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

Roel G.W. Verhaak, Katherine A. Hoadley, Elizabeth Purdom, Victoria Wang, Yuan Qi, Matthew D. Wilkerson, C. Ryan Miller, Li Ding, Todd Golub, Jill P. Mesirov, Gabriele Alexe, Michael Lawrence, Michael O'Kelly, Pablo Tamayo, Barbara A. Weir, Stacey Gabriel, Wendy Winckler, Supriya Gupta, Lakshmi Jakkula, Heidi S. FeilerJ. Graeme Hodgson, C. David James, Jann N. Sarkaria, Cameron Brennan, Ari Kahn, Paul T. Spellman, Richard K. Wilson, Terence P. Speed, Joe W. Gray, Matthew Meyerson, Gad Getz, Charles M. Perou, D. Neil Hayes

Research output: Contribution to journalArticle

3740 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)98-110
Number of pages13
JournalCancer Cell
Volume17
Issue number1
DOIs
StatePublished - Jan 19 2010

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Verhaak, R. G. W., Hoadley, K. A., Purdom, E., Wang, V., Qi, Y., Wilkerson, M. D., Miller, C. R., Ding, L., Golub, T., Mesirov, J. P., Alexe, G., Lawrence, M., O'Kelly, M., Tamayo, P., Weir, B. A., Gabriel, S., Winckler, W., Gupta, S., Jakkula, L., ... Hayes, D. N. (2010). Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell, 17(1), 98-110. https://doi.org/10.1016/j.ccr.2009.12.020