Integrated genomic characterization of oesophageal carcinoma

Author:  ["Jihun Kim","Reanne Bowlby","Andrew J. Mungall","A. Gordon Robertson","Robert D. Odze","Andrew D. Cherniack","Juliann Shih","Chandra Sekhar Pedamallu","Carrie Cibulskis","Andrew Dunford","Samuel R. Meier","Jaegil Kim","Benjamin J. Raphael","Hsin-Ta Wu","Alexandra M. Wong","Joseph E. Willis","Adam J. Bass","Sarah Derks","Katherine Garman","Shannon J. McCall","Maciej Wiznerowicz","Angeliki Pantazi","Michael Parfenov","Vésteinn Thorsson","Ilya Shmulevich","Varsha Dhankani","Michael Miller","Ryo Sakai","Kenneth Wang","Nikolaus Schultz","Ronglai Shen","Arshi Arora","Nils Weinhold","Francisco Sánchez-Vega","David P. Kelsen","Julia Zhang","Ina Felau","John Demchok","Charles S. Rabkin","M. Constanza Camargo","Jean Claude Zenklusen","Jay Bowen","Kristen Leraas","Tara M. Lichtenberg","Christina Curtis","Jose A. Seoane","Akinyemi I. Ojesina","David G. Beer","Margaret L. Gulley","Arjun Pennathur","James D. Luketich","Zhongren Zhou","Daniel J. Weisenberger","Rehan Akbani","Ju-Seog Lee","Wenbin Liu","Gordon B. Mills","Wei Zhang","Brian J Reid","Toshinori Hinoue","Peter W. Laird","Hui Shen","M. Blanca Piazuelo","Barbara G. Schneider","Michael McLellan","Amaro Taylor-Weiner","Carrie Cibulskis","Michael Lawrence","Kristian Cibulskis","Chip Stewart","Gad Getz","Eric Lander","Stacey B. Gabriel","Li Ding","Michael D. McLellan","Christopher A. Miller","Elizabeth L. Appelbaum","Matthew G. Cordes","Catrina C. Fronick","Lucinda A. Fulton","Elaine R. Mardis","Richard K. Wilson","Heather K. Schmidt","Robert S. Fulton","Adrian Ally","Miruna Balasundaram","Reanne Bowlby","Rebecca Carlsen","Eric Chuah","Noreen Dhalla","Robert A. Holt","Steven J. M. Jones","Katayoon Kasaian","Denise Brooks","Haiyan I. Li","Yussanne Ma","Marco A. Marra","Michael Mayo","Richard A. Moore","Andrew J. Mungall","Karen L. Mungall","A. Gordon Robertson","Jacqueline E. Schein","Payal Sipahimalani","Angela Tam","Nina Thiessen","Tina Wong","Andrew D. Cherniack","Juliann Shih","Chandra Sekhar Pedamallu","Rameen Beroukhim","Susan Bullman","Carrie Cibulskis","Bradley A. Murray","Gordon Saksena","Steven E. Schumacher","Stacey Gabriel","Matthew Meyerson","Angela Hadjipanayis","Raju Kucherlapati","Angeliki Pantazi","Michael Parfenov","Xiaojia Ren","Peter J. Park","Semin Lee","Melanie Kucherlapati","Lixing Yang","Stephen B. Baylin","Katherine A. Hoadley","Daniel J. Weisenberger","Moiz S. Bootwalla","Phillip H. Lai","David J. Van Den Berg","Mario Berrios","Andrea Holbrook","Rehan Akbani","Jun-Eul Hwang","Hee-Jin Jang","Wenbin Liu","John N. Weinstein","Ju-Seog Lee","Yiling Lu","Bo Hwa Sohn","Gordon Mills","Sahil Seth","Alexei Protopopov","Christopher A. Bristow","Harshad S. Mahadeshwar","Jiabin Tang","Xingzhi Song","Jianhua Zhang","Peter W. Laird","Toshinori Hinoue","Hui Shen","Juok Cho","Timothy Defrietas","Scott Frazer","Nils Gehlenborg","David I. Heiman","Michael S. Lawrence","Pei Lin","Samuel R. Meier","Michael S. Noble","Doug Voet","Hailei Zhang","Jaegil Kim","Paz Polak","Gordon Saksena","Lynda Chin","Gad Getz","Alexandra M. Wong","Benjamin J. Raphael","Hsin-Ta Wu","Semin Lee","Peter J. Park","Lixing Yang","Vésteinn Thorsson","Brady Bernard","Lisa Iype","Michael Miller","Sheila M. Reynolds","Ilya Shmulevich","Varsha Dhankani","Adam Abeshouse","Arshi Arora","Joshua Armenia","Ritika Kundra","Marc Ladanyi","Kjong-Van Lehmann","Jianjiong Gao","Chris Sander","Nikolaus Schultz","Francisco Sánchez-Vega","Ronglai Shen","Nils Weinhold","Debyani Chakravarty","Hongxin Zhang","Amie Radenbaugh","Apruva Hegde","Rehan Akbani","Wenbin Liu","John N. Weinstein","Lynda Chin","Christopher A. Bristow","Yiling Lu","Robert Penny","Daniel Crain","Johanna Gardner","Erin Curley","David Mallery","Scott Morris","Joseph Paulauskis","Troy Shelton","Candace Shelton","Jay Bowen","Jessica Frick","Julie M. Gastier-Foster","Mark Gerken","Kristen M. Leraas","Tara M. Lichtenberg","Nilsa C. Ramirez","Lisa Wise","Erik Zmuda","Katherine Tarvin","Charles Saller","Young Soo Park","Michael Button","Andre L. Carvalho","Rui Manuel Reis","Marcus Medeiros Matsushita","Fabiano Lucchesi","Antonio Talvane de Oliveira","Xuan Le","Oxana Paklina","Galiya Setdikova","Jae-Hyuck Lee","Joseph Bennett","Mary Iacocca","Lori Huelsenbeck-Dill","Olga Potapova","Olga Voronina","Ouida Liu","Victoria Fulidou","Crystal Cates","Alexis Sharp","Madhusmitara Behera","Seth Force","Fadio Khuri","Taofeek Owonikoko","Allan Pickens","Suresh Ramalingam","Gabriel Sica","Winand Dinjens","Anna van Nistelrooij","Bas Wijnhoven","George Sandusky","Serghei Stepa","Daniel Crain","Joseph Paulauskis","Robert Penny","Johanna Gardner","David Mallery","Scott Morris","Troy Shelton","Candace Shelton","Erin Curley","Hartmut Juhl","Carsten Zornig","Sun Young Kwon","David Kelsen","Hark Kyun Kim","John Bartlett","Jeremy Parfitt","Runjan Chetty","Gail Darling","Jennifer Knox","Rebecca Wong","Haila El-Zimaity","Geoffrey Liu","Alex Boussioutas","Do Young Park","Rafael Kemp","Carlos Gilberto Carlotti","Daniela Pretti da Cunha Tirapelli","Fabiano Pinto Saggioro","Ajith Kumar Sankarankutty","Houtan Noushmehr","Jose Sebastião dos Santos","Felipe Amstalden Trevisan","Jennifer Eschbacher","Michael Dubina","Eugene Mozgovoy","Frank Carey","Sally Chalmers","Ian Forgie","Andrew Godwin","Colleen Reilly","Rashna Madan","Zaid Naima","Daysha Ferrer-Torres","Michele Vinco","W. Kimryn Rathmell","Rajiv Dhir","James Luketich","Arjun Pennathur","Jaffer A. Ajani","Shannon J. McCall","Yelena Janjigian","David Kelsen","Marc Ladanyi","Laura Tang","M. Constanza Camargo","Jaffer A. Ajani","Jae-Ho Cheong","Sudha Chudamani","Jai Liu","Laxmi Lolla","Rashi Naresh","Todd Pihl","Qiang Sun","Yunhu Wan","Ye Wu","John A. Demchok","Ina Felau","Martin L. Ferguson","Kenna R. Mills Shaw","Margi Sheth","Roy Tarnuzzer","Zhining Wang","Liming Yang","Jean Claude Zenklusen","Carolyn M. Hutter","Heidi J. Sofia","Jiashan Zhang"]

Publication:  Nature

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Tags:  Oesophageal cancer   Mathematics

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.

Cite this article

The Cancer Genome Atlas Research Network., Analysis Working Group: Asan University., Kim, J. et al. Integrated genomic characterization of oesophageal carcinoma. Nature 541, 169–175 (2017). https://doi.org/10.1038/nature20805

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