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

• Published in: British Journal of Cancer 1999-06, Vol.80 (7), p.1080-1086
• Main Authors: Hsu, C-H, Yang, S-A, Wang, J-Y, Yu, H-S, Lin, S-R
• Format: Article
• Language: English
• Subjects: Aged; Arsenic - adverse effects; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Bowen's Disease - chemically induced; Bowen's Disease - genetics; Bowen's Disease - metabolism; Bowen's Disease - pathology; Cancer Research; Carcinoma, Basal Cell - chemically induced; Carcinoma, Basal Cell - genetics; Carcinoma, Basal Cell - metabolism; Carcinoma, Basal Cell - pathology; Carcinoma, Squamous Cell - chemically induced; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; DNA Mutational Analysis; Drug Resistance; Epidemiology; Female; Food toxicology; Humans; Immunohistochemistry; Male; Medical sciences; Middle Aged; Molecular Medicine; Mutation; Oncology; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Regular; regular-article; Skin Neoplasms - chemically induced; Skin Neoplasms - genetics; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Taiwan; Toxicology; Tropical medicine; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Water Pollutants, Chemical - adverse effects
• ISSN: 0007-0920; 1476-5381; 1532-1827
• DOI: 10.1038/sj.bjc.6690467

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.