EZH2 and cancer: CCA was also defined by two distinct DNA hypermethylation phenotypes, with one subgroup showing concurrent down-regulation of DNA demethylation enzyme TET1 and upregulation of histone methyltransferase EZH2 suggesting an epigenetic role in establishing the DNA hypermethylation phenotype of this subgroup, while the other subgroup had IDH and/or BAP1 mutations.84 EZH2 inhibitors are now in clinical development (e.g., tazemetostat for some EZH2, SMARCB1, or SMARCA4-mutated cancers, NCT03213665) and could be considered for the EZH2/TET1 hypermethylated subgroup, or for SMARCA/B-mutated BTCs.