1. ¹Department of Veterinary Comparative Biomedical Sciences, Louisiana State University, Baton Rouge, Louisiana, USA
2. ²Department of Environmental Studies, Louisiana State University, Baton Rouge, Louisiana, USA
3. ³Department of Pathology, Albany Medical College, Albany, New York, USA
4. ⁴Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA

Correspondence: Dr Vincent L. Wilson, Department of Environmental Studies, 1279 Energy, Coast and Environment, Louisiana State University, Baton Rouge, Louisiana 70803, USA. E-mail: Monster77@aol.com

Received 16 January 2007; Revised 19 March 2007; Accepted 3 April 2007; Published online 7 June 2007.

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 10⁶ 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.