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An integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR and NF1

Abstract

The Cancer Genome Atlas Network recently catalogued recurrent genomic abnormalities in glioblastoma (GBM). We describe a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical and Mesenchymal subtypes and integrate multi-dimensional genomic data to establish patterns of somatic mutations and DNA copy number. Aberrations and gene expression of EGFR, NF1, and PDGFRA/IDH1 each define Classical, Mesenchymal, and Proneural, respectively. Gene signatures of normal brain cell types show a strong relation between subtypes and different neural lineages potentially indicative of distinct cell of origin. Additionally, response to aggressive therapy differed by subtype with greatest benefit in Classical and no benefit in Proneural. We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies.

Associated Data Files

Individual platform gene level expression measurements for 202 samples

Unified and integrated dataset created by combining the three individual sets using factor analysis

Validation dataset combined from four public cohorts

The file CancerCell_GBM_validation.data.txt was posted on June 1, 2012 and supercedes Validation.txt

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