1. Comprehensive molecular characterization of gastric adenocarcinoma
- Author
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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 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, 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, Van Den Berg, David J., Baylin, Stephen B., Herman, James G., Murray, Bradley A., Askoy, B. Arman, Ciriello, Giovanni, Dresdner, Gideon, Gao, Jianjiong, Gross, Benjamin, Jacobsen, Anders, Lee, William, Ramirez, Ricardo, Sander, Chris, Senbabaoglu, Yasin, Sinha, Rileen, Sumer, S. Onur, Sun, Yichao, Thorsson, Vésteinn, Iype, Lisa, Kramer, Roger W., Kreisberg, Richard, Rovira, Hector, Tasman, Natalie, Ng, Santa Cruz Sam, 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, Smitry, Dolzhansky, Oleg, Rathmell, W. Kimryn, Brzezinski, Jakub, Ibbs, Matthew, Korski, Konstanty, Kycler, Witold, ŁaŸniak, 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, M. Constanza, 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, Broad Institute of MIT and Harvard, Massachusetts Institute of Technology. Department of Biology, Getz, Gad Asher, Sougnez, Carrie L, Jung, Joonil, Lander, Eric Steven, Lin, Pei, Meyerson, Matthew L, and Voet, Douglas
- Subjects
Male ,Herpesvirus 4, Human ,Proteome ,Biology ,Adenocarcinoma ,Bioinformatics ,MLH1 ,Article ,Epstein-Barr virus associated gastric carcinoma ,Germline mutation ,Stomach Neoplasms ,medicine ,Humans ,Multidisciplinary ,CpG Island Methylator Phenotype ,Genome, Human ,digestive, oral, and skin physiology ,medicine.disease ,digestive system diseases ,Lynch syndrome ,3. Good health ,Gene Expression Regulation, Neoplastic ,Mutation ,Cancer research ,Female ,DNA mismatch repair ,Gastric Carcinoma with Lymphoid Stroma - 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., National Institutes of Health (U.S.) (Grant 5U24CA143799), National Institutes of Health (U.S.) (Grant 5U24CA143835), National Institutes of Health (U.S.) (Grant 5U24CA143840), National Institutes of Health (U.S.) (Grant 5U24CA143843), National Institutes of Health (U.S.) (Grant 5U24CA143845), National Institutes of Health (U.S.) (Grant 5U24CA143848), National Institutes of Health (U.S.) (Grant 5U24CA143858), National Institutes of Health (U.S.) (Grant 5U24CA143866), National Institutes of Health (U.S.) (Grant 5U24CA143867), National Institutes of Health (U.S.) (Grant 5U24CA143882), National Institutes of Health (U.S.) (Grant 5U24CA143883), National Institutes of Health (U.S.) (Grant 5U24CA144025), National Institutes of Health (U.S.) (Grant U54HG003067), National Institutes of Health (U.S.) (Grant U54HG003079), National Institutes of Health (U.S.) (Grant U54HG003273), National Institutes of Health (U.S.) (Grant P30CA16672)
- Published
- 2014