Clinical impact of IDH1 mutations and MGMT methylation in adult glioblastoma

Abstract

BackgroundImpact of Isocitrate dehydrogenase1 (IDH1) and O6-methylguanine-DNA methyltransferase (MGMT) in glioblastoma (GBM) have been of great interest due to their implications in prediction of prognosis of several types of cancer. It was aimed to investigate the clinical role of IDH1 mutation and MGMT methylation pattern among GBM patients versus non-neuro-oncological diseases (NND) patients and their impact on survival criteria.MethodsFormalin-fixed paraffin-embedded (FFPE) tissue sections of 58 GBM and 20 non-neuro-oncological diseases patients were recruited and IDH1 mutation and MGMT methylation was detected using Cast-PCR technology and Methyl II quantitative PCR approach, respectively. Results were assessed with other clinicopathological criteria and survival patterns.ResultsIDH1 mutation was detected among 15 GBM cases (15/58) and it was not reported among NND (P = 0.011). Receiver operating characteristic (ROC) curve was plotted to discriminate between MGMT methylation among studied groups. Patients with MGMT methylation ≥ 66% were reported as high methylation, which was recorded significantly in 51.7% and 100% of GBM cases and NND, respectively. Both showed significant difference with performance status, while MGMT methylation was significantly related with tumor size and tumor location. IDH1 mutation and MGMT methylation reported significant increase with GB patients revealed complete response to treatment. Survival pattern was better for IDH1 mutation and MGMT high methylation as compared to IDH1 wild type or MGMT low–moderate methylation, respectively, and favorable survival was detected when both were combined than using either of them alone.ConclusionDetection of IDH1 mutation and MGMT methylation among GB patients could aid in prediction of their response to treatment and their survival patterns, and their combination is better than using any of them alone.