PATH-28. EXTENT AND PROGNOSTIC VALUE OF MGMT PROMOTOR METHYLATION DEPEND ON IDH MUTATION AND 1p19q CO-DELETION IN GLIOMA WHO GRADE II

Abstract

Abstract INTRODUCTION Methylation of the promotor region of the O6-methylguanin-DNA-methyltransferase (MGMT) gene is associated with increased survival in low- and high-grade glioma. It is unknown whether this association also applies to the 2016 WHO categories of glioma WHO grade II. MATERIAL AND METHODS We retrospectively searched the institutional database of the Center for Neuro-Oncology for patients with glioma WHO grade II. Patients were assigned to one of three groups according to the 2016 WHO classification system: 1. 1p19q co-deleted oligodendroglioma, IDH mutant; 2. 1p19q non-codeleted astrocytoma, IDH mutant; 3. 1p19q non-codeleted astrocytoma, IDH wild-type. MGMT methylation status was analysed using Sanger sequencing of the CpG sites 74-98 within the MGMT promotor region. The total number of methylated CpG sites was calculated for each patient. RESULTS 155 patients with glioma WHO grade II were encountered, including 81 1p19q co-deleted, IDH mutant oligodendrogliomas; 54 IDH mutant astrocytomas; and 20 IDH wild-type astrocytomas. The mean number of methylated CpG sites among oligodendrogliomas was significantly higher when compared to IDH mutant astrocytomas (18.9 ± 0.4 vs. 16.3 ± 0.6; p = 0.001). In turn, the number of methylated CpG sites among IDH mutant astrocytomas was higher when compared to IDH wild-type astrocytomas (16.3 ± 0.6 vs. 12.3 ± 1.9; p = 0.007). Median follow-up was estimated at 35 months. Median time to malignant progression was 87 months for all patients, and median overall survival was not reached. In the entire cohort, a larger number of methylated CpG sites was prognostic of overall survival and time to malignant progression. When analysed separately for the three WHO subgroups, a similar association was only retained in IDH wild-type astrocytoma. CONCLUSION In our series of WHO II gliomas, MGMT promotor methylation appeared strongly associated with 1p19q codeletion and IDH mutations. MGMT promotor methylation was only prognostic in IDH wild-type astrocytoma.