title: Significantly high levels of ultraviolet-specific mutations in the smoothened gene in basal cell carcinomas from DNA repair-deficient xeroderma pigmentosum patients.
abstract: The Sonic hedgehog (SHH) pathway is implicated in the etiology of the most common human cancer in Caucasians, the basal cell carcinoma (BCC). Mutations in the receptor of SHH, the patched gene, have been characterized in sporadic BCCs as well as those from patients with the rare genetic syndromes nevoid BCC and xeroderma pigmentosum (XP). To elucidate the role of UV in the deregulation of the SHH pathway, we analyzed for alterations of smoothened, a transmembrane signaling component regulated by patched, in BCCs and squamous cell carcinomas from UV hypersensitive XP patients. We find UV-specific smoothened mutations in 30% of XP BCCs, three times higher than those in sporadic Caucasian BCCs, confirming the high rate of UV-induced mutations in DNA repair-deficient XP patients. No alteration was found in XP squamous cell carcinomas, indicating the involvement of smoothened specifically in the development of BCC.
authors.affiliation: Laboratory of Genetic Instability and Cancer, UPR2169 CNRS, Institut André Lwoff, 94801 Villejuif, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Couvé-Privat
authors.forename: Bakar
authors.initials: B
authors.lastname: Bouadjar
authors.forename: Marie Françoise
authors.initials: MF
authors.lastname: Avril
authors.forename: Alain
authors.initials: A
authors.lastname: Sarasin
authors.forename: Leela
authors.initials: L
authors.lastname: Daya-Grosjean
mesh_terms: D002280:Basal Cell Carcinoma / Q000150:complications / Q000209:etiology / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000209:etiology / Q000235:genetics*; D004260:DNA Repair / Q000502:physiology; D006801:Humans; D009154:Mutation; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011956:Receptors, Cell Surface / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled; D012878:Skin Neoplasms / Q000150:complications / Q000209:etiology / Q000235:genetics*; D000072086:Smoothened Receptor; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014983:Xeroderma Pigmentosum / Q000150:complications / Q000235:genetics*
chemical_list: D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor