p53 gene mutations in human epithelial skin cancers

Area of Science:

• Oncology
• Molecular Biology
• Dermatology

Background:

• Skin cancers, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and Bowen's disease (BwD), are common malignancies.
• The p53 tumor suppressor gene and RAS proto-oncogene are frequently implicated in cancer development.

Purpose of the Study:

• To investigate the presence and patterns of p53 and RAS gene mutations in epithelial skin cancers.
• To explore the potential role of UV radiation in the genesis of these mutations.
• To correlate molecular findings with p53 protein accumulation.

Main Methods:

• Analysis of 38 epithelial skin cancers (19 BCCs, 13 SCCs, 6 BwDs) using polymerase chain reaction (PCR) and single-stranded conformation polymorphism (SSCP).
• Sequencing of identified mutations to characterize their nature (substitutions, deletions).
• Immunocytochemical staining for p53 protein accumulation in a subset of tumors using three anti-p53 antibodies.

Main Results:

• Mutations in the p53 gene were found in 48% of BCCs and 15% of SCCs; none were detected in BwDs.
• Seven of eleven characterized p53 mutations involved CC dimers, with a mutational pattern suggesting UV light as a causative agent.
• All mutated tumors were located on sun-exposed skin sites.
• p53 protein accumulation was observed in 3 out of 23 tumors, all of which had a mutated p53 gene.
• No activating RAS gene mutations were detected in any of the analyzed skin cancers.

Conclusions:

• The p53 gene is frequently mutated in basal cell carcinomas and, to a lesser extent, in squamous cell carcinomas.
• The specific mutation patterns strongly implicate UV radiation in the pathogenesis of p53 mutations in skin cancers.
• RAS gene mutations do not appear to play a significant role in the development of these human skin cancers.