title: 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.
  
  
  CONCLUSIONS
  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."
authors.affiliation: Anti Cancer Inc, 7917 Ostrow Street, San Diego, 92111 CA USA.|Department of Surgery, University of California, San Diego, CA USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
keywords: Aneuploidy; Cancer speciation; Chromosome instability; Global DNA hypomethylation; Methionine; Methionine dependence; Unbalanced transmethylation