michael",
				"Eberling Yvonne",
				"Troge Jennifer",
				"Grubor Vladimir",
				"Levy Dan",
				"Lundin P\u00e4r",
				"M\u00e5n\u00e9r Susanne",
				"Zetterberg Anders",
				"Hicks James",
				"Wigler Michael"
			],
			"DOI": "10.1101/gr.099622.109",
			"date": "2010-03-25",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer progression in humans is difficult to infer because we do not routinely sample patients at multiple stages of their disease. However, heterogeneous breast tumors provide a unique opportunity to study human tumor progression because they still contain evidence of early and intermediate subpopulations in the form of the phylogenetic relationships. We have developed a method we call Sector-Ploidy-Profiling (SPP) to study the clonal composition of breast tumors. SPP involves macro-dissecting tumors, flow-sorting genomic subpopulations by DNA content, and profiling genomes using comparative genomic hybridization (CGH). Breast carcinomas display two classes of genomic structural variation: (1) monogenomic and (2) polygenomic. Monogenomic tumors appear to contain a single major clonal subpopulation with a highly stable chromosome structure. Polygenomic tumors contain multiple clonal tumor subpopulations, which may occupy the same sectors, or separate anatomic locations. In polygenomic tumors, we show that heterogeneity can be ascribed to a few clonal subpopulations, rather than a series of gradual intermediates. By comparing multiple subpopulations from different anatomic locations, we have inferred pathways of cancer progression and the organization of tumor growth.",
			"category": 2,
			"name": "Navin Nicholas,2010"
		},
		{
			"PMID": 19880382,
			"title": "KEGG for representation and analysis of molecular networks involving diseases and drugs.",
			"journal": "Nucleic acids research",
			"authorList": [
				"Kanehisa Minoru",
				"Goto Susumu",
				"Furumichi Miho",
				"Tanabe Mao",
				"Hirakawa Mika"
			],
			"DOI": "10.1093/nar/gkp896",
			"date": "2010-02-01",
			"PMC": "",
			"citation": "",
			"abstract": "Most human diseases are complex multi-factorial diseases resulting from the combination of various genetic and environmental factors. In the KEGG database resource (http://www.genome.jp/kegg/), diseases are viewed as perturbed states of the molecular system, and drugs as perturbants to the molecular system. Disease information is computerized in two forms: pathway maps and gene/molecule lists. The KEGG PATHWAY database contains pathway maps for the molecular systems in both normal and perturbed states. In the KEGG DISEASE database, each disease is represented by a list of known disease genes, any known environmental factors at the molecular level, diagnostic markers and therapeutic drugs, which may reflect the underlying molecular system. The KEGG DRUG database contains chemical structures and/or chemical components of all drugs in Japan, including crude drugs and TCM (Traditional Chinese Medicine) formulas, and drugs in the USA and Europe. This database also captures knowledge about two types of molecular networks: the interaction network with target molecules, metabolizing enzymes, other drugs, etc. and the chemical structure transformation network in the history of drug development. The new disease/drug information resource named KEGG MEDICUS can be used as a reference knowledge base for computational analysis of molecular networks, especially, by integrating large-scale experimental datasets.",
			"category": 2,
			"name": "Kanehisa Minoru,2010"
		},
		{
			"PMID": 19847258,
			"title": "The DNA-damage response in human biology and disease.",
			"journal": "Nature",
			"authorList": [
				"Jackson Stephen P",
				"Bartek Jiri"
			],
			"DOI": "10.1038/nature08467",
			"date": "2009-12-04",
			"PMC": "",
			"citation": "",
			"abstract": "The prime objective for every life form is to deliver its genetic material, intact and unchanged, to the next generation. This must be achieved despite constant assaults by endogenous and environmental agents on the DNA. To counter this threat, life has evolved several systems to detect DNA damage, signal its presence and mediate its repair. Such responses, which have an impact on a wide range of cellular events, are biologically significant because they prevent diverse human diseases. Our improving understanding of DNA-damage responses is providing new avenues for disease management.",
			"category": 2,
			"name": "Jackson Stephen P,2009"
		},
		{
			"PMID": 19811654,
			"title": "Molecular models for intrastrand DNA G-quadruplexes.",
			"journal": "BMC structural biology",
			"authorList": [
				"Fogolari Federico",
				"Haridas Haritha",
				"Corazza Alessandra",
				"Viglino Paolo",
				"Cor\u00e0 Davide",
				"Caselle Michele",
				"Esposito Gennaro",
				"Xodo Luigi E"
			],
			"DOI": "10.1186/1472-6807-9-64",
			"date": "2009-12-11",
			"PMC": "",
			"citation": "",
			"abstract": "Independent surveys of human gene promoter regions have demonstrated an overrepresentation of G(3)X(n1)G3X(n2)G(3)X(n3)G(3) motifs which are known to be capable of forming intrastrand quadruple helix structures. In spite of the widely recognized importance of G-quadruplex structures in gene regulation and growing interest around this unusual DNA structure, there are at present only few such structures available in the Nucleic Acid Database. In the present work we generate by molecular modeling feasible G-quadruplex structures which may be useful for interpretation of experimental data.",
			"category": 2,
			"name": "Fogolari Federico,2009"
		},
		{
			"PMID": 19805033,
			"title": "Evolution in health and medicine Sackler colloquium: Somatic evolutionary genomics: mutations during development cause highly variable genetic mosaicism with risk of cancer and neurodegeneration.",
			"journal": "Proceedings of the National Academy of Sciences of the United States of America",
			"authorList": [
				"Frank Steven A"
			],
			"DOI": "10.1073/pnas.0909343106",
			"date": "2010-03-10",
			"PMC": "",
			"citation": "",
			"abstract": "Somatic mutations must happen often during development because of the large number of cell divisions to expand from a single-cell zygote to a full organism. A mutation in development carries forward to all descendant cells, causing genetic mosaicism. Widespread genetic mosaicism may influence diseases that derive from a few genetically altered cells, such as cancer. I show how to predict the expected amount of mosaicism and the variation in mosaicism between individuals. I then calculate the predicted risk of cancer derived from developmental mutations. The calculations show that a significant fraction of cancer in later life likely arises from developmental mutations in early life. In addition, much of the variation in the risk of cancer between individuals may arise from variation in the degree of genetic mosaicism set in early life. I also suggest that certain types of neurodegeneration, such as amyotrophic lateral sclerosis (ALS), may derive from a small focus of genetically altered cells. If so, then the risk of ALS would be influenced by developmental mutations and the consequent variation in genetic mosaicism. New technologies promise the ability to measure genetic mosaicism by sampling a large number of cellular genomes within an individual. The sampling of many genomes within an individual will eventually allow one to reconstruct the cell lineage history of genetic change in a single body. Somatic evolutionary genomics will follow from this technology, providing new insight into the origin and progression of disease with increasing age.",
			"category": 2,
			"name": "Frank Steven A,2010"
		},
		{
			"PMID": 19755842,
			"title": "The protein tyrosine phosphatase receptor D, a broadly inactivated tumor suppressor regulating STAT function.",
			"journal": "Cell cycle (Georgetown, Tex.)",
			"authorList": [
				"Chan Timothy A",
				"Heguy Adriana"
			],
			"DOI": "",
			"date": "2010-01-14",
			"PMC": "",
			"citation": "",
			"abstract": "",
			"category": 2,
			"name": "Chan Timothy A,2010"
		},
		{
			"PMID": 19754664,
			"title": "Genetic characterization of breast cancer and implications for clinical management.",
			"journal": "Journal of cellular and molecular medicine",
			"authorList": [
				"Geyer Felipe C",
				"Lopez-Garcia Maria A",
				"Lambros Maryou B",
				"Reis-Filho Jorge S"
			],
			"DOI": "10.1111/j.1582-4934.2009.00906.x",
			"date": "2010-10-28",
			"PMC": "",
			"citation": "",
			"abstract": "Breast cancer is a genetic disease caused by the accumulation of mutations in neoplastic cells. In the last few years, high-throughput microarray-based molecular analysis has provided increasingly more coherent information about the genetic aberrations in breast cancer. New biomarkers and molecular techniques are slowly becoming part of the diagnostic and prognostic armamentarium available for pathologists and oncologists to tailor the therapy for breast cancer patients. In this review, we will focus on the contribution of breast cancer somatic genetics to our understanding of breast cancer biology and its impact on breast cancer patient management.",
			"category": 2,
			"name": "Geyer Felipe C,2010"
		},
		{
			"PMID": 19669758,
			"title": "The benefits of molecular pathology in the diagnosis of musculoskeletal disease : part I of a two-part review: soft tissue tumors.",
			"journal": "Skeletal radiology",
			"authorList": [
				"Flanagan Adrienne M",
				"Delaney David",
				"O'Donnell Paul"
			],
			"DOI": "10.1007/s00256-009-0759-x",
			"date": "2010-04-08",
			"PMC": "",
			"citation": "",
			"abstract": "Bone and soft tissue metabolic and neoplastic diseases are increasingly characterized by their molecular signatures. This has resulted from increased knowledge of the human genome, which has contributed to the unraveling of molecular pathways in health and disease. Exploitation of this information has allowed it to be used for practical diagnostic purposes. The aim of the first part of this two-part review is to provide an up-to-date review of molecular genetic investigations that are available and routinely used by specialist musculoskeletal histopathologists in the diagnosis of neoplastic disease. Herein we focus on the benefits of employing well characterized somatic mutations in soft tissue lesions that are commonly employed in diagnostic pathology today. The second part highlights the known somatic and germline mutations implicated in osteoclast-rich lesions of bone, and the genetic changes that disturb phosphate metabolism and result in a variety of musculoskeletal phenotypes. Finally, a brief practical guide of how to use and provide a molecular pathology service is given.",
			"category": 2,
			"name": "Flanagan Adrienne M,2010"
		},
		{
			"PMID": 19657110,
			"title": "Recurring mutations found by sequencing an acute myeloid leukemia genome.",
			"journal": "The New England journal of medicine",
			"authorList": [
				"Mardis Elaine R",
				"Ding Li",
				"Dooling David J",
				"Larson David E",
				"McLellan Michael D",
				"Chen Ken",
				"Koboldt Daniel C",
				"Fulton Robert S",
				"Delehaunty Kim D",
				"McGrath Sean D",
				"Fulton Lucinda A",
				"Locke Devin P",
				"Magrini Vincent J",
				"Abbott Rachel M",
				"Vickery Tammi L",
				"Reed Jerry S",
				"Robinson Jody S",
				"Wylie Todd",
				"Smith Scott M",
				"Carmichael Lynn",
				"Eldred James M",
				"Harris Christopher C",
				"Walker Jason",
				"Peck Joshua B",
				"Du Feiyu",
				"Dukes Adam F",
				"Sanderson Gabriel E",
				"Brummett Anthony M",
				"Clark Eric",
				"McMichael Joshua F",
				"Meyer Rick J",
				"Schindler Jonathan K",
				"Pohl Craig S",
				"Wallis John W",
				"Shi Xiaoqi",
				"Lin Ling",
				"Schmidt Heather",
				"Tang Yuzhu",
				"Haipek Carrie",
				"Wiechert Madeline E",
				"Ivy Jolynda V",
				"Kalicki Joelle",
				"Elliott Glendoria",
				"Ries Rhonda E",
				"Payton Jacqueline E",
				"Westervelt Peter",
				"Tomasson Michael H",
				"Watson Mark A",
				"Baty Jack",
				"Heath Sharon",
				"Shannon William D",
				"Nagarajan Rakesh",
				"Link Daniel C",
				"Walter Matthew J",
				"Graubert Timothy A",
				"DiPersio John F",
				"Wilson Richard K",
				"Ley Timothy J"
			],
			"DOI": "10.1056/NEJMoa0903840",
			"date": "2009-09-21",
			"PMC": "",
			"citation": "",
			"abstract": "The full complement of DNA mutations that are responsible for the pathogenesis of acute myeloid leukemia (AML) is not yet known.",
			"category": 2,
			"name": "Mardis Elaine R,2009"
		},
		{
			"PMID": 19636358,
			"title": "Aneuploidy and improved growth are coincident but not causal in a yeast cancer model.",
			"journal": "PLoS biology",
			"authorList": [
				"Li Xin Chenglin",
				"Schimenti John C",
				"Tye Bik K"
			],
			"DOI": "10.1371/journal.pbio.1000161",
			"date": "2009-11-17",
			"PMC": "",
			"citation": "",
			"abstract": "Cancer cells have acquired mutations that alter their growth. Aneuploidy that typify cancer cells are often assumed to contribute to the abnormal growth characteristics. Here we test the idea of a link between aneuploidy and mutations allowing improved growth, using Saccharomyces cerevisiae containing a mcm4 helicase allele that was shown to cause cancer in mice. Yeast bearing this mcm4 allele are prone to undergoing a \"hypermutable phase\" characterized by a changing karyotype, ultimately yielding progeny with improved growth properties. When such progeny are returned to a normal karyotype by mating, their improved growth remains. Genetic analysis shows their improved growth is due to mutations in just a few loci. In sum, the effects of the mcm4 allele in mice are recapitulated in yeast, and the aneuploidy is not required to maintain improved growth.",
			"category": 2,
			"name": "Li Xin Chenglin,2009"
		},
		{
			"PMID": 11287972,
			"title": "",
			"journal": "",
			"authorList": [],
			"DOI": "",
			"date": "",
			"PMC": "",
			"citation": "Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344:1031\u20137.",
			"abstract": "",
			"category": 0,
			"name": "Druker BJ, 2001;344:1031\u20137"
		},
		{
			"PMID": 15118073,
			"title": "",
			"journal": "",
			"authorList": [],
			"DOI": "",
			"date": "",
			"PMC": "",
			"citation": "Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non\u2013small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129\u201339.",
			"abstract": "",
			"category": 0,
			"name": "Lynch TJ, 2004;350:2129\u201339"
		},
		{
			"PMID": 15118125,
			"title": "",
			"journal": "",
			"authorList": [],
			"DOI": "",
			"date": "",
			"PMC": "",
			"citation": "Paez JG, J\u00e4nne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304:1497\u2013500.",
			"abstract": "",
			"category": 0,
			"name": "Paez JG, 2004;304:1497\u2013500"
		},
		{
			"PMID": 17625570,
			"title": "",
			"journal": "",
			"authorList": [],
			"DOI": "",
			"date": "",
			"PMC": "",
			"citation": "Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448:561\u20136.",
			"abstract": "",
			"category": 0,
			"name": "Soda M, 2007;448:561\u20136"
		},
		{
			"PMID": 23190221,
			"title": "",
			"journal": "",
			"authorList": [],
			"DOI": "",
			"date": "",
			"PMC": "PMC3777383",
			"citation": "Cortes JE, Kantarjian H, Shah NP, et al. Ponatinib in refractory Philadelphia chromosome\u2013positive leukemias. N Engl J Med. 2012;367:2075\u201388.",
			"abstract": "",
			"category": 0,
			"name": "Cortes JE, 2012;367:2075\u201388"
		},
		{
			"PMID": 25923549,
			"title": "",
			"journal": "",
			"authorList": [],
			"DOI": "",
			"date": "",
			"PMC": "",
			"citation": "J\u00e4nne PA, Yang JC, Kim DW, et al. AZD9291 in EGFR inhibitor\u2013resistant non\u2013 small-cell lung cancer. N Engl J Med. 2015;372:1689\u201399.",
			"abstract": "",
			"category": 0,
			"name": "J\u00e4nne PA, 2015;372:1689\u201399"
		},
		{
			"PMID": 25923550,
			"title": "",
			"journal": "",
			"authorList": [],
			"DOI": "",
			"date": "",
			"PMC": "",
			"citation": "Sequist LV, Soria JC, Goldman JW, et al. Rociletinib in EGFR-mutated non\u2013small-cell lung cancer. N Engl J Med. 2015;372:1700\u20139.",
			"abstract": "",
			"category": 0,
			"name": "Sequist LV, 2015;372:1700\u20139"
		},
		{
			"PMID": 24670165,
			"title": "",
			"journal": "",
			"authorList": [],
			"DOI": "",
			"date": "",
			"PMC": "PMC4079055",
			"citation": "Shaw AT, Kim DW, Mehra R, et al. Ceritinib in ALK-rearranged non\u2013small-cell lung cancer. N Engl J Med. 2014;370:1189\u201397.",
			"abstract": "",
			"category": 0,
			"name": "Shaw AT, 2014;370:1189\u201397"
		},
		{
			"PMID": 25153538,
			"title": "",
			"journal": "",
			"authorList": [],
			"DOI": "",
			"date": "",
			"PMC": "",
			"citation": "Gadgeel SM, Gandhi L, Riely GJ, et al. Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study. Lancet Oncol. 2014;15:1119\u201328.",
			"abstract": "",
			"category": 0,
			"name": "Gadgeel SM,AF-002JG"
		},
		{
			"PMID": 20979469,
			"title": "",
			"journal": "",
			"authorList": [],
			"DOI": "",
			"date": "",
			"PMC": "PMC3014291",
			"citation": "Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non\u2013small-cell lung cancer. N Engl J Med. 2010;363:1693\u2013703.",
			"abstract": "",
			"category": 0,
			"name": "Kwak EL, 2010;363:1693\u2013703"
		},
		{
			"PMID": 25979929,
			"title": "",
			"journal": "",
			"authorList": [],
			"DOI": "",
			"date": "",
			"PMC": "PMC4435823",
			"citation": "Katayama R, Lovly CM, Shaw AT. Therapeutic targeting of anaplastic lymphoma kinase in lung cancer: a paradigm for precision cancer medicine. Clin Cancer Res. 2015;21:2227\u201335.",
			"abstract": "",
			"category": 0,
			"name": "Katayama R, 2015;21:2227\u201335"
		},
		{
			"PMID": -699566,
			"title": "",
			"journal": "",
			"authorList": [],
			"DOI": "",
			"date": "",
			"PMC": "",
			"citation": "Camidge DR, Bazhenova L, Salgia R, et al. Safety and efficacy of brigatinib (AP26113) in advanced malignancies, including ALK+ non-small cell lung cancer (NSCLC). J Clin Oncol. 2015;33:8062. abstract.",
			"abstract": "",
			"category": 0,
			"name": "Camidge DR,AP26113"
		},
		{
			"PMID": 24675041,
			"title": "",
			"journal": "",
			"authorList": [],
			"DOI": "",
			"date": "",
			"PMC": "PMC4068971",
			"citation": "Friboulet L, Li N, Katayama R, et al. The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discov. 2014;4:662\u201373.",
			"abstract": "",
			"category": 0,
			"name": "Friboulet L, 2014;4:662\u201373"
		},
		{
			"PMID": -515501,
			"title": "",
			"journal": "",
			"authorList": [],
			"DOI": "",
			"date": "",
			"PMC": "",
			"citation": "Katayama R, Yanagitani N, Koike S, et al. Resistance mechanisms to ALK inhibitors. American Association for Cancer Research; Philadelphia: 2015.",
			"abstract": "",
			"category": 0,
			"name": "Katayama R, American Association for Cancer Research; Philadelphia: 2015"
		},
		{
			"PMID": 24819116,
			"title": "",
			"journal": "",
			"authorList": [],
			"DOI": "",
			"date": "",
			"PMC": "",
			"citation": "Johnson TW, Richardson PF, Bailey S, et al. Discovery of (10R)-7-amino-12-fluoro -2,10,16-trimethyl-15-oxo-10,15,16,17 -tetrahydro-2H-8,4-(metheno)pyrazolo [4,3-h][2,5,11]-benzoxadiazacyclotetra decine-3-carbonitrile (PF-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) with preclinical brain exposure and broad-spectrum potency against ALK-resistant mutations. J Med Chem. 2014;57:4720\u201344.",
			"abstract": "",
			"category": 0,
			"name": "Johnson TW,10R"
		},
		{
			"PMID": 26144315,
			"title": "",
			"journal": "",
			"authorList": [],
			"DOI": "",
			"date": "",
			"PMC": "PMC4504786",
			"citation": "Zou HY, Friboulet L, Kodack DP, et al. PF-06463922, an ALK/ROS1 inhibitor, overcomes resistance to first and second generation ALK inhibitors in preclinical models. Cancer Cell. 2015;28:70\u201381.",
			"abstract": "",
			"category": 0,
			"name": "Zou HY, 2015;28:70\u201381"
		},
		{
			"PMID": 20979473,
			"title": "",
			"journal": "",
			"authorList": [],
			"DOI": "",
			"date": "",
			"PMC": "",
			"citation": "Choi YL, Soda M, Yamashita Y, et al. EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med. 2010;363:1734\u20139.",
			"abstract": "",
			"category": 0,
			"name": "Choi YL, 2010;363:1734\u20139"
		},
		{
			"PMID": 25264305,
			"title": "",
			"journal": "",
			"authorList": [],
			"DOI": "",
			"date": "",
			"PMC": "PMC4264527",
			"citation": "Shaw AT, Ou SH, Bang YJ, et al. Crizotinib in ROS1-rearranged non\u2013small-cell lung cancer. N Engl J Med. 2014;371:1963\u201371.",
			"abstract": "",
			"category": 0,
			"name": "Shaw AT, 2014;371:1963\u201371"
		},
		{
			"PMID": 25384085,
			"title": "",
			"journal": "",
			"authorList": [],
			"DOI": "",
			"date": "",
			"PMC": "",
			"citation": "Zheng Z, Liebers M, Zhelyazkova B, et al. Anchored multiplex PCR for targeted next-generation sequencing. Nat Med. 2014;20:1479\u201384.",
			"abstract": "",
			"category": 0,
			"name": "Zheng Z, 2014;20:1479\u201384"
		},
		{
			"PMID": 24518097,
			"title": "",
			"journal": "",
			"authorList": [],
			"DOI": "",
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