Analysis of the tumor suppressor gene p53 in xeroderma pigmentosum fibroblasts.

Genetic risk factor(s) for skin cancers have been described in patients with xeroderma pigmentosum (XP). The tumor suppressor gene, p53, is one of the most frequently mutated genes found in human tumors. To evaluate the role of XP-related genetic defects in the p53 gene, skin fibroblast cell lines derived from XP donors were analysed for mutations in exons 5-9 (the regions of gene highly susceptible for mutations) by single-strand conformation polymorphism (SSCP) and nucleotide sequencing. Of the five XP-derived fibroblasts (complementation group A) and two control fibroblast cell lines, only one XP cell line showed an aberrant SSCP banding pattern in the region of the p53 gene (comprising the 7th exon and neighbouring intronic sequences). Nucleotide sequencing of this region confirmed a mutation in the 7th intron adjacent to the 7th exon, which did not affect the RNA splice site. These results suggest that constitutional/germ-line mutations in the p53 gene may not play a role in the occurrence of skin carcinomas in XP patients.