Carcinogen-specific mutation pattern in the p53 tumour suppressor gene in UV radiation-induced basal cell carcinoma.
OBJECTIVE
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.
Weihrauch
M
M
Abteilung Arbeitsmedizin, Medizinische Hochschule Hannover, Carl-Neubergstrasse 1, 30625 Hannover, Germany. Weihrauch.Markus@mh-hannover.de
Bader
M
M
Lehnert
G
G
Wittekind
C
C
Tannapfel
A
A
Wrbitzky
R
R
D001483:Base Sequence; D002273:Carcinogens / Q000633:toxicity*; D002280:Basal Cell Carcinoma / Q000209:etiology / Q000235:genetics*; D017931:DNA Primers; D016158:Genes, p53; D005858:Germany; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000235:genetics*; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D002273:Carcinogens; D017931:DNA Primers