MUTATIONS OF THE K-RAS AND P53 GENES IN GASTRIC ADENOCARCINOMAS FROM A HIGH-INCIDENCE REGION AROUND FLORENCE, ITALY

K-ras and p53 gene mutations in intestinal-type gastric carcinomas fro m a high-incidence area around Florence, Italy, were studied by single strand conformation polymorphism and DNA sequencing analysis. Single- strand conformation polymorphism analysis of K-ras indicated aberrant bands in 13 of 34 cases. Sequencing revealed point mutations in 7 (inc luding two at a previously unreported site in codon 11), a significant ly higher frequency than reported in countries other than Japan. No K- ras mutations were identified in stage III tumors. Single-strand confo rmation polymorphisms in p53 exons 5-8 occurred in 30 of 34 cases, wit h mutations identifiable by direct sequencing in 65% of the eases. Of these, 91% were base substitutions, a value similar to that usually re ported, but the percentage of G:C to A:T transitions (90% in this stud y, 89% in all published European cases combined) differed significantl y from that in Oriental cases (48%). The percentage of A:T to G:C tran sitions was greater in Oriental (22%) than European cases (2%), as was also true for transversions (30% in Oriental tumors, 9% in European t umors). The frequency of mutations at CpG sites (14%) varied significa ntly from the 67% in cases from a neighboring region in Italy. Helicob acter pylori infection was established in 19 cases and was somewhat mo re common in cases lacking a p53 mutation.