Of note, mutations of these DNA methylation-modifying genes are relatively rare (Figure 2A), including DNMT1 (5%), DNMT3A (2.7%), DNMT3B (4%), TET1 (4%), TET2 (2%), and TET3 (2.4%); however, DNMT3A and TET2 are relatively high at the protein level but vary with different ages, while the levels of DNMT1, DNMT3B, and TET3 are moderate or relatively low (Figure 2B); and the expression of these genes correlates, either positively (for DNMT3A, DNMT3B, and TET3) or negatively (for DNMT1, TET1, and TET2), with the overall survival of ICC patients (Figure 2C). This evidence concerns the gene DNMT3B and intrahepatic cholangiocarcinoma.