OBJECTIVES: Basal cell carcinoma (BCC) is mainly caused by high and long-term UV radiation. UV radiation causes DNA damage in various genes. Mutations of the p53 tumour suppressor gene have been identified in a wide variety of human cancers. The aim of the study was to analyse specific p53 mutations in BCCs in workers exposed to high and long-term UV radiation. METHODS: The mutation pattern of the p53 tumour suppressor gene was analysed in tissue from 12 patients with UV-related BCC. All patients had a suspected occupational disease notified within the period 1995-1999. As a control, 20 BCC skin samples removed from areas definitively unexposed to sunlight were analysed. The specific mutations were determined by direct sequencing of codon 4 to 9 of the p53 gene in carcinomatous and adjacent non-neoplastic tissue after microdissection. Immunohistochemical analysis was performed to detect p53 protein. RESULTS: p53 mutations were detected in 7/12 cases (58%). Point mutations were found in six cases (50%). In one case a deletion of 24 base pairs was observed. The most frequent mutations we found were CC-->TT base-pair changes in four and C-->T mutations in two cases. Within the control group specific p53 mutations were found in 11 cases (55%) without any C-->T predominance. No case showed CC-->TT mutations. CONCLUSIONS: Mutations of the p53 tumour suppressor gene in UV-associated BCC are frequent events. A predominance of C-->T mutations and tandem CC-->TT base-pair changes were observed in the sunlight-exposed cases only supporting the idea of site-directed mutagenesis by UV radiation in human BCC.
OBJECTIVES:Basal cell carcinoma (BCC) is mainly caused by high and long-term UV radiation. UV radiation causes DNA damage in various genes. Mutations of the p53tumour suppressor gene have been identified in a wide variety of humancancers. The aim of the study was to analyse specific p53 mutations in BCCs in workers exposed to high and long-term UV radiation. METHODS: The mutation pattern of the p53tumour suppressor gene was analysed in tissue from 12 patients with UV-related BCC. All patients had a suspected occupational disease notified within the period 1995-1999. As a control, 20 BCC skin samples removed from areas definitively unexposed to sunlight were analysed. The specific mutations were determined by direct sequencing of codon 4 to 9 of the p53 gene in carcinomatous and adjacent non-neoplastic tissue after microdissection. Immunohistochemical analysis was performed to detect p53 protein. RESULTS:p53 mutations were detected in 7/12 cases (58%). Point mutations were found in six cases (50%). In one case a deletion of 24 base pairs was observed. The most frequent mutations we found were CC-->TT base-pair changes in four and C-->T mutations in two cases. Within the control group specific p53 mutations were found in 11 cases (55%) without any C-->T predominance. No case showed CC-->TT mutations. CONCLUSIONS: Mutations of the p53tumour suppressor gene in UV-associated BCC are frequent events. A predominance of C-->T mutations and tandem CC-->TT base-pair changes were observed in the sunlight-exposed cases only supporting the idea of site-directed mutagenesis by UV radiation in human BCC.
Authors: Jean Y Tang; Albert S Chiou; Julian M Mackay-Wiggan; Michelle Aszterbaum; Anita M Chanana; Wayne Lee; Joselyn A Lindgren; Maria Acosta Raphael; Bobbye J Thompson; David R Bickers; Ervin H Epstein Journal: Cancer Prev Res (Phila) Date: 2014-01-17
Authors: Wannit Tongkao-On; Clare Gordon-Thomson; Katie M Dixon; Eric J Song; Tan Luu; Sally E Carter; Vanessa B Sequeira; Vivienne E Reeve; Rebecca S Mason Journal: Dermatoendocrinol Date: 2013-01-01