p53 gene mutations in human epithelial skin cancers
Molès, J.P.; Moyret, C.; Guillot, B.; Jeanteur, P.; Guilhou, J.J.; Theillet, C.; Basset-Sèguin, N.
Oncogene 8(3): 583-588
1993
ISSN/ISBN: 0950-9232 PMID: 8437842 Document Number: 407871
In the present study we analysed 38 epithelial skin cancers, 19 basal cell carinomas (BCCs), 13 squamous cell carcinomas (SCCs) and six Bowen diseases (BwDs), using a combination of polymerase chain reaction (PCR) and single-stranded conformation polymorphism (SSCP) techniques for the presence of p53 and RAS gene mutations. Whereas 48% (9/19) of the BCCs tested presented a mutated p53 gene, the frequency was lower (15%, 2/13) in our series of SCCs and negative in the BwDs. Nine of the 11 characterized mutations were single-nucleotide substitutions and, interestingly, seven of these involved CC dimers, where a C was changed into a T or a G (three C fwdarw T transitions and four C fwdarw G transversions). This mutational pattern, added to the fact that all the mutated tumors occurred at sun-exposed body sites, implicates UV light in their genesis. Furthermore, we observed two internal deletions of 6 and 24 bp whose flanking sequences contained two or three Cs on either strand. In addition to molecular detection, we searched for p53 protein accumulation, by immunocytochemical staining in a subset of 3 epithelial skin tumors (nine bearing a mutation, 14 which scored negative in our assay). Three commercially available anti-p53 antibodies (PAb CM1, mAbs DO7 and 1801) were used, and 3/23 (all showing a mutated p53 gene) presented specific nuclear staining. In contrast to other reported data we could not detect any activating RAS gene mutation in our series of human skin cancers.