Comprehensive molecular characterization of gastric adenocarcinoma

Adam J. Bass, Vesteinn Thorsson, Ilya Shmulevich, Sheila M. Reynolds, Michael Miller, Brady Bernard, Toshinori Hinoue, Peter W. Laird, Christina Curtis, Hui Shen, Daniel J. Weisenberger, Nikolaus Schultz, Ronglai Shen, Nils Weinhold, David P. Kelsen, Reanne Bowlby, Andy Chu, Katayoon Kasaian, Andrew J. Mungall, A. Gordon RobertsonPayal Sipahimalani, Andrew D. Cherniack, Gad Getz, Yingchun Liu, Michael S. Noble, Chandra Pedamallu, Carrie Sougnez, Amaro Taylor-Weiner, Rehan Akbani, Ju Seog Lee, Wenbin Liu, Gordon B. Mills, Da Yang, Wei Zhang, Angeliki Pantazi, Michael Parfenov, Margaret Gulley, M. Blanca Piazuelo, Barbara G. Schneider, Jihun Kim, Alex Boussioutas, Margi Sheth, John A. Demchok, Charles S. Rabkin, Joseph E. Willis, Sam Ng, Katherine Garman, David G. Beer, Arjun Pennathur, Lihua Zou, Cancer Genome Atlas Research Network

Research output: Contribution to journalArticlepeer-review

3098 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)202-209
Number of pages8
JournalNature
Volume513
Issue number7517
DOIs
StatePublished - Sep 11 2014

ASJC Scopus subject areas

  • General

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