title: Mutation and abnormal expression of the p53 gene in the viral skin carcinogenesis of epidermodysplasia verruciformis.
abstract: Patients suffering from epidermodysplasia verruciformis are prone to nonmelanoma skin cancers, due to an inherited abnormal susceptibility to the oncogenic human papillomavirus type 5. Genotoxic sunlight ultraviolet B radiations are likely to be a cofactor. Lesions of two human-papillomavirus-type-5-infected epidermodysplasia verruciformis patients collected during an 8 y period were retrospectively studied for p53 mutations in exons 5 through 8 by a polymerase chain reaction single-strand conformation polymorphism technique and/or by DNA sequencing of amplified exons. Mutations were detected in 11 of 26 (42.3%) specimens, including five (62.5%) squamous cell carcinomas, three (33.3%) Bowen's carcinomas in situ, two (40%) actinic keratoses, and one (33%) benign lesion. The nine mutations characterized by sequencing were shown to be missense and to affect mutational hotspots in human cancers. Five were C-->T transitions at dicytidine sites considered as ultraviolet signature mutations. Two were transversions (C-->G and C-->A) at dicytidine sites and two were C-->T transitions at nondipyrimidine sites. A marked p53 immunoreactivity was disclosed in 72.7% of 11 invasive carcinomas, 55.6% of nine carcinomas in situ, 37.5% of eight actinic keratoses, and one of three benign lesions. This includes 81.8% of 11 specimens with a p53 mutation but also 50% of 14 specimens with no mutation detected. A dysfunction of the p53 gene is thus likely to play a part in epidermodysplasia verruciformis carcinogenesis, either due to ultraviolet-B-induced p53 mutations, as in nonmelanoma skin cancers in the general population, or involving other mutagens or mechanisms. The part played by human papillomavirus type 5 proteins expressed in epidermodysplasia verruciformis keratinocytes remains to be determined.
authors.affiliation: Unité des Papillomavirus, Institut Pasteur, Paris, France.
authors.forename: K
authors.initials: K
authors.lastname: Padlewska
authors.forename: N
authors.initials: N
authors.lastname: Ramoz
authors.forename: P
authors.initials: P
authors.lastname: Cassonnet
authors.forename: G
authors.initials: G
authors.lastname: Riou
authors.forename: M
authors.initials: M
authors.lastname: Barrois
authors.forename: S
authors.initials: S
authors.lastname: Majewski
authors.forename: O
authors.initials: O
authors.lastname: Croissant
authors.forename: S
authors.initials: S
authors.lastname: Jablonska
authors.forename: G
authors.initials: G
authors.lastname: Orth
mesh_terms: D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D004819:Epidermodysplasia Verruciformis / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D016158:Genes, p53; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications*; D011230:Precancerous Conditions / Q000378:metabolism; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2