Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Verhaak, RGW, Hoadley, KA, Purdom, E, Wang, V, Qi, Y, Wilkerson, MD, C Miller, R, 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, J Hodgson, G, C James, D, Sarkaria, JN, Brennan, C, Kahn, A, Spellman, PT, Wilson, RK, Speed, TP, Gray, JW, Meyerson, M, Getz, G, Perou, CM, D Hayes, N |
Corporate Authors | Cancer Genome Atlas Research Network |
Journal | Cancer Cell |
Volume | 17 |
Issue | 1 |
Pages | 98-110 |
Date Published | 2010 Jan 19 |
ISSN | 1878-3686 |
Keywords | Adult, Aged, Brain Neoplasms, DNA Mutational Analysis, Factor Analysis, Statistical, Gene Dosage, Gene Expression, Gene Expression Profiling, Glioblastoma, Humans, Isocitrate Dehydrogenase, Middle Aged, Mutation, Neurofibromatosis 1, Oligonucleotide Array Sequence Analysis, Prognosis, Receptor, Epidermal Growth Factor, Receptor, Platelet-Derived Growth Factor alpha |
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. |
URL | http://linkinghub.elsevier.com/retrieve/pii/S1535-6108(09)00432-2 |
DOI | 10.1016/j.ccr.2009.12.020 |
Pubmed | |
Alternate Journal | Cancer Cell |
PubMed ID | 20129251 |
PubMed Central ID | PMC2818769 |
Grant List | P50CA58223 / CA / NCI NIH HHS / United States CA127716 / CA / NCI NIH HHS / United States U24CA126561 / CA / NCI NIH HHS / United States U54 HG003067 / HG / NHGRI NIH HHS / United States P50 CA108961 / CA / NCI NIH HHS / United States U54HG003273 / HG / NHGRI NIH HHS / United States L30 CA104183-02 / CA / NCI NIH HHS / United States U24CA126551 / CA / NCI NIH HHS / United States U24CA126543 / CA / NCI NIH HHS / United States U24CA126554 / CA / NCI NIH HHS / United States U24CA126544 / CA / NCI NIH HHS / United States U24 CA126551 / CA / NCI NIH HHS / United States U54HG003067 / HG / NHGRI NIH HHS / United States CA108961 / CA / NCI NIH HHS / United States UL1 RR024992 / RR / NCRR NIH HHS / United States U54 HG003273 / HG / NHGRI NIH HHS / United States P50 CA058223 / CA / NCI NIH HHS / United States L30 CA104183-01 / CA / NCI NIH HHS / United States R01 NS049720 / NS / NINDS NIH HHS / United States U54HG003079 / HG / NHGRI NIH HHS / United States U24 CA126554 / CA / NCI NIH HHS / United States P50 CA097257 / CA / NCI NIH HHS / United States R01 CA127716 / CA / NCI NIH HHS / United States U24 CA126561 / CA / NCI NIH HHS / United States U24 CA143848 / CA / NCI NIH HHS / United States RR023248 / RR / NCRR NIH HHS / United States U24 CA126543 / CA / NCI NIH HHS / United States U24CA126563 / CA / NCI NIH HHS / United States U24CA126546 / CA / NCI NIH HHS / United States U54 HG003079 / HG / NHGRI NIH HHS / United States CA097257 / CA / NCI NIH HHS / United States NS49720 / NS / NINDS NIH HHS / United States K12 RR023248 / RR / NCRR NIH HHS / United States L30 CA104183 / CA / NCI NIH HHS / United States F30 ES019449 / ES / NIEHS NIH HHS / United States U24 CA126546 / CA / NCI NIH HHS / United States U24 CA126563 / CA / NCI NIH HHS / United States U24 CA126544 / CA / NCI NIH HHS / United States |