Comprehensive molecular characterization of gastric adenocarcinoma

被引：5383

作者：

Bass, Adam J. ^{[1
,2
]}

Thorsson, Vesteinn ^{[3
]}

Shmulevich, Ilya ^{[3
]}

Reynolds, Sheila M. ^{[3
]}

Miller, Michael ^{[3
]}

Bernard, Brady ^{[3
]}

Hinoue, Toshinori ^{[4
]}

Laird, Peter W. ^{[4
]}

Curtis, Christina ^{[5
]}

Shen, Hui ^{[4
]}

Weisenberger, Daniel J. ^{[4
]}

Schultz, Nikolaus ^{[6
]}

Shen, Ronglai ^{[7
]}

Weinhold, Nils ^{[6
]}

Keiser, David P. ^{[8
]}

Bowlby, Reanne ^{[9
]}

Sipahimalani, Payal ^{[9
]}

Cherniack, Andrew D. ^{[10
]}

Getz, Gad ^{[10
]}

Liu, Yingchun ^{[10
]}

Noble, Michael S. ^{[10
]}

Pedamallu, Chandra ^{[10
]}

Sougnez, Carrie ^{[10
]}

Taylor-Weiner, Amaro ^{[10
]}

Akbani, Rehan ^{[11
]}

Lee, Ju-Seog ^{[11
,12
]}

Liu, Wenbin ^{[11
]}

Mills, Gordon B. ^{[12
]}

Yang, Da ^{[13
]}

Zhang, Wei ^{[13
]}

Pantazi, Angeliki ^{[14
]}

Parfenov, Michael ^{[14
]}

Gulley, Margaret ^{[15
]}

Piazuelo, M. Blanca ^{[16
]}

Schneider, Barbara G. ^{[16
]}

Kim, Jihun ^{[17
]}

Boussioutas, Alex ^{[18
]}

Sheth, Margi ^{[19
]}

Demchok, John A. ^{[19
]}

Rabkin, Charles S. ^{[20
]}

Willis, Joseph E. ^{[21
]}

Ng, Sam ^{[22
]}

Garman, Katherine ^{[24
]}

Beer, David G. ^{[25
]}

Pennathur, Arjun ^{[26
]}

Raphael, Benjamin J. ^{[27
]}

Wu, Hsin-Ta ^{[27
,28
]}

Odze, Robert ^{[29
]}

Kim, Hark K. ^{[30
]}

Bowen, Jay ^{[31
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[2] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA

[3] Inst Syst Biol, Seattle, WA 98109 USA

[4] Univ So Calif, USC Epigenome Ctr, Los Angeles, CA 90033 USA

[5] Univ So Calif, Dept Prevent Med, USC Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA

[6] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA

[7] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA

[8] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA

[9] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada

[10] Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA

[11] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA

[12] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA

[13] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

[14] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA

[15] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA

[16] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA

[17] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul 138736, South Korea

[18] Univ Melbourne, Sir Peter MacCallum Canc Dept Oncol, East Melbourne 3002, Australia

[19] NCI, Bethesda, MD 20892 USA

[20] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[21] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA

[22] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA

[23] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA

[24] Duke Univ, Dept Med, Div Gastroenterol, Durham, NC 27710 USA

[25] Univ Michigan, Ctr Canc, Dept Thorac Surg, Ann Arbor, MI 48109 USA

[26] Univ Pittsburgh, Pittsburgh, PA 15213 USA

[27] Brown Univ, Dept Comp Sci, Providence, RI 02912 USA

[28] Brown Univ, Ctr Computat Mol Biol, Providence, RI 02912 USA

[29] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[30] Natl Canc Ctr, Goyang 410769, South Korea

[31] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA

[32] Washington Univ, Genome Inst, St Louis, MO 63108 USA

[33] Greater Poland Canc Ctr, PL-61866 Poznan, Poland

[34] Katholieke Univ Leuven, Dept Elect Engn ESAT STADIUS, Leuven, Belgium

[35] Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Dept Genom Med, Houston, TX 77054 USA

[36] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA

[37] Johns Hopkins Univ, Canc Biol Div, Baltimore, MD 21231 USA

[38] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA

[39] Int Genom Consortium, Phoenix, AZ 85004 USA

[40] Buck Inst Res Aging, Novato, CA 94945 USA

[41] Chonnam Natl Univ, Sch Med, Kwangju 501746, South Korea

[42] City Clin Oncol Dispensary, St Petersburg 198255, Russia

[43] Cureline Inc, San Francisco, CA 94080 USA

[44] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA

[45] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[46] Christiana Care Hlth Syst, Helen Graham Canc Ctr & Res Inst, Newark, DE 19713 USA

[47] Keimyung Univ, Sch Med, Taegu 700712, South Korea

[48] St Josephs Healthcare Hamilton, Ontario Tumour Bank, Hamilton, ON L8N 3Z5, Canada

[49] Kingston Gen Hosp, Ontario Tumour Bank, Kingston, ON K7L 5H6, Canada

[50] Ontario Inst Canc Res, Ontario Tumour Bank, Toronto, ON M5G 0A3, Canada

来源：

NATURE | 2014年 / 513卷 / 7517期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

SOMATIC MUTATIONS; GENE-EXPRESSION; CELL LYMPHOMAS; EBV-INFECTION; CANCER; EXOME; METHYLATION; SUBTYPES; KINASE; CLASSIFICATION;

D O I：

10.1038/nature13480

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Gastric cancer is a leading cause of cancer deaths, but analysis of 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 roalmap for patient stratification and trials of targeted therapies.

引用

页码：202 / 209

页数：8

共 40 条

[1]

[Anonymous], 2013, IARC Cancer Base

[2]

Simultaneous tyrosine and serine phosphorylation of STAT3 transcription factor is involved in Rho A GTPase oncogenic transformation [J].

Aznar, S ;

Valerón, PF ;

del Rincon, SV ;

Pérez, LF ;

Perona, R ;

Lacal, JC .

MOLECULAR BIOLOGY OF THE CELL, 2001, 12 (10) :3282-3294

[3]

Implication of the β2-microglobulin gene in the generation of tumor escape phenotypes [J].

Bernal, Monica ;

Ruiz-Cabello, Francisco ;

Concha, Angel ;

Paschen, Annette ;

Garrido, Federico .

CANCER IMMUNOLOGY IMMUNOTHERAPY, 2012, 61 (09) :1359-1371

[4]

Recent patterns in gastric cancer: A global overview [J].

Bertuccio, Paola ;

Chatenoud, Liliane ;

Levi, Fabio ;

Praud, Delphine ;

Ferlay, Jacques ;

Negri, Eva ;

Malvezzi, Matteo ;

La Vecchia, Carlo .

INTERNATIONAL JOURNAL OF CANCER, 2009, 125 (03) :666-673

[5]

Boussioutas A, 2003, CANCER RES, V63, P2569

[6]

PD-L1 Expression Is Characteristic of a Subset of Aggressive B-cell Lymphomas and Virus-Associated Malignancies [J].

Chen, Benjamin J. ;

Chapuy, Bjoern ;

Jing Ouyang ;

Sun, Heather H. ;

Roemer, Margaretha G. M. ;

Xu, Mina L. ;

Yu, Hongbo ;

Fletcher, Christopher D. M. ;

Freeman, Gordon J. ;

Shipp, Margaret A. ;

Rodig, Scott J. .

CLINICAL CANCER RESEARCH, 2013, 19 (13) :3462-3473

[7]

The endocytic protein GRAF1 is directed to cell-matrix adhesion sites and regulates cell spreading [J].

Doherty, Gary J. ;

Ahlund, Monika K. ;

Howes, Mark T. ;

Moren, Bjorn ;

Parton, Robert G. ;

McMahon, Harvey T. ;

Lundmark, Richard .

MOLECULAR BIOLOGY OF THE CELL, 2011, 22 (22) :4380-4389

[8]

Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity [J].

Dulak, Austin M. ;

Stojanov, Petar ;

Peng, Shouyong ;

Lawrence, Michael S. ;

Fox, Cameron ;

Stewart, Chip ;

Bandla, Santhoshi ;

Imamura, Yu ;

Schumacher, Steven E. ;

Shefler, Erica ;

McKenna, Aaron ;

Carter, Scott L. ;

Cibulskis, Kristian ;

Sivachenko, Andrey ;

Saksena, Gordon ;

Voet, Douglas ;

Ramos, Alex H. ;

Auclair, Daniel ;

Thompson, Kristin ;

Sougnez, Carrie ;

Onofrio, Robert C. ;

Guiducci, Candace ;

Beroukhim, Rameen ;

Zhou, Zhongren ;

Lin, Lin ;

Lin, Jules ;

Reddy, Rishindra ;

Chang, Andrew ;

Landrenau, Rodney ;

Pennathur, Arjun ;

Ogino, Shuji ;

Luketich, James D. ;

Golub, Todd R. ;

Gabriel, Stacey B. ;

Lander, Eric S. ;

Beer, David G. ;

Godfrey, Tony E. ;

Getz, Gad ;

Bass, Adam J. .

NATURE GENETICS, 2013, 45 (05) :478-U37

[9]

Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial [J].

Fuchs, Charles S. ;

Tomasek, Jiri ;

Yong, Cho Jae ;

Dumitru, Filip ;

Passalacqua, Rodolfo ;

Goswami, Chanchal ;

Safran, Howard ;

dos Santos, Lucas Vieira ;

Aprile, Giuseppe ;

Ferry, David R. ;

Melichar, Bohuslav ;

Tehfe, Mustapha ;

Topuzov, Eldar ;

Zalcberg, John Raymond ;

Chau, Ian ;

Campbell, William ;

Sivanandan, Choondal ;

Pikiel, Joanna ;

Koshiji, Minori ;

Hsu, Yanzhi ;

Liepa, Astra M. ;

Gao, Ling ;

Schwartz, Jonathan D. ;

Tabernero, Josep .

LANCET, 2014, 383 (9911) :31-39

[10]

Geddert H, 2010, ANAL CELL PATHOL, V33, P143, DOI [10.1155/2010/453764, 10.3233/ACP-CLO-2010-0540]

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