Integrated genomic characterization of endometrial carcinoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-05-01

AUTHORS

Gad Getz, Stacey B. Gabriel, Kristian Cibulskis, Eric Lander, Andrey Sivachenko, Carrie Sougnez, Mike Lawrence, Cyriac Kandoth, David Dooling, Robert Fulton, Lucinda Fulton, Joelle Kalicki-Veizer, Michael D. McLellan, Michelle O’Laughlin, Heather Schmidt, Richard K. Wilson, Kai Ye, Li Ding, Elaine R. Mardis, Adrian Ally, Miruna Balasundaram, Inanc Birol, Yaron S. N. Butterfield, Rebecca Carlsen, Candace Carter, Andy Chu, Eric Chuah, Hye-Jung E. Chun, Noreen Dhalla, Ranabir Guin, Carrie Hirst, Robert A. Holt, Steven J. M. Jones, Darlene Lee, Haiyan I. Li, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Patrick Plettner, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Richard J. Varhol, A. Gordon Robertson, Andrew D. Cherniack, Itai Pashtan, Gordon Saksena, Robert C. Onofrio, Steven E. Schumacher, Barbara Tabak, Scott L. Carter, Bryan Hernandez, Jeff Gentry, Helga B. Salvesen, Kristin Ardlie, Gad Getz, Wendy Winckler, Rameen Beroukhim, Stacey B. Gabriel, Matthew Meyerson, Angela Hadjipanayis, Semin Lee, Harshad S. Mahadeshwar, Peter Park, Alexei Protopopov, Xiaojia Ren, Sahil Seth, Xingzhi Song, Jiabin Tang, Ruibin Xi, Lixing Yang, Dong Zeng, Raju Kucherlapati, Lynda Chin, Jianhua Zhang, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Elizabeth Buda, D. Neil Hayes, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Joel S. Parker, Charles M. Perou, Jeff Roach, Yan Shi, Janae V. Simons, Mathew G. Soloway, Donghui Tan, Michael D. Topal, Scot Waring, Junyuan Wu, Katherine A. Hoadley, Stephen B. Baylin, Moiz S. Bootwalla, Phillip H. Lai, Timothy J. Triche Jr, David J. Van Den Berg, Daniel J. Weisenberger, Peter W. Laird, Hui Shen, Lynda Chin, Jianhua Zhang, Gad Getz, Juok Cho, Daniel DiCara, Scott Frazer, David Heiman, Rui Jing, Pei Lin, Will Mallard, Petar Stojanov, Doug Voet, Hailei Zhang, Lihua Zou, Michael Noble, Mike Lawrence, Sheila M. Reynolds, Ilya Shmulevich, B. Arman Aksoy, Yevgeniy Antipin, Giovanni Ciriello, Gideon Dresdner, Jianjiong Gao, Benjamin Gross, Anders Jacobsen, Marc Ladanyi, Boris Reva, Chris Sander, Rileen Sinha, S. Onur Sumer, Barry S. Taylor, Ethan Cerami, Nils Weinhold, Nikolaus Schultz, Ronglai Shen, Stephen Benz, Ted Goldstein, David Haussler, Sam Ng, Christopher Szeto, Joshua Stuart, Christopher C. Benz, Christina Yau, Wei Zhang, Matti Annala, Bradley M. Broom, Tod D. Casasent, Zhenlin Ju, Han Liang, Guoyan Liu, Yiling Lu, Anna K. Unruh, Chris Wakefield, John N. Weinstein, Nianxiang Zhang, Yuexin Liu, Russell Broaddus, Rehan Akbani, Gordon B. Mills, Christopher Adams, Thomas Barr, Aaron D. Black, Jay Bowen, John Deardurff, Jessica Frick, Julie M. Gastier-Foster, Thomas Grossman, Hollie A. Harper, Melissa Hart-Kothari, Carmen Helsel, Aaron Hobensack, Harkness Kuck, Kelley Kneile, Kristen M. Leraas, Tara M. Lichtenberg, Cynthia McAllister, Robert E. Pyatt, Nilsa C. Ramirez, Teresa R. Tabler, Nathan Vanhoose, Peter White, Lisa Wise, Erik Zmuda, Nandita Barnabas, Charlenia Berry-Green, Victoria Blanc, Lori Boice, Michael Button, Adam Farkas, Alex Green, Jean MacKenzie, Dana Nicholson, Steve E. Kalloger, C. Blake Gilks, Beth Y. Karlan, Jenny Lester, Sandra Orsulic, Mark Borowsky, Mark Cadungog, Christine Czerwinski, Lori Huelsenbeck-Dill, Mary Iacocca, Nicholas Petrelli, Brenda Rabeno, Gary Witkin, Elena Nemirovich-Danchenko, Olga Potapova, Daniil Rotin, Andrew Berchuck, Michael Birrer, Phillip DiSaia, Laura Monovich, Erin Curley, Johanna Gardner, David Mallery, Robert Penny, Sean C. Dowdy, Boris Winterhoff, Linda Dao, Bobbie Gostout, Alexandra Meuter, Attila Teoman, Fanny Dao, Narciso Olvera, Faina Bogomolniy, Karuna Garg, Robert A. Soslow, Douglas A. Levine, Mikhail Abramov, John M. S. Bartlett, Sugy Kodeeswaran, Jeremy Parfitt, Fedor Moiseenko, Blaise A. Clarke, Marc T. Goodman, Michael E. Carney, Rayna K. Matsuno, Jennifer Fisher, Mei Huang, W. Kimryn Rathmell, Leigh Thorne, Linda Van Le, Rajiv Dhir, Robert Edwards, Esther Elishaev, Kristin Zorn, Russell Broaddus, Paul J. Goodfellow, David Mutch, Nikolaus Schultz, Yuexin Liu, Rehan Akbani, Andrew D. Cherniack, Ethan Cerami, Nils Weinhold, Hui Shen, Katherine A. Hoadley, Ari B. Kahn, Daphne W. Bell, Pamela M. Pollock, Chen Wang, David A.Wheeler, Eve Shinbrot, Beth Y. Karlan, Andrew Berchuck, Sean C. Dowdy, Boris Winterhoff, Marc T. Goodman, A. Gordon Robertson, Rameen Beroukhim, Itai Pashtan, Helga B. Salvesen, Peter W. Laird, Michael Noble, Joshua Stuart, Li Ding, Cyriac Kandoth, C. Blake Gilks, Robert A. Soslow, Paul J. Goodfellow, David Mutch, Russell Broaddus, Wei Zhang, Gordon B. Mills, Raju Kucherlapati, Elaine R. Mardis, Douglas A. Levine, Brenda Ayala, Anna L. Chu, Mark A. Jensen, Prachi Kothiyal, Todd D. Pihl, Joan Pontius, David A. Pot, Eric E. Snyder, Deepak Srinivasan, Ari B. Kahn, Kenna R. Mills Shaw, Margi Sheth, Tanja Davidsen, Greg Eley Martin L. Ferguson, John A. Demchok, Liming Yang, Mark S. Guyer, Bradley A. Ozenberger, Heidi J. Sofia, Cyriac Kandoth, Nikolaus Schultz, Andrew D. Cherniack, Rehan Akbani, Yuexin Liu, Hui Shen, A. Gordon Robertson, Itai Pashtan, Ronglai Shen, Christopher C. Benz, Christina Yau, Peter W. Laird, Li Ding, Wei Zhang, Gordon B. Mills, Raju Kucherlapati, Elaine R. Mardis, Douglas A. Levine

ABSTRACT

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours. More... »

PAGES

67-73

Journal

TITLE

Nature

ISSUE

7447

VOLUME

497

Author Affiliations

  • The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, Massachusetts 02142, USA.
  • The Genome Institute, Washington University, St Louis, 63108, Missouri, USA
  • Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.
  • Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
  • Department of Clinical Medicine, University of Bergen, 5020, Bergen, Norway
  • Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
  • Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Department of Genomic Medicine, Institute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.
  • Informatics Program, Boston Children’s Hospital, Boston, Massachusetts 02115, USA.
  • Institute for Pharmacogenetics and Individualized Therapy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
  • Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
  • Department of Internal Medicine, Division of Medical Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
  • Department of Biology, University of North Carolina at Chapel Hill, North Carolina 27599, USA.
  • Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
  • Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
  • Research Computing Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
  • Cancer Biology Division, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland 21231, USA.
  • University of Southern California Epigenome Center, University of Southern California, Los Angeles, California 90089, USA.
  • Institute for Systems Biology, Seattle, Washington 98109, USA.
  • Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
  • Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
  • Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California 94158, USA.
  • Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
  • Department of Biomolecular Engineering and Center for Biomolecular Science and Engineering, University of California Santa Cruz, Santa Cruz, California 95064, USA.
  • Buck Institute for Age Research, Novato, California 94945, USA.
  • Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Tampere University of Technology Korkeakoulunkatu 10, FI-33720 Tampere, Finland.
  • Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • The Research Institute at Nationwide Children’s Hospital, Columbus, Ohio 43205, USA.
  • The Ohio State University, Columbus, Ohio 43210, USA.
  • Asterand, Detroit, Michigan 48202, USA.
  • University of North Carolina, Chapel Hill, North Carolina 27599, USA.
  • Department of Pathology & Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada.
  • Women’s Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
  • Helen F Graham Cancer Center at Christiana Care, Newark, Delaware 19713, USA.
  • Cureline, Inc., South San Francisco, California 94080, USA.
  • Duke University Medical Center, Duke Cancer Institute, Durham, North Carolina 27710, USA.
  • Harvard Medical School, Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA.
  • University of California Medical Center, Irvine, Orange California 92868, USA.
  • GOG Tissue Bank, The Research Institute at Nationwide Children’s Hospital, Columbus, Ohio 43205, USA.
  • International Genomics Consortium, Phoenix, Arizona 85004, USA.
  • Department of OB Gyn, Division of Gynecologic Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA.
  • Department of Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.
  • Department of Surgery, Gynecology Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
  • Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
  • N. N. Blokhin Russian Cancer Research Center RAMS, Moscow 115478, Russia.
  • Ontario Tumour Bank, Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada.
  • Ontario Tumour Bank, London Health Sciences Centre, London, Ontario N6A 5A5, Canada.
  • St Petersburg Academic University, St Petersburg 199034, Russia.
  • Department of Pathology, University Health Network, Toronto, Ontario M5G 2C4, Canada.
  • Cedars-Sinai Medical Center, Los Angeles, California 90024, USA.
  • University of Hawaii, Honolulu, Hawaii 96813, USA.
  • University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
  • Washington University School of Medicine, St Louis, Missouri 63110, USA.
  • SRA International, Fairfax, Virgina 22033, USA.
  • Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane 4059, Australia.
  • Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota 55905, USA.
  • Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
  • The Cancer Genome Atlas Program Office, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • MLF Consulting, Arlington, Maryland 02474, USA.
  • National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature12113

    DOI

    http://dx.doi.org/10.1038/nature12113

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1004984574

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23636398


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