P53 MUTATIONS ARE COMMON AND EARLY EVENTS THAT PRECEDE TUMOR INVASIONIN SQUAMOUS-CELL NEOPLASIA OF THE SKIN

Mutations of the p53 gene are the most common genetic abnormality desc ribed in human cancer; p53 mutations have recently been reported in mo re than half of the cases of squamous cell carcinomas of the skin. We have previously reported positive p53 immunostaining in Bowen's diseas e and actinic keratosis. To determine if this abnormal immunostaining reflects p53 mutation or alternative pathways of p53 protein inactivat ion we have performed direct sequencing of p53 in 20 further cases of Bowen's disease. We found eight mutations in 20 cases, seven of which would produce alterations in the p53 protein product. Our results sugg est that p53 mutation is an early event in malignant conversion, frequ ently preceding invasion in squamous cell neoplasia of the skin. The t ype and site of the observed mutations reflect known mutational hotspo ts and support the role of ultraviolet radiation in the pathogenesis o f these tumors.