IDH mutations frequently occur in WHO grade II and III diffuse
gliomas and have favorable prognosis compared to wild-type
tumors. However, whether IDH mutations in WHO grade II and II diffuse
gliomas predict enhanced sensitivity to adjuvant radiation (RT) or
chemotherapy (CHT) is still being debated. Recent studies have identified recurrent mutations in the promoter region of
telomerase reverse transcriptase (TERT) in
gliomas. We previously demonstrated that TERT promoter mutations may be promising
biomarkers in
glioma survival prognostication when combined with IDH mutations. This study analyzed IDH and TERT promoter mutations in 295 WHO grade II and III diffuse
gliomas treated with or without adjuvant
therapies to explore their impact on the sensitivity of
tumors to genotoxic
therapies. IDH mutations were found in 216 (73.2%) patients and TERT promoter mutations were found in 112 (38%) patients. In multivariate analysis, IDH mutations (p < 0.001) were independent prognostic factors for PFS and OS in patients receiving genotoxic
therapies while TERT promoter mutations were not. In univariate analysis, IDH and TERT promoter mutations were not significant prognostic factors in patients who did not receive genotoxic
therapies. Adjuvant RT and CHT were factors independently impacting PFS (RT p = 0.001, CHT p = 0.026) in IDH mutated WHO grade II and III diffuse
gliomas but not in IDH wild-type group. Univariate and multivariate analyses demonstrated TERT promoter mutations further stratified IDH wild-type WHO grade II and III diffuse
gliomas into two subgroups with different responses to genotoxic
therapies. Adjuvant RT and CHT were significant parameters influencing PFS in the IDH wt/TERT mut subgroup (RT p = 0.015, CHT p = 0.015) but not in the IDH wt/TERT wt subgroup. Our data demonstrated that IDH mutated WHO grade II and III diffuse
gliomas had better PFS and OS than their IDH wild-type counterparts when genotoxic
therapies were administered after surgery. Importantly, we also found that TERT promoter mutations further stratify IDH wild-type WHO grade II and III diffuse
gliomas into two subgroups with different responses to adjuvant
therapies. Taken together, TERT promoter mutations may predict enhanced sensitivity to genotoxic
therapies in IDH wild-type WHO grade II and III diffuse
gliomas and may justify intensified treatment in this subgroup.