The Tumor Biomarker Series: IDH

Mutations in two isoforms of isocitrate dehydrogenase (IDH1 and IDH2) are relevant to clinical practice. Mutations in IDH1 are frequent (70-80%) in WHO grade II & III astrocytomas, oligodendrogliomas, oligoastrocytomas, as well as secondary glioblastomas. Mutations in IDH2 have also been detected in these tumor types, but far less frequently. The finding of an IDH mutation in an infiltrating glioma is associated with a substantially improved prognosis, grade for grade. Indeed, IDH-mutant GBMs are associated with longer survival time than IDH wild-type anaplastic astrocytomas! More than 90% of IDH1 mutations involve a base exchange of guanine to adenine within codon 132, resulting in an amino acid change from arginine to histidine (R132H). The resulting protein alteration can be detected immunohistochemically. Of course, other mutations in IDH1 and mutations in IDH2 cannot be detected in this manner, but protein sequencing can be used to pick up these less common mutations if necessary.