(TIGAR) was lower in patients with glioma harboring IDH1 mutations compared with that in patients with IDH1‐WT. TIGAR‐knockdown increases the radiosensitivity of glioma cells; in U87MG cells, IDH1‐R132H suppressed TIGAR expression. Chromatin immunoprecipitation assays revealed increased levels of re

Isocitrate dehydrogenase 1 (IDH1) is the most frequently mutated gene in World Health Organization grade II-III and secondary glioma. The majority of IDH1 mutation cases involve the substitution from arginine to histidine at codon 132 (IDH1-R132H). Although the oncogenic role of IDH1‐R132H has been confirmed, patients with IDH1‐R132H brain tumors exhibit a better response to radiotherapy compared with those with wild‐type (WT) IDH1. In the present study, the potential mechanism of radiosensitization mediated by IDH1‐R132H was investigated by overexpressing IDH1-R132H in U87MG glioma cells. The results demonstrated decreased clonogenic capacity of IDH1‐R132H‐expressing cells, as well as delayed repair of DNA double‐strand breaks compared with IDH1‐WT. Data from The Cancer Genome Atlas were analyzed, which demonstrated that the expression of TP53‐induced glycolysis and apoptosis regulator (TIGAR) was lower in patients with glioma harboring IDH1 mutations compared with that in patients with IDH1‐WT. TIGAR‐knockdown increases the radiosensitivity of glioma cells; in U87MG cells, IDH1‐R132H suppressed TIGAR expression. Chromatin immunoprecipitation assays revealed increased levels of repressive H3K9me3 markers at the TIGAR promoter in IDH1‐R132H compared with IDH1‐WT. These data indicated that IDH1-R132H may overcome radioresistance in glioma cells through epigenetic suppression of TIGAR expression. However, these favorable effects were not observed in U87MG glioma stem‐like cells. The results of the present study provide an improved understanding of the functionality of IDH1 mutations in glioma cells, which may improve the therapeutic efficacy of radiotherapy.