August 9, 2016: MGMT promoter methylation in glioblastoma
August 9, 2016
MGMT promoter methylation in glioblastoma
MGMT (O6-methylguanine-DNA methyltransferase) promoter methylation is the strongest independent prognostic factor of outcome in patients with malignant gliomas. MGMT promoter methylation is predictive of greater response to temozolomide and other alkylating agents in glioblastoma. MGMT is a DNA-repair enzyme which removes the alkyl group from the O6position of guanine. High levels of MGMT activity in glioma cells antagonizes the therapeutic effect of alkylating agents, such as temozolomide. Hypermethylation of the MGMT gene promoter leads to silencing of MGMT expression, resulting in diminished DNA-repair and increased apoptosis, and hence an increased response to therapy and a better prognosis.
- Hegi ME, Diserens A-C, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. New England Journal of Medicine 2005; 352: 997-1003.
Submitted by Surabhi Ranjan, M.B.B.S., Neuro-oncology Fellow, National Institutes of Health/The Johns Hopkins University.
Dr. Ranjan report no disclosures.