The somatic genomic landscape of glioblastoma.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Brennan, CW; Verhaak, RGW; McKenna, A; Campos, B; Noushmehr, H; Salama, SR; Zheng, S; Chakravarty, D; Sanborn, JZ; Berman, SH; Beroukhim, R; Bernard, B; Wu, C-J; Genovese, G; Shmulevich, I; Barnholtz-Sloan, J; Zou, L; Vegesna, R; Shukla, SA; Ciriello, G; Yung, WK; Zhang, W; Sougnez, C; Mikkelsen, T; Aldape, K; Bigner, DD; Van Meir, EG; Prados, M; Sloan, A; Black, KL; Eschbacher, J; Finocchiaro, G; Friedman, W; Andrews, DW; Guha, A; Iacocca, M; O'Neill, BP; Foltz, G; Myers, J; Weisenberger, DJ; Penny, R; Kucherlapati, R; Perou, CM; Hayes, DN; Gibbs, R; Marra, M; Mills, GB; Lander, E; Spellman, P; Wilson, R; Sander, C; Weinstein, J; Meyerson, M; Gabriel, S; Laird, PW; Haussler, D; Getz, G; Chin, L; TCGA Research Network,

Published Date

  • October 10, 2013

Published In

Volume / Issue

  • 155 / 2

Start / End Page

  • 462 - 477

PubMed ID

  • 24120142

Pubmed Central ID

  • 24120142

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2013.09.034

Language

  • eng

Conference Location

  • United States