原发性肝癌染色体8p、16q遗传变异的研究

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。

Study on Genetic Alterations in Chromosomes 8p and 16q in Primary Hepatocellular Carcinoma

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.