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 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.

DOI: 10.1016/j.ccr.2009.12.020

8 Figures and Tables

0200040006000200920102011201220132014201520162017
Citations per Year

37,760 Citations

Semantic Scholar estimates that this publication has 37,760 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Verhaak2010IntegratedGA, title={Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1.}, author={Roel G. W. Verhaak and Katherine A Hoadley and Elizabeth Purdom and Victoria Wang and Yuan Qi and Matthew D. Wilkerson and C Ryan Miller and Li Ding and Todd R. Golub and Jill P. Mesirov and Gabriele Alexe and Michael Lawrence and Michael J. T. O'Kelly and Pablo Tamayo and Barbara A. Weir and Stacey Bolk Gabriel and Wendy Winckler and Supriya Gupta and Lakshmi R . Jakkula and Heidi S. Feiler and John Graeme Hodgson and C. David James and Jann N. Sarkaria and Cameron W. Brennan and Ari B. Kahn and Paul T. Spellman and Richard K. Wilson and Terence P. Speed and Joe W. Gray and Matthew Meyerson and Gad Getz and Charles M. Perou and D. Neil Hayes}, journal={World neurosurgery}, year={2010}, volume={74 1}, pages={4-5} }