IDHwildtype

IDH-wildtype refers to the absence of mutations in the isocitrate dehydrogenase genes IDH1 and IDH2. This molecular status is most commonly discussed in the context of gliomas, where it serves as a major classifier alongside histology. IDH-wildtype tumors do not carry the common IDH1 R132H mutation detectable by routine immunohistochemistry and typically require molecular sequencing to confirm the absence of IDH1/IDH2 mutations.

In the current WHO CNS tumor classification, IDH status is an essential component of integrated diagnoses. IDH-wildtype gliomas are contrasted with IDH-mutant gliomas, which generally have a different natural history and prognosis. The presence or absence of IDH mutations helps refine diagnostic categories, including astrocytomas and oligodendrogliomas, and informs prognosis and potential treatment approaches.

Clinically, IDH-wildtype gliomas are often associated with a poorer prognosis compared with IDH-mutant gliomas when matched for grade, and they may behave more aggressively. This status can influence management decisions, including considerations for treatment intensity, surveillance, and eligibility for targeted or experimental therapies.

Testing approaches include immunohistochemistry for IDH1 R132H, followed by sequencing of IDH1 and IDH2 for noncanonical mutations if needed. Comprehensive molecular profiling using next-generation sequencing can confirm IDH status and assess additional coexisting alterations. While the term is most frequently applied to gliomas, IDH-wildtype status may be relevant in other IDH-mutant–focused oncological contexts, though its clinical implications are best defined within neuro-oncology.