The molecular mechanism of gastric tumourigenesis has not yet been clarified, although investigators have postulated that differentiated adenocarcinoma may arise from pre-existing adcnoma, similarly to the colorectal adenoma-carcinoma sequence. An allelotype analysis has been performed to identify chromosomal regions which are frequently deleted in gastric tumours and to examine the significance of the adenoma-carcinoma sequence in gastric tumourigenesis. Forty-five gastric tumours, 20 adenomas, and 25 differentiatcd adenocarcinomas were examined for loss of heterozygosity (LOH) using 39 microsatellite markers covering each non-acrocentric chromosome arm. Frequent LOH in the adenocarcinomas was observed on chromosomes 2q (33 per cen), 4p (33 per centt), 5q (50 per cent), 6p (33 pre cent), 7q (43 per cent), 11q (36 per cent), 14q (38 per cent), 17p (45 per cent), 18q (36 per cent), and 21q (40 per cent). In contrast, the incidence of LOH in adenomas did not exceed 10 per cent at any of
the loci examined. In addition to the p53 gene on 17p and the DCC gene on 18q, which are known to be frequently deleted in differentiated adenocarcinomas of the stomach, other unknown tumour suppressor genes on the above-mentioned chromosomes may also be inactivated. these observations suggest that the adenoma-carcinoma sequence is not a major pathway in gastric tumourigenesis.
In a recent allelotypic analysis of differentiated adcnocarcinoma of the stomach, loss of heterozygosity (LOH) was found frequently on chromosomes 2q, 4p, 5q, 6p, 7q, 11q, 14q, 17p, 18q, and 21q, To clarify the sequence of these chromosomal losses during gastric carclnogenctss, microsatellite analysis of the chromosome arms deacribcd adove was performed in 25 early and 29 advanced differentiated adenocarcinomas of the stomach. LOH on chese chromosome arms fell within a range of 20-50 per cent. On 4p, 7q, 14q, 17p, and 21q, LOH was detected st a similar frequency in both early and advanced carcinomas, while LOH on 2q, 5q, 6p, 11q, and 18q was observed more than twice as frequently in advanced than in carly lesions. Mean fractional allelic losses (FALs) were U・221 in early and U・413 in advanced carcinomas, representing a significant difference P<0・05). These results suggest that LOH on 4p, 7q, 14q, 17p and 21q is a relatively early event, while LOH on 2q, 5q, 6p, 11q, and 18qtypically accumulates during the progression of gastric carcinogenesis. Less