Integrated genomic and molecular characterization of cervical cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-01-23

AUTHORS

Robert D. Burk, Zigui Chen, Charles Saller, Katherine Tarvin, Andre L. Carvalho, Cristovam Scapulatempo-Neto, Henrique C. Silveira, José H. Fregnani, Chad J. Creighton, Matthew L. Anderson, Patricia Castro, Sophia S. Wang, Christina Yau, Christopher Benz, A. Gordon Robertson, Karen Mungall, Lynette Lim, Reanne Bowlby, Sara Sadeghi, Denise Brooks, Payal Sipahimalani, Richard Mar, Adrian Ally, Amanda Clarke, Andrew J. Mungall, Angela Tam, Darlene Lee, Eric Chuah, Jacqueline E. Schein, Kane Tse, Katayoon Kasaian, Yussanne Ma, Marco A. Marra, Michael Mayo, Miruna Balasundaram, Nina Thiessen, Noreen Dhalla, Rebecca Carlsen, Richard A. Moore, Robert A. Holt, Steven J. M. Jones, Tina Wong, Angeliki Pantazi, Michael Parfenov, Raju Kucherlapati, Angela Hadjipanayis, Jonathan Seidman, Melanie Kucherlapati, Xiaojia Ren, Andrew W. Xu, Lixing Yang, Peter J. Park, Semin Lee, Brenda Rabeno, Lori Huelsenbeck-Dill, Mark Borowsky, Mark Cadungog, Mary Iacocca, Nicholas Petrelli, Patricia Swanson, Akinyemi I. Ojesina, Xuan Le, George Sandusky, Sally N. Adebamowo, Teniola Akeredolu, Clement Adebamowo, Sheila M. Reynolds, Ilya Shmulevich, Candace Shelton, Daniel Crain, David Mallery, Erin Curley, Johanna Gardner, Robert Penny, Scott Morris, Troy Shelton, Jia Liu, Laxmi Lolla, Sudha Chudamani, Ye Wu, Michael Birrer, Michael D. McLellan, Matthew H. Bailey, Christopher A. Miller, Matthew A. Wyczalkowski, Robert S. Fulton, Catrina C. Fronick, Charles Lu, Elaine R. Mardis, Elizabeth L. Appelbaum, Heather K. Schmidt, Lucinda A. Fulton, Matthew G. Cordes, Tiandao Li, Li Ding, Richard K. Wilson, Janet S. Rader, Behnaz Behmaram, Denise Uyar, William Bradley, John Wrangle, Alessandro Pastore, Douglas A. Levine, Fanny Dao, Jianjiong Gao, Nikolaus Schultz, Chris Sander, Marc Ladanyi, Mark Einstein, Randall Teeter, Stephen Benz, Nicolas Wentzensen, Ina Felau, Jean C. Zenklusen, Clara Bodelon, John A. Demchok, Liming Yang, Margi Sheth, Martin L. Ferguson, Roy Tarnuzzer, Hannah Yang, Mark Schiffman, Jiashan Zhang, Zhining Wang, Tanja Davidsen, Olayinka Olaniyan, Carolyn M. Hutter, Heidi J. Sofia, Dmitry A. Gordenin, Kin Chan, Steven A. Roberts, Leszek J. Klimczak, Carter Van Waes, Zhong Chen, Anthony D. Saleh, Hui Cheng, Jeremy Parfitt, John Bartlett, Monique Albert, Angel Arnaout, Harman Sekhon, Sebastien Gilbert, Myron Peto, Jerome Myers, Jodi Harr, John Eckman, Julie Bergsten, Kelinda Tucker, Leigh Anne Zach, Beth Y. Karlan, Jenny Lester, Sandra Orsulic, Qiang Sun, Rashi Naresh, Todd Pihl, Yunhu Wan, Howard Zaren, Jennifer Sapp, Judy Miller, Paul Drwiega, Akinyemi I. Ojesina, Bradley A. Murray, Hailei Zhang, Andrew D. Cherniack, Carrie Sougnez, Chandra Sekhar Pedamallu, Lee Lichtenstein, Matthew Meyerson, Michael S. Noble, David I. Heiman, Doug Voet, Gad Getz, Gordon Saksena, Jaegil Kim, Juliann Shih, Juok Cho, Michael S. Lawrence, Nils Gehlenborg, Pei Lin, Rameen Beroukhim, Scott Frazer, Stacey B. Gabriel, Steven E. Schumacher, Kristen M. Leraas, Tara M. Lichtenberg, Erik Zmuda, Jay Bowen, Jessica Frick, Julie M. Gastier-Foster, Lisa Wise, Mark Gerken, Nilsa C. Ramirez, Ludmila Danilova, Leslie Cope, Stephen B. Baylin, Helga B. Salvesen, Christopher P. Vellano, Zhenlin Ju, Lixia Diao, Hao Zhao, Zechen Chong, Michael C. Ryan, Emmanuel Martinez-Ledesma, Roeland G. Verhaak, Lauren Averett Byers, Yuan Yuan, Ken Chen, Shiyun Ling, Gordon B. Mills, Yiling Lu, Rehan Akbani, Sahil Seth, Han Liang, Jing Wang, Leng Han, John N. Weinstein, Christopher A. Bristow, Wei Zhang, Harshad S. Mahadeshwar, Huandong Sun, Jiabin Tang, Jianhua Zhang, Xingzhi Song, Alexei Protopopov, Kenna R. Mills Shaw, Lynda Chin, Oluwole Olabode, Akinyemi I. Ojesina, Philip DiSaia, Amie Radenbaugh, David Haussler, Jingchun Zhu, Josh Stuart, Prabhakar Chalise, Devin Koestler, Brooke L. Fridley, Andrew K. Godwin, Rashna Madan, Giovanni Ciriello, Cathleen Martinez, Kelly Higgins, Therese Bocklage, J. Todd Auman, Charles M. Perou, Donghui Tan, Joel S. Parker, Katherine A. Hoadley, Matthew D. Wilkerson, Piotr A. Mieczkowski, Tara Skelly, Umadevi Veluvolu, D. Neil Hayes, W. Kimryn Rathmell, Alan P. Hoyle, Janae V. Simons, Junyuan Wu, Lisle E. Mose, Matthew G. Soloway, Saianand Balu, Shaowu Meng, Stuart R. Jefferys, Tom Bodenheimer, Yan Shi, Jeffrey Roach, Leigh B. Thorne, Lori Boice, Mei Huang, Corbin D. Jones, Rosemary Zuna, Joan Walker, Camille Gunderson, Carie Snowbarger, David Brown, Katherine Moxley, Kathleen Moore, Kelsi Andrade, Lisa Landrum, Robert Mannel, Scott McMeekin, Starla Johnson, Tina Nelson, Esther Elishaev, Rajiv Dhir, Robert Edwards, Rohit Bhargava, Daniel G. Tiezzi, Jurandyr M. Andrade, Houtan Noushmehr, Carlos Gilberto Carlotti, Daniela Pretti da Cunha Tirapelli, Daniel J. Weisenberger, David J. Van Den Berg, Dennis T. Maglinte, Moiz S. Bootwalla, Phillip H. Lai, Timothy Triche, Elizabeth M. Swisher, Kathy J. Agnew, Carl Simon Shelley, Peter W. Laird, Julie Schwarz, Perry Grigsby, David Mutch

ABSTRACT

Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, one of the largest comprehensive genomic studies of cervical cancer to date. We observed notable APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targets CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2), and the BCAR4 long non-coding RNA, which has been associated with response to lapatinib. Integration of human papilloma virus (HPV) was observed in all HPV18-related samples and 76% of HPV16-related samples, and was associated with structural aberrations and increased target-gene expression. We identified a unique set of endometrial-like cervical cancers, comprised predominantly of HPV-negative tumours with relatively high frequencies of KRAS, ARID1A and PTEN mutations. Integrative clustering of 178 samples identified keratin-low squamous, keratin-high squamous and adenocarcinoma-rich subgroups. These molecular analyses reveal new potential therapeutic targets for cervical cancers. More... »

PAGES

378-384

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  • Journal

    TITLE

    Nature

    ISSUE

    7645

    VOLUME

    543

    Author Affiliations

  • Albert Einstein College of Medicine, Bronx, 10461, New York, New York, USA
  • Analytical Biological Services, Inc., 19801, Wilmington, Delaware, USA
  • Barretos Cancer Hospital, Barretos, Sao Paulo, Brazil
  • Baylor College of Medicine, 77030, Houston, Texas, USA
  • Beckman Research Institute of City of Hope, 91010, Duarte, California, USA
  • Buck Institute for Research on Aging, 94945, Novato, California, USA
  • Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, V5Z 4S6, Vancouver, British Columbia, Canada
  • Harvard Medical School, 02115, Boston, Massachusetts, USA
  • Helen F. Graham Cancer Center and Research Institute at Christiana Care Health Services, Inc., 19713, Newark, Delaware, USA
  • University of Alabama at Birmingham, 35294, Birmingham, Alabama, USA
  • ILSbio, LLC, 21620, Chestertown, Maryland, USA
  • Indiana University School of Medicine, 46202, Indianapolis, Indiana, USA
  • Institute of Human Virology, Nigeria, Abuja, Nigeria
  • Institute for Systems Biology, 98109, Seattle, Washington, USA
  • International Genomics Consortium, 85004, Phoenix, Arizona, USA
  • Leidos Biomedical, 20850, Rockville, Maryland, USA
  • Massachusetts General Hospital, 02114, Boston, Massachusetts, USA
  • McDonnell Genome Institute at Washington University, 63108, St Louis, Missouri, USA
  • Medical College of Wisconsin, 53226, Milwaukee, Wisconsin, USA
  • Medical University of South Carolina, 29425, Charleston, South Carolina, USA
  • Memorial Sloan Kettering Cancer Center, 10065, New York, New York, USA
  • Montefiore Medical Center, Bronx, 10461, New York, New York, USA
  • NantOmics, 95060, Santa Cruz, California, USA
  • National Cancer Institute, 20892, Bethesda, Maryland, USA
  • National Hospital, Abuja, Nigeria
  • National Human Genome Research Institute, 20892, Bethesda, Maryland, USA
  • National Institute of Environmental Health Sciences, 27709, Durham, North Carolina, USA
  • National Institute on Deafness and Other Communication Disorders, 20892, Bethesda, Maryland, USA
  • Ontario Tumour Bank, London Health Sciences Centre, N6A 5A5, London, Ontario, Canada
  • Ontario Tumour Bank, Ontario Institute for Cancer Research, M5G 0A3, Toronto, Ontario, Canada
  • Ontario Tumour Bank, The Ottawa Hospital, K1H 8L6, Ottawa, Ontario, Canada
  • Oregon Health and Science University, 97201, Portland, Oregon, USA
  • Penrose-St Francis Health Services, 80906, Colorado Springs, Colorado, USA
  • Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 90048, Los Angeles, California, USA
  • SRA International, 22033, Fairfax, Virginia, USA
  • St Joseph’s Candler Health System, 31406, Savannah, Georgia, USA
  • The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, 02142, Cambridge, Massachusetts, USA
  • The Research Institute at Nationwide Children’s Hospital, 43205, Columbus, Ohio, USA
  • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, 21287, Baltimore, Maryland, USA
  • The University of Bergen, Bergen, Norway
  • The University of Texas MD Anderson Cancer Center, 77030, Houston, Texas, USA
  • University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria
  • University of California, Irvine, 92668, Orange, California, USA
  • University of California Santa Cruz, 95064, Santa Cruz, California, USA
  • University of Kansas Medical Center, 66160, Kansas City, Kansas, USA
  • University of Lausanne, Lausanne, Switzerland
  • University of New Mexico Health Sciences Center, 87131, Albuquerque, New Mexico, USA
  • University of North Carolina at Chapel Hill, 27599, Chapel Hill, North Carolina, USA
  • University of Oklahoma Health Sciences Center, 73104, Oklahoma City, Oklahoma, USA
  • University of Pittsburgh, 15213, Pittsburgh, Pennsylvania, USA
  • University of São Paulo, Ribeirão Preto Medical School, 14049-900, Ribeirão Preto, São Paulo, Brazil
  • University of Southern California, 90033, Los Angeles, California, USA
  • University of Washington, 981095, Seattle, Washington, USA
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  • Van Andel Research Institute, 49503, Grand Rapids, Michigan, USA
  • Washington University in St Louis, 63110, St Louis, Missouri, USA
  • Clinical Trials linked to this publication

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature21386

    DOI

    http://dx.doi.org/10.1038/nature21386

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1074205537

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28112728


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