Isocitrate dehydrogenase 1 and 2 mutations in gliomas

Abstract

Over the past few years, new biomarkers have allowed a deeper insight into gliomagenesis and facilitated the identification of possible targets for glioma therapy. Isocitrate dehydrogenase (IDH) 1 and IDH2 mutations have been shown to be promising biomarkers for monitoring disease prognosis and predicting the response to treatment. This review summarizes recent findings in this field. Web of Science, Science Direct, and PubMed online databases were used to search for publications investigating the role of IDH in glioma. References were identified by searching for the keywords "IDH1 or IDH2 and glioma and diagnostic or predictive or prognostic" in papers published from January, 2008, to April, 2014. Only papers in English were reviewed. Publications available only as an abstract were not included. IDH1/2 mutations are tightly associated with grade II and III gliomas and secondary glioblastomas, with better prognosis and production of a recently described oncometabolite, 2-hydroxyglutarate (2HG). Although the contradictory positive effect of IDH mutation on prognosis and negative role of 2HG in tumor transformation remain unresolved, the future direction of personalized treatment strategies targeted to glioma development is likely to focus on IDH1/2 mutations.

Metabolomic profiling of the heart during acute ischemic preconditioning reveals a role for SIRT1 in rapid cardioprotective metabolic adaptation

“…2B). Typically this metabolite is associated with isocitrate dehydrogenase (ICDH) mutation in cancer, leading to its characterization as an oncometabolite [46]. Very recently it has been shown that 2-OHG accumulates in response to hypoxia [47,48], but the regulation of this phenomenon is unclear.…”

Association between IDH1/2 mutations and brain glioma grade

“…There is growing interest in the frequency of IDH1/2 mutations in different types of glioma (21). A few studies have reported on IDH1/2 mutation frequencies in different grades of oligodendroglioma and astrocytoma (19,22,23).…”

Glioma an overview of current classifications characteristics molecular biology and target therapies

“…One of these mutations (mostly in IDH1) occurs in about 80% of low-grade gliomas and secondary high-grade gliomas. IDH1 and IDH2 mutant cells produce an excess metabolic intermediate, 2-hydroxyglutarate, which binds to catalytic sites in key enzymes that are important in altering histone and DNA promoter methylation (82,83). Thus, mutations in IDH1 and IDH2 generate a "DNA CpG island methylator phenotype or CIMP" that causes promoter hypermethylation and concomitant silencing of tumor suppressor genes, such as DNA repair genes MGMT and ERCC1 (84).…”