IDH2 and cholangiocarcinoma: Mutations in IDH1 and IDH2 genes can lead to oncogenic effects by DNA hypermethylation and impairing cell differentiation.214 Up to 15% of patients with iCCA harbor IDH1 mutations with a large variety across geographic regions.172,215 In pCCA and dCCA these mutations are less frequent (0.8%).215 The oral IDH1 inhibitor ivosidenib was compared to placebo in pretreated CCA patients in the phase III ClarIDHy trial.