Potential Role of Methylation Marker in Glioma Supporting Clinical Decisions.

The /2 gene mutations, loss/mutation, 1p/19q status, and promoter methylation are increasingly used as prognostic or predictive biomarkers of gliomas. However, the effect of their combination on radiation therapy outcome is discussable. Previously, we demonstrated that the c.G395A; p.R132H mutation was associated with longer survival in grade II astrocytoma and GBM (Glioblastoma). Here we analyzed the promoter methylation status in patients with a known mutation status in codon 132 of , followed by clinical and genetic data analysis based on the two statuses. After a subtotal tumor resection, the patients were treated using IMRT (Intensity-Modulated Radiation Therapy) with 6 MeV photons. The total dose was: 54 Gy for astrocytoma II, 60 Gy for astrocytoma III, 60 Gy for glioblastoma, 2 Gy per day, with 24 h intervals, five days per week. The patients with promoter methylation and somatic mutation (OS = 40 months) had a better prognosis than those with methylation alone (OS = 18 months). In patients with astrocytoma anaplasticum ( = 7) with the p.R132H mutation and hypermethylated , the prognosis was particularly favorable (median OS = 47 months). In patients with astrocytoma II meeting the above criteria, the prognosis was also better than in those not meeting those criteria. The mutation appears more relevant for the prognosis than methylation. The p.R132H mutation combined with hypermethylation seems to be the most advantageous for treatment success. Patients not meeting those criteria may require more aggressive treatments.