Therapy enhancing chromosome instability may be advantageous for <i>IDH1</i> ^R132H/WT gliomas.

ABSTRACT: Recently revised brain tumor classification suggested a glioma treatment strategy that takes into consideration molecular variants in IDH1 and TP53 marker genes. While pathogenic variants of IDH1 and TP53 can be accompanied by chromosomal instability (CIN), the impact of IDH1 and TP53 mutations on genome stability remains unstudied. Elevated CIN might provide therapeutic targets, based on synergistic effects of chemotherapy with CIN-inducing drugs. Using an assay based on human artificial chromosomes, we investigated the impact of common glioma missense mutations in IDH1 and TP53 on chromosome transmission and demonstrated that IDH1R132H and TP53R248Q variants elevate CIN. We next found enhanced CIN levels and the sensitivity of IDH1 ^R1

SUBMITTER: Goncharov NV 

PROVIDER: S-EPMC11822378 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature