The Somatic Genomic Landscape of Glioblastoma | Zendy

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The Somatic Genomic Landscape of Glioblastoma

Author(s) -

Cameron Brennan,

Roel G.W. Verhaak,

Aaron McKenna,

Benito Campos,

Houtan Noushmehr,

Sofie R. Salama,

Siyuan Zheng,

Debyani Chakravarty,

Zack Sanborn,

Samuel H. Berman,

Rameen Beroukhim,

Brady Bernard,

ChangJiun Wu,

Giannicola Genovese,

Ilya Shmulevich,

Jill S. BarnholtzSloan,

Lihua Zou,

Rahulsimham Vegesna,

Sachet A. Shukla,

Giovanni Ciriello,

W. K. Alfred Yung,

Wei Zhang,

Carrie Sougnez,

Tom Mikkelsen,

Kenneth Aldape,

Darell D. Bigner,

Erwin G. Van Meir,

Michael D. Prados,

Andrew E. Sloan,

Keith L. Black,

Jennifer Eschbacher,

Gaetano Finocchiaro,

William A. Friedman,

David W. Andrews,

Abhijit Guha,

Mary Iacocca,

Brian Patrick O’Neill,

Greg Foltz,

Jerome Myers,

Daniel J. Weisenberger,

Robert Penny,

Raju Kucherlapati,

Charles M. Perou,

D. Neil Hayes,

Richard A. Gibbs,

Marco A. Marra,

Gordon B. Mills,

Eric S. Lander,

Paul T. Spellman,

Richard K. Wilson,

Chris Sander,

John N. Weinstein,

Matthew Meyerson,

Stacey Gabriel,

Peter W. Laird,

David Haussler,

Gad Getz,

Lynda Chin,

Christopher C. Benz,

Wendi Barrett,

Quinn T. 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 C. Sugarman,

Patricia Swanson,

Kennedy Yalamanchii,

Ilana P. Otey,

Yingchun Spring Liu,

Yonghong Xiao,

J. Todd Auman,

PengChieh Chen,

Angela Hadjipanayis,

Eunjung Lee,

Semin Lee,

Peter J. Park,

Jonathan G. Seidman,

Lixing Yang,

Steven N. Kalkanis,

Laila Poisson,

Aditya Raghunathan,

Lisa Scarpace,

Ryan Bressler,

Andrea Eakin,

Lisa Iype,

Richard Kreisberg,

Kalle Lein,

Sheila M. Reynolds,

Hector Rovira,

Vésteinn Thórsson,

Matti Annala,

Joseph Paulauskis,

Erin Curley,

Martha Hatfield,

David Mallery,

Scott Morris,

Troy Shelton,

Candace Shelton,

Mark E. 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 P. Dunn,

Caterina Giannini,

Bülent Arman Aksoy,

Yevgeniy Antipin,

Laetitia Borsu,

Ethan Cerami,

Jianjiong Gao,

Benjamin Groß,

Anders J. Skanderup,

Marc Ladanyi,

Alex E. Lash,

Yupu Liang,

Boris Reva,

Nikolaus Schultz,

Ronglai Shen,

Nicholas D. Socci,

Agnès Viale,

Martin L. Ferguson,

Qingrong Chen,

John A. Demchok,

Laura A. L. Dillon,

Kenna Shaw,

Margi Sheth,

Roy Tarnuzzer,

Linghua Wang,

Liming Yang,

Tanja M. Davidsen,

Mark S. Guyer,

Bradley A. Ozenberger,

Heidi J. Sofia,

Julie Bergsten,

John Eckman,

Jodi Harr,

Christine Smith,

Kelly J. Tucker,

Cindy Winemiller,

Leigh Anne Zach,

Julia Y. Ljubimova,

Greg Eley,

Brenda Ayala,

Mark A. Jensen,

A Kahn,

Todd Pihl,

David Pot,

Yunhu Wan,

Nathan Hansen,

Parvi Hothi,

Biaoyang Lin,

Nameeta Shah,

JaeGeun Yoon,

Ching C. Lau,

Michael E. Berens,

Kristin Ardlie,

Scott L. Carter,

Andrew D. Cherniack,

Mike Noble,

Juok Cho,

Kristian Cibulskis,

Daniel DiCara,

Scott Frazer,

Nils Gehlenborg,

Jeff Gentry,

David I. Heiman,

Jaegil Kim,

Rui Jing,

Michael S. Lawrence,

Pei Lin,

Will Mallard,

Robert C. Onofrio,

Gordon Saksena,

Steve Schumacher,

Petar Stojanov,

Barbara Tabak,

Doug Voet,

Hailei Zhang,

Nathan N. Dees,

Jun Li,

Lucinda Fulton,

Robert S. Fulton,

Krishna-Latha Kanchi,

Elaine R. Mardis,

Stephen B. Baylin,

Larry A. Harshyne,

Mark L. Cohen,

Karen Devine,

Scott R. VandenBerg,

Mitchel S. Berger,

Yichao Li,

Brian Craft,

Kyle Ellrott,

Mary J. Goldman,

Theodore C. Goldstein,

Mia Grifford,

Singer Ma,

Sam Ng,

Joshua M. Stuart,

Teresa Swatloski,

Peter Waltman,

Jing Zhu,

Robin M. Foss,

Barbara Frentzen,

Raquel G. McTiernan,

Anthony T. Yachnis,

Yong Mao,

Rehan Akbani,

Oliver Bögler,

Gregory N. Fuller,

Wenbin Liu,

Yuexin Liu,

Yiling Lu,

Alexei Protopopov,

Xiaojia Ren,

Youting Sun,

Jianhua Zhang,

Ken Chen,

Arnoud Boot,

Phillip H. Lai,

Timothy J. Triche,

David Van Den Berg,

David H. Gutmann,

Norman L. Lehman,

Daniel J. Brat,

Jeffrey J. Olson,

Gena M. Mastrogianakis,

Narra S. Devi,

Zhaobin Zhang,

Eric Lipp,

Roger E. McLendon

Publication year - 2013

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2013.09.034

Subject(s) - biology , somatic cell , glioblastoma , genetics , computational biology , evolutionary biology , cancer research , gene

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.

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