Conclusions

Aberrant methylation patterns in genomic DNA may be one of the causative factors responsible for the progression and pathogenesis of a variety of human cancers (Figure 2.3). Alterations in methylation status due to DNA hypomethylation may produce chromosomal instability, rearrangement, and mutations in critical genes, whereas DNA hypermethylation may lead to silencing of

□NA Hypermethylglliin

□NA Hypermethylglliin

Ch romosomal JnstabH Hy i- Mutation Gi-nc exii-'oss;;^

DNA Hypomethyialion

FIGURE 2.3 Effects of genome-wide DNA hypermethylation and hypomethylation on chromosomal instability, mutation, and gene expression.

tumor suppressor genes responsible for checking the uncontrolled growth of cancer cells and acquired drug resistance against cytotoxic agents. Due to its reversible nature, DNA methylation phenomena could be exploited as a "turn off and turn on" switch for gene expression in cancer pathogenesis and the reversal of drug resistance.13 Alterations in genome-wide methylation may be prevented by providing balanced dietary supplements such as folate, which is an important carbon donor for methylation reaction. Folate deficiency leading to abnormal methylenetetrahydrofolate reductase gene (1p36) expression and altered DNA methylation status has been correlated with an increased risk of cancers.79

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