LOSS OF P53 GENE MUTATION AFTER IRRADIATION IS ASSOCIATED WITH INCREASED AGGRESSIVENESS IN RECURRING HEAD AND NECK-CANCER

The p53 gene plays a pivotal role in the control of a checkpoint durin g G(1) and in the apoptotic program, It has been postulated that alter ations of p53 may influence radiosensitivity and prognosis in several malignancies, We studied the p53 gene status of 35 consecutive head an d neck cancer patients who failed primary radiotherapy (RT) in preirra diated and postirradiated tumor samples using DNA single-strand confor mational polymorphism analysis, Sixteen of 35 (46%) preirradiated samp les presented with band shifts suggestive of point mutations in one or two exons, Eleven of these tumors (69%) showed the same shift even in the postirradiated samples. Exons 5 and 8 were prevalently affected i n this group, Five tumors (31%) lost the mutation following RT, The mi ssed mutations clustered in exon 7, All mutations were confirmed by se quencing, Actuarial analysis demonstrated increased survival in patien ts with tumors bearing a p53 gene mutation in both preirradiated and p ostirradiated samples (P = 0.05 and P = 0.01, respectively), We also f ound that loss of p53 gene mutation in postirradiated cancers is assoc iated with a significantly shorter disease-free interval (P < 0.02) an d a worse prognosis (P < 0.05), A possible explanation in such cases i s clonal selection by RT of more aggressive and radioresistant cell su bpopulations, which are wild-type for the p53 gene, Taken together, ou r data suggest that not only p53 gene status but also the pattern of m utations could modulate the response of tumor cell to RT in vivo.