Methylation of MGMT promoter as a prognostic marker of glioblastoma

Introduction. Glioblastoma is the most common malignant brain tumor in adults with a poor prognosis. Treatment of patients includes surgical resection, radiation and the alkylating agent temozolomide (TMZ). The therapeutic efficacy of TMZ is due to its ability to damage DNA and induce apoptosis, but it is neutralized by the expression of the DNA repair enzyme O6-methylguanine-DNA-methyltransferase (MGMT). Methylation of the MGMT gene promoter suppresses the synthesis of the corresponding enzyme and increases the cytotoxic efficiency of TMZ.Aim. To determine the MGMT promoter methylation in glioblastoma patients and to evaluate the prognostic significance of this phenomenon.Materials and methods. Bisulfite-treated DNA samples isolated from formalin-fixed paraffin-embedded tumor tissues obtained from glioblastoma patients were analyzed. MGMT methylation was assessed by qualitative methylation-specific polymerase chain reaction. The prognostic significance of this phenomenon in conjunction with a number of other clinical parameters was assessed by means of univariate and multivariate analysis.Results. MGMT promoter methylation was found to be one of the most significant favorable prognostic factors of glioblastoma: the likelihood of disease reappearance or a fatal outcome at a specific point in time is approximately two-fold lower in such patients than in those with intact MGMT.Conclusion. The methylation-specific polymerase chain reaction, which is routinely used in clinical practice, adequately assesses MGMT methylation status as a prognostic factor, but it does not allow for the evaluation of its predictive potential.