P53 MUTATION SPECTRUM IN JAPANESE BOWENS-DISEASE SUGGESTS A ROLE FOR MUTAGENS OTHER THAN ULTRAVIOLET-LIGHT

The Japanese have a much tower incidence of nonmelanoma skin cancers ( NMSCs) than Caucasians, presumably due in part to their skin type conf erring relative protection from ultraviolet light radiation (UVR). To examine the contribution of environmental or endogenous mutagens other than UVR, which ape expected to be relatively more important to the o verall 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 (presumabl y related to UVR), 3 transversions and 4 frameshift mutations. The mut ational spectrum seen in our study contrasts with that we previously f ound 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 th at environmental mutagens other than UVR that preferentially induce de letion or insertion mutations may play an important role in the tumori genesis of Japanese Bowen's disease, and warrants further investigatio n. (C) 1997 Wiley-Liss, Inc.