Mutations in IDH

In IDHm-positive cancers, mutations in IDH1 or IDH2 result in a gain of function activity that may disrupt normal cellular metabolism by producing the oncometabolite 2-hydroxyglutarate (2 HG). A buildup of 2-HG further induces global changes in DNA and histone methylation, causing cells to be blocked in an immature state, where they fail to differentiate. The accumulation of these cells may result in tumor progression.