P16UV mutations in human skin epithelial tumors

The p16 gene expresses two alternative transcripts (p16 alpha and p16 beta) involved in tumor suppression via the retinoblastoma (Rb) or p53 pathways. Disruption of these pathways can occur through inactivation of p16 or p53, or activating mutations of cyclin dependant kinase 4 gene (Cdk4). We searc hed for p16, Cdk4 and p53 gene mutations in 20 squamous cell carcinomas (SS Cs), 1 actinic keratosis (AK), and 28 basal cell carcinomas (BCCs), using P CR-SSCP. A deletion and methylation analysis of p16 was also performed. Six different mutations (12%) were detected in exon 2 of p16 (common to p16 al pha and p16 beta), in five out of 21 squamous lesions (24%) (one AK and fou r SCCs) and one out of 28 BCCs (3.5%), These included four (66%) ultraviole t (UV)-type mutations (two tandems CC : GC to TT : AA transitions and two C : G to T : A transitions at dipyrimidic site) and two transversions, P53 m utations were present in 18 samples (37%), mostly of UV type. Of these, onl y two (one BCC and one AK) harboured simultaneously mutations of p16, but w ith no consequence on p16 beta transcript. Our data demonstrate for the fir st time the presence of p16 UV induced mutations in non melanoma skin cance r, particularly in the most aggressive SCC type, and support that p16 and p 53 are involved in two independent pathways in skin carcinogenesis.