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Nature. 2014 Sep 11;513(7517):202-9. doi: 10.1038/nature13480. Epub 2014 Jul 23.

Comprehensive molecular characterization of gastric adenocarcinoma.

Collaborators (315)

Bass AJ, Thorsson V, Shmulevich I, Reynolds SM, Miller M, Bernard B, Hinoue T, Laird PW, Curtis C, Shen H, Weisenberger DJ, Schultz N, Shen R, Weinhold N, Kelsen DP, Bowlby R, Chu A, Kasaian K, Mungall AJ, Robertson AG, Sipahimalani P, Cherniack AD, Getz G, Liu Y, Noble MS, Pedamallu C, Sougnez C, Taylor-Weiner A, Akbani R, Lee JS, Liu W, Mills GB, Yang D, Zhang W, Pantazi A, Parfenov M, Gulley M, Piazuelo MB, Schneider BG, Kim J, Boussioutas A, Sheth M, Demchok JA, Rabkin CS, Willis JE, Ng S, Garman K, Beer DG, Pennathur A, Raphael BJ, Wu HT, Odze R, Kim HK, Bowen J, Leraas KM, Lichtenberg TM, Weaver S, McLellan M, Wiznerowicz M, Sakai R, Getz G, Sougnez C, Lawrence MS, Cibulskis K, Lichtenstein L, Fisher S, Gabriel SB, Lander ES, Ding L, Niu B, Ally A, Balasundaram M, Birol I, Bowlby R, Brooks D, Butterfield YS, Carlsen R, Chu A, Chu J, Chuah E, Chun HJ, Clarke A, Dhalla N, Guin R, Holt RA, Jones SJ, Kasaian K, Lee D, Li HA, Lim E, Ma Y, Marra MA, Mayo M, Moore RA, Mungall AJ, Mungall KL, Ming Nip K, Robertson AG, Schein JE, Sipahimalani P, Tam A, Thiessen N, Beroukhim R, Carter SL, Cherniack AD, Cho J, Cibulskis K, DiCara D, Frazer S, Fisher S, Gabriel SB, Gehlenborg N, Heiman DI, Jung J, Kim J, Lander ES, Lawrence MS, Lichtenstein L, Lin P, Meyerson M, Ojesina AI, Sekhar Pedamallu C, Saksena G, Schumacher SE, Sougnez C, Stojanov P, Tabak B, Taylor-Weiner A, Voet D, Rosenberg M, Zack TI, Zhang H, Zou L, Protopopov A, Santoso N, Parfenov M, Lee S, Zhang J, Mahadeshwar HS, Tang J, Ren X, Seth S, Yang L, Xu AW, Song X, Pantazi A, Xi R, Bristow CA, Hadjipanayis A, Seidman J, Chin L, Park PJ, Kucherlapati R, Akbani R, Ling S, Liu W, Rao A, Weinstein JN, Kim SB, Lee JS, Lu Y, Mills G, Laird PW, Hinoue T, Weisenberger DJ, Bootwalla MS, Lai PH, Shen H, Triche T Jr, Van Den Berg DJ, Baylin SB, Herman JG, Getz G, Chin L, Liu Y, Murray BA, Noble MS, Askoy BA, Ciriello G, Dresdner G, Gao J, Gross B, Jacobsen A, Lee W, Ramirez R, Sander C, Schultz N, Senbabaoglu Y, Sinha R, Sumer SO, Sun Y, Weinhold N, Thorsson V, Bernard B, Iype L, Kramer RW, Kreisberg R, Miller M, Reynolds SM, Rovira H, Tasman N, Shmulevich I, Ng S, Haussler D, Stuart JM, Akbani R, Ling S, Liu W, Rao A, Weinstein JN, Verhaak RG, Mills GB, Leiserson MD, Raphael BJ, Wu HT, Taylor BS, Black AD, Bowen J, Carney JA, Gastier-Foster JM, Helsel C, Leraas KM, Lichtenberg TM, McAllister C, Ramirez NC, Tabler TR, Wise L, Zmuda E, Penny R, Crain D, Gardner J, Lau K, Curely E, Mallery D, Morris S, Paulauskis J, Shelton T, Shelton C, Sherman M, Benz C, Lee JH, Fedosenko K, Manikhas G, Potapova O, Voronina O, Belyaev D, Dolzhansky O, Rathmell WK, Brzezinski J, Ibbs M, Korski K, Kycler W, Laźniak R, Leporowska E, Mackiewicz A, Murawa D, Murawa P, Spychała A, Suchorska WM, Tatka H, Teresiak M, Wiznerowicz M, Abdel-Misih R, Bennett J, Brown J, Iacocca M, Rabeno B, Kwon SY, Penny R, Gardner J, Kemkes A, Mallery D, Morris S, Shelton T, Shelton C, Curley E, Alexopoulou I, Engel J, Bartlett J, Albert M, Park DY, Dhir R, Luketich J, Landreneau R, Janjigian YY, Kelsen DP, Cho E, Ladanyi M, Tang L, McCall SJ, Park YS, Cheong JH, Ajani J, Camargo MC, Alonso S, Ayala B, Jensen MA, Pihl T, Raman R, Walton J, Wan Y, Demchok JA, Eley G, Mills Shaw KR, Sheth M, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Davidsen T, Hutter CM, Sofia HJ, Burton R, Chudamani S, Liu J.

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.

PMID:
25079317
PMCID:
PMC4170219
DOI:
10.1038/nature13480
[Indexed for MEDLINE]
Free PMC Article

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