title: Single base instability is promoted in vulvar lichen sclerosus.
abstract: Single base substitution mutations in codons 248 and 273 of TP53 and codon 12 Kirsten-ras (KRAS) are commonly found in human carcinomas. To determine whether these mutations also occur in normal and inflamed tissues from which carcinomas arise, we utilized the ultra-sensitive polymerase chain reaction/restriction endonuclease/ligase chain reaction mutation assay. Ninety samples of genital skin, including lichen sclerosus (LS) affected skin, adjacent normal and non-adjacent normal, were assayed. Mutations were detected in 103 of 349 assays and consisted of KRAS G34A, G34T, G35A, and TP53 C742T, G818C, C817T, and G818A mutations. Mutant prevalence varied from 1 to 20 per 10(6) wild-type cells. Mutations occurred significantly more frequently in LS (78/224 (35%)) than adjacent normal (20/88 (23%)) and non-adjacent normal genital skin (5/38 (13%)). KRAS G34A mutation was relatively common to all classes of specimen, whereas TP53 gene C742T and G818C mutations were significantly more frequent in LS than normal genital skin. In matched samples, immunohistochemistry evaluation of p53 protein expression revealed the presence of epidermal p53 clones in LS whose presence and number significantly correlated with the presence of TP53 C742T and G818C mutations. Based on these results, it appears oncogenic point mutations occur in normal genital skin, and are selected for in LS.
authors.affiliation: Department of Veterinary Comparative Biomedical Sciences, Louisiana State University, Baton Rouge, Louisiana, USA.
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Tapp
authors.forename: Jingtao
authors.initials: J
authors.lastname: Feng
authors.forename: J Wesley
authors.initials: JW
authors.lastname: Jones
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Carlson
authors.forename: Vincent L
authors.initials: VL
authors.lastname: Wilson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D017354:Point Mutation / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D007724:Vulvar Lichen Sclerosus / Q000235:genetics*; D014846:Vulvar Neoplasms / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins