Methylation, mutation and cancer
- 1 January 1992
- Vol. 14 (1) , 33-36
- https://doi.org/10.1002/bies.950140107
Abstract
The fifth base in human DNA, 5‐methylcytosine, is inherently mutagenic. This has led to marked changes in the distribution of the CpG methyl acceptor site and an 80% depletion in its frequency of occurrence in vertebrate DNA. The coding regions of many genes contain CpGs which are methylated in sperm and serve as hot spots for mutation in human genetic diseases. Fully 30–40% of all human germline point mutations are thought to be methylation induced even though the CpG dinucleotide is under‐represented and efficient cellular repair systems exist. Importantly, tumor suppressor genes such as p53 also contain methylated CpGs and these serve as hot spots for mutations in some, but not all, human cancers. Comparison of the spectrum of mutations present in this gene in different human cancers allows for predictions to be made on the molecular mechanisms of tumorigenesis.Keywords
This publication has 22 references indexed in Scilit:
- CpG Islands in vertebrate genomesPublished by Elsevier ,2004
- The expected equilibrium of the CpG dinucleotide in vertebrate genomes under a mutation model.Proceedings of the National Academy of Sciences, 1990
- A sensitive genetic assay for the detection of cytosine deamination: determination of rate constants and the activation energyBiochemistry, 1990
- Repeat-induced G-C to A-T Mutations in NeurosporaScience, 1989
- In vitro correction of G o T mispairs to G o C pairs in nuclear extracts from human cellsNature, 1989
- A specific mismatch repair event protects mammalian cells from loss of 5-methylcytosineCell, 1987
- CpG-rich islands and the function of DNA methylationNature, 1986
- DNA cytosine methylation and heat-induced deaminationBioscience Reports, 1986
- Molecular basis of base substitution hotspots in Escherichia coliNature, 1978
- Heat-induced deamination of cytosine residues in deoxyribonucleic acidBiochemistry, 1974