title: UV fingerprints predominate in the PTCH mutation spectra of basal cell carcinomas independent of clinical phenotype.
abstract: Basal cell carcinoma (BCC) shows a wide interpatient variation in lesion accrual. To determine whether certain tumorigenic fingerprints and potentially predisposing patched (PTCH) tumor suppressor single-nucleotide polymorphisms (SNPs) are distributed differently among sporadic BCC patients, we compared the PTCH mutation spectra in early-onset BCC (first lesion at age < 35 years), regular BCC (first lesion at age > or = 35 years and < 10 lesions), and multiple BCC (> or = 10 lesions). The PTCH gene was mutated in 29 of 60 cases (48%). Most of the PTCH mutations bore the UV fingerprint (i.e., C --> T or tandem CC --> TT transitions at dipyrimidine sites). However, neither the proportion nor the spectra of exonic PTCH mutations differed significantly among the three groups. A large number of SNPs (IVS10+99C/T, IVS11-51G/C, 1665T/C, 1686C/T, IVS15+9G/C, IVS16-80G/C, IVS17+21G/A, and 3944C/T or its combinations) were also detected, but again their incidence did not differ significantly among the groups. Interestingly, expression of the IVS16-80G/C and the IVS17+21G/A genotype did not achieve the Hardy-Weinberg equilibrium in patients with regular and/or early-onset BCC. These data suggest that a (UV-) mutated PTCH gene is important for sporadic BCC formation independent of clinical phenotype and that the IVS16-80G/C and/or IVS17+21G/A SNP site might be important for tumorigenesis in certain BCC patients.
authors.affiliation: Research Unit for Photodermatology, Department of Dermatology, Medical University of Graz, Graz, Austria.
authors.forename: Ellen
authors.initials: E
authors.lastname: Heitzer
authors.forename: Anita
authors.initials: A
authors.lastname: Lassacher
authors.forename: Franz
authors.initials: F
authors.lastname: Quehenberger
authors.forename: Helmut
authors.initials: H
authors.lastname: Kerl
authors.forename: Peter
authors.initials: P
authors.lastname: Wolf
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000378:metabolism*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010641:Phenotype; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface