Significance of CpG methylation for solar UV-induced mutagenesis and carcinogenesis in skin

Photochemistry and Photobiology
Hironobu Ikehata, Tetsuya Ono

Abstract

Mutations detected in the p53 gene in human nonmelanoma skin cancers show a highly UV-specific mutation pattern, a dominance of C --> T base substitutions at dipyrimidine sites plus frequent CC --> TT tandem substitutions, indicating a major involvement of solar UV in the skin carcinogenesis. These mutations also have another important characteristic of frequent occurrences at CpG dinucleotide sites, some of which actually show prominent hotspots in the p53 gene. Although mammalian solar UV-induced mutation spectra were studied intensively in the aprt gene using rodent cultured cells and the UV-specific mutation pattern was confirmed, the second characteristic of the p53 mutations in human skin cancers had not been reproduced. However, studies with transgenic mouse systems developed thereafter for mutation research, which harbor methyl CpG-abundant transgenes as mutation markers, yielded complete reproductions of the situation of the human skin cancer mutations in terms of both the UV-specific pattern and the frequent occurrence at CpG sites. In this review, we evaluate the significance of the CpG methylation for solar UV mutagenesis in the mammalian genome, which would lead to skin carcinogenesis. We propose that the UV-specif...Continue Reading

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Citations

Dec 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Anastasia Tsaalbi-ShtylikNiels de Wind
Jul 12, 2012·Photochemistry and Photobiology·Jean CadetThierry Douki
Jan 26, 2008·The Journal of Investigative Dermatology·Anita LassacherPeter Wolf
Aug 29, 2019·Photochemistry and Photobiology·Hironobu IkehataMasayuki Yamamoto

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