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Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1


Verhaak, RGW; Hoadley, KA; Purdom, E; Wang, V; Qi, Y; Wilkerson, MD; Miller, CR; Ding, L; Golub, T; Mesirov, JP; Alexe, G; Lawrence, M; O'Kelly, M; Tamayo, P; Weir, BA; Gabriel, S; Winckler, W; Gupta, S; Jakkula, L; Feiler, HS; Hodgson, JG; James, CD; Sarkaria, JN; Brennan, C; Kahn, A; Spellman, PT; Wilson, RK; Speed, TP; Gray, JW; Meyerson, M; Getz, G; Perou, CM; Hayes, DN
2010-01-19
CANCER CELL
Journal Article
17
1
98-110
The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM). We describe a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes and integrate multidimensional genomic data to establish patterns of somatic mutations and DNA copy number. Aberrations and gene expression of EGFR, NF1, and PDGFRA/IDH1 each define the Classical, Mesenchymal, and Proneural subtypes, respectively. Gene signatures of normal brain cell types show a strong relationship between subtypes and different neural lineages. Additionally, response to aggressive therapy differs by subtype, with the greatest benefit in the Classical subtype and no benefit in the Proneural subtype. We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies.
CELL PRESS
NEURAL STEM-CELLS; RECURSIVE PARTITIONING ANALYSIS; MALIGNANT GLIOMA; MOLECULAR SUBTYPES; MULTIFORME TUMORS; COPY NUMBER; EXPRESSION; MUTATIONS; RECEPTOR; REVEALS
10.1016/j.ccr.2009.12.020
Refer to copyright notice on published article.

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Creation Date 2010-01-19 12:00:00