Integrated genomic characterization of oesophageal carcinoma
Young Soo Park(University of Ulsan), Jihun Kim (Eli and Edythe Broad Foundation), Rebecca Carlsen(Canada's Michael Smith Genome Sciences Centre), Reanne Bowlby(Canada's Michael Smith Genome Sciences Centre), Marco A. Marra(BC Cancer Agency), Robert A. Holt(Canada's Michael Smith Genome Sciences Centre), Steven J. M. Jones(Canada's Michael Smith Genome Sciences Centre), Adrian Ally(Canada's Michael Smith Genome Sciences Centre), Denise Brooks(BC Cancer Agency), Angela Tam(Canada's Michael Smith Genome Sciences Centre), Miruna Balasundaram(BC Cancer Agency), Payal Sipahimalani(Canada's Michael Smith Genome Sciences Centre), Haiyan I. Li(BC Cancer Agency), Karen L. Mungall(BC Cancer Agency), Richard A. Moore(BC Cancer Agency), Tina Wong(Canada's Michael Smith Genome Sciences Centre), Reanne Bowlby(Canada's Michael Smith Genome Sciences Centre), Eric Chuah(BC Cancer Agency), Michael Mayo(Canada's Michael Smith Genome Sciences Centre), Jacqueline E. Schein(Canada's Michael Smith Genome Sciences Centre), Yussanne Ma(BC Cancer Agency), Katayoon Kasaian(BC Cancer Agency), Noreen Dhalla(Canada's Michael Smith Genome Sciences Centre), Andrew J. Mungall(Canada's Michael Smith Genome Sciences Centre), A. Gordon Robertson(BC Cancer Agency), Nina Thiessen (Canada's Michael Smith Genome Sciences Centre), Robert D. Odze(Harvard University), Matthew Meyerson(Dana-Farber Cancer Institute), Robert D. Odze (Brigham and Women's Hospital), Nils Gehlenborg(Harvard University), Kristian Cibulskis(Broad Institute), Andrew D. Cherniack(Broad Institute), Michael S. Lawrence(Eli and Edythe Broad Foundation), Jaegil Kim(University of Ulsan), Timothy Defrietas(Eli and Edythe Broad Foundation), Michael S. Noble(Eli and Edythe Broad Foundation), Michael Lawrence(Eli and Edythe Broad Foundation), Doug Voet(Eli and Edythe Broad Foundation), Andrew Dunford(Broad Institute), Juliann Shih(Eli and Edythe Broad Foundation), David I. Heiman(Broad Institute), Amaro Taylor-Weiner(Harvard University), Gad Getz(Massachusetts General Hospital), Eric Lander(Broad Institute), Lynda Chin(Broad Institute), Carrie Cibulskis(Eli and Edythe Broad Foundation), Bradley A. Murray(Eli and Edythe Broad Foundation), Pei Lin(Eli and Edythe Broad Foundation), Andrew D. Cherniack(Eli and Edythe Broad Foundation), Paz Polak(Massachusetts General Hospital), Susan Bullman(Broad Institute), Gad Getz (Eli and Edythe Broad Foundation), Scott Frazer(Broad Institute), Chandra Sekhar Pedamallu(Broad Institute), Rameen Beroukhim(Dana-Farber Cancer Institute), Gordon Saksena(Eli and Edythe Broad Foundation), Chip Stewart(Eli and Edythe Broad Foundation), Stacey B. Gabriel(Eli and Edythe Broad Foundation), Stacey Gabriel(Eli and Edythe Broad Foundation), Samuel R. Meier(Eli and Edythe Broad Foundation), Juok Cho(Eli and Edythe Broad Foundation), Hailei Zhang(Memorial Sloan Kettering Cancer Center), Steven E. Schumacher(Eli and Edythe Broad Foundation), Matthew Meyerson(Dana-Farber Cancer Institute), Chandra Sekhar Pedamallu(Broad Institute), Rameen Beroukhim(Broad Institute), Susan Bullman (Eli and Edythe Broad Foundation), Juliann Shih(Eli and Edythe Broad Foundation), Andrew D. Cherniack(Dana-Farber Cancer Institute), Sarah Derks(Dana-Farber Cancer Institute), Adam J. Bass(Dana-Farber Cancer Institute), Juliann Shih(Eli and Edythe Broad Foundation), Benjamin J. Raphael(Brown University), Alexandra M. Wong(Brown University), Hsin-Ta Wu(Brown University), Benjamin J. Raphael (Brown University), Joseph E. Willis(Case Western Reserve University), Joseph E. Willis(Case Western Reserve University), Adam J. Bass(Dana-Farber Cancer Institute), Sarah Derks(Amsterdam UMC Location Vrije Universiteit Amsterdam), Shannon J. McCall(Duke University), Crystal Cates(Duke University), Katherine Garman(Duke University), Alexis Sharp (Duke University), Maciej Wiznerowicz(Poznan University of Medical Sciences), Maciej Wiznerowicz(Poznan University of Medical Sciences), Michael Parfenov(Harvard University), Xiaojia Ren (Harvard University), Angeliki Pantazi(Harvard University), Melanie Kucherlapati(Harvard University), Raju Kucherlapati(Brigham and Women's Hospital), Angela Hadjipanayis(Harvard University), Angeliki Pantazi(Environment and Health Group (United States)), Alexei Protopopov(Environment and Health Group (United States)), Angeliki Pantazi(Harvard University), Xiaojia Ren (Harvard University), Angeliki Pantazi(Harvard University), Ilya Shmulevich (Institute for Systems Biology), Ilya Shmulevich(Institute for Systems Biology), Vésteinn Thorsson(Institute for Systems Biology), Sheila M. Reynolds(Institute for Systems Biology), Vésteinn Thorsson(Institute for Systems Biology), Michael Miller(Institute for Systems Biology), Brady Bernard(Institute for Systems Biology), Lisa Iype(Institute for Systems Biology), Varsha Dhankani(Institute for Systems Biology), Ryo Sakai(iMinds), Ryo Sakai(KU Leuven), Kenneth Wang(Mayo Clinic), Francisco Sánchez-Vega(Memorial Sloan Kettering Cancer Center), Jianjiong Gao(Memorial Sloan Kettering Cancer Center), Debyani Chakravarty (Memorial Sloan Kettering Cancer Center), Nikolaus Schultz(Memorial Sloan Kettering Cancer Center), Joshua Armenia(Memorial Sloan Kettering Cancer Center), Ritika Kundra(Memorial Sloan Kettering Cancer Center), Nikolaus Schultz(Memorial Sloan Kettering Cancer Center), Hongxin Zhang(Broad Institute), Nikolaus Schultz(Memorial Sloan Kettering Cancer Center), Arshi Arora(Memorial Sloan Kettering Cancer Center), Ronglai Shen(Memorial Sloan Kettering Cancer Center), Nikolaus Schultz (Memorial Sloan Kettering Cancer Center), Nils Weinhold(Memorial Sloan Kettering Cancer Center), Kjong-Van Lehmann(Memorial Sloan Kettering Cancer Center), Adam Abeshouse(Memorial Sloan Kettering Cancer Center), Chris Sander (Memorial Sloan Kettering Cancer Center), Nils Weinhold(Memorial Sloan Kettering Cancer Center), David Kelsen(Memorial Sloan Kettering Cancer Center), David P. Kelsen(Memorial Sloan Kettering Cancer Center), Yelena Janjigian (Memorial Sloan Kettering Cancer Center), Kenna R. Mills Shaw(The University of Texas MD Anderson Cancer Center), John A. Demchok(National Cancer Institute), Margi Sheth(National Cancer Institute), Martin L. Ferguson(National Cancer Institute), Roy Tarnuzzer(National Cancer Institute), Liming Yang(National Cancer Institute), John Demchok(National Cancer Institute), Jiashan Zhang(National Cancer Institute), Zhining Wang(National Cancer Institute), Jean Claude Zenklusen (National Cancer Institute), Julia Zhang(The University of Texas MD Anderson Cancer Center), Ina Felau(National Cancer Institute), Jean Claude Zenklusen(National Cancer Institute), M. Constanza Camargo (Division of Cancer Epidemiology and Genetics), M. Constanza Camargo(Division of Cancer Epidemiology and Genetics), Charles S. Rabkin(National Cancer Institute), Kristen M. Leraas(Nationwide Children's Hospital), Kristen Leraas(Nationwide Children's Hospital), Lisa Wise (Nationwide Children's Hospital), Tara M. Lichtenberg(Nationwide Children's Hospital), Jay Bowen(Nationwide Children's Hospital), Jay Bowen(Nationwide Children's Hospital), Mark Gerken(Nationwide Children's Hospital), Erik Zmuda(Nationwide Children's Hospital), Jessica Frick(Nationwide Children's Hospital), Nilsa C. Ramirez(Nationwide Children's Hospital), Julie M. Gastier-Foster(Nationwide Children's Hospital), Christina Curtis (Stanford University), Jose A. Seoane(Stanford University), Akinyemi I. Ojesina(University of Alabama at Birmingham), Akinyemi I. Ojesina(University of Alabama at Birmingham), David G. Beer (Michigan Center for Translational Pathology), Daysha Ferrer-Torres(Michigan Center for Translational Pathology), Margaret L. Gulley(University of North Carolina at Chapel Hill), James D. Luketich(University of Pittsburgh Medical Center), James Luketich (University of Pittsburgh Medical Center), Arjun Pennathur(University of Pittsburgh Medical Center), Arjun Pennathur(University of Pittsburgh Medical Center), Zhongren Zhou(University of Rochester), Daniel J. Weisenberger (University of Southern California), Daniel J. Weisenberger(University of Southern California), Wenbin Liu(The University of Texas MD Anderson Cancer Center), Rehan Akbani(The University of Texas MD Anderson Cancer Center), Rehan Akbani(The University of Texas MD Anderson Cancer Center), Apruva Hegde(The University of Texas MD Anderson Cancer Center), Wenbin Liu (The University of Texas MD Anderson Cancer Center), John N. Weinstein(The University of Texas MD Anderson Cancer Center), Gordon B. Mills(The University of Texas MD Anderson Cancer Center), Ju-Seog Lee(Chonnam National University Hwasun Hospital), Gordon 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), Brian J Reid(Fred Hutch Cancer Center), Peter W. Laird(Van Andel Institute), Toshinori Hinoue (Van Andel Institute), Hui Shen(Van Andel Institute), Toshinori Hinoue(Van Andel Institute), M. Blanca Piazuelo (Vanderbilt University Medical Center), Barbara G. Schneider(Vanderbilt University Medical Center), Michael McLellan(James S. McDonnell Foundation), Elizabeth L. Appelbaum(James S. McDonnell Foundation), Lucinda A. Fulton(James S. McDonnell Foundation), Elaine R. Mardis(James S. McDonnell Foundation), Michael D. McLellan(James S. McDonnell Foundation), Robert S. Fulton(James S. McDonnell Foundation), Heather K. Schmidt (James S. McDonnell Foundation), Richard K. Wilson(James S. McDonnell Foundation), Catrina C. Fronick(James S. McDonnell Foundation), Matthew G. Cordes(James S. McDonnell Foundation), Christopher A. Miller(James S. McDonnell Foundation), Li Ding(Washington University in St. Louis), Nils Gehlenborg(Eli and Edythe Broad Foundation), Lixing Yang(Harvard University), Semin Lee(Harvard University), Amaro Taylor-Weiner(Harvard University), Peter J. Park (Brigham and Women's Hospital), Peter J. Park(Brigham and Women's Hospital), Gad Getz(Eli and Edythe Broad Foundation), Gad Getz(Massachusetts General Hospital), Paz Polak (Eli and Edythe Broad Foundation), Li Ding(James S. McDonnell Foundation), Rameen Beroukhim(Dana-Farber Cancer Institute), Steven E. Schumacher(Broad Institute), Angela Hadjipanayis(Harvard University), Melanie Kucherlapati (Harvard University), Raju Kucherlapati(Harvard University), Peter J. Park(Brigham and Women's Hospital), Stephen B. Baylin(Sidney Kimmel Comprehensive Cancer Center), Katherine A. Hoadley(University of North Carolina at Chapel Hill), Phillip H. Lai(USC Norris Comprehensive Cancer Center), Mario Berrios (USC Norris Comprehensive Cancer Center), Andrea Holbrook(USC Norris Comprehensive Cancer Center), Moiz S. Bootwalla(USC Norris Comprehensive Cancer Center), David J. Van Den Berg(University of Southern California), Kenna R. Mills Shaw(The University of Texas MD Anderson Cancer Center), Hee-Jin Jang(The University of Texas MD Anderson Cancer Center), Jun-Eul Hwang(The University of Texas MD Anderson Cancer Center), Bo Hwa Sohn (The University of Texas MD Anderson Cancer Center), Ju-Seog Lee(Chonnam National University Hwasun Hospital), Jun-Eul Hwang(The University of Texas MD Anderson Cancer Center), Lynda Chin(Broad Institute), Christopher A. Bristow(The University of Texas MD Anderson Cancer Center), Jianhua Zhang(National Cancer Institute), Jiabin Tang(The University of Texas MD Anderson Cancer Center), Lynda Chin (Eli and Edythe Broad Foundation), Sahil Seth(The University of Texas MD Anderson Cancer Center), Harshad S. Mahadeshwar(The University of Texas MD Anderson Cancer Center), Alexei Protopopov(Environment and Health Group (United States)), Xingzhi Song(The University of Texas MD Anderson Cancer Center), Marc Ladanyi(Memorial Sloan Kettering Cancer Center), Laura Tang(Memorial Sloan Kettering Cancer Center), Marc Ladanyi (Memorial Sloan Kettering Cancer Center), Amie Radenbaugh(University of California, Santa Cruz), Daniel Crain(Translational Genomics Research Institute), Robert Penny(Translational Genomics Research Institute), Candace Shelton(Translational Genomics Research Institute), Johanna Gardner(Translational Genomics Research Institute), Troy Shelton(Translational Genomics Research Institute), Candace Shelton (Translational Genomics Research Institute), David Mallery(Translational Genomics Research Institute), Robert Penny(Translational Genomics Research Institute), Scott Morris(Translational Genomics Research Institute), Erin Curley(Translational Genomics Research Institute), Joseph Paulauskis(Translational Genomics Research Institute), Katherine Tarvin (Analytical Biological Services (United States)), Charles Saller(Analytical Biological Services (United States)), Michael Button(Michigan Science Center), Andre L. Carvalho (Hospital de Câncer de Barretos), Rui Manuel Reis(University of Minho), Rui Manuel Reis(University of Minho), Marcus Medeiros Matsushita(Hospital de Câncer de Barretos), Fabiano Lucchesi(Hospital de Câncer de Barretos), Antonio Talvane de Oliveira(Hospital de Câncer de Barretos), Xuan Le(Washington College), Galiya Setdikova(Botkin Hospital), Oxana Paklina (Botkin Hospital), Jae-Hyuck Lee(Chonnam National University Hwasun Hospital), Mary Iacocca (Christiana Care Health System), Lori Huelsenbeck-Dill(Christiana Care Health System), Joseph Bennett(Christiana Care Health System), Olga Voronina(Sunesis (United States)), Victoria Fulidou(Sunesis (United States)), Olga Potapova(Sunesis (United States)), Ouida Liu (Sunesis (United States)), Allan Pickens(Emory University), Seth Force(Emory University), Suresh Ramalingam (Emory University), Gabriel Sica(Emory University), Madhusmitara Behera(Emory University), Fadio Khuri(Emory University), Taofeek Owonikoko(Emory University), Winand Dinjens(Erasmus MC Cancer Institute), Anna van Nistelrooij (Erasmus MC Cancer Institute), Bas Wijnhoven(Erasmus MC Cancer Institute), Anna van Nistelrooij(Erasmus MC Cancer Institute), George Sandusky(Indiana University – Purdue University Indianapolis), Serghei Stepa(Institutul Oncologic din Republica Moldova), Hartmut Juhl(Dermatologikum Hamburg), Carsten Zornig(Israelitisches Krankenhaus), Sun Young Kwon(Keimyung University), Hark Kyun Kim(National Cancer Center), John Bartlett(Ontario Institute for Cancer Research), Jeremy Parfitt(London Health Sciences Centre), Jennifer Knox(Princess Margaret Cancer Centre), Rebecca Wong(Princess Margaret Cancer Centre), Geoffrey Liu(Princess Margaret Cancer Centre), Haila El-Zimaity (Princess Margaret Cancer Centre), Runjan Chetty(Princess Margaret Cancer Centre), Gail Darling(Princess Margaret Cancer Centre), Alex Boussioutas(Peter MacCallum Cancer Centre), Do Young Park(University of Ulsan), Rafael Kemp(Universidade de São Paulo), Ajith Kumar Sankarankutty(Universidade de São Paulo), Jose Sebastião dos Santos (Universidade de São Paulo), Daniela Pretti da Cunha Tirapelli(Universidade de São Paulo), Carlos Gilberto Carlotti(Universidade de São Paulo), Felipe Amstalden Trevisan(Universidade de São Paulo), Fabiano Pinto Saggioro(Clinics Hospital of Ribeirão Preto), Houtan Noushmehr(Universidade de São Paulo), Jennifer Eschbacher(St. Joseph's Hospital and Medical Center), Michael Dubina (Saint Petersburg Academic University), Eugene Mozgovoy(Saint Petersburg Academic University), Sally Chalmers (Ninewells Hospital), Ian Forgie(Ninewells Hospital), Frank Carey(Ninewells Hospital), Zaid Naima(University of Kansas Medical Center), Colleen Reilly(University of Kansas Medical Center), Rashna Madan (University of Kansas Medical Center), Andrew Godwin(University of Kansas Medical Center), Michele Vinco(University of Michigan), W. Kimryn Rathmell(University of North Carolina at Chapel Hill), Rajiv Dhir(University of Pittsburgh), Jaffer A. Ajani(The University of Texas MD Anderson Cancer Center), Jaffer A. Ajani (The University of Texas MD Anderson Cancer Center), Jae-Ho Cheong(Yonsei University), Sudha Chudamani(Leidos (United States)), Laxmi Lolla (Leidos (United States)), Jai Liu(Leidos (United States)), Ye Wu(Leidos (United States)), Qiang Sun (Aptara (United States)), Yunhu Wan(Capital Meeting Planning), Todd Pihl(Aptara (United States)), Rashi Naresh(Capital Meeting Planning), Heidi J. Sofia(National Institutes of Health), Carolyn M. Hutter (National Institutes of Health)
Cited by 1,846Open Access
Abstract
Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies. The Cancer Genome Atlas Research Network report integrated genomic and molecular analyses of 164 squamous cell carcinomas and adenocarcinomas of the oesophagus; they find genomic and molecular features that differentiate squamous and adenocarcinomas of the oesophagus, and strong similarities between oesophageal adenocarcinomas and the chromosomally unstable variant of gastric adenocarcinoma, suggesting that gastroesophageal adenocarcinoma is a single disease entity. The Cancer Genome Atlas Research Network reports integrated genomic and molecular analyses of 164 squamous cell carcinomas and adenocarcinomas of the oesophagus. They identify genomic and molecular features that differentiate oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. They find that the genomic profiles of oesophageal adenocarcinomas are more similar to those for gastric adenocarcinoma, suggesting that these might be classified together. Separate consideration of adenocarcinoma and squamous cell carcinoma—and further molecular characterization of these cancers—may be helpful in clinical trials and for developing targeted drug therapies.
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