Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma.
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.
Noushmehr
Houtan
H
USC Epigenome Center, University of Southern California, Los Angeles, CA 90033, USA.
Weisenberger
Daniel J
DJ
Diefes
Kristin
K
Phillips
Heidi S
HS
Pujara
Kanan
K
Berman
Benjamin P
BP
Pan
Fei
F
Pelloski
Christopher E
CE
Sulman
Erik P
EP
Bhat
Krishna P
KP
Verhaak
Roel G W
RG
Hoadley
Katherine A
KA
Hayes
D Neil
DN
Perou
Charles M
CM
Schmidt
Heather K
HK
Ding
Li
L
Wilson
Richard K
RK
Van Den Berg
David
D
Shen
Hui
H
Bengtsson
Henrik
H
Neuvial
Pierre
P
Cope
Leslie M
LM
Buckley
Jonathan
J
Herman
James G
JG
Baylin
Stephen B
SB
Laird
Peter W
PW
Aldape
Kenneth
K
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
D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
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