학술논문
Comprehensive molecular characterization of gastric adenocarcinoma
Document Type
Academic Journal
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, Gordon A.; Sipahimalani, Payal; Cherniack, Andrew; Getz, Gad; Liu, Yingchun; Noble, Michael S.; Pedamallu, Chandra; Sougnez, Carrie; Akbani, Rehan; Lee, Ju-Seog; Liu, Wenbin; Mills, Gordon B.; Yang, Da; Zhang, Wei; Pantazi, Angeliki; Gulley, Margaret; Piazuelo, Blanca M.; 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 S. N.; Carlsen, Rebecca; Chu, Justin; Chuah, Eric; Chun, Hye-Jung E.; Clarke, Amanda; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Jones, Steven J. M.; Lee, Darlene; Li, Haiyan A.; Lim, Emilia; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Karen L.; Nip, Ka Ming; Schein, Jacqueline E.; Tam, Angela; Thiessen, Nina; Beroukhim, Rameen; Carter, Scott L.; Cherniack, Andrew D.; Cho, Juok; DiCara, Daniel; Frazer, Scott; Gehlenborg, Nils; Heiman, David I.; Jung, Joonil; Kim, Jaegil; Lin, Pei; Meyerson, Matthew; Ojesina, Akinyemi I.; Pedamallu, Chandra Sekhar; Saksena, Gordon; Schumacher, Steven E.; Stojanov, Petar; Tabak, Barbara; Voet, Doug; Rosenberg, Mara; Zack, Travis I.; Zhang, Hailei; Zou, Lihua; Protopopov, Alexei; Santoso, Netty; Parfenov, Michael; Lee, Semin; Zhang, Jianhua; Mahadeshwar, Harshad S.; Tang, Jiabin; Ren, Xiaojia; Seth, Sahil; Yang, Lixing; Xu, Andrew W.; Song, Xingzhi; Xi, Ruibin; Bristow, Christopher A.; Hadjipanayis, Angela; Seidman, Jonathan; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Ling, Shiyun; Rao, Arvind; Weinstein, John N.; Kim, Sang-Bae; Lu, Yiling; Mills, Gordon; Bootwalla, Moiz S.; Lai, Phillip H.; Triche, Timothy, Jr; Van Den Berg, David J.; Baylin, Stephen B.; Herman, James G.; Murray, Bradley A.; Askoy, Arman B.; Ciriello, Giovanni; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Lee, William; Ramirez, Ricardo; Sander, Chris; Senbabaoglu, Yasin; Sinha, Rileen; Sumer, Onur S.; Sun, Yichao; Thorsson, Vésteinn; Iype, Lisa; Kramer, Roger W.; Kreisberg, Richard; Rovira, Hector; Tasman, Natalie; Haussler, David; Stuart, Josh M.; Verhaak, Roeland G. W.; Leiserson, Mark D. M.; Taylor, Barry S.; Black, Aaron D.; Carney, Julie Ann; Gastier-Foster, Julie M.; Helsel, Carmen; McAllister, Cynthia; Ramirez, Nilsa C.; Tabler, Teresa R.; Wise, Lisa; Zmuda, Erik; Penny, Robert; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Curely, Erin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Shelton, Troy; Shelton, Candace; Sherman, Mark; Benz, Christopher; Lee, Jae-Hyuk; Fedosenko, Konstantin; Manikhas, Georgy; Potapova, Olga; Voronina, Olga; Belyaev, Dmitry; Dolzhansky, Oleg; Rathmell, Kimryn W.; Brzezinski, Jakub; Ibbs, Matthew; Korski, Konstanty; Kycler, Witold; Łaźniak, Radoslaw; Leporowska, Ewa; Mackiewicz, Andrzej; Murawa, Dawid; Murawa, Pawel; Spychała, Arkadiusz; Suchorska, Wiktoria M.; Tatka, Honorata; Teresiak, Marek; Abdel-Misih, Raafat; Bennett, Joseph; Brown, Jennifer; Iacocca, Mary; Rabeno, Brenda; Kwon, Sun-Young; Kemkes, Ariane; Curley, Erin; Alexopoulou, Iakovina; Engel, Jay; Bartlett, John; Albert, Monique; Park, Do-Youn; Dhir, Rajiv; Luketich, James; Landreneau, Rodney; Janjigian, Yelena Y.; Cho, Eunjung; Ladanyi, Marc; Tang, Laura; McCall, Shannon J.; Park, Young S.; Cheong, Jae-Ho; Ajani, Jaffer; Camargo, Constanza M.; Alonso, Shelley; Ayala, Brenda; Jensen, Mark A.; Pihl, Todd; Raman, Rohini; Walton, Jessica; Wan, Yunhu; Eley, Greg; Mills Shaw, Kenna R.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude; Davidsen, Tanja; Hutter, Carolyn M.; Sofia, Heidi J.; Burton, Robert; Chudamani, Sudha; Liu, Jia
Source
Nature. Sep 11, 2014 513(7517):202-209
Subject
Language
English
ISSN
0028-0836
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.