Is DNA methylation the new guardian of the genome?

Abstract

Background: It has been known for more than 100 years that aneuploidy is an essence of cancer. The question is what keeps the genome stable, thereby preventing aneuploidy. For the past 25 years, it has been proposed that p53 is the “guardian of the genome.” However, it has been shown that inactivation of p53 does not cause aneuploidy. Another essence of cancer is global DNA hypomethylation, which causes destabilization of the genome and subsequent aneupoloidy. Yet, another essence of cancer is excessive use of methionine, resulting in methionine dependence. Methionine dependence is due to possible “metabolic reprogramming” due to carcinogens, including chemical agents and infectious organisms, such as Helicobacter pylori, that result in altered and excessive transmethylation in cancer cells. Cancer cells appear to have a “methyl-sink” whereby methyl groups are diverted from DNA. Conclusion: DNA hypomethylation destabilizes the genome, leading to aneuploidy and subsequent selection and speciation into autonomous cancers, leading to the conclusion that DNA methylation is the “guardian of the genome.”