Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma

Cancer Cell. 2010 May 18;17(5):510-22. doi: 10.1016/j.ccr.2010.03.017. Epub 2010 Apr 15.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • CpG Islands*
  • DNA Methylation*
  • Glioblastoma / genetics*
  • Glioblastoma / pathology
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Mutation
  • Phenotype

Substances

  • Isocitrate Dehydrogenase
  • IDH1 protein, human