IDH2 and neoplasm: These alterations inhibit the normal function of the IDH enzyme in converting isocitrate to α-ketoglutarate [77] and instead drive the conversion of α-ketoglutarate to R(-)-2-hydroxyglutarate [35], a metabolite that may contribute to tumor development. IDH mutations likely represent an early step in tumorigenesis because such alterations are also observed commonly in preexisting lower grade lesions [78].