Comprehensive molecular characterization of gastric adenocarcinoma
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Author(s)
Getz, Gad Asher
Sougnez, Carrie L
Jung, Joonil
Lander, Eric Steven
Lin, Pei
Voet, Douglas
Meyerson, Matthew L.
Date Issued
September 2014
Journal
Nature
Publisher
Nature Publishing Group
Citation
Bass, Adam J. et al. “Comprehensive Molecular Characterization of Gastric Adenocarcinoma.” Nature 513, 7517 (July 2014): 202–209 © 2014 Macmillan Publishers Limited
Version
Final published version
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.
MIT Department
Broad Institute of MIT and Harvard
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1038/NATURE13480
