A genetically encoded fluorescent sensor enables sensitive and specific detection of IDH mutant associated oncometabolite D-2-hydroxyglutarate.

ABSTRACT: D-2-hydroxyglutarate (D-2-HG) is an oncometabolite that accumulates due to mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2). D-2-HG may be used as a surrogate marker for IDH1/2 mutant cancers, yet simple and specific methods for D-2-HG detection are limited. Here, we present the development and characterization of a genetically encoded fluorescent sensor of D-2-HG (D2HGlo). D2HGlo responds to clinically relevant concentrations of D-2-HG, demonstrates exceptional selectivity and can quantify D-2-HG in various body fluids and glioma tumor supernatants. Additionally, analysis of tumor lysates using D2HGlo accurately predicted the IDH mutational status of gliomas. The successful quantification of D-2-HG within contrived samples suggests that D2HGlo may facilitate the detection and monito

SUBMITTER: Choate KA 

PROVIDER: S-EPMC11909988 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature