PP25. DISTRIBUTION OF IDH1 AND TERT MUTATIONS AND MGMT METHYLATION IN ADULT LOWER GRADE GLIOMA

IDH1 encodes for isocitrate dehydrogenase which catalyzes the oxidative carboxylation of isocitrate to α-ketoglutarate. Mutations in IDH1 are heterozygous and affect only codon 132. IDH1 mutation results in global hypermethylation (G-CIMP phenotype) and is significantly associated with MGMT promoter methylation. Tumours exhibiting both TERT mutations and IDH1/2 mutations have been previously reported to be primarily of oligodendroglial histology. In this study, IDH1 mutation analysis was performed by direct sequencing using BigDye® Terminator v3.1 cycle sequencing kit and the ABI 3730 DNA analyser in a cohort of 135 lower grade glioma at first presentation, comprising 84 grade II and 51 grade III tumours of astrocytic, oligodendroglial and mixed histologies. The incidence of TERT mutation was also determined in 52 of these cases. MGMT methylation analysis was carried out using MS-PCR in 130 tumours. IDH1 and TERT mutation and MGMT methylation was correlated with overall survival for patients for whom data was available. The incidences of IDH1 R132H mutation, MGMT methylation and TERT mutation in the whole cohort were 57%, 55% and 36% respectively. IDH1 R132H mutations were significantly more common in grade II tumours compared to grade III tumours (67% vs 41%; p = 0.004). In contrast, there was no significant difference in the incidence of MGMT methylation or TERT mutation based on the histological grade (p = 0.855 and p = 0.559, respectively). In grade II tumours, IDH1 R132H mutations were present more frequently in oligodendroglioma (81%) and oligoastrocytoma (82%) compared to astrocytoma (51%) (p = 0.005). Similarly, MGMT was significantly methylated in grade II oligodendroglioma (69%) and oligoastrocytoma (75%) than astrocytoma (35%) (p = 0.001). There were no differences in the incidence of TERT mutation in histological subgroups. IDH1 R132H mutation was a positive prognostic indicator of overall survival independent of grade (p < 0.0001). However, presence of MGMT methylation was significantly associated with increased overall survival in grade III tumours only (p = 0.006).