[6] In humans, DNA methylation occurs at the 5′ position of the pyrimidine ring of the cytosine residues within CpG sites to form 5-methylcytosines.
[7] In cancers, loss of expression of genes occurs about 10 times more frequently by transcription silencing (caused by promoter hypermethylation of CpG islands) than by mutations.
[8] In contrast, in colon tumors compared to adjacent normal-appearing colonic mucosa, there are about 600 to 800 heavily methylated CpG islands in promoters of genes in the tumors while these CpG islands are not methylated in the adjacent mucosa.
On average, each microRNA represses or inhibits transcriptional expression of several hundred target genes.
Thus microRNAs with hypermethylated promoters may be allowing enhanced transcription of hundreds to thousands of genes in a cancer.
However, recently, Gagnon et al.[14] showed that as many as 75% of microRNAs may be shuttled back into the nucleus of cells.
[15] DNA repair genes are frequently repressed in cancers due to hypermethylation of CpG islands within their promoters.
[16] About seventeen types of cancer are frequently deficient in one or more DNA repair genes due to hypermethylation of their promoters.
PARP1 and FEN1 are essential genes in the error-prone and mutagenic DNA repair pathway microhomology-mediated end joining.