Comprehensive molecular characterization of gastric adenocarcinoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-07-23

AUTHORS

Adam J. Bass, Vesteinn Thorsson, Ilya Shmulevich, Sheila M. Reynolds, Michael Miller, Brady Bernard, Toshinori Hinoue, Peter W. Laird, Christina Curtis, Hui Shen, Daniel J. Weisenberger, Nikolaus Schultz, Ronglai Shen, Nils Weinhold, David P. Kelsen, Reanne Bowlby, Andy Chu, Katayoon Kasaian, Andrew J. Mungall, A. Gordon Robertson, Payal Sipahimalani, Andrew Cherniack, Gad Getz, Yingchun Liu, Michael S. Noble, Chandra Pedamallu, Carrie Sougnez, Amaro Taylor-Weiner, Rehan Akbani, Ju-Seog Lee, Wenbin Liu, Gordon B. Mills, Da Yang, Wei Zhang, Angeliki Pantazi, Michael Parfenov, Margaret Gulley, M. Blanca Piazuelo, Barbara G. Schneider, Jihun Kim, Alex Boussioutas, Margi Sheth, John A. Demchok, Charles S. Rabkin, Joseph E. Willis, Sam Ng, Katherine Garman, David G. Beer, Arjun Pennathur, Benjamin J. Raphael, Hsin-Ta Wu, Robert Odze, Hark K. Kim, Jay Bowen, Kristen M. Leraas, Tara M. Lichtenberg, Stephanie Weaver, Michael McLellan, Maciej Wiznerowicz, Ryo Sakai, Gad Getz, Carrie Sougnez, Michael S. Lawrence, Kristian Cibulskis, Lee Lichtenstein, Sheila Fisher, Stacey B. Gabriel, Eric S. Lander, Li Ding, Beifang Niu, Adrian Ally, Miruna Balasundaram, Inanc Birol, Reanne Bowlby, Denise Brooks, Yaron S. N. Butterfield, Rebecca Carlsen, Andy Chu, Justin Chu, Eric Chuah, Hye-Jung E. Chun, Amanda Clarke, Noreen Dhalla, Ranabir Guin, Robert A. Holt, Steven J. M. Jones, Katayoon Kasaian, Darlene Lee, Haiyan A. Li, Emilia Lim, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen L. Mungall, Ka Ming Nip, A. Gordon Robertson, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Rameen Beroukhim, Scott L. Carter, Andrew D. Cherniack, Juok Cho, Kristian Cibulskis, Daniel DiCara, Scott Frazer, Sheila Fisher, Stacey B. Gabriel, Nils Gehlenborg, David I. Heiman, Joonil Jung, Jaegil Kim, Eric S. Lander, Michael S. Lawrence, Lee Lichtenstein, Pei Lin, Matthew Meyerson, Akinyemi I. Ojesina, Chandra Sekhar Pedamallu, Gordon Saksena, Steven E. Schumacher, Carrie Sougnez, Petar Stojanov, Barbara Tabak, Amaro Taylor-Weiner, Doug Voet, Mara Rosenberg, Travis I. Zack, Hailei Zhang, Lihua Zou, Alexei Protopopov, Netty Santoso, Michael Parfenov, Semin Lee, Jianhua Zhang, Harshad S. Mahadeshwar, Jiabin Tang, Xiaojia Ren, Sahil Seth, Lixing Yang, Andrew W. Xu, Xingzhi Song, Angeliki Pantazi, Ruibin Xi, Christopher A. Bristow, Angela Hadjipanayis, Jonathan Seidman, Lynda Chin, Peter J. Park, Raju Kucherlapati, Rehan Akbani, Shiyun Ling, Wenbin Liu, Arvind Rao, John N. Weinstein, Sang-Bae Kim, Ju-Seog Lee, Yiling Lu, Gordon Mills, Peter W. Laird, Toshinori Hinoue, Daniel J. Weisenberger, Moiz S. Bootwalla, Phillip H. Lai, Hui Shen, Timothy Triche Jr, David J. Van Den Berg, Stephen B. Baylin, James G. Herman, Gad Getz, Lynda Chin, Yingchun Liu, Bradley A. Murray, Michael S. Noble, r B. Arman Askoy, Giovanni Ciriello, Gideon Dresdner, Jianjiong Gao, Benjamin Gross, Anders Jacobsen, William Lee, Ricardo Ramirez, Chris Sander, Nikolaus Schultz, Yasin Senbabaoglu, Rileen Sinha, S. Onur Sumer, Yichao Sun, Nils Weinhold, Vésteinn Thorsson, Brady Bernard, Lisa Iype, Roger W. Kramer, Richard Kreisberg, Michael Miller, Sheila M. Reynolds, Hector Rovira, Natalie Tasman, Ilya Shmulevich, Sam Ng, David Haussler, Josh M. Stuart, Rehan Akbani, Shiyun Ling, Wenbin Liu, Arvind Rao, John N. Weinstein, Roeland G. W. Verhaak, Gordon B. Mills, Mark D. M. Leiserson, Benjamin J. Raphael, Hsin-Ta Wu, Barry S. Taylor, Aaron D. Black, Jay Bowen, Julie Ann Carney, Julie M. Gastier-Foster, Carmen Helsel, Kristen M. Leraas, Tara M. Lichtenberg, Cynthia McAllister, Nilsa C. Ramirez, Teresa R. Tabler, Lisa Wise, Erik Zmuda, Robert Penny, Daniel Crain, Johanna Gardner, Kevin Lau, Erin Curely, David Mallery, Scott Morris, Joseph Paulauskis, Troy Shelton, Candace Shelton, Mark Sherman, Christopher Benz, Jae-Hyuk Lee, Konstantin Fedosenko, Georgy Manikhas, Olga Potapova, Olga Voronina, Dmitry Belyaev, Oleg Dolzhansky, W. Kimryn Rathmell, Jakub Brzezinski, Matthew Ibbs, Konstanty Korski, Witold Kycler, Radoslaw Łaźniak, Ewa Leporowska, Andrzej Mackiewicz, Dawid Murawa, Pawel Murawa, Arkadiusz Spychała, Wiktoria M. Suchorska, Honorata Tatka, Marek Teresiak, Maciej Wiznerowicz, Raafat Abdel-Misih, Joseph Bennett, Jennifer Brown, Mary Iacocca, Brenda Rabeno, Sun-Young Kwon, Robert Penny, Johanna Gardner, Ariane Kemkes, David Mallery, Scott Morris, Troy Shelton, Candace Shelton, Erin Curley, Iakovina Alexopoulou, Jay Engel, John Bartlett, Monique Albert, Do-Youn Park, Rajiv Dhir, James Luketich, Rodney Landreneau, Yelena Y. Janjigian, David P. Kelsen, Eunjung Cho, Marc Ladanyi, Laura Tang, Shannon J. McCall, Young S. Park, Jae-Ho Cheong, Jaffer Ajani, M. Constanza Camargo, Shelley Alonso, Brenda Ayala, Mark A. Jensen, Todd Pihl, Rohini Raman, Jessica Walton, Yunhu Wan, John A. Demchok, Greg Eley, Kenna R. Mills Shaw, Margi Sheth, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean Claude Zenklusen, Tanja Davidsen, Carolyn M. Hutter, Heidi J. Sofia, Robert Burton, Sudha Chudamani, Jia Liu

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. More... »

PAGES

202-209

Journal

TITLE

Nature

ISSUE

7517

VOLUME

513

Author Affiliations

  • Department of Medical Oncology and the Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 02215, Boston, Massachusetts, USA
  • Institute for Systems Biology, 98109, Seattle, Washington, USA
  • USC Epigenome Center, University of Southern California, 90033, Los Angeles, California, USA
  • Department of Preventive Medicine, University of Southern California, USC/Norris Comprehensive Cancer Center, 90033, Los Angeles, California, USA
  • Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 10065, New York, New York, USA
  • Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 10065, New York, New York, USA
  • Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.
  • Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
  • The Eli and Edythe L. Broad Institute, 02142, Cambridge, Massachusetts, USA
  • Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, 77030, Houston, Texas, USA
  • Department of Systems Biology, University of Texas MD Anderson Cancer Center, 77030, Houston, Texas, USA
  • Department of Pathology, University of Texas MD Anderson Cancer Center, 77030, Texas, USA
  • Department of Medicine, Harvard Medical School, 02215, Boston, Massachusetts, USA
  • Department of Pathology and Laboratory Medicine, University of North Carolina-Chapel Hill, 27599, Chapel HillChapel Hill, North Carolina, USA
  • Department of Medicine, Vanderbilt University Medical Center, 2215 Garland Avenue, Nashville, Tennessee 37232, USA.
  • Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 138-736, Seoul, South Korea
  • Sir Peter MacCallum Cancer Department of Oncology, University of Melbourne, 3002, East Melbourne, Australia
  • National Cancer Institute, 20892, Bethesda, Maryland, USA
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, 20892, Bethesda, Maryland, USA
  • Department of Pathology, Case Western Reserve University, 44106, Cleveland, Ohio, USA
  • Department of Biomolecular Engineering and Center for Biomolecular Science and Engineering, University of California-Santa Cruz, 95064, Santa Cruz, California, USA
  • Division of Gastroenterology, Department of Medicine, Duke University, 27710, Durham, North Carolina, USA
  • Department of Thoracic Surgery, University of Michigan Cancer Center, 48109, Ann Arbor, Michigan, USA
  • University of Pittsburgh, 15213, Pittsburgh, Pennsylvania, USA
  • Department of Computer Science & Center for Computational Molecular Biology, Brown University, 115 Waterman Street, Providence, Rhode Island 02912, USA.
  • Department of Pathology, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA.
  • National Cancer Center, 410-769, Goyang, Republic of Korea
  • The Research Institute at Nationwide Children's Hospital, 43205, Columbus, Ohio, USA
  • The Genome Institute, Washington University, 63108, St Louis, Missouri, USA
  • Greater Poland Cancer Centre, Garbary, 15, 61-866, Poznan, Poland.
  • Department of Electrical Engineering-ESAT (STADIUS), KU Leuven, Leuven, Belgium
  • Department of Genomic Medicine, Institute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, 77054, Houston, Texas, USA
  • The Center for Biomedical Informatics, Harvard Medical School, 02115, Boston, Massachusetts, USA
  • Cancer Biology Division, Johns Hopkins University, 21231, Baltimore, Maryland, USA
  • Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, 94143-0128, San Francisco, California, USA
  • International Genomics Consortium, 85004, Phoenix, Arizona, USA
  • Buck Institute for Research on Aging, 94945, Novato, California, USA
  • Chonnam National University Medical School, 501-746, Gwangju, Republic of Korea
  • City Clinical Oncology Dispensary, 198255, Saint Petersburg, Russia
  • Cureline, Inc., 94080, South San Francisco, California, USA
  • Departments of Medicine and Genetics, University of North Carolina at Chapel Hill, 27599, Chapel Hill, North Carolina, USA
  • Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System, 19713, Newark, Delaware, USA
  • Keimyung University School of Medicine, 700-712, Daegu, Republic of Korea
  • Ontario Tumour Bank - Hamilton site, St. Joseph’s Healthcare Hamilton, Hamilton, Ontario L8N 3Z5, Canada.
  • Ontario Tumour Bank - Kingston site, Kingston General Hospital, Kingston, Ontario K7L 5H6, Canada.
  • Ontario Tumour Bank, Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada.
  • Pusan National University Hospital, 602-739, Busan, Republic of Korea
  • Department of Pathology, Memorial Sloan-Kettering Cancer Center, 10065, New York, New York, USA
  • Department of Pathology, Duke University, 27710, Durham, North Carolina, USA
  • Department of Surgery, Yonsei University College of Medicine, 120-752, Seoul, Republic of Korea
  • Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, 77030, Houston, Texas, USA
  • SRA International, 22033, Fairfax, Virginia, USA
  • Center for Biomedical Informatics and Information Technology, National Cancer Institute, 20850, Rockville, Maryland, USA
  • National Human Genome Research Institute, 20892, Bethesda, Maryland, USA
  • SAIC-Frederick, Inc., 21702, Frederick, Maryland, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature13480

    DOI

    http://dx.doi.org/10.1038/nature13480

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1035707124

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25079317


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