IDHmutant

IDHmutant refers to tumors in which the isocitrate dehydrogenase (IDH) gene is mutated, most commonly IDH1 or IDH2. In the central nervous system, IDH mutations are most well characterized in gliomas, where they are typically early driver events and define a distinct molecular subset with clinical and biological differences from IDH-wildtype tumors. IDH mutations often result in the production of an oncometabolite, 2-hydroxyglutarate, which alters cellular metabolism and epigenetic regulation.

In gliomas, IDH-mutant tumors include astrocytomas and oligodendrogliomas. Oligodendrogliomas are defined by IDH mutation plus 1p/19q codeletion; astrocytomas are IDH-mutant without 1p/19q codeletion and frequently harbor TP53 and ATRX alterations. IDH-wildtype glioblastomas represent a separate, more aggressive category. The presence of IDH mutation is a major molecular prognostic factor, with IDH-mutant gliomas generally associated with longer overall and progression-free survival and occurring in younger patients.

Classification systems, including the WHO CNS tumor framework (most recently CNS5), incorporate IDH mutation status as a key determinant of diagnostic and prognostic grouping. Therapeutic implications include selection of treatment intensity and eligibility for clinical trials; there are ongoing efforts to develop targeted therapies against IDH-mutant enzymes, with some agents approved for other IDH-mutant cancers, though their role in gliomas remains under investigation.

IDHmutant status is used primarily in neuro-oncology but the term can also apply to IDH mutations found in other cancers, such as cholangiocarcinoma, chondrosarcoma, and hematologic malignancies, where IDH mutations likewise influence biology and treatment approaches.