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PMID: 20129251 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

Cancer cell ·Vol. 17 ·No. 1 ·2010-01-19 ·Pages 98-110

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

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.

MeSH Terms
Adult Aged Brain Neoplasms/classification,genetics,pathology DNA Mutational Analysis ErbB Receptors/genetics Factor Analysis, Statistical Gene Dosage Gene Expression Gene Expression Profiling Glioblastoma/classification,genetics,pathology Humans Isocitrate Dehydrogenase/genetics Middle Aged Mutation Neurofibromatosis 1/genetics Oligonucleotide Array Sequence Analysis Prognosis Receptor, Platelet-Derived Growth Factor alpha/genetics
Chemicals
Isocitrate Dehydrogenase IDH1 protein, human EGFR protein, human ErbB Receptors Receptor, Platelet-Derived Growth Factor alpha
Authors & Affiliations
34 authors, click to expand affiliations / ORCID
Verhaak Roel G W
The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
Hoadley Katherine A
Purdom Elizabeth
Wang Victoria
Qi Yuan
Wilkerson Matthew D
Miller C Ryan
Ding Li
Golub Todd
Mesirov Jill P
Alexe Gabriele
Lawrence Michael
O'Kelly Michael
Tamayo Pablo
Weir Barbara A
Gabriel Stacey
Winckler Wendy
Gupta Supriya
Jakkula Lakshmi
Feiler Heidi S
Hodgson J Graeme
James C David
Sarkaria Jann N
Brennan Cameron
Kahn Ari
Spellman Paul T
Wilson Richard K
Speed Terence P
Gray Joe W
Meyerson Matthew
Getz Gad
Perou Charles M
Hayes D Neil
Cancer Genome Atlas Research Network
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Article Info
Journal
Cancer cell
Abbr.
Cancer Cell
ISSN
1878-3686
DOI
10.1016/j.ccr.2009.12.020
Published
2010-01-19
Pages
98-110
Language
English
Region
United States
NLM ID
101130617
PMCID
PMC2818769
Subset
IM
Grants
NCI NIH HHS · P50CA58223 · United States
NCI NIH HHS · CA127716 · United States
NCI NIH HHS · U24CA126561 · United States
NHGRI NIH HHS · U54HG003067 · United States
NCI NIH HHS · P50 CA058223 · United States
NCI NIH HHS · L30 CA104183-01 · United States
NINDS NIH HHS · R01 NS049720 · United States
NCI NIH HHS · U24 CA126561 · United States
NCI NIH HHS · CA097257 · United States
NINDS NIH HHS · NS49720 · United States
NHGRI NIH HHS · U54 HG003067 · United States
NCI NIH HHS · P50 CA108961 · United States
NHGRI NIH HHS · U54HG003273 · United States
NCI NIH HHS · L30 CA104183-02 · United States
NCI NIH HHS · U24CA126551 · United States
NCI NIH HHS · U24CA126543 · United States
NCI NIH HHS · U24CA126554 · United States
NCI NIH HHS · U24CA126544 · United States
NCI NIH HHS · U24 CA126551 · United States
NCI NIH HHS · CA108961 · United States
NCRR NIH HHS · UL1 RR024992 · United States
NHGRI NIH HHS · U54 HG003273 · United States
NHGRI NIH HHS · U54HG003079 · United States
NCI NIH HHS · U24 CA126554 · United States
NCI NIH HHS · P50 CA097257 · United States
NCI NIH HHS · R01 CA127716 · United States
NCI NIH HHS · U24 CA143848 · United States
NCRR NIH HHS · RR023248 · United States
NCI NIH HHS · U24 CA126543 · United States
NCI NIH HHS · U24CA126563 · United States
NCI NIH HHS · U24CA126546 · United States
NHGRI NIH HHS · U54 HG003079 · United States
NCRR NIH HHS · K12 RR023248 · United States
NCI NIH HHS · U24 CA143867 · United States
NCI NIH HHS · L30 CA104183 · United States
NIEHS NIH HHS · F30 ES019449 · United States
NCI NIH HHS · U24 CA126546 · United States
NCI NIH HHS · U24 CA126563 · United States
NCI NIH HHS · U24 CA126544 · United States
External Links
PubMed source DOI: 10.1016/j.ccr.2009.12.020 PMC Full Text View journal details
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