Prognostic significance of MGMT promoter methylation in diffuse glioma patients

Abstract

Current treatment options for diffuse glioma patients include maximum safe resection followed by a combination of radiation therapy and chemotherapy with alkylating agents. The DNA-repair enzyme O 6 -methylguanine-DNA methyltransferase (MGMT) counteracts the cytotoxic effect of alkylating agents and mediates chemoresistance. Disruption of the DNA methylation mechanism in diffuse glioma cells results in epigenetic silencing of MGMT through methylation of cytidinephosphate-guanosine dinucleotides (CpG) in the promoter region. The methylation status of MGMT is widely accepted to be a strong prognostic factor in diffuse glioma patients. This study was designed to screen Serbian diffuse glioma patients for hypermethylation of the MGMT promoter and to estimate its impact on overall survival. The results obtained in our study on 33 samples of diffuse glioma detected a positive methylation status in 17 patients (51.5%) by methylation-specific polymerase chain reaction. The positive methylation status of the MGMT promoter did not correlate with overall survival. In this study group, the patients older than 50 years had significantly lower overall survival in comparison with younger patients (7 months-19 months median survival). Extent of tumour resection also had influence on overall survival of patients. The relevance of the MGMT promoter methylation status should be further evaluated in a larger study and in association with other markers. ARTICLE HISTORY

MGMT Promoter Methylation as a Prognostic Factor in Primary Glioblastoma: A Single-Institution Observational Study

“…This was much longer than older patients (>80 years), who had a survival time of 1.6 months [ 32 ]. Furthermore, Jovanović et al observed that in comparison to younger patients, people over the age of 50 had considerably poorer overall survival rates (median survival ranged from 7 to 19 months) [ 24 ], which is in accordance with our results. The OS in our younger study group was over twice as long (20 months with methylation and 14 months without methylation) as in the older group.…”

“…Even in patients with nonresectable GBM, promoter methylation status played a crucial role in the survival prognosis [ 29 ]. Conversely, Jovanovic et al showed that MGMT promoter methylation was not associated with the survival results of diffuse glioma patients [ 24 ]. In our study, 18 out of 41 patients had MGMT promoter methylation, which accounted for 43%.…”

“…Moreover, a previous study demonstrated that patients with an IDH1 gene mutation and MGMT promoter methylation who underwent radiation had a more favorable prognosis compared to patients with methylation of MGMT promoter alone [ 19 ]. Although the positive predictive value of MGMT promoter methylation in glioblastoma patients is widely acknowledged, the prognostic value remains unclear or controversial [ 20 , 21 , 22 , 23 , 24 , 25 ].…”

The Significance of MGMT Promoter Methylation Status in Diffuse Glioma

“…The MSP data were analyzed using the previously reported semi-quantitative approach, which relies on an ImageJ software comparison of the intensities of the methylated (M) and unmethylated (U) MSP bands ( Figure S6 in the Supplementary Materials ) [ 23 ]. In this manner, the MGMT methylation status was evaluated in 36 glioma patients and 3 negative control samples (meningioma, hemangiopericytoma, and peripheral blood leukocytes of a healthy individual).…”

“…The aim of this study was to make a new effort to resolve the dilemma of whether the MGMT promoter methylation status has prognostic value for diffuse glioma samples from Serbian patients. Previously, although a significant improvement was observed in overall survival with TMZ treatment (the median survival was 15 months) in comparison with diffuse glioma patients without treatment (the median survival was 5 months), it was not interrelated with the MGMT promoter methylation status [ 22 , 23 ]. Currently, the MGMT promoter methylation status is investigated in the context of the clinical data, the choice of method for its assessment (real-time methylation-specific PCR (qMSP) vs. previous methylation-specific PCR (MSP)), and the IDH1 /2 mutation status.…”