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.

DOI: 10.1016/j.cell.2014.04.004

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@article{Brennan2013TheSG, title={The Somatic Genomic Landscape of Glioblastoma}, author={Cameron W. Brennan and Roel G. W. Verhaak and Aaron McKenna and Benito Campos and Houtan Noushmehr and Sofie R. Salama and Siyuan Zheng and Debyani Chakravarty and J. Zachary Sanborn and Samuel H. Berman and Rameen Beroukhim and Brady Bernard and Chang-Jiun Wu and Giannicola Genovese and Ilya Shmulevich and Jill S. Barnholtz-Sloan and Lihua Zou and Rahulsimham Vegesna and Sachet Ashok Shukla and Giovanni Ciriello and W . K . Alfred Yung and Wei Zhang and Carrie L. Sougnez and Tom Mikkelsen and Kenneth D. Aldape and Darell D Bigner and Erwin G. Van Meir and Michael D . Prados and Andrew E. Sloan and Keith L. Black and Jennifer Eschbacher and Gaetano Finocchiaro and William Friedman and David W. Andrews and Abhijit Guha and Mary Iacocca and Brian Patrick O’Neill and Greg Foltz and Jerome Myers and Daniel J. Weisenberger and Robert J Penny and Raju Kucherlapati and Charles M. Perou and D. Neil Hayes and Richard A. Gibbs and Marco A. Marra and Gordon B. Mills and Eric S. Lander and Paul T. Spellman and Richard K. Wilson and Chris Sander and John N. Weinstein and Matthew Meyerson and Stacey Bolk Gabriel and Peter W. Laird and David Haussler and Gad Getz and Lynda Chin}, journal={Cell}, year={2013}, volume={155}, pages={462-477} }