MLH1, DCLK1, CDO1, ZSCAN18, ZFG331, p14, p16, DAPK, CCND2, CDH13, GRIN2B, RUNX3, TWIST1, EGFR and LKB1 are most of all CpG sites that have exhibited hypermethylation and then loss of function in CCA tumorigenesis [31,32,33,34,35,36,37,38,39,40]. The gene discussed is CDKN2A; the disease is cholangiocarcinoma.