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

Houtan Noushmehr, Daniel J. Weisenberger, Kristin Diefes, Heidi S. Phillips, Kanan Pujara, Benjamin P. Berman, Fei Pan, Christopher E. Pelloski, Erik P. Sulman, Krishna P. Bhat, Roel G.W. Verhaak, Katherine A. Hoadley, D. Neil Hayes, Charles M. Perou, Heather K. Schmidt, Li Ding, Richard K. Wilson, David Van Den Berg, Hui Shen, Henrik BengtssonPierre Neuvial, Leslie M. Cope, Jonathan Buckley, James G. Herman, Stephen B. Baylin, Peter W. Laird, Kenneth Aldape

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)510-522
Number of pages13
JournalCancer cell
Volume17
Issue number5
DOIs
StatePublished - May 18 2010

    Fingerprint

Keywords

  • CELLCYCLE
  • DNA
  • HUMDISEASE

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Noushmehr, H., Weisenberger, D. J., Diefes, K., Phillips, H. S., Pujara, K., Berman, B. P., Pan, F., Pelloski, C. E., Sulman, E. P., Bhat, K. P., Verhaak, R. G. W., Hoadley, K. A., Hayes, D. N., Perou, C. M., Schmidt, H. K., Ding, L., Wilson, R. K., Van Den Berg, D., Shen, H., ... Aldape, K. (2010). Identification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma. Cancer cell, 17(5), 510-522. https://doi.org/10.1016/j.ccr.2010.03.017