PBRM1 and cholangiocarcinoma: Driver mutations in genes related to chromatin modification and DNA methylation, such as SMARCA4, PBRM1, BAP1, ARID1A, WHSC1, DNMT3A, and EZH2 were frequently identified [2,40], implying that the mutation in these epigenetic modifiers could be the primary event preceding epigenetic dysregulation, thus regulating the transcriptome driving the CCA.