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Comprehensive molecular characterization of gastric adenocarcinoma

Author(s)
Getz, Gad Asher; Sougnez, Carrie L; Jung, Joonil; Lander, Eric Steven; Lin, Pei; Voet, Douglas; Meyerson, Matthew L.; ... Show more Show less
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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.
Date issued
2014-09
URI
http://hdl.handle.net/1721.1/116734
Department
Broad Institute of MIT and Harvard; Massachusetts Institute of Technology. Department of Biology
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
ISSN
0028-0836
1476-4687

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