title: Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma.
abstract: We have profiled promoter DNA methylation alterations in 272 glioblastoma tumors in the context of The Cancer Genome Atlas (TCGA). We found that a distinct subset of samples displays concerted hypermethylation at a large number of loci, indicating the existence of a glioma-CpG island methylator phenotype (G-CIMP). We validated G-CIMP in a set of non-TCGA glioblastomas and low-grade gliomas. G-CIMP tumors belong to the proneural subgroup, are more prevalent among lower-grade gliomas, display distinct copy-number alterations, and are tightly associated with IDH1 somatic mutations. Patients with G-CIMP tumors are younger at the time of diagnosis and experience significantly improved outcome. These findings identify G-CIMP as a distinct subset of human gliomas on molecular and clinical grounds.
authors.affiliation: USC Epigenome Center, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Houtan
authors.initials: H
authors.lastname: Noushmehr
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisenberger
authors.forename: Kristin
authors.initials: K
authors.lastname: Diefes
authors.forename: Heidi S
authors.initials: HS
authors.lastname: Phillips
authors.forename: Kanan
authors.initials: K
authors.lastname: Pujara
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Berman
authors.forename: Fei
authors.initials: F
authors.lastname: Pan
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Pelloski
authors.forename: Erik P
authors.initials: EP
authors.lastname: Sulman
authors.forename: Krishna P
authors.initials: KP
authors.lastname: Bhat
authors.forename: Roel G W
authors.initials: RG
authors.lastname: Verhaak
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Hoadley
authors.forename: D Neil
authors.initials: DN
authors.lastname: Hayes
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.forename: Heather K
authors.initials: HK
authors.lastname: Schmidt
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Richard K
authors.initials: RK
authors.lastname: Wilson
authors.forename: David
authors.initials: D
authors.lastname: Van Den Berg
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Henrik
authors.initials: H
authors.lastname: Bengtsson
authors.forename: Pierre
authors.initials: P
authors.lastname: Neuvial
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Cope
authors.forename: Jonathan
authors.initials: J
authors.lastname: Buckley
authors.forename: James G
authors.initials: JG
authors.lastname: Herman
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Baylin
authors.forename: Peter W
authors.initials: PW
authors.lastname: Laird
authors.forename: Kenneth
authors.initials: K
authors.lastname: Aldape
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D009154:Mutation; D010641:Phenotype
chemical_list: D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
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