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

Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1.
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DOI:
10.1016/j.ccr.2009.12.020
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发表时间:
2010-01-19
期刊:
影响因子:
50.3
通讯作者:
Cancer Genome Atlas Research Network
Cancer Genome Atlas Research Network
中科院分区:
医学1区
文献类型:
--
作者:
Verhaak RG;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;Cancer Genome Atlas Research Network

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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. Additionally, response to aggressive therapy differs 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.
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