Frequent Microsatellite Instability and Loss of Heterozygosity in the Region Including BRCA1 (17q21) in Young Patients with Gastric Cancer

It is known that nearly 5% of gastric carcinomas arise under the age of 40. To elucidate genetic alterations in these patients, we performed studies using microsatellite assay in 27 gastric cancers under 35 years of age, composed of 5 well and 22 poorly differentiated adenocarcinomas. We detected replication errors (RERs) in 18 (67%) of 27 tumors, but no germline mutation in DNA mismatch repair genes (hMLH1 and hMSH2), except fory 3 somatic mutations in the hMLH1 gene. Loss of heterozygosity (LOH) at D17S855, located on chromosome 17q21 (BRCA1), was detected in 8 (40%) of 20 informative cases. In 12 (44%) of 27 cases, LOH on chromosome 17q12-21 including the BRCA1 was found in several neighboring markers in this region, while no mutation was found in the BRCA1 gene. Four (40%) of 10 scirrhous type gastric cancers exhibited wide allelic deletions on chromosome 17q12-21. These results overall suggest that young gastric cancer patients display highly frequent micro-satellite instability that might be due to defect of DNA repair system rather than hMLH1 and hMSH2. In addition, chromosome 17q12-21 including BRCA1 locus may contain a candidate for tumor suppressor gene, particularly in scirrhous type gastric cancers arising in young patients.