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Allele loss in human gastric carcinomas - relation to tumor progression and differentiation
Abstract:
The sequence of genetic changes associated with the development of gastric carcinoma remains unclarified despite the numerous genetic and chromosomal abnormalities that have been implicated so far in this process. We investigated the frequency and pattern of allele loss in 68 gastric carcinomas, with the aim of identifying genetic changes putatively involved in the histologic differentiation and/or progression of gastric cancer. Allele loss was investigated using 12 RFLP and 11 microsatellite markers localized at 22 different loci from 9 autosomal chromosomes. Allele loss in at least one chromosome arm was detected in 41 out of the 68 cases (60%). A high ratio of allele loss was significantly associated with the masculine gender and aneuploidy. The chromosome arms most commonly affected were 3p (57%), 17p (44%), and 6q (32%). Alterations 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 chromosomes are early events in gastric tumorigenesis. Genetic changes at 5q and 17p loci were only observed in gastric carcinomas of the intestinal and atypical (unclassified) types, thereby indicating a possible role of genes located at these chromosome arms in the differentiation of gastric carcinoma.
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