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Mutational spectrum of p53 gene in arsenic-related skin cancers from the blackfoot disease endemic area of Taiwan
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  • Published: 07 May 1999

Mutational spectrum of p53 gene in arsenic-related skin cancers from the blackfoot disease endemic area of Taiwan

  • C-H Hsu2,
  • S-A Yang1,
  • J-Y Wang3,
  • H-S Yu1 &
  • …
  • S-R Lin2 

British Journal of Cancer volume 80, pages 1080–1086 (1999)Cite this article

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Summary

To understand the role of p53 tumour suppressor gene in the carcinogenesis of arsenic-related skin cancers from the blackfoot disease endemic area of Taiwan, we collected tumour samples from 23 patients with Bowen’s disease, seven patients with basal cell carcinomas (BCC) and nine patients with squamous cell carcinomas (SCC). The result showed that p53 gene mutations were found in 39% of cases with Bowen’s disease (9/23), 28.6% of cases with BCC (2/7) and 55.6% of cases with SCC (5/9). Most of the mutation sites were located on exon 5 and exon 8. Moreover, the results from direct sequencing indicated that missense mutations were found at codon 149 (C→T) in one case, codon 175 (G→A) in three cases, codon 273 (G→C) in three cases, codon 292 (T→A) in one case, codon 283 (G→T) in one case, codon 172 (T→C) in one case and codon 284 (C→A) in one case. In addition, silent mutations were also found in four cases. These mutations were located at codons 174, 253, 289 and 298 respectively. In immunohistochemistry analysis, p53 overexpression was found in 43.5% (10/23) of cases with Bowen’s disease, 14% (1/7) of cases with BCC and 44% (4/9) of cases with SSC. These findings showed that p53 gene mutation rate in arsenic-related skin cancers from the blackfoot disease endemic area of Taiwan is high and that the mutation types are different from those in UV-induced skin cancers.

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  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

References

  • Berg, R. J., van Kranen, H. J., Rebel, H. G., de Vries, A., van Vloten, W. A., Van Kreijl, C. F., van der Leun, J. C. & de Gruijl, F. R. (1996). Early p53 alteration in mouse skin carcinogenesis by UVB radiation: immunohistochemical detection of mutant p53 protein in clusters of preneoplastic epidermal cells. Proc Natl Acad Sci USA 93: 274–278.

    Article  CAS  Google Scholar 

  • Bishop, J. M. (1991). Molecular themes in oncogenesis. Cell 64: 235–248.

    Article  CAS  Google Scholar 

  • Brash, D. E., Rudolph, J. A., Simon, J. A., Lin, A., McKenna, G. J., Baden, H. P., Halperin, A. J. & Ponten, J. (1991). A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc Natl Acad Sci USA 88: 1012–1018.

    Article  Google Scholar 

  • Brown, K. G. & Chen, C. J. (1995). Significance of exposure assessment to analysis of cancer risk from inorganic arsenic in drinking water in Taiwan. Risk Anal 15: 475–484.

    Article  CAS  Google Scholar 

  • Cavigelli, M., Li, W. W., Lin, A., Su, B., Yoshioka, K. & Karin, M. (1996). The tumor promoter arsenite stimulates AP-1 activity by inhibiting JNK phosphatase. EMBO J 15: 6269–6279.

    Article  CAS  PubMed Central  Google Scholar 

  • Chen, C. J., Wu, M., Lee, S. S., Wang, J. D., Cheng, S. H. & Wu, H. Y. (1988). Atherogenicity and carcinogenicity of high-arsenic artesian well water. Multiple risk factors and related malignant neoplasms of blackfoot disease. Arteriosclerosis 8: 452–460.

    Article  CAS  Google Scholar 

  • Chiang, H. A., Guo, H. R., Hong, C. L., Lin, S. M. & Lee, E. F. (1993). The incidence of bladder cancer in black foot disease endemic area in Taiwan. Br J Urol 71: 274–278.

    Article  CAS  Google Scholar 

  • Chiou, H. Y., Hsueh, Y. M., Liaw, K. F., Horng, S. F., Chiang, M. H., Pu, Y. S., Lin, J. S., Huang, C. H. & Chen, C. J. (1995). Incidence of internal cancers and ingested inorganic arsenic: a seven-year follow-up study in Taiwan. Cancer Res 55: 1296–1300.

    CAS  PubMed  Google Scholar 

  • Debec, C., Courgeon, A. M., Mainground, M. & Maisonhaute, C. (1990). The response of the centrosome to heat shock and related stresses in a Drosophila cell line. J Cell Sci 96: 403–412.

    CAS  PubMed  Google Scholar 

  • Drouin, R. & Therrien, J. P. (1997). UVB-induced cyclobutane pyrimidine dimer frequency correlates with skin cancer mutational hotspots in p53. Protochem Photobiol 66: 719–726.

    Article  CAS  Google Scholar 

  • Hsueh, Y. M., Cheng, G. S., Wu, M. M., Yu, H. S., Kuo, T. L. & Chen, C. J. (1995). Multiple risk factors associated with arsenic-induced skin cancer, effects of chronic liver disease and malnutritional status. Br J Cancer 7: 109–114.

    Article  Google Scholar 

  • Hsueh, Y. M., Huang, C. C., Wu, W. L., Chen, H. M., Yang, M. H., Lue, L. C. & Chen, C. J. (1998). Urinary levels of inorganic and organic arsenic metabolites among residents in arseniasis-hyperendemic area in Taiwan. J Toxicol Environ Health 54: 431–444.

    Article  CAS  Google Scholar 

  • Inga, A., Scott, G., Monti, P., Aprile, A., Abbondandolo, A., Burns, P. A. & Fronza, G. (1998). Ultraviolet-light induced p53 mutational spectrum in yeast is indistinguishable from p53 mutations in human skin cancer. Carcinogenesis 19: 741–746.

    Article  CAS  Google Scholar 

  • Innis, M. A., Myambo, K. B., Gelfand, D. H., Brow, M. A., Tseng, W. P., Chu, H. M., How, S. W., Fong, J. M., Lin, C. S. & Yeh, S. (1988). DNA sequencing with Thermus-aquaticus DNA polymerase and direct sequencing of polymerase chain reaction-amplified DNA. Proc Natl Acad Sci USA 85: 9436

    Article  CAS  Google Scholar 

  • Lee, T. C., Takata, N., Lamb, P. W., Gilmer, T. M. & Barrett, J. C. (1988). Induction of gene amplification by arsenic. Science 241: 79–81.

    Article  CAS  Google Scholar 

  • Lee-Chen, S. F., Gurr, J. R. & Jan, K. Y. (1993). Arsenite enhances DNA double-strand breaks and cell killing of methyl methanesulfonate-treated cells by inhibiting the excision of alkali-labile sites. Mutat Res 294: 21–28.

    Article  CAS  Google Scholar 

  • Lin, S. R., Lee, Y. J. & Tsai, J. H. (1994). Mutations of the p53 gene in human functional adrenal neoplasms. J Clin Endocrin Metab 78: 483–491.

    CAS  Google Scholar 

  • Lubbe, J., Kleihues, P. & Burg, G. (1994). The tumor suppression gene p53 and its significance for dermatology. Hautarzt 45: 741–745.

    Article  CAS  Google Scholar 

  • Lynn, S., Shiung, J. N., Gurr, J. R. & Jan, K. Y. (1998). Arsenite stimulates poly (ADP-ribosylation) by generation of nitric oxide. Free Biol Med 24: 442–449.

    Article  CAS  Google Scholar 

  • Magos, L. (1991). Epidemiological and experimental aspects of metal carcinogenesis: physicochemical properties, kinetics, and active species. Environ Health Perspect 95: 157–189.

    Article  CAS  PubMed Central  Google Scholar 

  • Matsumura, Y., Nishigori, C., Yagi, T., Imamura, S. & Takebe, H. (1996). Characterization of p53 gene mutations in basal-cell carcinomas: comparison between sun-exposed and less-exposed skin areas. Int J Cancer 65: 778–780.

    Article  CAS  Google Scholar 

  • Nakazawa, H., English, D., Randell, P. L., Nakazawa, K., Martel, N., Armstrong, B. K. & Yamasaki, H. (1994). UV and skin cancer specific p53 gene mutation in normal skin as a biologically relevant exposure measurement. Proc Natl Acad Sci USA 91: 360–364.

    Article  CAS  Google Scholar 

  • Nagano, T., Ueda, M. & Ichihashi, M. (1993). Expression of p53 protein is an early event in ultraviolet light-induced cutaneous squamous cell carcinogenesis. Arch Dermatol 129: 1157–1161.

    Article  CAS  Google Scholar 

  • Nataraj, A. J., Black, H. S. & Ananthaswamy, H. N. (1996). Signature p53 mutation at DNA cross-linking sites in 8-methoxypsoralen and ultraviolet A (PUVA)-induced murine skin cancers. Proc Natl Acad Sci USA 93: 7961–7965.

    Article  CAS  Google Scholar 

  • Oram, Y., Orengo, I., Baer, S. C. & Ocal, T. (1994). p53 protein expression in squamous cell carcinomas from sun-exposed and non-sun-exposed sites. J Am Acad Dermatol 31: 417–422.

    Article  CAS  Google Scholar 

  • Pan, T. C., Horng, C. J., Lin, S. R., Lin, T. H. & Huang, C. W. (1993). Simultaneous determination of Zn, Cd, Pb, and Cu in urine of patients with blackfoot disease using anodic stripping voltammetry. Biol Trace Elem Res 38: 233–241.

    Article  CAS  Google Scholar 

  • Sambrook, J., Fritsch, E. F. & Maniatis, T. (1989). Molecular Cloning, 2nd edn, A Laboratory Manual. Cold Spring Harbor Laboratory: New York

    Google Scholar 

  • Sato, M., Nishigori, C., Zghal, M., Yagi, T. & Takebe, H. (1993). Ultraviolet-specific mutations in p53 gene in skin tumors in Xeroderma pigmentosum patients. Cancer Res 53: 2944–2946.

    CAS  PubMed  Google Scholar 

  • Shibata, A., Ohneseit, P. F., Tsai, Y. C., Spruck, CH III, Nichols, P. W., Chiang, H. S., Lai, M. K. & Jones, P. A. (1994). Mutational spectrum in p53 gene in bladder tumors from the endemic area of black foot disease in Taiwan. Carcinogenesis 15: 1085–1087.

    Article  CAS  Google Scholar 

  • Tseng, C. H., Chong, C. K., Chen, C. J., Lin, B. J. & Tai, T. Y. (1995). Abnormal peripheral microcirculation in seemingly normal subjects living in blackfoot-disease-hyperendemic villages in Taiwan. Int J Microcirc: Clin Exp 15: 21–27.

    Article  CAS  Google Scholar 

  • Tseng, W. P. et al (1968). Prevalence of skin cancer in an endemic area of chronic arsenism in Taiwan. J Natl Cancer I 40: 453

    CAS  Google Scholar 

  • van Kranen, H. J., de Gruijl, F. R., de Vries, A., Sontag, Y., Wester, P. W., Senden, H. C., Rozemuller, E. & van Kreijl, C. F. (1995). Frequent p53 alterations but low incidence of ras mutations in UV-B-induced skin tumors of hairless mice. Carcinogenesis 16: 1141–1147.

    Article  CAS  Google Scholar 

  • van Kranen, H. J., de Laat, A., van de Ven, J., Wester, P. W., de Vries, A., Berg, R. J., van Kreijl, C. F. & de Gruijl, F. R. (1997). Low incidence of p53 mutations in UVA (365-nm)-induced induced skin tumors in hairless mice. Cancer Res 57: 1238–1240.

    CAS  PubMed  Google Scholar 

  • Weyers, W., Bonczkowitz, M., Weyers, I., Bittinger, A. & Schill, W-B (1996). Melanoma in situ versus melanocytic hyperplasia in sun-damaged skin: assessment of the significance of histopathologic criteria for differential diagnosis. Am J Dermatopathol 18: 560–566.

    Article  CAS  Google Scholar 

  • Wu, M. M., Kuo, T. L., Hwang, Y. H. & Chen, C. J. (1989). Dose-response relation between arsenic concentration in well water and mortality from cancers and vascular diseases. Am J Epidemiol 130: 1123–1132.

    Article  CAS  Google Scholar 

  • Ziegler, A., Leffell, D. J. & Kunala, S. (1993). Mutation hotspots due to sunlight in the p53 gene of nonmelanoma skin cancer. Proc Natl Acad Sci USA 90: 4216–4220.

    Article  CAS  Google Scholar 

  • Ziegler, A., Jonason, A. S., Leffell, D. J., Simon, J. A., Sharma, H. W., Kimmelman, J., Remington, L., Sachs, T. & Brash, D. E. (1994). Sunburn and p53 in the onset of skin cancer. Nature 372: 773–776.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Departments of Dermatology, Kaohsiung Medical College, No. 100, Shih-Chuan 1st Road, Kaohsiung, 80317, Taiwan

    S-A Yang & H-S Yu

  2. Departments of Clinical Pathology, Kaohsiung Medical College, No. 100, Shih-Chuan 1st Road, Kaohsiung, 80317, Taiwan

    C-H Hsu & S-R Lin

  3. Departments of Surgery, Kaohsiung Medical College, No. 100, Shih-Chuan 1st Road, Kaohsiung, 80317, Taiwan

    J-Y Wang

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From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

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Hsu, CH., Yang, SA., Wang, JY. et al. Mutational spectrum of p53 gene in arsenic-related skin cancers from the blackfoot disease endemic area of Taiwan. Br J Cancer 80, 1080–1086 (1999). https://doi.org/10.1038/sj.bjc.6690467

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  • Received: 27 April 1998

  • Revised: 17 November 1998

  • Accepted: 23 November 1998

  • Published: 07 May 1999

  • Issue date: 01 June 1999

  • DOI: https://doi.org/10.1038/sj.bjc.6690467

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Keywords

  • p53 gene
  • arsenic-related skin cancers

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