P53 MUTATIONS IN NONMELANOMA SKIN-CANCER OF THE HEAD AND NECK - MOLECULAR EVIDENCE FOR FIELD CANCERIZATION

Multiple and distinct p53 mutations were detected by DNA sequence anal ysis in tumor and adjacent nonmalignant skin samples from eight patien ts with nomnelanoma skin cancer of the head and neck, providing unambi guous evidence for field cancerization. The mutations consisted of C-- >T transitions at dipyrimidine sequences (30% of all single base subst itutions), T-->C transitions (47%), and G-->T transversions (12%), sug gesting that other carcinogens may act along with UV radiation in the development of nomnelanoma skin cancer. Patient interviews revealed th at, in addition to substantial exposure to solar UV radiation, most ha d a history of smoking and were exposed to carcinogens from industrial or agricultural sources. These data show that extensive molecular epi demiological investigations are necessary to elucidate risk factors as sociated with the disease in localities where patients often report su bstantial exposure to environmental carcinogens.