Comprehensive molecular characterization of human colon and rectal cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-07-18

AUTHORS

Donna M. Muzny, Matthew N. Bainbridge, Kyle Chang, Huyen H. Dinh, Jennifer A. Drummond, Gerald Fowler, Christie L. Kovar, Lora R. Lewis, Margaret B. Morgan, Irene F. Newsham, Jeffrey G. Reid, Jireh Santibanez, Eve Shinbrot, Lisa R. Trevino, Yuan-Qing Wu, Min Wang, Preethi Gunaratne, Lawrence A. Donehower, Chad J. Creighton, David A. Wheeler, Richard A. Gibbs, Michael S. Lawrence, Douglas Voet, Rui Jing, Kristian Cibulskis, Andrey Sivachenko, Petar Stojanov, Aaron McKenna, Eric S. Lander, Stacey Gabriel, Gad Getz, Li Ding, Robert S. Fulton, Daniel C. Koboldt, Todd Wylie, Jason Walker, David J. Dooling, Lucinda Fulton, Kim D. Delehaunty, Catrina C. Fronick, Ryan Demeter, Elaine R. Mardis, Richard K. Wilson, Andy Chu, Hye-Jung E. Chun, Andrew J. Mungall, Erin Pleasance, A. Gordon Robertson, Dominik Stoll, Miruna Balasundaram, Inanc Birol, Yaron S. N. Butterfield, Eric Chuah, Robin J. N. Coope, Noreen Dhalla, Ranabir Guin, Carrie Hirst, Martin Hirst, Robert A. Holt, Darlene Lee, Haiyan I. Li, Michael Mayo, Richard A. Moore, Jacqueline E. Schein, Jared R. Slobodan, Angela Tam, Nina Thiessen, Richard Varhol, Thomas Zeng, Yongjun Zhao, Steven J. M. Jones, Marco A. Marra, Adam J. Bass, Alex H. Ramos, 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, Gad Getz, Matthew Meyerson, Alexei Protopopov, Juinhua Zhang, Angela Hadjipanayis, Eunjung Lee, Ruibin Xi, Lixing Yang, Xiaojia Ren, Hailei Zhang, Narayanan Sathiamoorthy, Sachet Shukla, Peng-Chieh Chen, Psalm Haseley, Yonghong Xiao, Semin Lee, Jonathan Seidman, Lynda Chin, Peter J. Park, Raju Kucherlapati, J. Todd Auman, Katherine A. Hoadley, Ying Du, 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 Soloway, Lisle E. Mose, Stuart R. Jefferys, Saianand Balu, Brian D. O’Connor, Jan F. Prins, Derek Y. Chiang, D. Neil Hayes, Charles M. Perou, Toshinori Hinoue, Daniel J. Weisenberger, Dennis T. Maglinte, Fei Pan, Benjamin P. Berman, David J. Van Den Berg, Hui Shen, Timothy Triche Jr, Stephen B. Baylin, Peter W. Laird, Gad Getz, Michael Noble, Doug Voet, Gordon Saksena, Nils Gehlenborg, Daniel DiCara, Juinhua Zhang, Hailei Zhang, Chang-Jiun Wu, Spring Yingchun Liu, Sachet Shukla, Michael S. Lawrence, Lihua Zhou, Andrey Sivachenko, Pei Lin, Petar Stojanov, Rui Jing, Richard W. Park, Marc-Danie Nazaire, Jim Robinson, Helga Thorvaldsdottir, Jill Mesirov, Peter J. Park, Lynda Chin, Vesteinn Thorsson, Sheila M. Reynolds, Brady Bernard, Richard Kreisberg, Jake Lin, Lisa Iype, Ryan Bressler, Timo Erkkilä, Madhumati Gundapuneni, Yuexin Liu, Adam Norberg, Tom Robinson, Da Yang, Wei Zhang, Ilya Shmulevich, Jorma J. de Ronde, Nikolaus Schultz, Ethan Cerami, Giovanni Ciriello, Arthur P. Goldberg, Benjamin Gross, Anders Jacobsen, Jianjiong Gao, Bogumil Kaczkowski, Rileen Sinha, B. Arman Aksoy, Yevgeniy Antipin, Boris Reva, Ronglai Shen, Barry S. Taylor, Timothy A. Chan, Marc Ladanyi, Chris Sander, Rehan Akbani, Nianxiang Zhang, Bradley M. Broom, Tod Casasent, Anna Unruh, Chris Wakefield, Stanley R. Hamilton, R. Craig Cason, Keith A. Baggerly, John N. Weinstein, David Haussler, Christopher C. Benz, Joshua M. Stuart, Stephen C. Benz, J. Zachary Sanborn, Charles J. Vaske, Jingchun Zhu, Christopher Szeto, Gary K. Scott, Christina Yau, Sam Ng, Ted Goldstein, Kyle Ellrott, Eric Collisson, Aaron E. Cozen, Daniel Zerbino, Christopher Wilks, Brian Craft, Paul Spellman, Robert Penny, Troy Shelton, Martha Hatfield, Scott Morris, Peggy Yena, Candace Shelton, Mark Sherman, Joseph Paulauskis, Julie M. Gastier-Foster, Jay Bowen, Nilsa C. Ramirez, Aaron Black, Robert Pyatt, Lisa Wise, Peter White, Monica Bertagnolli, Jen Brown, Timothy A. Chan, Gerald C. Chu, Christine Czerwinski, Fred Denstman, Rajiv Dhir, Arnulf Dörner, Charles S. Fuchs, Jose G. Guillem, Mary Iacocca, Hartmut Juhl, Andrew Kaufman, Bernard Kohl III, Xuan Van Le, Maria C. Mariano, Elizabeth N. Medina, Michael Meyers, Garrett M. Nash, Phillip B. Paty, Nicholas Petrelli, Brenda Rabeno, William G. Richards, David Solit, Pat Swanson, Larissa Temple, Joel E. Tepper, Richard Thorp, Efsevia Vakiani, Martin R. Weiser, Joseph E. Willis, Gary Witkin, Zhaoshi Zeng, Michael J. Zinner, Carsten Zornig, 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, Jon Whitmore, 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, Kenna R. Mills Shaw, Laura A. L. Dillon, Ken Buetow, Tanja Davidsen, John A. Demchok, Greg Eley, Martin Ferguson, Peter Fielding, Carl Schaefer, Margi Sheth, Liming Yang, Mark S. Guyer, Bradley A. Ozenberger, Jacqueline D. Palchik, Jane Peterson, Heidi J. Sofia, Elizabeth Thomson.

ABSTRACT

To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase ε (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression. More... »

PAGES

330-337

Journal

TITLE

Nature

ISSUE

7407

VOLUME

487

Author Affiliations

  • Human Genome Sequencing Center, Baylor College of Medicine, 77030, Houston, Texas, USA
  • Department of Biology and Biochemistry, University of Houston, 77204, Houston, Texas, USA
  • Dan L. Duncan Cancer Center, Human Genome Sequencing Center, Baylor College of Medicine, 77030, Houston, Texas, USA
  • The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, 02142, Cambridge, Massachusetts, USA
  • Medical Sequencing Analysis and Informatics, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, 02142, Cambridge, Massachusetts, USA
  • Department of Systems Biology, Harvard University, 02115, Boston, Massachusetts, 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 Genetics, Washington University School of Medicine, 63108, St Louis, Missouri, USA
  • The Genome Institute, Washington University School of Medicine, St Louis, Missouri 63108 USA.
  • Siteman Cancer Center, Washington University School of Medicine, 63108, St Louis, Missouri, USA
  • Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, V5Z 1L3, Vancouver, British Columbia, Canada
  • Department of Medical Oncology, Dana-Farber Cancer Institute, 02115, Boston, Massachusetts, USA
  • Department of Pathology, Harvard Medical School, 02115, Boston, Massachusetts, USA
  • Department of Medical Oncology, Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, 02115, Boston, Massachusetts, USA
  • Division of Genetics, Brigham and Women’s Hospital, Boston, Massachusetts 02115, USA.
  • The Center for Biomedical Informatics, Harvard Medical School, 02115, Boston, Massachusetts, USA
  • Informatics Program, Children’s Hospital, 02115, Boston, Massachusetts, USA
  • Department of Genetics, Harvard Medical School, 02115, Boston, Massachusetts, USA
  • Department of Dermatology, Harvard Medical School, 02115, Boston, Massachusetts, USA
  • Institute for Pharmacogenetics and Individualized Therapy, University of North Carolina at Chapel Hill, 27599, Chapel Hill, North Carolina, USA
  • Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 27599, Chapel Hill, North Carolina, USA
  • Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, 27599, Chapel Hill, North Carolina, USA
  • Department of Biology, University of North Carolina at Chapel Hill, 27599, Chapel Hill, North Carolina, USA
  • Department of Genetics, University of North Carolina at Chapel Hill, 27599, Chapel Hill, North Carolina, USA
  • Department of Computer Science, University of North Carolina at Chapel Hill, 27599, Chapel Hill, North Carolina, USA
  • Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, 27599, Chapel Hill, North Carolina, USA
  • Department of Internal Medicine, Division of Medical Oncology, University of North Carolina at Chapel Hill, 27599, Chapel Hill, North Carolina, USA
  • University of Southern California Epigenome Center, University of Southern California, 90089, Los Angeles, California, USA
  • Cancer Biology Division, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, 21231, Baltimore, Maryland, USA
  • Institute for Systems Biology, 98109, Seattle, Washington, USA
  • Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, 77030, Houston, Texas, USA
  • Divisions of Experimental Therapy, Molecular Biology, Surgical Oncology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
  • 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
  • Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, 10065, New York, New York, USA
  • Department of Pathology, Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, 10065, New York, New York, USA
  • 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, 77030, Houston, Texas, USA
  • Howard Hughes Medical Institute, University of California Santa Cruz, 95064, Santa Cruz, California, USA
  • Buck Institute for Age Research, 94945, Novato, California, USA
  • Department of Biomolecular Engineering and Center for Biomolecular Science and Engineering, University of California Santa Cruz, 95064, Santa Cruz, California, USA
  • Division of Hematology/Oncology, University of California San Francisco, 94143, San Francisco, California, USA
  • Department of Molecular and Medical Genetics, Oregon Health and Science University, 97239, Portland, Oregon, USA
  • International Genomics Consortium, 85004, Phoenix, Arizona, USA
  • Department of Pediatrics, The Ohio State University College of Medicine, 43205, Columbus, Ohio, USA
  • Nationwide Children’s Hospital Biospecimen Core Resource, The Research Institute at Nationwide Children’s Hospital, Columbus, Ohio 43205, USA.
  • Department of Pathology, The Ohio State University College of Medicine, 43205, Columbus, Ohio, USA
  • Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, 02115, Brookline, Massachusetts, USA
  • Department of Pathology, Christiana Care Health Services, Newark, Delaware 19718, USA.
  • Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, 02115, Brookline, Massachusetts, USA
  • Department of Surgery, Helen F. Graham Cancer Center at Christiana Care, 19718, Newark, Delaware, USA
  • Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
  • Klinik für Chirurgie, Krankenhaus Alten Eichen, 22527, Hamburg, Germany
  • Department of Medicine, Brigham and Women’s Hospital, 02115, Brookline, Massachusetts, USA
  • Department of Surgery, Memorial Sloan-Kettering Cancer Center, 10065, New York, New York, USA
  • Indivumed Inc., 20895, Kensington, Maryland, USA
  • ILSbio, LLC, 21620, Chestertown, Maryland, USA
  • Department of Pathology, Memorial Sloan-Kettering Cancer Center, 10065, New York, New York, USA
  • Department of Surgery, Brigham and Women’s Hospital, Brookline, 02115, Massachusetts, USA
  • Tissue and Blood Repository, Brigham and Women’s Hospital, Brookline, 02115, Massachusetts, USA
  • Department of Medicine, Memorial Sloan-Kettering Cancer Center, 10065, New York, New York, USA
  • Dept of Radiation Oncology, University of North Carolina School of Medicine, 27599, Chapel Hill, North Carolina, USA
  • Department of Pathology, Case Medical Center, 44106, Cleveland, Ohio, USA
  • Chirugische Klinik, Israelitisches Krankenhaus, 22297, Hamburg, Germany
  • SRA International, Virginia22033, Fairfax, USA
  • The Cancer Genome Atlas Program Office, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA
  • Center for Biomedical Informatics and Information Technology (CBIIT), National Cancer Institute, National Institutes of Health, 20852, Rockville, Maryland, USA
  • Scimentis, LLC, 30666, Statham, Georgia, USA
  • MLF Consulting, 02474, Arlington, Massachusetts, USA
  • National Human Genome Research Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature11252

    DOI

    http://dx.doi.org/10.1038/nature11252

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1010619765

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/22810696


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