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Abstract
To understand the role of p53 tumor suppressor gene in the
carcinogenesis of arsenic-related skin cancers from the
blackfoot disease endemic area of Taiwan, we collected tumor
samples from 19 patients with Bowen*s diseases, 5 patients with
basal cell carcinomas (BCC), and 4 patients with squamous cell
carcinomas (SCC). The results showed that p53 gene mutations
were found in 36% of cases with Bowen*s diseases (7/19), 20% of
cases with BCC (1/5) and 50% of cases with SCC (2/4). Most of
the mutation sit were located on exon 5 and exon 8. Moreover,
the results from direct sequencing indicated that mutation spots
were at codon 149 (C→T), which would result in the substitution
of tyrosine for serine in the protein, codon 175 (G→A), which
would result in the substitution of histidine for arginine in
the protein, codon 273 (G→C) which would result in the
substitution of proline for arginine in the protein, and codon
292 (T→A), which would result in the substitution of glutamine
for leucine in the protein. addition, silent mutations were
also found in 2 cases. These mutations were located at codon 174
and codon 298, respectively. In immunohistochemistry analysis,
p53 overexpression was found in 47% of cases with Bowen*s
diseasse and 50% of cases with SCC. These findings showed that
p53 gene mutation rate in arsenic-related 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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