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Objective:  O6methylguanine-DNA methyltransferase ( MGMT ) promoter methylation is a biomarker widely used to predict the sensitivity of  IDH -wildtype glioblastoma to temozolomide therapy. Given that the  IDH  status has critical effects on the survival and epigenetic features of glioblastoma, we aimed to assess the role of  MGMT  promoter methylation in  IDH -mutant glioblastoma.    Methods:  This study included 187  IDH -mutant glioblastomas and used 173  IDH -wildtype glioblastomas for comparison. Kaplan-Meier curves and multivariate Cox regression were used to study the predictive effects.    Results:  Compared with  IDH -wildtype glioblastomas,  IDH -mutant glioblastomas showed significantly higher ( P  < 0.0001)  MGMT  promoter methylation. We demonstrated that  MGMT  promoter methylation status, as determined by a high cutoff value (≥30%) in pyrosequencing, could be used to significantly stratify the survival of 50  IDH -mutant glioblastomas receiving temozolomide therapy (cohort A); this result was validated in another cohort of 25  IDH -mutant glioblastomas (cohort B). The median progression-free survival and median overall survival in cohort A were 9.33 and 13.76 months for unmethylated cases, and 18.37 and 41.61 months for methylated cases, and in cohort B were 6.97 and 9.10 months for unmethylated cases, and 23.40 and 26.40 months for methylated cases. In addition, we confirmed that the  MGMT  promoter methylation was significantly ( P  = 0.0001) correlated with longer OS in  IDH -mutant patients with GBM, independently of age, gender distribution, tumor type (primary or recurrent/secondary), and the extent of resection.    Conclusions:   MGMT  promoter methylation has predictive value in  IDH -mutant glioblastoma, but its cutoff value should be higher than that for  IDH -wildtype glioblastoma.

Predictive value of MGMT promoter methylation on the survival of TMZ treated <i>IDH</i>-mutant glioblastoma