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Nature. 2017 Jan 12;541(7636):169-175. doi: 10.1038/nature20805. Epub 2017 Jan 4.

Integrated genomic characterization of oesophageal carcinoma.

Cancer Genome Atlas Research Network; Analysis Working Group: Asan University; BC Cancer Agency; Brigham and Women’s Hospital; Broad Institute; Brown University; Case Western Reserve University; Dana-Farber Cancer Institute; Duke University; Greater Poland Cancer Centre; Harvard Medical School; Institute for Systems Biology; KU Leuven; Mayo Clinic; Memorial Sloan Kettering Cancer Center; National Cancer Institute; Nationwide Children’s Hospital; Stanford University; University of Alabama; University of Michigan; University of North Carolina; University of Pittsburgh; University of Rochester; University of Southern California; University of Texas MD Anderson Cancer Center; University of Washington; Van Andel Research Institute; Vanderbilt University; Washington University; Genome Sequencing Center: Broad Institute; Washington University in St. Louis; Genome Characterization Centers: BC Cancer Agency; Broad Institute; Harvard Medical School; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University; University of North Carolina; University of Southern California Epigenome Center; University of Texas MD Anderson Cancer Center; Van Andel Research Institute; Genome Data Analysis Centers: Broad Institute; Brown University:; Harvard Medical School; Institute for Systems Biology; Memorial Sloan Kettering Cancer Center; University of California Santa Cruz; University of Texas MD Anderson Cancer Center; Biospecimen Core Resource: International Genomics Consortium; Research Institute at Nationwide Children’s Hospital; Tissue Source Sites: Analytic Biologic Services; Asan Medical Center; Asterand Bioscience; Barretos Cancer Hospital; BioreclamationIVT; Botkin Municipal Clinic; Chonnam National University Medical School; Christiana Care Health System; Cureline; Duke University; Emory University; Erasmus University; Indiana University School of Medicine; Institute of Oncology of Moldova; International Genomics Consortium; Invidumed; Israelitisches Krankenhaus Hamburg; Keimyung University School of Medicine; Memorial Sloan Kettering Cancer Center; National Cancer Center Goyang; Ontario Tumour Bank; Peter MacCallum Cancer Centre; Pusan National University Medical School; Ribeirão Preto Medical School; St. Joseph’s Hospital &Medical Center; St. Petersburg Academic University; Tayside Tissue Bank; University of Dundee; University of Kansas Medical Center; University of Michigan; University of North Carolina at Chapel Hill; University of Pittsburgh School of Medicine; University of Texas MD Anderson Cancer Center; Disease Working Group: Duke University; Memorial Sloan Kettering Cancer Center; National Cancer Institute; University of Texas MD Anderson Cancer Center; Yonsei University College of Medicine; Data Coordination Center: CSRA Inc.; Project Team: National Institutes of Health.

Collaborators (346)

Kim J, Bowlby R, Mungall AJ, Robertson AG, Odze RD, Cherniack AD, Shih J, Pedamallu CS, Cibulskis C, Dunford A, Meier SR, Kim J, Raphael BJ, Wu HT, Wong AM, Willis JE, Bass AJ, Derks S, Garman K, McCall SJ, Wiznerowicz M, Pantazi A, Parfenov M, Thorsson V, Shmulevich I, Dhankani V, Miller M, Sakai R, Wang K, Schultz N, Shen R, Arora A, Weinhold N, Sánchez-Vega F, Kelsen DP, Zhang J, Felau I, Demchok J, Rabkin CS, Camargo MC, Zenklusen JC, Bowen J, Leraas K, Lichtenberg TM, Curtis C, Seoane JA, Ojesina AI, Beer DG, Gulley ML, Pennathur A, Luketich JD, Zhou Z, Weisenberger DJ, Akbani R, Lee JS, Liu W, Mills GB, Zhang W, Reid BJ, Hinoue T, Laird PW, Shen H, Piazuelo MB, Schneider BG, McLellan M, Taylor-Weiner A, Cibulskis C, Lawrence M, Cibulskis K, Stewart C, Getz G, Lander E, Gabriel SB, Ding L, McLellan MD, Miller CA, Appelbaum EL, Cordes MG, Fronick CC, Fulton LA, Mardis ER, Wilson RK, Schmidt HK, Fulton RS, Ally A, Balasundaram M, Bowlby R, Carlsen R, Chuah E, Dhalla N, Holt RA, Jones SJ, Kasaian K, Brooks D, Li HI, Ma Y, Marra MA, Mayo M, Moore RA, Mungall AJ, Mungall KL, Robertson AG, Schein JE, Sipahimalani P, Tam A, Thiessen N, Wong T, Cherniack AD, Shih J, Pedamallu CS, Beroukhim R, Bullman S, Cibulskis C, Murray BA, Saksena G, Schumacher SE, Gabriel S, Meyerson M, Hadjipanayis A, Kucherlapati R, Pantazi A, Parfenov M, Ren X, Park PJ, Lee S, Kucherlapati M, Yang L, Baylin SB, Hoadley KA, Weisenberger DJ, Bootwalla MS, Lai PH, Van Den Berg DJ, Berrios M, Holbrook A, Akbani R, Hwang JE, Jang HJ, Liu W, Weinstein JN, Lee JS, Lu Y, Sohn BH, Mills G, Seth S, Protopopov A, Bristow CA, Mahadeshwar HS, Tang J, Song X, Zhang J, Laird PW, Hinoue T, Shen H, Cho J, Defrietas T, Frazer S, Gehlenborg N, Heiman DI, Lawrence MS, Lin P, Meier SR, Noble MS, Voet D, Zhang H, Kim J, Polak P, Saksena G, Chin L, Getz G, Wong AM, Raphael BJ, Wu HT, Lee S, Park PJ, Yang L, Thorsson V, Bernard B, Iype L, Miller M, Reynolds SM, Shmulevich I, Dhankani V, Abeshouse A, Arora A, Armenia J, Kundra R, Ladanyi M, Lehmann KV, Gao J, Sander C, Schultz N, Sánchez-Vega F, Shen R, Weinhold N, Chakravarty D, Zhang H, Radenbaugh A, Hegde A, Akbani R, Liu W, Weinstein JN, Chin L, Bristow CA, Lu Y, Penny R, Crain D, Gardner J, Curley E, Mallery D, Morris S, Paulauskis J, Shelton T, Shelton C, Bowen J, Frick J, Gastier-Foster JM, Gerken M, Leraas KM, Lichtenberg TM, Ramirez NC, Wise L, Zmuda E, Tarvin K, Saller C, Park YS, Button M, Carvalho AL, Reis RM, Matsushita MM, Lucchesi F, de Oliveira AT, Le X, Paklina O, Setdikova G, Lee JH, Bennett J, Iacocca M, Huelsenbeck-Dill L, Potapova O, Voronina O, Liu O, Fulidou V, Cates C, Sharp A, Behera M, Force S, Khuri F, Owonikoko T, Pickens A, Ramalingam S, Sica G, Dinjens W, van Nistelrooij A, Wijnhoven B, Sandusky G, Stepa S, Crain D, Paulauskis J, Penny R, Gardner J, Mallery D, Morris S, Shelton T, Shelton C, Curley E, Juhl H, Zornig C, Kwon SY, Kelsen D, Kim HK, Bartlett J, Parfitt J, Chetty R, Darling G, Knox J, Wong R, El-Zimaity H, Liu G, Boussioutas A, Park DY, Kemp R, Carlotti CG, da Cunha Tirapelli DP, Saggioro FP, Sankarankutty AK, Noushmehr H, Dos Santos JS, Trevisan FA, Eschbacher J, Dubina M, Mozgovoy E, Carey F, Chalmers S, Forgie I, Godwin A, Reilly C, Madan R, Naima Z, Ferrer-Torres D, Vinco M, Rathmell WK, Dhir R, Luketich J, Pennathur A, Ajani JA, McCall SJ, Janjigian Y, Kelsen D, Ladanyi M, Tang L, Camargo MC, Ajani JA, Cheong JH, Chudamani S, Liu J, Lolla L, Naresh R, Pihl T, Sun Q, Wan Y, Wu Y, Demchok JA, Felau I, Ferguson ML, Shaw KR, Sheth M, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Hutter CM, Sofia HJ, Zhang J, Demchok JA, Felau I, Ferguson ML, Shaw KR, Sheth M, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Hutter CM, Sofia HJ, Zhang J.

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.

PMID:
28052061
PMCID:
PMC5651175
DOI:
10.1038/nature20805
[Indexed for MEDLINE]
Free PMC Article

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