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Identification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma

Cancer Cell. Volume 17: p510-522, 18 May 2010 10.1016/j.ccr.2010.03.017

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.

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TCGA samples reported in this paper as either G-CIMP, Cluster 2, or Cluster 3 are in the following TCGA data.archives

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