The somatic genomic landscape of glioblastoma Journal Article


Authors: Brennan, C. W.; Verhaak, R. G. W.; McKenna, A.; Campos, B.; Noushmehr, H.; Salama, S. R.; Zheng, S.; Chakravarty, D.; Sanborn, J. Z.; Berman, S. H.; Beroukhim, R.; Bernard, B.; Wu, C. J.; Genovese, G.; Shmulevich, I.; Barnholtz-Sloan, J.; Zou, L.; Vegesna, R.; Shukla, S. A.; Ciriello, G.; Yung, W. K.; Zhang, W.; Sougnez, C.; Mikkelsen, T.; Aldape, K.; Bigner, D. D.; Van Meir, E. G.; Prados, M.; Sloan, A.; Black, K. L.; Eschbacher, J.; Finocchiaro, G.; Friedman, W.; Andrews, D. W.; Guha, A.; Iacocca, M.; O'Neill, B. P.; Foltz, G.; Myers, J.; Weisenberger, D. J.; Penny, R.; Kucherlapati, R.; Perou, C. M.; Hayes, D. N.; Gibbs, R.; Marra, M.; Mills, G. B.; Lander, E.; Spellman, P.; Wilson, R.; Sander, C.; Weinstein, J.; Meyerson, M.; Gabriel, S.; Laird, P. W.; Haussler, D.; Getz, G.; Chin, L.
Article Title: The somatic genomic landscape of glioblastoma
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. © 2013 Elsevier Inc.
Journal Title: Cell
Volume: 155
Issue: 2
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2013-10-10
Start Page: 462
End Page: 477
Language: English
DOI: 10.1016/j.cell.2013.09.034
PROVIDER: scopus
PUBMED: 24120142
PMCID: PMC3910500
DOI/URL:
Notes: --- - Cited By (since 1996):1 - "Export Date: 1 November 2013" - "CODEN: CELLB" - "Source: Scopus"
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Cameron Brennan
    226 Brennan
  2. Chris Sander
    210 Sander
  3. Samuel Hart Berman
    17 Berman