Relationship Between Genetic Instability Of Chromosome 17q21 And Clinical Pathological Behaviors In Chinese With Gastric Cancer

Background Gastric cancer is one of the most common cancers in our country. Growing evidence suggest that accumulation of multiple alteration, such as activation of protooncogenes and inactivation of tumor suppressor genes, is responsible for the development and progression of grastric cancer, and inactivation of tumor suppressor genes is more important. Genetic instability of oncogene such as microsatellite instability (MSI), loss of heterozygosity (LOH) is probably associated with the gene mutations in responsible for tumorigenesis, which play important role in tumor clinical pathology. Thibodeau et al found the alterations in microsatellite sequences at high frequency in tumors of the hereditary non-polyposis colon carcinoma (HNPCC) syndrome. Jackson & Loeb found that the alterations of microsatellite length are believed to result from strand slippage intermediates that arise during replication. In non-tumor cells, as well as in yeast and Escherichia coli, these slippage intermediates are repaired by the mismatch repair system. However, in tumor cells the mismatch repair system can't repair, thus defective mismatch repair is believed to be responsible for MSI. MSI is regarded as a marker of a high risk for cancer, and that is indeed an efficient approach for detecting defective DNA mismatch repair, because the mismatch repair genes have no marked hot-spots for mutations. According to Knudson's two-hit hypothesis of TSG (tumor suppressor gene) inactivation, the common chromosomal region of loss of heterozygosity is a potential site harbouring TSG, thus LOH is regarded as a valuable molecular genetic marker to find TSG.Since MSI has been observed in many cases of sporadic cancers, numerous studies on MSI have been done in a wide variety of human malignancies.However, the studies of MSI and LOH of gastric cancer are concentrated on genetic instability of P53, P16 and FHIT, but the studies of gene nm23 and BRCA1 are very few. Steeg et al. found that gene nm23 has the relationship with tumor metastasis, and it was a metastasis-suppressor gene, because its production nm23H₁ protein/NDPK could specifically suppress tumor metastasis, The nm23H₁ gene, an important anti-oncogene located at 17 th chromosome (17q21), was carried a lot of research which mostly concentrated on immunohistochemistry research of nm23H₁ protein/NDPK expression. But there were few researches that related to heredity mutation of gene nm23H₁. The association of the BRCA1 gene with susceptibility to breast and ovarian cancer has been strongly supported. After that, Elena et al. found that BRCA1 might play an important role in the development of colon cancer, but there were very few studies that had done to research the relationship of gastric cancer and MSI, LOH of gene BRCA1. The present study was undertaken to investigate MSI and LOH of locus D17S396, D17S579 and D17S855, which locate in the chromosomal region 17q21 of Chinese with gastric cancer, and their influence on the expression of nm23H₁ and BRCA1 genes of gastric cancer, which might discover the mechanism of genetic instability of gastric cancer. In this study, we analysed a set of 48 gastric tumors for abnormalities in DNA, protein and clinical pathological levels to clarify the participation of nm23H₁ and BRCA1 in gastric cancer. Objective To investigate MSI and LOH of locus D17S396, D17S579 and D17S855, and their effect on the expression of nm23H₁ and BRCA1 of gastric cancer, which would provide experimental basis for clinical treatment and prognosis analysis of gastric cancer.Methods (1) The technology of extraction DNA from paraffin-embedded materials. (2) Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and displaying band by ordinary silver stain. (3) Expression of nm23H₁ and BRCA1 was detected by Envision immuno-histochemistry. (4) Leica-Qwin computer imagingtechniques. (5) SPSS statistic software analyzed the experimental results. Results (1) In the forty cases of gastric cancer, the frequency of MSI, LOH and nm23H₁ protein were 20.00%, 17.50% and...