GENETIC INSTABILITY IN THE 9Q22.3 REGION IS A LATE EVENT IN THE DEVELOPMENT OF SQUAMOUS-CELL CARCINOMA

Squamous cell carcinoma (SCC) of the skin represents a group of neopla sms which is associated with exposure to UV light. Recently, we obtain ed data suggesting that invasive skin cancer and its precursors derive from one original neoplastic clone. Here, the analysis were extended by loss of heterozygosity (LOH) analysis in the chromosome 9q22.3 regi on. A total of 85 samples, taken from twenty-two sections of sun-expos ed sites, corresponding to normal epidermis, morphological normal cell s with positive immune-staining for the p53 protein (p53 patches), dys plasias, cancer in situ (CIS) and squamous cell carcinomas (SCC) of th e skin were analysed. Overall, about 70% of p53 patches had mutations in the p53 gene but not LOH in the p53 gene or 9q22.3 region. Approxim ately 70% of the dysplasias showed p53 mutations of which about 40% ha d LOH in the p53 region but not in the 9q22.3 region. In contrast, abo ut 65% of SCC and CIS displayed LOH in the 9q22.3 region, as well as f requent (80%) mutations and/or LOH in the p53 gene. These findings str ongly suggest that alterations in the p53 gene is an early event in th e progression towards SCC, whereas malignant development involves LOH and alterations in at least one (or several) tumor suppressor genes lo cated in chromosome 9q22.3.