1. The Somatic Genomic Landscape of Glioblastoma
- Author
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Cameron W. Brennan, Roel G.W. Verhaak, Aaron McKenna, Benito Campos, Houtan Noushmehr, Sofie R. Salama, Siyuan Zheng, Debyani Chakravarty, J. Zachary Sanborn, Samuel H. Berman, Rameen Beroukhim, Brady Bernard, Chang-Jiun Wu, Giannicola Genovese, Ilya Shmulevich, Jill Barnholtz-Sloan, Lihua Zou, Rahulsimham Vegesna, Sachet A. Shukla, Giovanni Ciriello, W.K. Yung, Wei Zhang, Carrie Sougnez, Tom Mikkelsen, Kenneth Aldape, Darell D. Bigner, Erwin G. Van Meir, Michael Prados, Andrew Sloan, Keith L. Black, Jennifer Eschbacher, Gaetano Finocchiaro, William Friedman, David W. Andrews, Abhijit Guha, Mary Iacocca, Brian P. O’Neill, Greg Foltz, Jerome Myers, Daniel J. Weisenberger, Robert Penny, Raju Kucherlapati, Charles M. Perou, D. Neil Hayes, Richard Gibbs, Marco Marra, Gordon B. Mills, Eric Lander, Paul Spellman, Richard Wilson, Chris Sander, John Weinstein, Matthew Meyerson, Stacey Gabriel, Peter W. Laird, David Haussler, Gad Getz, Lynda Chin, Christopher Benz, Wendi Barrett, Quinn Ostrom, Yingli Wolinsky, Bikash Bose, Paul T. Boulos, Madgy Boulos, Jenn Brown, Christine Czerinski, Matthew Eppley, Thelma Kempista, Teresa Kitko, Yakov Koyfman, Brenda Rabeno, Pawan Rastogi, Michael Sugarman, Patricia Swanson, Kennedy Yalamanchii, Ilana P. Otey, Yingchun Spring Liu, Yonghong Xiao, J.Todd Auman, Peng-Chieh Chen, Angela Hadjipanayis, Eunjung Lee, Semin Lee, Peter J. Park, Jonathan Seidman, Lixing Yang, Steven Kalkanis, Laila M. Poisson, Aditya Raghunathan, Lisa Scarpace, Ryan Bressler, Andrea Eakin, Lisa Iype, Richard B. Kreisberg, Kalle Leinonen, Sheila Reynolds, Hector Rovira, Vesteinn Thorsson, Matti J. Annala, Joseph Paulauskis, Erin Curley, Martha Hatfield, David Mallery, Scott Morris, Troy Shelton, Candace Shelton, Mark Sherman, Peggy Yena, Lucia Cuppini, Francesco DiMeco, Marica Eoli, Emanuela Maderna, Bianca Pollo, Marco Saini, Saianand Balu, Katherine A. Hoadley, Ling Li, C. Ryan Miller, Yan Shi, Michael D. Topal, Junyuan Wu, Gavin Dunn, Caterina Giannini, Brian P. O'Neill, B. Arman Aksoy, Yevgeniy Antipin, Laetitia Borsu, Ethan Cerami, Jianjiong Gao, Benjamin Gross, Anders Jacobsen, Marc Ladanyi, Alex Lash, Yupu Liang, Boris Reva, Nikolaus Schultz, Ronglai Shen, Nicholas D. Socci, Agnes Viale, Martin L. Ferguson, Qing-Rong Chen, John A. Demchok, Laura A.L. Dillon, Kenna R. Mills Shaw, Margi Sheth, Roy Tarnuzzer, Zhining Wang, Liming Yang, Tanja Davidsen, Mark S. Guyer, Bradley A. Ozenberger, Heidi J. Sofia, Julie Bergsten, John Eckman, Jodi Harr, Christine Smith, Kelly Tucker, Cindy Winemiller, Leigh Anne Zach, Julia Y. Ljubimova, Greg Eley, Brenda Ayala, Mark A. Jensen, Ari Kahn, Todd D. Pihl, David A. Pot, Yunhu Wan, Nathan Hansen, Parvi Hothi, Biaoyang Lin, Nameeta Shah, Jae-geun Yoon, Ching Lau, Michael Berens, Kristin Ardlie, Scott L. Carter, Andrew D. Cherniack, Mike Noble, Juok Cho, Kristian Cibulskis, Daniel DiCara, Scott Frazer, Stacey B. Gabriel, Nils Gehlenborg, Jeff Gentry, David Heiman, Jaegil Kim, Rui Jing, Eric S. Lander, Michael Lawrence, Pei Lin, Will Mallard, Robert C. Onofrio, Gordon Saksena, Steve Schumacher, Petar Stojanov, Barbara Tabak, Doug Voet, Hailei Zhang, Nathan N. Dees, Li Ding, Lucinda L. Fulton, Robert S. Fulton, Krishna-Latha Kanchi, Elaine R. Mardis, Richard K. Wilson, Stephen B. Baylin, Larry Harshyne, Mark L. Cohen, Karen Devine, Andrew E. Sloan, Scott R. VandenBerg, Mitchel S. Berger, Daniel Carlin, Brian Craft, Kyle Ellrott, Mary Goldman, Theodore Goldstein, Mia Grifford, Singer Ma, Sam Ng, Joshua Stuart, Teresa Swatloski, Peter Waltman, Jing Zhu, Robin Foss, Barbara Frentzen, Raquel McTiernan, Anthony Yachnis, Yong Mao, Rehan Akbani, Oliver Bogler, Gregory N. Fuller, Wenbin Liu, Yuexin Liu, Yiling Lu, Gordon Mills, Alexei Protopopov, Xiaojia Ren, Youting Sun, W.K. Alfred Yung, Jianhua Zhang, Ken Chen, John N. Weinstein, Moiz S. Bootwalla, Phillip H. Lai, Timothy J. Triche, David J. Van Den Berg, David H. Gutmann, Norman L. Lehman, Erwin G. VanMeir, Daniel Brat, Jeffrey J. Olson, Gena M. Mastrogianakis, Narra S. Devi, Zhaobin Zhang, Darell Bigner, Eric Lipp, and Roger McLendon
- Subjects
Male ,Telomerase ,Proteome ,REGULAÇÃO GÊNICA ,Somatic cell ,Mesenchymal Glioblastoma ,PDGFRA ,Computational biology ,Biology ,medicine.disease_cause ,Article ,General Biochemistry, Genetics and Molecular Biology ,medicine ,Humans ,Gene Regulatory Networks ,Gene ,Genetics ,Glioblastoma cell ,Mutation ,Brain Neoplasms ,Biochemistry, Genetics and Molecular Biology(all) ,Gene Expression Profiling ,Phenotype ,Gene expression profiling ,DNA methylation ,Cancer research ,Female ,Glioblastoma ,Signal Transduction - Abstract
SummaryWe describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.
- Published
- 2013
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