학술논문
Comprehensive molecular characterization of gastric adenocarcinoma
Document Type
article
Author
Bass, Adam J; Thorsson, Vesteinn; Shmulevich, Ilya; Reynolds, Sheila M; Miller, Michael; Bernard, Brady; Hinoue, Toshinori; Laird, Peter W; Curtis, Christina; Shen, Hui; Weisenberger, Daniel J; Schultz, Nikolaus; Shen, Ronglai; Weinhold, Nils; Kelsen, David P; Bowlby, Reanne; Chu, Andy; Kasaian, Katayoon; Mungall, Andrew J; Robertson, A Gordon; Sipahimalani, Payal; Cherniack, Andrew; Getz, Gad; Liu, Yingchun; Noble, Michael S; Pedamallu, Chandra; Sougnez, Carrie; Taylor-Weiner, Amaro; Akbani, Rehan; Lee, Ju-Seog; Liu, Wenbin; Mills, Gordon B; Yang, Da; Zhang, Wei; Pantazi, Angeliki; Parfenov, Michael; Gulley, Margaret; Piazuelo, M Blanca; Schneider, Barbara G; Kim, Jihun; Boussioutas, Alex; Sheth, Margi; Demchok, John A; Rabkin, Charles S; Willis, Joseph E; Ng, Sam; Garman, Katherine; Beer, David G; Pennathur, Arjun; Raphael, Benjamin J; Wu, Hsin-Ta; Odze, Robert; Kim, Hark K; Bowen, Jay; Leraas, Kristen M; Lichtenberg, Tara M; Weaver, Stephanie; McLellan, Michael; Wiznerowicz, Maciej; Sakai, Ryo; Lawrence, Michael S; Cibulskis, Kristian; Lichtenstein, Lee; Fisher, Sheila; Gabriel, Stacey B; Lander, Eric S; Ding, Li; Niu, Beifang; Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Brooks, Denise; Butterfield, Yaron SN; Carlsen, Rebecca; Chu, Justin; Chuah, Eric; Chun, Hye-Jung E; Clarke, Amanda; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A; Jones, Steven JM; Lee, Darlene; Li, Haiyan A; Lim, Emilia; Ma, Yussanne; Marra, Marco A; Mayo, Michael; Moore, Richard A; Mungall, Karen L; Ming Nip, Ka; Schein, Jacqueline E
Source
Nature. 513(7517)
Subject
Language
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.