Both IDH-mutant and IDH-wild-type gliomas may acquire mutations in MMR genes and subsequent MMR protein loss as a protective response to alkylating agents, particularly temozolomide (TMZ).14–16 IDH-mutant astrocytomas that developed MMR gene mutations were significantly more likely to have been treated with TMZ compared to IDH-mutant astrocytomas which did not gain a mutation in MMR genes (P = .0073), but no significant difference was noted in IDH-wild-type glioblastomas with and without MMR mutation development (P = .2110) (Table 2). This evidence concerns the gene MRC1 and central nervous system cancer.