Frequent allelic imbalance at chromosome 13q in gastric cancer in Korea

Abstract

Background: Gastric cancer is one of the most frequent cancers in the world. The genetic mechanisms that result in the development of gastric neoplasia are poorly understood. Several studies have suggested that intestinal type and diffuse carcinomas may have different genetic lesions. H. pylori has been implicated as a co-factor in gastric carcinoma, but only a small number of individuals infected by H. pylori develops this cancer. Specific types of host genetic makeup may in part explain this outcome. The availability of highly polymorphic microsatellite markers throughout the genome can accelerate the search for new genes involved in cancer development. A high percentage of gastric cancers display allelic imbalance (AI) at various loci, characterized both by replicator errors (RER) and loss of heterozignsity (LOH). Aims: To identify genetic loci frequently altered in gastric carcinoma, by using allelic imbalance analysis in intestinal and diffuse gastric carcinomas. Methods: Biopsies from 15 gastric carcinomas from Korean patients were stained with the Genta stain, evaluated and graded for the presence of H. pylori and carcinoma. Genomic DNA was extracted from paraffin embedded tissues. End-labeled microsatellite markers D1S191, D2S123, D13S170 and TP53 were used to amplify tumor and non-neoplastic DNA. PeR products were separated in 6% denaturing polyacrylamide gels. Microsatellite instability (MI) was defined as a band shift in either of the two alleles in two or more markers. LOH was determined by a loss or decrease in intensity of a band present in the tumor, relative to the same band in the normal allele. Results: Eleven tumors were of intestinal type and four were diffuse carcinomas. Microsatellite instability was found less frequently in non-signet ring cell diffuse carcinomas. Six out of fifteen tumors (40%) displayed MI at 2 or more loci. D13S170 was the marker with more frequent MI 9/15 tumors (60%). In addition, there was frequent loss of heterozigosity (LOH) at the D 13S 170 locus in carcinoma tissues. Conclusions: The microsatellite marker D13S170 is very sensitive to detect allelic instability in gastric carcinomas in a population in Korea. This marker revealed a high level of LOH in this region of the genome (13q22-q31) suggesting that a tumor suppressor gene located in this region may be involved in gastric carcinogenesis.