The most prevalent genetic alterations identified in CCA affect key networks such as DNA repair (TP53) [83,84], the WNT–CTNNB1 pathway [85], tyrosine kinase signaling (KRAS, BRAF, SMAD4, and FGFR2) [86,87,88], protein tyrosine phosphatase (PTPN3) [89], epigenetic (IDH1 and IDH2) [83,84,90,91] and chromatin-remodeling factors (histone-lysine N-methyltransferase 2C, also known as MLL3) [86], including the SWI/SNF complex (ARID1A, PBRM1, and BAP1) [83,84,90,91] and deregulated Notch signaling, which is a key component in cholangiocyte differentiation and biliary duct development. Here, KMT2C is linked to cholangiocarcinoma.