Impact of MGMT Promoter Methylation as a Prognostic Marker in Patients with High Grade Glioma: A Single-Center Observational Study

Abstract

Objectives: 1) To correlate the methylation status of the O-6-methylguanine-DNA-methyltransferase (MGMT promoter gene) and response to alkylating agent-based treatment in high-grade gliomas. Background: The MGMT gene is epigenetically silenced by promoter hypermethylation in gliomas and this modification has emerged as a relevant predictor of therapeutic response. Methods: 20 cases of high-grade glioma were analyzed for MGMT promoter methylation by methylation-specific PCR. Response to treatment and overall survival data were recorded and data analysed. Results: MGMT promoter methylation was found in 60% of gliomas by methylation-specific PCR. The mean survival time of glioblastoma patients submitted to adjuvant therapy was significantly higher among patients with MGMT promoter methylation (P = 0.035) and methylation status was an independent predictive factor that was associated with improved prognosis. Discussion and Conclusion: MGMT promoter methylation status was a more reliable predictor of response to adjuvant therapy and prognosis of high-grade gliomas. A subset of patients received irinotecan and bevacizumab in the second line setting and patients with unmethylated MGMT seemed to do better than the MGMT promoter methylated group.

State of Radiomics in Glioblastoma

“…49 In independent clinical trials, the level of MGMT expression was inversely correlated with clinical survival after temozolomide treatment. [50][51][52][53] The expression of MGMT in glioblastomas is regulated both transcriptionally 54 and post-transcriptionally. 55 In terms of transcriptional regulation, methylation of the MGMT promoter (MGMTp) region is associated with suppression of gene expression.…”