title: TP53 mutations in squamous-cell carcinomas of the conjunctiva: evidence for UV-induced mutagenesis.
abstract: Squamous cell carcinoma of the conjunctiva is associated with sun exposure and often occurs in HIV-positive individuals. We have analysed TP53 mutations in 21 cases of squamous cell carcinoma and 22 controls with benign conjunctival lesions from a region (Uganda, Africa) with a high prevalence of heavy sun exposure and HIV infection. TP53 mutations were detected in 11 cases (52%) and 3 controls (14%). Seven of the mutations (6 in cases and 1 in controls) were CC-->TT transitions, a molecular signature of mutagenesis by solar UV rays. A similar prevalence (56%) of TP53 mutations was found in 18 squamous cell carcinoma cases positive for epidermodysplasia verruciformis human papillomavirus types. The prevalence of CC-->TT transitions reported here is the highest observed in any cancer type and matches that of skin cancers in subjects with xeroderma pigmentosum, an inherited disease with hypersensitivity to UV damage. These results confirm at the molecular level the causal role of solar UV rays in the aetiology of squamous cell carcinoma of the conjunctiva and suggest that infection with epidermodysplasia verruciformis types of human papillomavirus may act as a cofactor to increase the sensitivity of conjunctiva cells to UV-induced mutagenesis.
authors.affiliation: Department of Ophthalmology, Makerere University, PO Box 7072, Kampala, Uganda.
authors.forename: Charles
authors.initials: C
authors.lastname: Ateenyi-Agaba
authors.forename: Min
authors.initials: M
authors.lastname: Dai
authors.forename: Florence
authors.initials: F
authors.lastname: Le Calvez
authors.forename: Edward
authors.initials: E
authors.lastname: Katongole-Mbidde
authors.forename: Anouk
authors.initials: A
authors.lastname: Smet
authors.forename: Massimo
authors.initials: M
authors.lastname: Tommasino
authors.forename: Silvia
authors.initials: S
authors.lastname: Franceschi
authors.forename: Pierre
authors.initials: P
authors.lastname: Hainaut
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
mesh_terms: D000328:Adult; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D003230:Conjunctival Neoplasms / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004252:DNA Mutational Analysis; D004819:Epidermodysplasia Verruciformis / Q000235:genetics; D005091:Exons; D016158:Genes, p53; D015658:HIV Infections / Q000150:complications; D006801:Humans; D008875:Middle Aged; D016296:Mutagenesis; D009154:Mutation; D010865:Pilot Projects; D012878:Skin Neoplasms / Q000235:genetics*; D016082:Solar System; D014454:Uganda; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics
chemical_list: D004247:DNA