Comprehensive genomic characterization of squamous cell lung cancers View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-09-09

AUTHORS

Peter S. Hammerman, Michael S. Lawrence, Douglas Voet, Rui Jing, Kristian Cibulskis, Andrey Sivachenko, Petar Stojanov, Aaron McKenna, Eric S. Lander, Stacey Gabriel, Gad Getz, Carrie Sougnez, Marcin Imielinski, Elena Helman, Bryan Hernandez, Nam H. Pho, Matthew Meyerson, Andy Chu, Hye-Jung E. Chun, Andrew J. Mungall, Erin Pleasance, A. Gordon Robertson, Payal Sipahimalani, Dominik Stoll, Miruna Balasundaram, Inanc Birol, Yaron S. N. Butterfield, Eric Chuah, Robin J. N. Coope, Richard Corbett, Noreen Dhalla, Ranabir Guin, An He, Carrie Hirst, Martin Hirst, Robert A. Holt, Darlene Lee, Haiyan I. Li, Michael Mayo, Richard A. Moore, Karen Mungall, Ka Ming Nip, Adam Olshen, Jacqueline E. Schein, Jared R. Slobodan, Angela Tam, Nina Thiessen, Richard Varhol, Thomas Zeng, Yongjun Zhao, Steven J. M. Jones, Marco A. Marra, Gordon Saksena, Andrew D. Cherniack, Stephen E. Schumacher, Barbara Tabak, Scott L. Carter, Nam H. Pho, Huy Nguyen, Robert C. Onofrio, Andrew Crenshaw, Kristin Ardlie, Rameen Beroukhim, Wendy Winckler, Peter S. Hammerman, Gad Getz, Matthew Meyerson, Alexei Protopopov, Jianhua Zhang, Angela Hadjipanayis, Semin Lee, Ruibin Xi, Lixing Yang, Xiaojia Ren, Hailei Zhang, Sachet Shukla, Peng-Chieh Chen, Psalm Haseley, Eunjung Lee, Lynda Chin, Peter J. Park, Raju Kucherlapati, Nicholas D. Socci, Yupu Liang, Nikolaus Schultz, Laetitia Borsu, Alex E. Lash, Agnes Viale, Chris Sander, Marc Ladanyi, J. Todd Auman, Katherine A. Hoadley, Matthew D. Wilkerson, Yan Shi, Christina Liquori, Shaowu Meng, Ling Li, Yidi J. Turman, Michael D. Topal, Donghui Tan, Scot Waring, Elizabeth Buda, Jesse Walsh, Corbin D. Jones, Piotr A. Mieczkowski, Darshan Singh, Junyuan Wu, Anisha Gulabani, Peter Dolina, Tom Bodenheimer, Alan P. Hoyle, Janae V. Simons, Matthew G. Soloway, Lisle E. Mose, Stuart R. Jefferys, Saianand Balu, Brian D. O’Connor, Jan F. Prins, Jinze Liu, Derek Y. Chiang, D. Neil Hayes, Charles M. Perou, Leslie Cope, Ludmila Danilova, Daniel J. Weisenberger, Dennis T. Maglinte, Fei Pan, David J. Van Den Berg, Timothy Triche Jr, James G. Herman, Stephen B. Baylin, Peter W. Laird, Gad Getz, Michael Noble, Doug Voet, Gordon Saksena, Nils Gehlenborg, Daniel DiCara, Jinhua Zhang, Hailei Zhang, Chang-Jiun Wu, Spring Yingchun Liu, Michael S. Lawrence, Lihua Zou, Andrey Sivachenko, Pei Lin, Petar Stojanov, Rui Jing, Juok Cho, Marc-Danie Nazaire, Jim Robinson, Helga Thorvaldsdottir, Jill Mesirov, Peter J. Park, Lynda Chin, Nikolaus Schultz, Rileen Sinha, Giovanni Ciriello, Ethan Cerami, Benjamin Gross, Anders Jacobsen, Jianjiong Gao, B. Arman Aksoy, Nils Weinhold, Ricardo Ramirez, Barry S. Taylor, Yevgeniy Antipin, Boris Reva, Ronglai Shen, Qianxing Mo, Venkatraman Seshan, Paul K. Paik, Marc Ladanyi, Chris Sander, Rehan Akbani, Nianxiang Zhang, Bradley M. Broom, Tod Casasent, Anna Unruh, Chris Wakefield, R. Craig Cason, Keith A. Baggerly, John N. Weinstein, David Haussler, Christopher C. Benz, Joshua M. Stuart, Jingchun Zhu, Christopher Szeto, Gary K. Scott, Christina Yau, Sam Ng, Ted Goldstein, Peter Waltman, Artem Sokolov, Kyle Ellrott, Eric A. Collisson, Daniel Zerbino, Christopher Wilks, Singer Ma, Brian Craft, Matthew D. Wilkerson, J. Todd Auman, Katherine A. Hoadley, Ying Du, Christopher Cabanski, Vonn Walter, Darshan Singh, Junyuan Wu, Anisha Gulabani, Tom Bodenheimer, Alan P. Hoyle, Janae V. Simons, Matthew G. Soloway, Lisle E. Mose, Stuart R. Jefferys, Saianand Balu, J. S. Marron, Yufeng Liu, Kai Wang, Jinze Liu, Jan F. Prins, D. Neil Hayes, Charles M. Perou, Chad J. Creighton, Yiqun Zhang, William D. Travis, Natasha Rekhtman, Joanne Yi, Marie C. Aubry, Richard Cheney, Sanja Dacic, Douglas Flieder, William Funkhouser, Peter Illei, Jerome Myers, Ming-Sound Tsao, Robert Penny, David Mallery, Troy Shelton, Martha Hatfield, Scott Morris, Peggy Yena, Candace Shelton, Mark Sherman, Joseph Paulauskis, Matthew Meyerson, Stephen B. Baylin, Ramaswamy Govindan, Rehan Akbani, Ijeoma Azodo, David Beer, Ron Bose, Lauren A. Byers, David Carbone, Li-Wei Chang, Derek Chiang, Andy Chu, Elizabeth Chun, Eric Collisson, Leslie Cope, Chad J. Creighton, Ludmila Danilova, Li Ding, Gad Getz, Peter S. Hammerman, D. Neil Hayes, Bryan Hernandez, James G. Herman, John Heymach, Cristiane Ida, Marcin Imielinski, Bruce Johnson, Igor Jurisica, Jacob Kaufman, Farhad Kosari, Raju Kucherlapati, David Kwiatkowski, Marc Ladanyi, Michael S. Lawrence, Christopher A. Maher, Andy Mungall, Sam Ng, William Pao, Martin Peifer, Robert Penny, Gordon Robertson, Valerie Rusch, Chris Sander, Nikolaus Schultz, Ronglai Shen, Jill Siegfried, Rileen Sinha, Andrey Sivachenko, Carrie Sougnez, Dominik Stoll, Joshua Stuart, Roman K. Thomas, Sandra Tomaszek, Ming-Sound Tsao, William D. Travis, Charles Vaske, John N. Weinstein, Daniel Weisenberger, Dennis A. Wigle, Matthew D. Wilkerson, Christopher Wilks, Ping Yang, Jianjua John Zhang, Mark A. Jensen, Robert Sfeir, Ari B. Kahn, Anna L. Chu, Prachi Kothiyal, Zhining Wang, Eric E. Snyder, Joan Pontius, Todd D. Pihl, Brenda Ayala, Mark Backus, Jessica Walton, Julien Baboud, Dominique L. Berton, Matthew C. Nicholls, Deepak Srinivasan, Rohini Raman, Stanley Girshik, Peter A. Kigonya, Shelley Alonso, Rashmi N. Sanbhadti, Sean P. Barletta, John M. Greene, David A. Pot, Ming-Sound Tsao, Bizhan Bandarchi-Chamkhaleh, Jeff Boyd, JoEllen Weaver, Dennis A. Wigle, Ijeoma A. Azodo, Sandra C. Tomaszek, Marie Christine Aubry, Christiane M. Ida, Ping Yang, Farhad Kosari, Malcolm V. Brock, Kristen Rodgers, Marian Rutledge, Travis Brown, Beverly Lee, James Shin, Dante Trusty, Rajiv Dhir, Jill M. Siegfried, Olga Potapova, Konstantin V. Fedosenko, Elena Nemirovich-Danchenko, Valerie Rusch, Maureen Zakowski, Mary V. Iacocca, Jennifer Brown, Brenda Rabeno, Christine Czerwinski, Nicholas Petrelli, Zhen Fan, Nicole Todaro, John Eckman, Jerome Myers, W. Kimryn Rathmell, Leigh B. Thorne, Mei Huang, Lori Boice, Ashley Hill, Robert Penny, David Mallery, Erin Curley, Candace Shelton, Peggy Yena, Carl Morrison, Carmelo Gaudioso, John M. S. Bartlett, Sugy Kodeeswaran, Brent Zanke, Harman Sekhon, Kerstin David, Hartmut Juhl, Xuan Van Le, Bernard Kohl, Richard Thorp, Nguyen Viet Tien, Nguyen Van Bang, Howard Sussman, Bui Duc Phu, Richard Hajek, Nguyen Phi Hung, Khurram Z. Khan, Thomas Muley, Kenna R. Mills Shaw, Margi Sheth, Liming Yang, Ken Buetow, Tanja Davidsen, John A. Demchok, Greg Eley, Martin Ferguson, Laura A. L. Dillon, Carl Schaefer, Mark S. Guyer, Bradley A. Ozenberger, Jacqueline D. Palchik, Jane Peterson, Heidi J. Sofia, Elizabeth Thomson, Peter S. Hammerman, D. Neil Hayes, Matthew D. Wilkerson, Nikolaus Schultz, Ron Bose, Andy Chu, Eric A. Collisson, Leslie Cope, Chad J. Creighton, Gad Getz, James G. Herman, Bruce E. Johnson, Raju Kucherlapati, Marc Ladanyi, Christopher A. Maher, Gordon Robertson, Chris Sander, Ronglai Shen, Rileen Sinha, Andrey Sivachenko, Roman K. Thomas, William D. Travis, Ming-Sound Tsao, John N. Weinstein, Dennis A. Wigle, Stephen B. Baylin, Ramaswamy Govindan, Matthew Meyerson

ABSTRACT

Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers. More... »

PAGES

519-525

Journal

TITLE

Nature

ISSUE

7417

VOLUME

489

Author Affiliations

  • Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
  • The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USA
  • Department of Systems Biology, Harvard University, Boston, Massachusetts 02115, USA.
  • Genetic Analysis Platform, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, 02142, Cambridge, Massachusetts, USA
  • Department of Pathology, Harvard Medical School, 02115, Boston, Massachusetts, USA
  • Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.
  • Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California 94143, USA.
  • Department of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Division of Genetics, Brigham and Women’s Hospital, 02115, Boston, Massachusetts, USA
  • The Center for Biomedical Informatics, Harvard Medical School, 02115, Boston, Massachusetts, USA
  • Department of Medical Oncology, Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
  • Department of Dermatology, Harvard Medical School, 02115, Boston, Massachusetts, USA
  • Informatics Program, Children's Hospital, 02115, Boston, Massachusetts, USA
  • Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
  • Department of Pathology and Human Oncology & Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, 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.
  • Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
  • Department of Biology, University of North Carolina at Chapel Hill, 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, Chapel Hill, North Carolina 27599, USA.
  • Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
  • Department of Computer Science, University of Kentucky, Lexington, Kentucky 40506, USA.
  • Department of Internal Medicine, Division of Medical Oncology, 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 90033, USA.
  • Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
  • Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
  • Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Division of Pathology and Laboratory Medicine, 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.
  • Howard Hughes Medical Institute, University of California Santa Cruz, Santa Cruz, California 95064, USA.
  • Buck Institute for Age Research, Novato, California 94945, USA.
  • Department of Biomolecular Engineering and Center for Biomolecular Science and Engineering, University of California Santa Cruz, Santa Cruz, California 95064, USA.
  • Division of Hematology/Oncology, University of California San Francisco, 94143, San Francisco, California, USA
  • Department of Statistics and Operations Research, University of North Carolina Medical Center, Chapel Hill, North Carolina 27599, USA.
  • Human Genome Sequencing Center and Dan L. Duncan Cancer Center Division of Biostatistics, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Department of Pathology, Memorial Sloan Kettering Cancer Center, 10065, New York, New York, USA
  • Department of Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.
  • Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
  • Department of Pathology, University of Pittsburgh Cancer Center, Pittsburgh, Pennsylvania 15213, USA.
  • Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
  • Department of Pathology, University of North Carolina Medical Center, Chapel Hill, North Carolina 27599, USA.
  • Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
  • Department of Pathology, Penrose-St. Francis Health System, Colorado Springs, Colorado 80907, USA.
  • Department of Pathology and Medical Biophysics, Ontario Cancer Institute and Princess Margaret Hospital, Toronto, Ontario M5G 2MY, Canada.
  • International Genomics Consortium, Phoenix, Arizona 85004, USA.
  • Division of Oncology, Department of Medicine and The Genome Institute, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
  • Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
  • Department of Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • The University of Texas MD Anderson Cancer Center, 77030, Houston, Texas, USA
  • Departments of Hematology/Oncology and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
  • Ontario Cancer Institute, IBM Life Sciences Discovery Centre, Toronto, Ontario M5G 1L7, Canada.
  • Max Planck Institute for Neurological Research, Cologne D-50866, Germany.
  • Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
  • Department of Pharmacology and Chemical Biology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15232, USA.
  • Department of Translational Cancer Genomics, Center of Integrated Oncology, University of Cologne, Cologne D-50924, Germany.
  • SRA International, Fairfax, Virginia 22033, USA.
  • Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.
  • Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
  • Department of Surgery, Johns Hopkins School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287, USA.
  • Department of Oncology, Johns Hopkins School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287, USA.
  • Department of Pathology, Johns Hopkins School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287, USA.
  • Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
  • Cureline, South San Francisco, 94080, California, USA
  • City Clinical Oncology Dispensary, St Petersburg 197022, Russia.
  • Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
  • Helen F. Graham Cancer Center, Newark, Delaware 19713, USA.
  • St Joseph Medical Center, Towson, Maryland 21204, USA.
  • Department of Pathology, UNC Tissue Procurement Facility, UNC Lineberger Cancer Center, Chapel Hill, North Carolina 27599, USA.
  • Ontario Tumour Bank, Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada.
  • Ontario Tumour Bank – Ottawa site, The Ottawa Hospital, Ottawa, Ontario K1H 8L6, Canada.
  • Indivumed GmbH, Hamburg, Falkenried 88, Haus D D-20251, Germany.
  • Indivumed Inc, Kensington, Maryland 20895, USA.
  • ILSBio, LLC, Chestertown, Maryland 21620, USA.
  • Ministry of Health, 138A Giang Vo Street, Hanoi, Vietnam.
  • Hue Central Hospital, Hue City, 16 Le Loi, Hue, Vietnam.
  • Stanford University Medical Center, 94305, Stanford, California, USA
  • Center for Minority Health Research, University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
  • National Cancer Institute, 43 Quan Su Street, Hanoi, Vietnam.
  • ILSBio LLC, Chestertown, Maryland 21620, USA.
  • ThoraxKlinik, Heidelberg University Hospital, Heidelberg 69126, Germany.
  • The Cancer Genome Atlas Program Office, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Center for Biomedical Informatics and Information Technology (CBIIT), National Cancer Institute, National Institutes of Health, Rockville, Maryland 20852, USA.
  • MLF Consulting, 02474, Arlington, Maryland, USA
  • National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Clinical Trials linked to this publication

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature11404

    DOI

    http://dx.doi.org/10.1038/nature11404

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1006014163

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/22960745


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