IDHMutation in Glioma

Importance

Over the past 4 years, our understanding of gliomagenesis and the practice of neuro-oncology have been radically changed by the discovery of mutations involving the isocitrate dehydrogenase (IDH) enzymes.IDHmutation has been found to be an inciting event in gliomagenesis and to have a profound effect on the molecular and genetic route of oncogenic progression and on clinical outcome.

Objectives

To review the role of IDH enzymes in normal physiology and describe aberrations in theIDHpathway that are associated with gliomagenesis, to review recent work examining the effect ofIDH-targeted therapy in cancers harboringIDHmutation, and to determine how this work has expanded our understanding of the role ofIDHin the development and progression of glioma.

Evidence Review

A systematic review of the literature dating from 2008, whenIDHmutation was discovered to be clinically significant in glioma, to 2013 was performed using the PubMed database. The following search terms were used:IDH,IDH1,IDH2, andisocitrate dehydrogenase, in conjunction withgliomaorleukemia. The search was limited to articles published in English. Further hand searching was performed using a review of the pertinent references from the identified publications. All identified original articles were investigated for content and critiqued by Z.T. and S.D.

Findings

IDHmutation is an early event in gliomagenesis and has significant implications for glioma progression and tumor behavior. Early evidence suggests thatIDHmay be a therapeutic target inIDH-mutant gliomas.

Conclusions and Relevance

IDHmutation is a central and defining event in the development and progression of glioma and may be a key target for future therapies for these types of neoplasms.