Comprehensive genomic characterization defines human glioblastoma genes and core pathways View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-09-04

AUTHORS

Roger McLendon, Allan Friedman, Darrell Bigner, Erwin G. Van Meir, Daniel J. Brat, Gena M. Mastrogianakis, Jeffrey J. Olson, Tom Mikkelsen, Norman Lehman, Ken Aldape, W. K. Alfred Yung, Oliver Bogler, Scott VandenBerg, Mitchel Berger, Michael Prados, Donna Muzny, Margaret Morgan, Steve Scherer, Aniko Sabo, Lynn Nazareth, Lora Lewis, Otis Hall, Yiming Zhu, Yanru Ren, Omar Alvi, Jiqiang Yao, Alicia Hawes, Shalini Jhangiani, Gerald Fowler, Anthony San Lucas, Christie Kovar, Andrew Cree, Huyen Dinh, Jireh Santibanez, Vandita Joshi, Manuel L. Gonzalez-Garay, Christopher A. Miller, Aleksandar Milosavljevic, Larry Donehower, David A. Wheeler, Richard A. Gibbs, Kristian Cibulskis, Carrie Sougnez, Tim Fennell, Scott Mahan, Jane Wilkinson, Liuda Ziaugra, Robert Onofrio, Toby Bloom, Rob Nicol, Kristin Ardlie, Jennifer Baldwin, Stacey Gabriel, Eric S. Lander, Li Ding, Robert S. Fulton, Michael D. McLellan, John Wallis, David E. Larson, Xiaoqi Shi, Rachel Abbott, Lucinda Fulton, Ken Chen, Daniel C. Koboldt, Michael C. Wendl, Rick Meyer, Yuzhu Tang, Ling Lin, John R. Osborne, Brian H. Dunford-Shore, Tracie L. Miner, Kim Delehaunty, Chris Markovic, Gary Swift, William Courtney, Craig Pohl, Scott Abbott, Amy Hawkins, Shin Leong, Carrie Haipek, Heather Schmidt, Maddy Wiechert, Tammi Vickery, Sacha Scott, David J. Dooling, Asif Chinwalla, George M. Weinstock, Elaine R. Mardis, Richard K. Wilson, Gad Getz, Wendy Winckler, Roel G. W. Verhaak, Michael S. Lawrence, Michael O’Kelly, Jim Robinson, Gabriele Alexe, Rameen Beroukhim, Scott Carter, Derek Chiang, Josh Gould, Supriya Gupta, Josh Korn, Craig Mermel, Jill Mesirov, Stefano Monti, Huy Nguyen, Melissa Parkin, Michael Reich, Nicolas Stransky, Barbara A. Weir, Levi Garraway, Todd Golub, Matthew Meyerson, Lynda Chin, Alexei Protopopov, Jianhua Zhang, Ilana Perna, Sandy Aronson, Narayan Sathiamoorthy, Georgia Ren, Jun Yao, W. Ruprecht Wiedemeyer, Hyunsoo Kim, Sek Won Kong, Yonghong Xiao, Isaac S. Kohane, Jon Seidman, Peter J. Park, Raju Kucherlapati, Peter W. Laird, Leslie Cope, James G. Herman, Daniel J. Weisenberger, Fei Pan, David Van Den Berg, Leander Van Neste, Joo Mi Yi, Kornel E. Schuebel, Stephen B. Baylin, Devin M. Absher, Jun Z. Li, Audrey Southwick, Shannon Brady, Amita Aggarwal, Tisha Chung, Gavin Sherlock, James D. Brooks, Richard M. Myers, Paul T. Spellman, Elizabeth Purdom, Lakshmi R. Jakkula, Anna V. Lapuk, Henry Marr, Shannon Dorton, Yoon Gi Choi, Ju Han, Amrita Ray, Victoria Wang, Steffen Durinck, Mark Robinson, Nicholas J. Wang, Karen Vranizan, Vivian Peng, Eric Van Name, Gerald V. Fontenay, John Ngai, John G. Conboy, Bahram Parvin, Heidi S. Feiler, Terence P. Speed, Joe W. Gray, Cameron Brennan, Nicholas D. Socci, Adam Olshen, Barry S. Taylor, Alex Lash, Nikolaus Schultz, Boris Reva, Yevgeniy Antipin, Alexey Stukalov, Benjamin Gross, Ethan Cerami, Wei Qing Wang, Li-Xuan Qin, Venkatraman E. Seshan, Liliana Villafania, Magali Cavatore, Laetitia Borsu, Agnes Viale, William Gerald, Chris Sander, Marc Ladanyi, Charles M. Perou, D. Neil Hayes, Michael D. Topal, Katherine A. Hoadley, Yuan Qi, Sai Balu, Yan Shi, Junyuan Wu, Robert Penny, Michael Bittner, Troy Shelton, Elizabeth Lenkiewicz, Scott Morris, Debbie Beasley, Sheri Sanders, Ari Kahn, Robert Sfeir, Jessica Chen, David Nassau, Larry Feng, Erin Hickey, Jinghui Zhang, John N. Weinstein, Anna Barker, Daniela S. Gerhard, Joseph Vockley, Carolyn Compton, Jim Vaught, Peter Fielding, Martin L. Ferguson, Carl Schaefer, Subhashree Madhavan, Kenneth H. Buetow, Francis Collins, Peter Good, Mark Guyer, Brad Ozenberger, Jane Peterson, Elizabeth Thomson

ABSTRACT

Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multi-dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas—the most common type of adult brain cancer—and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol-3-OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer. More... »

PAGES

1061-1068

Journal

TITLE

Nature

ISSUE

7216

VOLUME

455

Author Affiliations

  • Department of Pathology,
  • Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
  • Winship Cancer Institute,
  • Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
  • Department of Neurosurgery,
  • Department of Neurological Surgery,
  • Department of Pathology, Henry Ford Hospital, Detroit, Michigan 48202, USA.
  • Department of Neuro-Oncology,
  • Department of Neurosurgery, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
  • Department of Neurosurgery, University of California San Francisco, San Francisco, California 94143, USA.
  • Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Graduate Program in Structural and Computational Biology and Molecular Biophysics,
  • Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Department of Molecular Virology and Microbiology, Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
  • The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
  • Department of Systems Biology, Harvard University, Boston, Massachusetts 02115, USA.
  • Department of Genetics, The Genome Center at Washington University, Washington University School of Medicine, St Louis, Missouri 63108, USA.
  • Center for Cancer Genome Discovery,
  • Department of Medical Oncology,
  • Department of Dermatology, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Center for Applied Cancer Science of the Belfer Institute for Innovative Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
  • Harvard Medical School-Partners HealthCare Center for Genetics and Genomics, Boston, Massachusetts 02115, USA.
  • Department of Cardiology, Children’s Hospital, Boston, Massachusetts 02115, USA.
  • Center for Biomedical Informatics,
  • Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • USC Epigenome Center, University of Southern California, Los Angeles, California 90089, USA.
  • Biometry and Clinical Trials Division,
  • Cancer Biology Division, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland 21231, USA.
  • Department of Molecular Biotechnology, Faculty of Bioscience and Engineering, Ghent University, Ghent B-9000, Belgium.
  • HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA.
  • Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Department of Genetics,
  • Department of Urology, Stanford University School of Medicine, Stanford, California 94305, USA.
  • Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
  • Department of Statistics,
  • Department of Molecular and Cellular Biology, University of California at Berkeley, Berkeley, California 95720, USA.
  • Walter and Eliza Hall Institute, Parkville, Victoria 3052, Australia.
  • Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
  • Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
  • Department of Physiology and Biophysics, Weill Cornell Graduate School of Medical Sciences, New York, New York 10065, USA.
  • Genomics Core Laboratory, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
  • Department of Pathology, Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
  • Department of Pathology and Laboratory Medicine,
  • Department of Internal Medicine, Division of Medical Oncology, Lineberger Comprehensive Cancer Center, 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.
  • International Genomics Consortium, Phoenix, Arizona 85004, USA.
  • Computational Biology Division, Translational Genomics Research Institute, Phoenix, Arizona 85004, USA.
  • SRA International, Fairfax, Virginia 22033, USA.
  • Center For Biomedical Informatics and Information Technology, National Cancer Institute, Rockville, Maryland 20852, USA.
  • Department of Bioinformatics and Computational Biology, M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
  • National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • MLF Consulting, Arlington, Massachusetts 02474, USA.
  • National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature07385

    DOI

    http://dx.doi.org/10.1038/nature07385

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1039570773

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/18772890


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