IDH1 is intrinsically tumor-suppressive but functionally attenuated by the glutamate-rich cerebral environment.

Recurrent heterozygous mutation of isocitrate dehydrogenase 1 gene (), predominantly resulting in histidine substitution at arginine 132, was first identified in glioma. The biological significance of IDH1, however, has been controversial, and its prevalent association with glioma remains enigmatic. Although recent studies indicate that IDH1 is nonessential to tumor growth or even anti-tumor growth, whether IDH1 initiates gliomagenesis remains obscure.

Functional requirement of a wild-type allele for mutant IDH1 to suppress anchorage-independent growth through redox homeostasis.

Mutations of isocitrate dehydrogenase 1 (IDH1) gene are most common in glioma, arguably preceding all known genetic alterations during tumor development. IDH1 mutations nearly invariably target the enzymatic active site Arg132, giving rise to the predominant IDH1. Cells harboring IDH1 -heterozygous mutation produce 2-hydroxyglutarate (2-HG), which results in histone and DNA hypermethylation.