Work

2‐Hydoxyglutarate: D/Riving Pathology in gLiomaS

Year: 2015

Type: article

Abstract: Common pathways and mechanisms can be found in both cancers and inborn errors of metabolism. 2-Hydroxyglutarate (2-HG) acidurias and isocitrate dehydrogenase (IDH) 1/2 mutant tumors are examples of this phenomenon. 2-HG can exist in two chiral forms, D(R)-2-HG and L(S)-2-HG, which are elevated in D- and L-acidurias, respectively. D-2-HG was subsequently discovered to be synthesized in IDH 1/2 mutant tumors including ∼70% of intermediate-grade gliomas and secondary glioblastomas (GBM). Recent studies have revealed that L-2-HG is generated in hypoxia in IDH wild-type tumors. Both 2-HG enantiomers have similar structures as α-ketoglutarate (α-KG) and can competitively inhibit α-KG-dependent enzymes. This inhibition modulates numerous cellular processes, including histone and DNA methylation, and can ultimately impact oncogenesis. D-2-HG can be detected in vivo in glioma patients and animal models using advanced imaging modalities. Finally, pharmacologic inhibitors of mutant IDH 1/2 attenuate the production of D-2-HG and show great promise as therapeutic agents.

Source: Brain Pathology

DOI: 10.1111/bpa.12309

Authors: Daniel R. Wahl, Sriram Venneti

Institution: University of Michigan

Language: English

Topic: Glioma Diagnosis and Treatment

Subfield: Genetics

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Cancer Institute