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 - 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 -