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The Somatic Genomic Landscape of Glioblastoma
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 ,
Jill Barnholtz-Sloan ,
Wendi Barrett ,
Quinn Ostrom ,
Yingli Wolinsky ,
Keith L. Black ,
Bikash Bose ,
Paul T. Boulos ,
Madgy Boulos ,
Jenn Brown ,
Christine Czerinski ,
Matthew Eppley ,
Mary Iacocca ,
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 ,
Raju Kucherlapati ,
Steven Kalkanis ,
Tom Mikkelsen ,
Laila M. Poisson ,
Aditya Raghunathan ,
Lisa Scarpace ,
Brady Bernard ,
Ryan Bressler ,
Andrea Eakin ,
Lisa Iype ,
Richard B. Kreisberg ,
Kalle Leinonen ,
Sheila Reynolds ,
Hector Rovira ,
Vesteinn Thorsson ,
Ilya Shmulevich ,
Matti J. Annala ,
Robert Penny ,
Joseph Paulauskis ,
Erin Curley ,
Martha Hatfield ,
David Mallery ,
Scott Morris ,
Troy Shelton ,
Candace Shelton ,
Mark Sherman ,
Peggy Yena ,
Lucia Cuppini ,
Francesco DiMeco ,
Marica Eoli ,
Gaetano Finocchiaro ,
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 ,
Samuel H. Berman ,
Cameron W. Brennan ,
Ethan Cerami ,
Debyani Chakravarty ,
Giovanni Ciriello ,
Jianjiong Gao ,
Benjamin Gross ,
Anders Jacobsen ,
Marc Ladanyi ,
Alex Lash ,
Yupu Liang ,
Boris Reva ,
Chris Sander ,
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 ,
Jerome Myers ,
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 ,
Jennifer Eschbacher ,
Greg Foltz ,
Nathan Hansen ,
Parvi Hothi ,
Biaoyang Lin ,
Nameeta Shah ,
Jae-geun Yoon ,
Ching Lau ,
Michael Berens ,
Kristin Ardlie ,
Rameen Beroukhim ,
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 ,
Matthew Meyerson ,
Robert C. Onofrio ,
Gordon Saksena ,
Steve Schumacher ,
Carrie Sougnez ,
Petar Stojanov ,
Barbara Tabak ,
Doug Voet ,
Hailei Zhang ,
Lihua Zou ,
Gad Getz ,
Nathan N. Dees ,
Li Ding ,
Lucinda L. Fulton ,
Robert S. Fulton ,
Krishna-Latha Kanchi ,
Elaine R. Mardis ,
Richard K. Wilson ,
Stephen B. Baylin ,
David W. Andrews ,
Larry Harshyne ,
Mark L. Cohen ,
Karen Devine ,
Andrew E. Sloan ,
Scott R. VandenBerg ,
Mitchel S. Berger ,
Michael Prados ,
Daniel Carlin ,
Brian Craft ,
Kyle Ellrott ,
Mary Goldman ,
Theodore Goldstein ,
Mia Grifford ,
David Haussler ,
Singer Ma ,
Sam Ng ,
Sofie R. Salama ,
J. Zachary Sanborn ,
Joshua Stuart ,
Teresa Swatloski ,
Peter Waltman ,
Jing Zhu ,
Robin Foss ,
Barbara Frentzen ,
William Friedman ,
Raquel McTiernan ,
Anthony Yachnis ,
D. Neil Hayes ,
Charles M. Perou ,
Siyuan Zheng ,
Rahulsimham Vegesna ,
Yong Mao ,
Rehan Akbani ,
Kenneth Aldape ,
Oliver Bogler ,
Gregory N. Fuller ,
Wenbin Liu ,
Yuexin Liu ,
Yiling Lu ,
Gordon Mills ,
Alexei Protopopov ,
Xiaojia Ren ,
Youting Sun ,
Chang-Jiun Wu ,
W.K. Alfred Yung ,
Wei Zhang ,
Jianhua Zhang ,
Ken Chen ,
John N. Weinstein ,
Lynda Chin ,
Roel G.W. Verhaak ,
Houtan Noushmehr ,
Daniel J. Weisenberger ,
Moiz S. Bootwalla ,
Phillip H. Lai ,
Timothy J. Triche ,
David J. Van Den Berg ,
Peter W. Laird ,
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 ,
Roger McLendon
October 2013
October 2013
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Abstract
We 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.
Copyright © 2013 Elsevier Inc. All rights reserved.