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Cell DOI:10.1016/j.cell.2013.09.034

The somatic genomic landscape of glioblastoma.

Publication TypeJournal Article
Year of Publication2013
AuthorsBrennan, CW, Verhaak, RGW, McKenna, A, Campos, B, Noushmehr, H, Salama, SR, Zheng, S, Chakravarty, D, J Sanborn, Z, 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, D Hayes, N, 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
Corporate AuthorsTCGA Research Network
JournalCell
Volume155
Issue2
Pages462-77
Date Published2013 Oct 10
ISSN1097-4172
KeywordsBrain Neoplasms, Female, Gene Expression Profiling, Gene Regulatory Networks, Glioblastoma, Humans, Male, Mutation, Proteome, Signal Transduction
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.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S0092-8674(13)01208-7
DOI10.1016/j.cell.2013.09.034
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24120142?dopt=Abstract

Alternate JournalCell
PubMed ID24120142
PubMed Central IDPMC3910500
Grant ListU24CA143840 / CA / NCI NIH HHS / United States
U24CA126561 / CA / NCI NIH HHS / United States
P30 CA016672 / CA / NCI NIH HHS / United States
U24 CA143882 / CA / NCI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
P50 CA108961 / CA / NCI NIH HHS / United States
U54HG003273 / HG / NHGRI NIH HHS / United States
U24 CA143835 / CA / NCI NIH HHS / United States
U24CA143731 / CA / NCI NIH HHS / United States
U24CA126551 / CA / NCI NIH HHS / United States
U24CA126543 / CA / NCI NIH HHS / United States
U24CA126554 / CA / NCI NIH HHS / United States
U24 CA143866 / CA / NCI NIH HHS / United States
U24CA143858 / CA / NCI NIH HHS / United States
U24CA126544 / CA / NCI NIH HHS / United States
U24CA143882 / CA / NCI NIH HHS / United States
U24 CA126551 / CA / NCI NIH HHS / United States
U24CA144025 / CA / NCI NIH HHS / United States
U54HG003067 / HG / NHGRI NIH HHS / United States
U24 CA143845 / CA / NCI NIH HHS / United States
U24 CA143799 / CA / NCI NIH HHS / United States
P50 CA098258 / CA / NCI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
U24 CA144025 / CA / NCI NIH HHS / United States
U24CA143883 / CA / NCI NIH HHS / United States
U54HG003079 / HG / NHGRI NIH HHS / United States
U24 CA126554 / CA / NCI NIH HHS / United States
U24 CA143840 / CA / NCI NIH HHS / United States
U24 CA143843 / CA / NCI NIH HHS / United States
U24CA143867 / CA / NCI NIH HHS / United States
U24CA143835 / CA / NCI NIH HHS / United States
U24 CA126561 / CA / NCI NIH HHS / United States
U24 CA143858 / CA / NCI NIH HHS / United States
U24CA143843 / CA / NCI NIH HHS / United States
P30 CA015083 / CA / NCI NIH HHS / United States
U24 CA143848 / CA / NCI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
U24 CA126543 / CA / NCI NIH HHS / United States
U24CA143848 / CA / NCI NIH HHS / United States
U24CA126563 / CA / NCI NIH HHS / United States
U24CA126546 / CA / NCI NIH HHS / United States
U54 HG003079 / HG / NHGRI NIH HHS / United States
U24CA143799 / CA / NCI NIH HHS / United States
U24 CA143883 / CA / NCI NIH HHS / United States
U24CA143866 / CA / NCI NIH HHS / United States
U24CA143845 / CA / NCI NIH HHS / United States
U24 CA143867 / CA / NCI NIH HHS / United States
U24 CA126546 / CA / NCI NIH HHS / United States
U24 CA126563 / CA / NCI NIH HHS / United States
U24 CA126544 / CA / NCI NIH HHS / United States