MICROSATELLITE ALTERATIONS IN ADENOMA AND DIFFERENTIATED ADENOCARCINOMA OF THE STOMACH

In order to elucidate the significance of the adenoma-carcinoma sequen ce in gastric carcinogenesis from a genetic point of view, we examined microsatellite alterations (replication error and loss of heterozygos ity) on chromosomes 2p (D2S123), 3p (D3S1317), 5q (D5S409), 9p (IFNA), and 13q (D13S153) as well as p53 gene mutations in 13 adenomas and 23 differentiated adenocarcinomas including 8 early carcinomas of the st omach. Replication error was detected in only one of the adenomas (8%, 1/13) at the D5S409 locus and in none at the other loci, and loss of heterozygosity was also an infrequent event found in one adenoma (14%, 1/7 informative cases) at D5S409 and in none at the other loci. A p53 gene mutation was detected in one (8%, 1/13) of the adenomas. Thus, m icrosatellite alterations and p53 gene mutations are rare events in ad enomas. In differentiated adenocarcinomas, replication error was detec ted in 4 (17%, 4/23) at single or multiple loci, and loss of heterozyg osity was observed frequently at D3S1317 (25%, 3/12), D5S409 (67%, 6/9 ), and IFNA (26%, 5/19). Mutations in the p53 gene were detected in 9 (39%, 9/23) of the differentiated adenocarcinomas. Microsatellite alte rations on several chromosomes and mutations in the p53 gene were freq uent in differentiated adenocarcinomas, even those at an early stage. These results suggest that the adenoma-carcinoma sequence is relativel y rare in gastric carcinogenesis, and that the majority of differentia ted adenocarcinomas of the stomach may develop through a de novo pathw ay.