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.
authors.affiliation: Human Oncology and Pathogenesis Program, Brain Tumor Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center, Department of Neurological Surgery, Weill Cornell Medical Center, New York, NY 10065, USA. Electronic address: cbrennan@mskcc.org.
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mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D009154:Mutation; D020543:Proteome / Q000032:analysis; D015398:Signal Transduction
chemical_list: D020543:Proteome