VARIATION OF P53 MUTATIONAL SPECTRA BETWEEN CARCINOMA OF THE UPPER AND LOWER RESPIRATORY-TRACT

Mutations of the p53 tumor suppressor gene are the most common genetic alterations associated with human cancer, Tumor-associated p53 mutati ons often show characteristic tissue-specific profiles which may infer environmentally induced mutational mechanisms. The p53 mutational fre quency and spectrum were determined for 95 carcinomas of the upper and lower respiratory tract (32 lung and 63 upper respiratory tract), Mut ations were identified at a frequency of 30% in upper respiratory trac t (URT) tumors and 31% in lung tumors. All 29 identified mutations wer e single-base substitutions, Comparison of the frequency of specific b ase substitutions between lung and URT showed a striking difference, T ransitions occurred at a frequency of 68% in URT, but only 30% in lung . Mutations involving G:C-->A:T transitions, which are commonly report ed in gastric and esophageal tumors, were the most frequently identifi ed alteration in URT (11/19). Mutations involving G:C-->T:A transversi ons, which were relatively common in lung tumors (3/10) and are repres entative of tobacco smoke-induced mutations were rare in URT tumors (1 /19). Interestingly, G:C-->A:T mutations at CpG sites, which are chara cteristic of endogenous processes, were observed frequently in URT tum ors (9/19) but only rarely in lung tumors (1/10), suggesting that both endogenous and exogenous factors are responsible for the observed dif ferences in mutational spectra between the upper and lower respiratory systems.