@article {563841, title = {The somatic genomic landscape of glioblastoma.}, journal = {Cell}, volume = {155}, number = {2}, year = {2013}, month = {2013 Oct 10}, pages = {462-77}, 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.}, keywords = {Brain Neoplasms, Female, Gene Expression Profiling, Gene Regulatory Networks, Glioblastoma, Humans, Male, Mutation, Proteome, Signal Transduction}, issn = {1097-4172}, doi = {10.1016/j.cell.2013.09.034}, author = {Brennan, Cameron W and Verhaak, Roel G W and McKenna, Aaron and Campos, Benito and Noushmehr, Houtan and Salama, Sofie R and Zheng, Siyuan and Chakravarty, Debyani and Sanborn, J Zachary and Berman, Samuel H and Beroukhim, Rameen and Bernard, Brady and Wu, Chang-Jiun and Genovese, Giannicola and Shmulevich, Ilya and Barnholtz-Sloan, Jill and Zou, Lihua and Vegesna, Rahulsimham and Shukla, Sachet A and Ciriello, Giovanni and Yung, W K and Zhang, Wei and Sougnez, Carrie and Mikkelsen, Tom and Aldape, Kenneth and Bigner, Darell D and Van Meir, Erwin G and Prados, Michael and Sloan, Andrew and Black, Keith L and Eschbacher, Jennifer and Finocchiaro, Gaetano and Friedman, William and Andrews, David W and Guha, Abhijit and Iacocca, Mary and O{\textquoteright}Neill, Brian P and Foltz, Greg and Myers, Jerome and Weisenberger, Daniel J and Penny, Robert and Kucherlapati, Raju and Perou, Charles M and Hayes, D Neil and Gibbs, Richard and Marra, Marco and Mills, Gordon B and Lander, Eric and Spellman, Paul and Wilson, Richard and Sander, Chris and Weinstein, John and Meyerson, Matthew and Gabriel, Stacey and Laird, Peter W and Haussler, David and Getz, Gad and Chin, Lynda and TCGA Research Network} }