Background & objective: Previous studies have showed that chromosome 7q occurs a high frequency of loss of heterozygosity (LOH) in primary gastric carcinoma; D7S486 located in 7q31 is a locus with the highest frequency of LOH on 7q, which is significantly related to lymph node metastasis of tumor. Gastric carcinoma-related tumor suppressor genes (TSGs) might locate near the locus. In order to seek gastric carcinoma-related TSGs in a further narrow region, LOH of microsatellite marker loci on chromosome 7q31 was examined in primary gastric carcinoma to determine the minimal commonly deleted regions, and the possible roles of these regional deletions in gastric carcinoma pathogenesis were analyzed in this study.
Methods: Twelve microsatellite markers centering D7S486 locus on 7q31 region, with an average genetic distance of about 0.5 centimorgan (cM), were selected. DNAs were extracted from 78 specimens of gastric carcinoma and corresponding normal gastric mucosa tissues, amplified through multi-polymerase chain reaction (multi-PCR), and separated by electrophoresis. LOH of microsatellite marker loci was analyzed with GeneScan and Genotyper software to determine the minimal commonly deleted regions on 7q31. The possible roles of these regional deletions in gastric carcinoma pathogenesis were analyzed with consideration of clinicopathologic parameters.
Results: LOH of all 12 selected microsatellite marker loci was detected in primary gastric carcinoma, with the total frequency of 41.7% (40/72). The most frequent LOH was D7S486 locus (located in 7q31.2), with the frequency of 30.4% (17/56); the second was D7S650 locus (located in 7q31.3), with the frequency of 21.1% (8/38). Two minimal commonly deleted regions, D7S2543-D7S486 and D7S480-D7S650 (each span about 90 kb), were detected on 7q31 in primary gastric carcinoma. The LOH frequency of D7S2543-D7S486 region was significantly related to clinical stage and lymph node metastasis (P = 0.01, P = 0.03); the LOH frequency of D7S480-D7S650 region was significantly related to clinical stage (P = 0.03), and LOH of this region occurred only in the patients with stage III/IV tumor, T3/T4 primary lesion, or lymph node metastasis.
Conclusions: There are 2 minimal commonly deleted regions on 7q31 in primary gastric crcinoma, D7S2543-D7S486 and D7S480-D7S650. There might be TSGs in these 2 regions closely related to the progression of gastric carcinoma.