MB-06 * PROGNOSTIC IMPACT OF O6-METHYLGUANINE-DNA METHYLTRANSFERASE (MGMT) PROMOTER METHYLATION IN MEDULLOBLASTOMA

Abstract

BACKGROUND: O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that plays an important role in tumor resistance to alkylating agents. Recent study revealed that MGMT promoter methylation is associated with favorable outcomes in malignant glioma patients. However, MGMT status in pediatric medulloblastoma and the prognostic impact of this methylation status and clinical outcomes of this tumor has not been fully evaluated. The objective of this study is to investigate the association between MGMT methylation status and clinical outcomes for medulloblastoma patients. MATERIALS AND METHODS: Patients with medulloblastoma treated at our institution between 1995 and 2012 were reviewed retrospectively. Tumor tissues were obtained from formalin-fixed paraffin-embedded tumor samples. Methylation statuses of 18 CpG sites of MGMT promoter region were determined by bisulfite sequencing analysis. RESULTS: Tumor material and clinical information were available for 22 patients. Median follow-up period was 48 months (13-190 months). Median age at diagnosis was 8.5 years (1-23 years). After the first line treatment, 10 had been in complete remission, 8 had relapse of disease, 1 had progressive disease, 1 had stable disease and 2 were lost follow-up. The patients in complete remission had higher accumulation of methylated CpG sites (median 5, range 2-9) than the relapsed patients (median 2, range 1-4) (p = 0.036). CONCLUSION: The results indicated that MGMT promoter methylation correlates with favorable outcome of medulloblastoma.