TY - JOUR
T1 - Comprehensive molecular characterization of gastric adenocarcinoma
AU - Cancer Genome Atlas Research Network
AU - Bass, Adam J.
AU - Thorsson, Vesteinn
AU - Shmulevich, Ilya
AU - Reynolds, Sheila M.
AU - Miller, Michael
AU - Bernard, Brady
AU - Hinoue, Toshinori
AU - Laird, Peter W.
AU - Curtis, Christina
AU - Shen, Hui
AU - Weisenberger, Daniel J.
AU - Schultz, Nikolaus
AU - Shen, Ronglai
AU - Weinhold, Nils
AU - Kelsen, David P.
AU - Bowlby, Reanne
AU - Chu, Andy
AU - Kasaian, Katayoon
AU - Mungall, Andrew J.
AU - Robertson, A. Gordon
AU - Sipahimalani, Payal
AU - Cherniack, Andrew D.
AU - Getz, Gad
AU - Liu, Yingchun
AU - Noble, Michael S.
AU - Pedamallu, Chandra
AU - Sougnez, Carrie
AU - Taylor-Weiner, Amaro
AU - Akbani, Rehan
AU - Lee, Ju Seog
AU - Liu, Wenbin
AU - Mills, Gordon B.
AU - Yang, Da
AU - Zhang, Wei
AU - Pantazi, Angeliki
AU - Parfenov, Michael
AU - Gulley, Margaret
AU - Piazuelo, M. Blanca
AU - Schneider, Barbara G.
AU - Kim, Jihun
AU - Boussioutas, Alex
AU - Sheth, Margi
AU - Demchok, John A.
AU - Rabkin, Charles S.
AU - Willis, Joseph E.
AU - Ng, Sam
AU - Garman, Katherine
AU - Beer, David G.
AU - Pennathur, Arjun
AU - Eley, Greg
N1 - Funding Information:
Acknowledgements We are grateful to all the patients and families who contributed to this study and to C. Gunter and J. Weinstein for scientific editing, to M. Sheth for administrative support and to L. Omberg for support with the Sage Bionetworks Synapse platform. This work was supported by the Intramural Research Program and the following grants from the United States National Institutes of Health: 5U24CA143799, 5U24CA143835, 5U24CA143840, 5U24CA143843, 5U24CA143845, 5U24CA143848, 5U24CA143858, 5U24CA143866, 5U24CA143867, 5U24CA143882, 5U24CA143883, 5U24CA144025, U54HG003067, U54HG003079, U54HG003273 and P30CA16672.
Publisher Copyright:
©2014 Macmillan Publishers Limited. All rights reserved.
PY - 2014/9/11
Y1 - 2014/9/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84907270779&partnerID=8YFLogxK
U2 - 10.1038/nature13480
DO - 10.1038/nature13480
M3 - Article
C2 - 25079317
AN - SCOPUS:84907270779
SN - 0028-0836
VL - 513
SP - 202
EP - 209
JO - Nature
JF - Nature
IS - 7517
ER -