Comprehensive molecular characterization of gastric adenocarcinoma
Adam J. Bass(Harvard University Press), Natalie Tasman(Institute for Systems Biology), Brady Bernard(Institute for Systems Biology), Vésteinn Thórsson(Institute for Systems Biology), Roger Kramer(Institute for Systems Biology), Michael Miller(Institute for Systems Biology), Vésteinn Thórsson(University of Southern California), Ilya Shmulevich(University of Southern California), Lisa Iype(University of Southern California), Hector Rovira(University of Southern California), Richard Kreisberg(University of Southern California), Sheila M. Reynolds(Memorial Sloan Kettering Cancer Center), Timothy J. Triche(University of Southern California), Moiz S. Bootwalla(University of Southern California), Phillip H. Lai(University of Southern California), Toshinori Hinoue(University of Southern California), Hui Shen(University of Southern California), Toshinori Hinoue(University of Southern California), Daniel J. Weisenberger(University of Southern California), David Van Den Berg(University of Southern California), Peter W. Laird(University of Southern California), Christina Curtis(Broad Institute), Nikolaus Schultz(Broad Institute), Jianjiong Gao(Broad Institute), Nils Weinhold(Broad Institute), Yasin Şenbabaoğlu(Broad Institute), Rileen Sinha(Broad Institute), Anders Jacobsen(Broad Institute), Benjamin Groß(Memorial Sloan Kettering Cancer Center), Gideon Dresdner(Memorial Sloan Kettering Cancer Center), Ricardo Ramírez(Memorial Sloan Kettering Cancer Center), Chris Sander(Memorial Sloan Kettering Cancer Center), S. Onur Sumer(Memorial Sloan Kettering Cancer Center), r B. Arman Askoy(Memorial Sloan Kettering Cancer Center), William Lee(Memorial Sloan Kettering Cancer Center), Giovanni Ciriello(Memorial Sloan Kettering Cancer Center), Yichao Sun(University of North Carolina at Chapel Hill), Nikolaus Schultz(Memorial Sloan Kettering Cancer Center), Ronglai Shen(Memorial Sloan Kettering Cancer Center), Yelena Y. Janjigian(Memorial Sloan Kettering Cancer Center), David P. Kelsen(Memorial Sloan Kettering Cancer Center), David P. Kelsen(National Institutes of Health), Haiyan A. Li(National Institutes of Health), Amanda Clarke(National Institutes of Health), Noreen Dhalla(Canada's Michael Smith Genome Sciences Centre), Andy Chu(University of California, Santa Cruz), Andrew J. Mungall(Duke University), Justin Chu(University of Michigan), Nina Thiessen(University of Pittsburgh), Karen Mungall(Brown University), Emilia L. Lim(Brown University), Denise Brooks(Harvard University Press), Reanne Bowlby(Canada's Michael Smith Genome Sciences Centre), Miruna Balasundaram(Canada's Michael Smith Genome Sciences Centre), Darlene Lee(Canada's Michael Smith Genome Sciences Centre), Angela Tam(Canada's Michael Smith Genome Sciences Centre), Richard A. Moore(Canada's Michael Smith Genome Sciences Centre), Hye-Jung E. Chun(University of Washington), Michael Mayo(Canada's Michael Smith Genome Sciences Centre), A. Gordon Robertson(Canada's Michael Smith Genome Sciences Centre), Eric Chuah(Broad Institute), Steven J.M. Jones(Broad Institute), Rebecca Carlsen(Broad Institute), Katayoon Kasaian(Broad Institute), Marco A. Marra(Broad Institute), Payal Sipahimalani(Broad Institute), Yussanne Ma(University of Washington), Ranabir Guin(University of Washington), Robert A. Holt(University of British Columbia), Yaron S.N. Butterfield(University of British Columbia), Ka Ming Nip(University of British Columbia), Reanne Bowlby(University of British Columbia), Adrian Ally(University of British Columbia), Jacqueline E. Schein(University of British Columbia), İnanç Birol(University of British Columbia), Lihua Zou(University of British Columbia), Nils Gehlenborg(University of British Columbia), Yingchun Liu(University of British Columbia), Travis Zack(University of British Columbia), Scott L. Carter(University of British Columbia), Jaegil Kim(Ulsan College), Eric S. Lander(University of British Columbia), Petar Stojanov(University of British Columbia), Barbara Tabak(University of British Columbia), Andrew D. Cherniack(University of British Columbia), Gordon Saksena(University of British Columbia), Bradley A. Murray(University of British Columbia), Rameen Beroukhim(University of British Columbia), Lee Lichtenstein(University of British Columbia), Carrie Sougnez(University of British Columbia), Gad Getz(University of British Columbia), Chandra Sekhar Pedamallu(University of British Columbia), Juok Cho(University of British Columbia), Kristian Cibulskis(University of British Columbia), David I. Heiman(Broad Institute), Doug Voet(Broad Institute), Joonil Jung(Broad Institute), Sheila Fisher(Broad Institute), Hailei Zhang(Broad Institute), Scott Frazer(Broad Institute), Michael S. Lawrence(Broad Institute), Pei Lin(Broad Institute), Daniel DiCara(Broad Institute), Matthew Meyerson(Broad Institute), Andrew D. Cherniack(Broad Institute), Stacey Gabriel(Broad Institute), Amaro Taylor‐Weiner(Broad Institute), Michael S. Noble(Broad Institute), Steven E. Schumacher(Broad Institute), Mara Rosenberg(Broad Institute), Chandra Sekhar Pedamallu(Broad Institute), Akinyemi I. Ojesina(Broad Institute), Ju‐Seog Lee(Broad Institute), Arvind Rao(Broad Institute), John N. Weinstein(Broad Institute), Arvind Rao(Broad Institute), Rehan Akbani(Broad Institute), Shiyun Ling(The University of Texas MD Anderson Cancer Center), Wenbin Liu(The University of Texas MD Anderson Cancer Center), Rehan Akbani(The University of Texas MD Anderson Cancer Center), Ju‐Seog Lee(Chonnam National University), Sangbae Kim(The University of Texas MD Anderson Cancer Center), Gordon Mills (The University of Texas MD Anderson Cancer Center), Gordon B. Mills(The University of Texas MD Anderson Cancer Center), Gordon B. Mills(The University of Texas MD Anderson Cancer Center), Yiling Lu(The University of Texas MD Anderson Cancer Center), Wei Zhang(The University of Texas MD Anderson Cancer Center), Da Yang(The University of Texas MD Anderson Cancer Center), Jonathan G. Seidman(Harvard University), Netty Santoso(The University of Texas MD Anderson Cancer Center), Raju Kucherlapati(Harvard University), Angeliki Pantazi(Harvard University), Xiaojia Ren(The University of Texas MD Anderson Cancer Center), Angela Hadjipanayis(Harvard University), Angeliki Pantazi(Harvard University), Michael Parfenov(The University of Texas MD Anderson Cancer Center), Margaret L. Gulley(University of North Carolina at Chapel Hill), Barbara Schneider(The University of Texas MD Anderson Cancer Center), M. Blanca Piazuelo(The University of Texas MD Anderson Cancer Center), Young S. Park(Ulsan College), Jihun Kim(Ulsan College), Alex Boussioutas(University of Southern California), Roy Tarnuzzer(University of Southern California), Margi Sheth(University of Southern California), Margi Sheth(University of Southern California), Greg Eley(Johns Hopkins University), Zhining Wang(Johns Hopkins University), John A. Demchok(Broad Institute), Jean C. Zenklusen(Memorial Sloan Kettering Cancer Center), Liming Yang(Memorial Sloan Kettering Cancer Center), Kenna Shaw(Memorial Sloan Kettering Cancer Center), Charles S. Rabkin(Memorial Sloan Kettering Cancer Center), M. Constanza Camargo(Memorial Sloan Kettering Cancer Center), Joseph Willis(Memorial Sloan Kettering Cancer Center), David Haussler(Memorial Sloan Kettering Cancer Center), Sam Ng(Memorial Sloan Kettering Cancer Center), Sam Ng(Memorial Sloan Kettering Cancer Center), Joshua M. Stuart(Memorial Sloan Kettering Cancer Center), Katherine S. Garman(Memorial Sloan Kettering Cancer Center), David G. Beer(Memorial Sloan Kettering Cancer Center), Rodney J. Landreneau(Memorial Sloan Kettering Cancer Center), Rajiv Dhir(University of Pittsburgh), Arjun Pennathur(University of Pittsburgh), James D. Luketich(University of Pittsburgh), Benjamin J. Raphael(Brown University), Hsin-Ta Wu(Brown University), Benjamin J. Raphael(University of California, Santa Cruz), Mark D.M. Leiserson(University of California, Santa Cruz), Robert D. Odze(Brigham and Women's Hospital), Hark K. Kim(The University of Texas MD Anderson Cancer Center), Teresa R. Tabler(Nationwide Children's Hospital), Kristen Leraas(Nationwide Children's Hospital), Tara M. Lichtenberg(Nationwide Children's Hospital), Erik Zmuda(Nationwide Children's Hospital), Aaron D. Black(Nationwide Children's Hospital), Cynthia McAllister(Nationwide Children's Hospital), Jay Bowen(Nationwide Children's Hospital), Carmen Helsel(Nationwide Children's Hospital), Julie M. Gastier-Foster(Nationwide Children's Hospital), J A Carney(Nationwide Children's Hospital), Stephanie Weaver(Nationwide Children's Hospital), Nilsa C. Ramirez(Nationwide Children's Hospital), Lisa Wise(Nationwide Children's Hospital), Jay Bowen(Nationwide Children's Hospital), Beifang Niu(Washington University in St. Louis), Li Ding(Washington University in St. Louis), Michael D. McLellan(Washington University in St. Louis), Matthew Ibbs(Greater Poland Cancer Center), Ewa Leporowska(Greater Poland Cancer Center), Wiktoria Maria Suchorska(Greater Poland Cancer Center), Witold Kycler(Greater Poland Cancer Center), Maciej Wiznerowicz(Greater Poland Cancer Center), Honorata Tatka(Buck Institute for Research on Aging), Radoslaw Łaźniak(Greater Poland Cancer Center), Konstanty Korski(Greater Poland Cancer Center), Andrzej Maćkiewicz(Greater Poland Cancer Center), Arkadiusz Spychała(Greater Poland Cancer Center), Jakub Brzezinski(Greater Poland Cancer Center), Maciej Wiznerowicz(Greater Poland Cancer Center), M. Teresiak(Greater Poland Cancer Center), Dawid Murawa(University of North Carolina at Chapel Hill), P. Murawa(Greater Poland Cancer Center), Ryo Sakai(KU Leuven), Roeland Verhaak(The University of Texas MD Anderson Cancer Center), Sahil Seth(The University of Texas MD Anderson Cancer Center), Christopher A. Bristow(The University of Texas MD Anderson Cancer Center), Lynda Chin(The University of Texas MD Anderson Cancer Center), Harshad S. Mahadeshwar(The University of Texas MD Anderson Cancer Center), Xingzhi Song(The University of Texas MD Anderson Cancer Center), Jiabin Tang(The University of Texas MD Anderson Cancer Center), Alexei Protopopov(The University of Texas MD Anderson Cancer Center), Lynda Chin(The University of Texas MD Anderson Cancer Center), Jianhua Zhang(The University of Texas MD Anderson Cancer Center), Semin Lee(Center for Systems Biology), Lixing Yang(Christiana Care Health System), Ruibin Xi(Christiana Care Health System), Peter J. Park(Christiana Care Health System), Andrew Wei Xu(Christiana Care Health System), Stephen B. Baylin(Christiana Care Health System), James G. Herman(Johns Hopkins University), Barry S. Taylor(UCSF Helen Diller Family Comprehensive Cancer Center), Candace Shelton (Translational Genomics Research Institute), Scott Morris(Translational Genomics Research Institute), Ariane Kemkes(Translational Genomics Research Institute), Kevin Lau(Ontario Institute for Cancer Research), Candace Shelton(Ontario Institute for Cancer Research), Troy Shelton(Translational Genomics Research Institute), Joseph Paulauskis(Translational Genomics Research Institute), Erin Curely(Translational Genomics Research Institute), Johanna Gardner(Translational Genomics Research Institute), Daniel Crain(Translational Genomics Research Institute), Erin Curley(Translational Genomics Research Institute), Mark E. Sherman(Translational Genomics Research Institute), David Mallery(Translational Genomics Research Institute), Robert Penny(Translational Genomics Research Institute), Robert Penny(Translational Genomics Research Institute), Christopher C. Benz(Buck Institute for Research on Aging), Jae-Hyuk Lee(Chonnam National University), Konstantin Fedosenko(City Clinical Oncology Center), Georgy M. Manikhas(City Clinical Oncology Center), Olga Potapova(Sunesis (United States)), Dmitry Belyaev (Sunesis (United States)), O V Dolzhansky(Sunesis (United States)), Olga Voronina(Sunesis (United States)), W. Kimryn Rathmell(University of North Carolina at Chapel Hill), Jennifer R. Brown(Christiana Care Health System), Raafat Abdel‐Misih(Christiana Care Health System), Brenda Rabeno(Christiana Care Health System), Joseph Bennett(Christiana Care Health System), Mary Iacocca(Christiana Care Health System), Sun Young Kwon(Keimyung University), Iakovina Alexopoulou(St. Joseph’s Healthcare Hamilton), Jay Engel(Kingston General Hospital), John M.S. Bartlett(Ontario Institute for Cancer Research), Monique Albert(Ontario Institute for Cancer Research), Do-Youn Park(Pusan National University Hospital), Laura H. Tang(Memorial Sloan Kettering Cancer Center), Marc Ladanyi(Memorial Sloan Kettering Cancer Center), Eun‐Jung Cho(Memorial Sloan Kettering Cancer Center), Shannon J. McCall(Duke University), Jae‐Ho Cheong(Yonsei University), Jaffer A. Ajani(The University of Texas MD Anderson Cancer Center), Yunhu Wan(SRA International (United States)), Todd Pihl(SRA International (United States)), Jessica Walton(SRA International (United States)), Mark A. Jensen(SRA International (United States)), Rohini Raman(SRA International (United States)), Brenda Ayala(SRA International (United States)), Shelley Alonso(SRA International (United States)), Tanja M. Davidsen(National Cancer Institute), Carolyn M. Hutter(National Human Genome Research Institute), Heidi J. Sofia(National Human Genome Research Institute), Jia Liu(Science Applications International Corporation (United States)), Sudha Chudamani(Science Applications International Corporation (United States)), Robert Burton(Science Applications International Corporation (United States))
Cited by 6,478Open Access
Abstract
Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies. The Cancer Genome Atlas reports on molecular evaluation of 295 primary gastric adenocarcinomas and proposes a new classification of gastric cancers into 4 subtypes, which should help with clinical assessment and trials of targeted therapies. This contribution from The Cancer Genome Atlas (TCGA) project describes the molecular evaluation of 295 primary gastric adenocarcinomas. Based on the results, the authors propose a novel classification separating gastric cancers into four subtypes according to: Epstein–Barr virus positive status, microsatellite instability, chromosomal instability or genomic stability. Given the histologic and etiologic heterogeneity of gastric cancer identification of these subtypes, using a schema that can readily be applied to patient samples should help with patient stratification and trials of targeted therapies.
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