MGMT METHYLATION IS A PROGNOSTIC BIOMARKER IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Abstract

In young patients with newly diagnosed glioblastoma (GBM), methylation of the MGMT (O-6-methylguanine-DNA methyltransferase) gene promoter has been associated with improved prognosis.1 It is less clear if MGMT methylation is a prognostic biomarker in the elderly GBM patient population since patients >70 were excluded from the largest study documenting the association between methylation of MGMT and improved survival. Considering that the median age at diagnosis of GBM is 64, it is important to clarify the significance of MGMT methylation in elderly patients and determine whether it should influence treatment decisions in this large subset of patients. Methylation of MGMT silences transcription of the enzyme MGMT which repairs DNA damage that would otherwise lead to cell death. MGMT is an important mediator of resistance to alkylating agents including temozolomide, a standard agent administered to newly diagnosed patients with GBM.3–5 Consequently, this tissue biomarker is increasingly being incorporated into clinical trials and clinical practice. In order to assess the importance of MGMT methylation in elderly patients, we determined the association of MGMT methylation and survival in patients with GBM ≥70. ### Methods. After receiving approval from our institutional review board, we reviewed MGMT methylation status and clinical characteristics of 64 patients ≥70 with newly diagnosed GBM who underwent resection at our institution from 1998 to 2009. Patients were included if they had enough tissue for MGMT analysis, so this excluded patients who only had a biopsy (consistent with the prior study in younger patients). MGMT analysis was performed by extracting tumor genomic DNA from fixed, paraffin-embedded sections for …