PMID- 20129251 OWN - NLM STAT- MEDLINE DCOM- 20100302 LR - 20240104 IS - 1878-3686 (Electronic) IS - 1535-6108 (Print) IS - 1535-6108 (Linking) VI - 17 IP - 1 DP - 2010 Jan 19 TI - Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. PG - 98-110 LID - 10.1016/j.ccr.2009.12.020 [doi] AB - 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. CI - Copyright (c) 2010 Elsevier Inc. All rights reserved. FAU - Verhaak, Roel G W AU - Verhaak RG AD - The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA. FAU - Hoadley, Katherine A AU - Hoadley KA FAU - Purdom, Elizabeth AU - Purdom E FAU - Wang, Victoria AU - Wang V FAU - Qi, Yuan AU - Qi Y FAU - Wilkerson, Matthew D AU - Wilkerson MD FAU - Miller, C Ryan AU - Miller CR FAU - Ding, Li AU - Ding L FAU - Golub, Todd AU - Golub T FAU - Mesirov, Jill P AU - Mesirov JP FAU - Alexe, Gabriele AU - Alexe G FAU - Lawrence, Michael AU - Lawrence M FAU - O'Kelly, Michael AU - O'Kelly M FAU - Tamayo, Pablo AU - Tamayo P FAU - Weir, Barbara A AU - Weir BA FAU - Gabriel, Stacey AU - Gabriel S FAU - Winckler, Wendy AU - Winckler W FAU - Gupta, Supriya AU - Gupta S FAU - Jakkula, Lakshmi AU - Jakkula L FAU - Feiler, Heidi S AU - Feiler HS FAU - Hodgson, J Graeme AU - Hodgson JG FAU - James, C David AU - James CD FAU - Sarkaria, Jann N AU - Sarkaria JN FAU - Brennan, Cameron AU - Brennan C FAU - Kahn, Ari AU - Kahn A FAU - Spellman, Paul T AU - Spellman PT FAU - Wilson, Richard K AU - Wilson RK FAU - Speed, Terence P AU - Speed TP FAU - Gray, Joe W AU - Gray JW FAU - Meyerson, Matthew AU - Meyerson M FAU - Getz, Gad AU - Getz G FAU - Perou, Charles M AU - Perou CM FAU - Hayes, D Neil AU - Hayes DN CN - Cancer Genome Atlas Research Network LA - eng GR - P50CA58223/CA/NCI NIH HHS/United States GR - CA127716/CA/NCI NIH HHS/United States GR - U24CA126561/CA/NCI NIH HHS/United States GR - U54HG003067/HG/NHGRI NIH HHS/United States GR - P50 CA058223/CA/NCI NIH HHS/United States GR - L30 CA104183-01/CA/NCI NIH HHS/United States GR - R01 NS049720/NS/NINDS NIH HHS/United States GR - U24 CA126561/CA/NCI NIH HHS/United States GR - CA097257/CA/NCI NIH HHS/United States GR - NS49720/NS/NINDS NIH HHS/United States GR - U54 HG003067/HG/NHGRI NIH HHS/United States GR - P50 CA108961/CA/NCI NIH HHS/United States GR - U54HG003273/HG/NHGRI NIH HHS/United States GR - L30 CA104183-02/CA/NCI NIH HHS/United States GR - U24CA126551/CA/NCI NIH HHS/United States GR - U24CA126543/CA/NCI NIH HHS/United States GR - U24CA126554/CA/NCI NIH HHS/United States GR - U24CA126544/CA/NCI NIH HHS/United States GR - U24 CA126551/CA/NCI NIH HHS/United States GR - CA108961/CA/NCI NIH HHS/United States GR - UL1 RR024992/RR/NCRR NIH HHS/United States GR - U54 HG003273/HG/NHGRI NIH HHS/United States GR - U54HG003079/HG/NHGRI NIH HHS/United States GR - U24 CA126554/CA/NCI NIH HHS/United States GR - P50 CA097257/CA/NCI NIH HHS/United States GR - R01 CA127716/CA/NCI NIH HHS/United States GR - U24 CA143848/CA/NCI NIH HHS/United States GR - RR023248/RR/NCRR NIH HHS/United States GR - U24 CA126543/CA/NCI NIH HHS/United States GR - U24CA126563/CA/NCI NIH HHS/United States GR - U24CA126546/CA/NCI NIH HHS/United States GR - U54 HG003079/HG/NHGRI NIH HHS/United States GR - K12 RR023248/RR/NCRR NIH HHS/United States GR - U24 CA143867/CA/NCI NIH HHS/United States GR - L30 CA104183/CA/NCI NIH HHS/United States GR - F30 ES019449/ES/NIEHS NIH HHS/United States GR - U24 CA126546/CA/NCI NIH HHS/United States GR - U24 CA126563/CA/NCI NIH HHS/United States GR - U24 CA126544/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Cancer Cell JT - Cancer cell JID - 101130617 RN - EC 1.1.1.41 (Isocitrate Dehydrogenase) RN - EC 1.1.1.42. (IDH1 protein, human) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha) SB - IM MH - Adult MH - Aged MH - Brain Neoplasms/classification/*genetics/pathology MH - DNA Mutational Analysis MH - ErbB Receptors/*genetics MH - Factor Analysis, Statistical MH - Gene Dosage MH - Gene Expression MH - Gene Expression Profiling MH - Glioblastoma/classification/*genetics/pathology MH - Humans MH - Isocitrate Dehydrogenase/*genetics MH - Middle Aged MH - Mutation MH - Neurofibromatosis 1/*genetics MH - Oligonucleotide Array Sequence Analysis MH - Prognosis MH - Receptor, Platelet-Derived Growth Factor alpha/*genetics PMC - PMC2818769 MID - NIHMS166306 EDAT- 2010/02/05 06:00 MHDA- 2010/03/03 06:00 PMCR- 2011/01/19 CRDT- 2010/02/05 06:00 PHST- 2009/02/02 00:00 [received] PHST- 2009/09/03 00:00 [revised] PHST- 2009/12/04 00:00 [accepted] PHST- 2010/02/05 06:00 [entrez] PHST- 2010/02/05 06:00 [pubmed] PHST- 2010/03/03 06:00 [medline] PHST- 2011/01/19 00:00 [pmc-release] AID - S1535-6108(09)00432-2 [pii] AID - 10.1016/j.ccr.2009.12.020 [doi] PST - ppublish SO - Cancer Cell. 2010 Jan 19;17(1):98-110. doi: 10.1016/j.ccr.2009.12.020.