目的:分析人肝癌(HCC)组织中染色体8p、16q部分基因及染色体片段的遗传变异及与临床病理关系,初步筛选HCC相关的抑癌基因。方法:应用聚合酶链反应-变性聚丙烯酰胺凝胶-银染法分析45例HCC组织标本中染色体8p和16q的杂合性丢失(LOH)及微卫星不稳定性(MSI)。结果:发生LOH的总频率为68.89%(31/45),其中D16S511位点的发生LOH率最高为53.33%(24/45),其次是D8S261(39.02%,16/41)和D8S499(34.88%,15/43)。MSI出现的总频率为11.11%(5/45),出现在三个微卫星位点(D8S261、D8S499及D16S511)上。结论:染色体16q23、8p22-21.3及8p12区域的LOH发生频率高,其可能存在与HCC发生发展相关的新的抑癌基因,特定位点的遗传变异可能与HBV感染、临床病理恶性程度等预后因素相关。
Objective:To investigate the genetical alterations on chromosomes 8p and 16q in primary hepatocellular carcinoma(HCC),investigate the relationship between the gentical alterations and clinicopathologic features and try to screened some HCC-related tumor suppressor genes.Methods:Loss of heterozygosity(LOH) and microsatellite instability(MSI) on chromosome 8p and 16q in samples from thirty-five patients with HCC were examined by PCR-denaturing PAGE-silver staining.Results:The overall LOH frequency was 68.89%(31/45) at least one locus of 8 loci on the chromosomes.The frequency of Loci were 53.33%(31/45),39.02%(16/41)and34.88%(15/43)for D16S511,D8S261 and D8S499,respectively.The frequency of MSI was 11.11%(5/45) and the MSI was distributed on the three microsatellite markers(D16S511、D8S261 and D8S499).Conclusion:There may be a new putative tumor suppressor gene related to the occurrence and development on specific chromosome region 16q23,8p22-21.3 or 8p12 with high-frequent LOH.The genetic alterations on some specific loci were associated with prognosis factors as the positive HBsAg,differentiated degrees of HCC.