ALLELE LOSS IN HUMAN GASTRIC CARCINOMAS - RELATION TO TUMOR PROGRESSION AND DIFFERENTIATION

The sequence of genetic changes associated with the development of gas tric carcinoma remains unclarified despite the numerous genetic and ch romosomal abnormalities that have been implicated so far in this proce ss. We investigated the frequency and pattern of allele loss in 68 gas tric carcinomas, with the aim of identifying genetic changes putativel y involved in the histologic differentiation and/or progression of gas tric cancer. Allele loss was investigated using 12 RFLP and 11 microsa tellite markers localized at 22 different loci from 9 autosomal chromo somes. Allele loss in at least one chromosome arm was detected in 41 o ut of the 68 cases (60%). A high ratio of allele loss was significantl y associated with the masculine gender and aneuploidy. The chromosome arms most commonly affected were 3p (57%), 17p (44%), and 6q (32%). Al terations at these chromosome arms were also frequently found (greater than or equal to 40%) in the six less advanced gastric carcinomas of the series, thus suggesting that genetic changes involving these chrom osomes are early events in gastric tumorigenesis. Genetic changes at 5 q and 17p loci were only observed in gastric carcinomas of the intesti nal and atypical (unclassified) types, thereby indicating a possible r ole of genes located at these chromosome arms in the differentiation o f gastric carcinoma.