IDH mutations, particularly in IDH1 and IDH2, are frequently observed in various cancers, including gliomas, acute myeloid leukemia (AML), and chondrosarcomas. These mutations result in a neomorphic enzyme activity, leading to the excessive production of the oncometabolite D-2-hydroxyglutarate (D-2HG). Elevated D-2HG levels are implicated in oncogenesis through various mechanisms, including the inhibition of α-ketoglutarate dependent dioxygenases, which are crucial for cellular differentiation and DNA repair.
