Integrated genomic characterization of oesophageal carcinoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-01-04

AUTHORS

Jihun Kim, Reanne Bowlby, Andrew J. Mungall, A. Gordon Robertson, Robert D. Odze, Andrew D. Cherniack, Juliann Shih, Chandra Sekhar Pedamallu, Carrie Cibulskis, Andrew Dunford, Samuel R. Meier, Jaegil Kim, Benjamin J. Raphael, Hsin-Ta Wu, Alexandra M. Wong, Joseph E. Willis, Adam J. Bass, Sarah Derks, Katherine Garman, Shannon J. McCall, Maciej Wiznerowicz, Angeliki Pantazi, Michael Parfenov, Vésteinn Thorsson, Ilya Shmulevich, Varsha Dhankani, Michael Miller, Ryo Sakai, Kenneth Wang, Nikolaus Schultz, Ronglai Shen, Arshi Arora, Nils Weinhold, Francisco Sánchez-Vega, David P. Kelsen, Julia Zhang, Ina Felau, John Demchok, Charles S. Rabkin, M. Constanza Camargo, Jean Claude Zenklusen, Jay Bowen, Kristen Leraas, Tara M. Lichtenberg, Christina Curtis, Jose A. Seoane, Akinyemi I. Ojesina, David G. Beer, Margaret L. Gulley, Arjun Pennathur, James D. Luketich, Zhongren Zhou, Daniel J. Weisenberger, Rehan Akbani, Ju-Seog Lee, Wenbin Liu, Gordon B. Mills, Wei Zhang, Brian J Reid, Toshinori Hinoue, Peter W. Laird, Hui Shen, M. Blanca Piazuelo, Barbara G. Schneider, Michael McLellan, Amaro Taylor-Weiner, Carrie Cibulskis, Michael Lawrence, Kristian Cibulskis, Chip Stewart, Gad Getz, Eric Lander, Stacey B. Gabriel, Li Ding, Michael D. McLellan, Christopher A. Miller, Elizabeth L. Appelbaum, Matthew G. Cordes, Catrina C. Fronick, Lucinda A. Fulton, Elaine R. Mardis, Richard K. Wilson, Heather K. Schmidt, Robert S. Fulton, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert A. Holt, Steven J. M. Jones, Katayoon Kasaian, Denise Brooks, Haiyan I. Li, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen L. Mungall, A. Gordon Robertson, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Tina Wong, Andrew D. Cherniack, Juliann Shih, Chandra Sekhar Pedamallu, Rameen Beroukhim, Susan Bullman, Carrie Cibulskis, Bradley A. Murray, Gordon Saksena, Steven E. Schumacher, Stacey Gabriel, Matthew Meyerson, Angela Hadjipanayis, Raju Kucherlapati, Angeliki Pantazi, Michael Parfenov, Xiaojia Ren, Peter J. Park, Semin Lee, Melanie Kucherlapati, Lixing Yang, Stephen B. Baylin, Katherine A. Hoadley, Daniel J. Weisenberger, Moiz S. Bootwalla, Phillip H. Lai, David J. Van Den Berg, Mario Berrios, Andrea Holbrook, Rehan Akbani, Jun-Eul Hwang, Hee-Jin Jang, Wenbin Liu, John N. Weinstein, Ju-Seog Lee, Yiling Lu, Bo Hwa Sohn, Gordon Mills, Sahil Seth, Alexei Protopopov, Christopher A. Bristow, Harshad S. Mahadeshwar, Jiabin Tang, Xingzhi Song, Jianhua Zhang, Peter W. Laird, Toshinori Hinoue, Hui Shen, Juok Cho, Timothy Defrietas, Scott Frazer, Nils Gehlenborg, David I. Heiman, Michael S. Lawrence, Pei Lin, Samuel R. Meier, Michael S. Noble, Doug Voet, Hailei Zhang, Jaegil Kim, Paz Polak, Gordon Saksena, Lynda Chin, Gad Getz, Alexandra M. Wong, Benjamin J. Raphael, Hsin-Ta Wu, Semin Lee, Peter J. Park, Lixing Yang, Vésteinn Thorsson, Brady Bernard, Lisa Iype, Michael Miller, Sheila M. Reynolds, Ilya Shmulevich, Varsha Dhankani, Adam Abeshouse, Arshi Arora, Joshua Armenia, Ritika Kundra, Marc Ladanyi, Kjong-Van Lehmann, Jianjiong Gao, Chris Sander, Nikolaus Schultz, Francisco Sánchez-Vega, Ronglai Shen, Nils Weinhold, Debyani Chakravarty, Hongxin Zhang, Amie Radenbaugh, Apruva Hegde, Rehan Akbani, Wenbin Liu, John N. Weinstein, Lynda Chin, Christopher A. Bristow, Yiling Lu, Robert Penny, Daniel Crain, Johanna Gardner, Erin Curley, David Mallery, Scott Morris, Joseph Paulauskis, Troy Shelton, Candace Shelton, Jay Bowen, Jessica Frick, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Katherine Tarvin, Charles Saller, Young Soo Park, Michael Button, Andre L. Carvalho, Rui Manuel Reis, Marcus Medeiros Matsushita, Fabiano Lucchesi, Antonio Talvane de Oliveira, Xuan Le, Oxana Paklina, Galiya Setdikova, Jae-Hyuck Lee, Joseph Bennett, Mary Iacocca, Lori Huelsenbeck-Dill, Olga Potapova, Olga Voronina, Ouida Liu, Victoria Fulidou, Crystal Cates, Alexis Sharp, Madhusmitara Behera, Seth Force, Fadio Khuri, Taofeek Owonikoko, Allan Pickens, Suresh Ramalingam, Gabriel Sica, Winand Dinjens, Anna van Nistelrooij, Bas Wijnhoven, George Sandusky, Serghei Stepa, Daniel Crain, Joseph Paulauskis, Robert Penny, Johanna Gardner, David Mallery, Scott Morris, Troy Shelton, Candace Shelton, Erin Curley, Hartmut Juhl, Carsten Zornig, Sun Young Kwon, David Kelsen, Hark Kyun Kim, John Bartlett, Jeremy Parfitt, Runjan Chetty, Gail Darling, Jennifer Knox, Rebecca Wong, Haila El-Zimaity, Geoffrey Liu, Alex Boussioutas, Do Young Park, Rafael Kemp, Carlos Gilberto Carlotti, Daniela Pretti da Cunha Tirapelli, Fabiano Pinto Saggioro, Ajith Kumar Sankarankutty, Houtan Noushmehr, Jose Sebastião dos Santos, Felipe Amstalden Trevisan, Jennifer Eschbacher, Michael Dubina, Eugene Mozgovoy, Frank Carey, Sally Chalmers, Ian Forgie, Andrew Godwin, Colleen Reilly, Rashna Madan, Zaid Naima, Daysha Ferrer-Torres, Michele Vinco, W. Kimryn Rathmell, Rajiv Dhir, James Luketich, Arjun Pennathur, Jaffer A. Ajani, Shannon J. McCall, Yelena Janjigian, David Kelsen, Marc Ladanyi, Laura Tang, M. Constanza Camargo, Jaffer A. Ajani, Jae-Ho Cheong, Sudha Chudamani, Jai Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, John A. Demchok, Ina Felau, Martin L. Ferguson, Kenna R. Mills Shaw, Margi Sheth, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean Claude Zenklusen, Carolyn M. Hutter, Heidi J. Sofia, Jiashan Zhang

ABSTRACT

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies. More... »

PAGES

169-175

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  • Journal

    TITLE

    Nature

    ISSUE

    7636

    VOLUME

    541

    Author Affiliations

  • Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 05505, Songpa-gu, Seoul, Korea
  • Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, BC V5Z 4S6, Vancouver, Canada
  • Department of Pathology, Harvard Medical School, 02215, Boston, Massachusetts, USA
  • The Eli and Edythe L. Broad Institute of Massachusetts Institute Of Technology and Harvard University, 02142, Cambridge, Massachusetts, USA
  • Department of Medical Oncology, Dana-Farber Cancer Institute, 02115, Boston, Massachusetts, USA
  • Department of Computer Science & Center for Computational Molecular Biology, Brown University, 02912, Providence, Rhode Island, USA
  • Dept of Pathology, Case Medical Center, 44106, Cleveland, Ohio, USA
  • Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 02115, Boston, Massachusetts, USA
  • Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
  • Department of Pathology, Duke University, 27710, Durham, North Carolina, USA
  • Poznan University of Medical Sciences, 61-866, Poznan´, Poland
  • KEW Group Inc., 02139, Cambridge, MassachusettsUSA
  • Department of Genetics, Harvard Medical School, 02115, Boston, Massachusetts, USA
  • Institute for Systems Biology, 98109, Seattle, WashingtonUSA
  • iMinds Medical IT, KU Leuven 3001, Belgium
  • Division of Gastroenterology and Hepatology, Mayo Clinic, 55905, Rochester, Minnesota, USA
  • Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 10065, New York, New York, USA
  • Computational Biology Center, Memorial Sloan Kettering Cancer Center, 10065, New York, New York, USA
  • Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, 10065, New York, New York, USA
  • Department of Medicine, Memorial Sloan Kettering Cancer Center, 10065, New York, New York, USA
  • National Cancer Institute, 20892, Bethesda, Maryland, USA
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, 20892, Bethesda, Maryland, USA
  • The Research Institute at Nationwide Children's Hospital, 43205, Columbus, Ohio, USA
  • Department of Medicine, Division of Oncology and Department of Genetics, Stanford University School of Medicine, 94305, Stanford, California, USA
  • HudsonAlpha Institute for Biotechnology, 35806, Huntsville, Alabama, USA
  • Department of Thoracic Surgery, University of Michigan Comprehensive Cancer Center, 48109, Ann Arbor, Michigan, USA
  • Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, 27599, Chapel Hill, North Carolina, USA
  • Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, 15213, Pittsburgh, Pennsylvania, USA
  • Department of Pathology and Laboratory Medicine, University of Rochester, 14642, Rochester, New York, USA
  • Department of Biochemistry and Molecular Biology, University of Southern California, 90033, Los Angeles, California, USA
  • Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, 77030, Houston, Texas, USA
  • Department of Systems Biology, The University of Texas MD Anderson Cancer Center, 77030, Houston, Texas, USA
  • Department of Pathology, The University of Texas MD Anderson Cancer Center, 77030, Houston,, Texas, USA
  • Fred Hutchinson Cancer Research Center, 98109, North Seattle, Washington, USA
  • Center for Epigenetics, Van Andel Research Institute, 49503, Grand Rapids,, Michigan, USA
  • Department of Medicine, Division of Gastroenterology, Vanderbilt University Medical Center, 37232, Nashville, Tennessee, USA
  • McDonnell Genome Institute at Washington University, 63108, St. Louis, Missouri, USA
  • Department of Biomedical Informatics, Harvard Medical School, 02115, Boston, Massachusetts, USA
  • Department of Pathology, Massachusetts General Hospital, 02114, Boston, Massachusetts, USA
  • Department of Medicine, Washington University School of Medicine, 63108, St. Louis, Missouri, USA
  • Department of Medicine, Harvard Medical School, 02215, Boston, Massachusetts, USA
  • Department of Cancer Biology, Dana-Farber Cancer Institute, 02215, Boston, Massachusetts, USA
  • Division of Genetics, Brigham and Women’s Hospital, 02115, Boston, Massachusetts, USA
  • Cancer Biology Division, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, 21231, Baltimore, Maryland, USA
  • University of North Carolina, Lineberger Comprehensive Cancer Center, 27514, Chapel Hill, North Carolina, USA
  • University of Southern California, USC/Norris Comprehensive Cancer Center, 90033, Los Angeles, California, USA
  • Department of Preventive Medicine, University of Southern California, 90033, Los Angeles, California, USA
  • Department of Hemato-Oncology, Chonnam National University Medical School, Kwangju, Korea
  • Department of Systems Biology, Institute for Personalized Cancer Treatment, The University of Texas MD Anderson Cancer Center, 77030, Houston, Texas, USA
  • Department of Genomic Medicine, Institute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, 77054, Houston, Texas, USA
  • Department of Pathology, Memorial Sloan Kettering Cancer Center, 10065, New York, New York, USA
  • University of California Santa Cruz Genomics Institute, 95064, Santa Cruz, California, USA
  • International Genomics Consortium, 85004, Phoenix, Arizona, USA
  • Analytical Biological Services, Inc., 19801, Wilmington, Delaware, USA
  • Asterand Bioscience, 48202, Detroit, Michigan, USA
  • Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil
  • Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal
  • Department of Pathology, Barretos Cancer Hospital, Barretos, São Paulo, Brazil
  • Department of Radiology, Barretos Cancer Hospital, Barretos, São Paulo, Brazil
  • Department of Surgery, Barretos Cancer Hospital, Barretos, São Paulo, Brazil
  • Department of Research Pathology, BioreclamationIVT, 21620, Chestertown, Maryland, USA
  • Botkin Municipal Clinic, 125284, Moscow, Russia
  • Department of Pathology, Chonnam National University Medical School, Hwasun, Republic of Korea
  • Helen F Graham Cancer Center & Research Institute, Christiana Care Health System, 19713, Newark, Delaware, USA
  • Cureline Inc, South San Francisco, 94080, California, USA
  • Emory University and Winship Cancer Institute, 30322, Atlanta, Georgia, USA
  • Department of Pathology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, 3000 CA Rotterdam, The Netherlands
  • Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands
  • Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands
  • Department of Pathology & Laboratory Medicine, Indiana University School of Medicine, 46202, Indianapolis, Indiana, USA
  • Institute of Oncology of Moldova, Chisinau, Moldova
  • Indivumed GmbH, 20251, Hamburg, Germany
  • Israelitisches Krankenhaus Hamburg, 22297, Hamburg, Germany
  • Department of Pathology, Keimyung University School of Medicine, Daegu, Republic of Korea
  • Center for Gastric Cancer, National Cancer Center, Goyang, Republic of Korea
  • Ontario Tumour Bank, Ontario Institute for Cancer Research, M5G 0A3, Toronto, Ontario, Canada
  • Ontario Tumour Bank, London Health Science Centre, N6A 5A5, London, Canada
  • Princess Margaret Cancer Centre, M5G2M9, Toronto, Ontario, Canada
  • Sir Peter MacCallum Cancer Department of Oncology, University of Melbourne, 3002, Melbourne, Australia
  • Department of Pathology, Pusan National University Medical School, Pusan, Republic of Korea
  • Department of Surgery and Anatomy, Ribeirão Preto Medical School-FMRP, University of São Paulo, 14049-900, Brazil
  • Department of Pathology, Ribeirão Preto Medical School-FMRP, University of São Paulo, 14049-900, Brazil
  • Department of Genetics, Ribeirão Preto Medical School-FMRP, University of São Paulo, 14049-900, Brazil
  • Department of Pathology, St. Joseph’s Hospital and Medical Center, 85013, Phoenix, Arizona, USA
  • St. Petersburg Academic University RAS, 194021, St. Petersburg, Russia
  • Tayside Tissue Bank, University of Dundee, Ninewells Hospital and Medical School, 9SY, Dundee DD1, UK
  • University of Kansas Medical Center, Kansas City, 66160, Kansas, USA
  • Department of Pathology, University of Michigan, Ann Arbor, 48109, Michigan, USA
  • Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 27599, Chapel Hill, North Carolina, USA
  • Department of Pathology, University of Pittsburgh, 15213, Pittsburgh, Pennsylvania, USA
  • Department of GI Medical Oncology, University of Texas MD Anderson Cancer Center, 77030, Houston, Texas, USA
  • Department of Surgery, Yonsei University College of Medicine, 120-752, Seoul, Korea
  • Leidos Biomedical, 20850, Rockville, Maryland, USA
  • CSRA Inc., Falls Church, 22042, Virginia, USA
  • National Human Genome Research Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature20805

    DOI

    http://dx.doi.org/10.1038/nature20805

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1045212192

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28052061


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    36 schema:description Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.
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