DNMT1 and colorectal carcinoma: While treatment with 5-aza-deoxycytidine reduces tumor burden in mouse models of hereditary polyposis,66 DNMT1 deficiency predisposes mice to developing lymphomas.67 Additional studies indicate that, while DNA hypermethylation of specific loci drives CRC tumorigenesis,68,69 genome-wide hypomethylation is associated with chromosomal instability in CRC.70 Thus, mouse models are also beginning to demonstrate the nonrandomness of DNA hypomethylation and its likely association with aging and cancer predisposition (Figure 2; Table 2).