title: UV mutation signature in tumor suppressor genes involved in skin carcinogenesis in xeroderma pigmentosum patients.
abstract: Molecular analysis of p53 and patched (PTCH), two candidate tumor suppressor genes for non-melanocytic skin cancer, was performed in skin tumors from six patients affected by the cancer-prone disease xeroderma pigmentosum (XP). UV-specific p53 mutations were detected at a frequency of 38-50% in all the tumor types analysed, including melanomas. Additional analysis of PTCH mutations in the subset of eight basal call carcinomas (BCC) revealed a very high mutation frequency of this gene (90%) which exceeded that detected in the p53 gene in the same tumors (38%). PTCH mutations were predominantly UV-specific C>T transitions. This mutation pattern is different from that reported in BCC from normal donors where PTCH mutation frequency is 27% and mutations are frequently deletions and insertions. These findings suggest that PTCH mutations represent an earlier event in BCC development than p53 alterations and that the inability of XP patients to repair UV-induced PTCH mutations might significantly contribute to the early and frequent appearance of BCC observed in these patients.
authors.affiliation: Laboratory of Comparative Toxicology and Ecotoxicology, Istituto Superiore di Sanita, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: D'Errico
authors.forename: A
authors.initials: A
authors.lastname: Calcagnile
authors.forename: F
authors.initials: F
authors.lastname: Canzona
authors.forename: B
authors.initials: B
authors.lastname: Didona
authors.forename: P
authors.initials: P
authors.lastname: Posteraro
authors.forename: R
authors.initials: R
authors.lastname: Cavalieri
authors.forename: R
authors.initials: R
authors.lastname: Corona
authors.forename: I
authors.initials: I
authors.lastname: Vorechovsky
authors.forename: T
authors.initials: T
authors.lastname: Nardo
authors.forename: M
authors.initials: M
authors.lastname: Stefanini
authors.forename: E
authors.initials: E
authors.lastname: Dogliotti
mesh_terms: D000328:Adult; D000368:Aged; D002280:Basal Cell Carcinoma / Q000235:genetics; D002675:Child, Preschool; D005260:Female; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D016158:Genes, p53 / Q000502:physiology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D012878:Skin Neoplasms / Q000235:genetics*; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface