Monoallelic IDH1 R132H Mutation Mediates Glioma Cell Response to Anticancer Therapies via Induction of Senescence.

ABSTRACT: Heterozygous isocitrate dehydrogenase (IDH) R132H mutation (IDH1^R132H/WT) is an early event during gliomagenesis. Clinically, patients with glioma carrying mutant IDH1 respond better to antitumor therapies. However, the mechanism by which IDH1 mutations contribute to gliomagenesis and therapeutic response remains elusive. Here we report that senescence is involved in the improved therapeutic responses of mutant IDH1 glioma cells. Knocking-in IDH1^R132H/WT in glioma cells significantly enhanced gliomas cell senescence in response to temozolomide and radiation via a DNA-damage mediated mechanism. We further asked if senescence plays a role in IDH1^R132H/WT-induced gliomagenesis. Together with ATRX knockout and p53/RB loss, IDH1^R132H/WT transformed no

SUBMITTER: Zhan D 

PROVIDER: S-EPMC8568642 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature