IDH1 versus IDH2

What it is

IDH1 and IDH2 are the two related genes in which the IDH mutations relevant to gliomas occur. IDH1 mutations are far more common in gliomas than IDH2 mutations, and the single most common is a specific IDH1 mutation known as R132H.

Understanding IDH1 versus IDH2

Both IDH1 and IDH2 make versions of the isocitrate dehydrogenase enzyme, and a mutation in either can drive glioma development by producing the abnormal substance 2-hydroxyglutarate. In gliomas, the great majority of IDH mutations are in IDH1, and most of these are the R132H type — which is common enough that a specific antibody test (immunohistochemistry) can detect it directly on tumor tissue. Less common IDH1 mutations and IDH2 mutations are detected by genetic sequencing. For classification purposes, what matters most is whether an IDH mutation (in either gene) is present, since both have similar implications. Newer IDH inhibitor drugs can target both IDH1 and IDH2 mutations. Understanding IDH1 versus IDH2 clarifies where IDH mutations occur and how they are detected.

Why it matters

Understanding IDH1 versus IDH2 helps patients and families interpret testing — recognizing that most glioma IDH mutations are in IDH1 (often the R132H type), with both genes carrying similar implications for classification and treatment.