Tumor Susceptibility and Digestic System Tumor Susceptible Gene / 基础医学与临床

ABSTRACT

The carcinogenesis and development is a progress of multi-gene alterations in the human gastric cancer (HGC)．In order to determine the relation between the aberration of these genes and gastric cancer，we chose c-met (7q31)、hMLH1 (3p21)、E-cadherin (16q22.1) and HLA loci DQA1、DR2、DR3、DR4、DR7、DR9 and detected their changes in 32 tumor specimens of intestinal type HGC and 4 cell lines of gastric cancer by performing analysis of SSP/PCR、PCR/SSCP and MSI technigues．Our data show that none point mutation was detected in c-met gene．We examined two microsatellites loci D3S1298 and D3S1561 in hMLH1 gene and detected that 6 cases retain MSI (Microsatellite Instability) and 2 cases of LOH (Loss of Heterozygosity) at D3S1298 and 2 cases of MSI at D3S1561．We also examined E-cadherin gene at two microsatellites loci D16S3083 and D16S3095 close to the gene and detected that 5 cases retain MSI and 1 case of LOH at D16S3083 and no change at D16S3095．The point mutation incidence of HLA-DR4 loci is 9/20 (45%)，higher than the other loci in HLA-Ⅱ．High frequent deletion，expression deregulation and methylation of mts1/p16 gene were detected in cell lines and solid tumors from human gastric cancer patients． 　　Our data showed that the point mutation of c-met gene is not the main pattern of alteration in intestinal type HGC that is consistent with the previous results．E-cadherin and hMLH1 are related to intestinal type HGC but whether they are susceptibility gene still need further study．The point mutation of the HLA-Ⅱ loci DR4 is closely related to intestinal type HGC．Methylation of mts1/p16 gene 5 CpG island might be plays an important role in the carcinogenesis in HGC．