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. Int. J. Cancer 71:370‐372, 1997. © 1997 Wiley‐Liss Inc.

[1]  J. Rees,et al.  Genetic change in actinic keratoses. , 1996, Oncogene.

[2]  C. Harris,et al.  Deletions and insertions in the p53 tumor suppressor gene in human cancers: confirmation of the DNA polymerase slippage/misalignment model. , 1996, Cancer research.

[3]  Y. Matsumura,et al.  Characterization of p53 gene mutations in basal‐cell carcinomas: Comparison between sun‐exposed and less‐exposed skin areas , 1996, International journal of cancer.

[4]  Thierry Soussi,et al.  Somatic point mutations in the p53 gene of human tumors and cell lines: updated compilation , 1996, Nucleic Acids Res..

[5]  J. L. Stone,et al.  Nonmelanoma skin cancer in Japanese ethnic Hawaiians in Kauai, Hawaii: an incidence report. , 1995, Journal of the American Academy of Dermatology.

[6]  Robin Marks,et al.  An overview of skin cancers , 1995, Cancer.

[7]  A. Sober,et al.  Precursors to skin cancer , 1995, Cancer.

[8]  T. Sekiya,et al.  Aberrations of the tumor suppressor p53 gene and p53 protein in solar keratosis in human skin. , 1994, The Journal of investigative dermatology.

[9]  C. Harris,et al.  Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. , 1994, Cancer research.

[10]  E. Robbins Alcman's Partheneion: Legend and Choral Ceremony , 1994, The Classical Quarterly.

[11]  T. Soussi,et al.  Can we predict solar ultraviolet radiation as the causal event in human tumours by analysing the mutation spectra of the p53 gene? , 1994, Mutation research.

[12]  Y. Kubo,et al.  p53 gene mutations in human skin cancers and precancerous lesions: comparison with immunohistochemical analysis. , 1994, The Journal of investigative dermatology.

[13]  C. Campbell,et al.  p53 mutations are common and early events that precede tumor invasion in squamous cell neoplasia of the skin. , 1993, The Journal of investigative dermatology.

[14]  A. Ziegler,et al.  Mutation hotspots due to sunlight in the p53 gene of nonmelanoma skin cancers. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[15]  R Holliday,et al.  DNA methylation and mutation. , 1993, Mutation research.

[16]  E. Newcomb,et al.  p53 mutations in C57BL/6J murine thymic lymphomas induced by gamma-irradiation and N-methylnitrosourea. , 1992, Cancer research.

[17]  R. A. Metcalf,et al.  Mutational hot spot in the p53 gene in human hepatocellular carcinomas , 1991, Nature.

[18]  L. S. Ripley,et al.  Frameshift mutation: determinants of specificity. , 1990, Annual review of genetics.

[19]  Y. Kiyohara,et al.  Comparative aspects of melanoma and non-melanoma skin cancers in Japan. , 1989, The Journal of investigative dermatology.

[20]  T. Sekiya,et al.  Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[21]  M. Tada,et al.  MALIGNANT SKIN TUMORS AMONG DERMATOLOGY PATIENTS IN UNIVERSITY HOSPITALS OF JAPAN , 1984, The Journal of dermatology.