[9] DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development.

However, deamination of pyrimidines occurs at a 50-fold higher rate of approximately 200–300 events per cell per day,[8] and is potentially highly mutagenic.

[8] MBD4, which is employed in an initial step of base excision repair, specifically catalyzes the removal of T and U paired with guanine (G) within CpG sites.

[11] About 1/3 of all intragenic single base pair mutations in human cancers occur in CpG dinucleotides and are the result of C to T or G to A transitions.

For example, nearly 50% of somatic mutations of the tumor suppressor gene p53 in colorectal cancer are G:C to A:T transitions within CpG sites.

[10] Mono- and biallelic germline mutations of MBD4 have been identified in acute myeloid leukemias, uveal melanomas, and glioblastomas.

[16] These cases presented an inactivation of the second allele of MBD4 in tumor and were associated with a subsequent very high mutation burden at CpG dinucleotides.

[11] MBD4 mutations also occur in tumor samples of melanoma, ovarian, lung, esophageal and prostate cancers at frequencies between 0.5% and 8%.