IDH1

About IDH1

IDH1 on chromosome 2q34 encodes isocitrate dehydrogenase 1, a cytoplasmic enzyme that converts isocitrate to alpha ketoglutarate. Specific somatic mutations, most often R132H, give the enzyme a new function: producing 2 hydroxyglutarate, an oncometabolite that inhibits enzymes controlling DNA and histone methylation, altering gene expression and blocking normal cell differentiation. IDH1 mutations are found in most lower grade gliomas and secondary glioblastomas, in a subset of acute myeloid leukemia, and in cholangiocarcinoma and chondrosarcoma. In brain tumors, IDH status is now a core part of the World Health Organization classification, and IDH mutant gliomas generally have a better outlook than IDH wild type tumors. Inhibitors of mutant IDH1, such as ivosidenib, and the brain penetrant vorasidenib, approved in 2024 for certain gliomas, are examples of drugs targeting a cancer specific metabolic change.