Is DNA methylation the new guardian of the genome?

被引:27
|
作者
Hoffman, Robert M. [1 ,2 ]
机构
[1] Anti Canc Inc, 7917 Ostrow St, San Diego, CA 92111 USA
[2] Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA
来源
MOLECULAR CYTOGENETICS | 2017年 / 10卷
关键词
Methionine; Methionine dependence; Unbalanced transmethylation; Global DNA hypomethylation; Chromosome instability; Aneuploidy; Cancer speciation; POSITRON-EMISSION-TOMOGRAPHY; VIRUS 40-TRANSFORMED HUMAN; BRAIN-TUMOR XENOGRAFTS; ACID-DEFINED DIET; METHIONINE DEPENDENCE; RECOMBINANT METHIONINASE; MALIGNANT RAT; CANCER-CELLS; S-ADENOSYLMETHIONINE; METABOLIC DEFECT;
D O I
10.1186/s13039-017-0314-8
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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."
引用
收藏
页数:7
相关论文
共 50 条