p53 mutation spectrum in Japanese Bowen's disease suggests a role for mutagens other than ultraviolet light.
The Japanese have a much lower incidence of nonmelanoma skin cancers (NMSCs) than Caucasians, presumably due in part to their skin type conferring relative protection from ultraviolet light radiation (UVR). To examine the contribution of environmental or endogenous mutagens other than UVR, which are expected to be relatively more important to the overall burden of NMSCs in the Japanese, we directly sequenced exons 5-8 of the p53 tumour suppressor gene in 29 Japanese patients with Bowen's disease, an in situ squamous-cell carcinoma of the skin. We found 9 mutations, including two CC:GG to TT:AA tandem transitions (presumably related to UVR), 3 transversions and 4 frameshift mutations. The mutational spectrum seen in our study contrasts with that we previously found in Bowen's disease from a Caucasian population, in keeping with a different aetiology for Bowen's disease in the respective populations. The unexpectedly high prevalence of frameshift mutations suggests that environmental mutagens other than UVR that preferentially induce deletion or insertion mutations may play an important role in the tumorigenesis of Japanese Bowen's disease, and warrants further investigation.
Takata
M
M
Department of Dermatology, University of Newcastle upon Tyne, UK. takata@med.kanazawa-u.ac.jp
Rehman
I
I
Rees
J L
JL
D000368:Aged; D000369:Aged, 80 and over; D001913:Bowen's Disease / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D004251:DNA Transposable Elements; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D016158:Genes, p53 / Q000528:radiation effects; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009153:Mutagens; D017354:Point Mutation; D017384:Sequence Deletion; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D014466:Ultraviolet Rays
D004251:DNA Transposable Elements; D009153:Mutagens