肝细胞癌8号染色体微卫星变异的研究(英文)

目的探讨肝细胞癌(HCC)8号染色体微卫星变异的特点及其与临床病理的相关性。方法采用 MegaBACE 500型自动化 DNA 分析系统,对56例 HCC 中8号染色体上10个微卫星的杂合性缺失(LOH)、微卫旱不稳定性(MSI)和等位基因失衡(AI)3种变异特征进行检测。结果 56例 HCC 在8号染色体上10个基因座发生 LOH 的总频率为66.1%(37/56),MSI 的频率为12.5%(7/56),AI 的频率为19.6%(11/56)。LOH 以 D8S261最高为53.5%(23/43),其次为 D8S1721(52.5%)和 D8S1771(52.5%)。D8S277基因座,血清HBsAg 阳性患者的 LOH 频率显著高于 HBsAg 阴性者(P<0.01),D8S261、D8S298和 D8S1733基因座,血清 HBsAg 阴性患者的 LOH频率显著高于 HBsAg 阳性者(P<0.01);D8S298和 D8S1771基因座.肿瘤直径>3cm 的 LOH 率明显高于≤3cm 组(P<0.05和 P<0.01);在 D8S1721基因座,无包膜或包膜不完整的肿瘤的 LOH 显著高于包膜完整的肿瘤(P<0.01);D8S298和 D8S1771基因座,肝内转移者的 LOH 明显高于无肝内转移者(P<0.05)。MSI 和 AI 与 HCC 临床病理学特点无明显相关性。结论 HCC 的8号染色体上存在广泛的微卫星变异,其中以代表肿瘤抑制基因路径的 LOH 方式在 HCC 的发生和发展过程中起重要作用,代表错配修复基因路径的 MSI 的作用次之。特定基因座的 LOH 与临床和病理学参数有一定的相关性。

Microsatellite Alterations on Chromosome 8 of Hepatocellular Carcinoma

Objective:To study the features of microsatellite alterations on chromosome 8 and their asso- ciation with clinicopathological characteristics of hepatocellular carcinoma(HCC).Methods:Ten highly- polymorphic microsatellite markers on chromosome 8 were selected to be detected for loss of heterozygosity (LOH),microsateIlite instability(MSI)and allelic imbalance(AI)in 56 HCC using MegaBACE 500 auto- matic DNA analysis system.Results:LOH was found in 37 of 56 HCC(66.1%)on at least 1 locus,and the top three loci were D8S261(53.5%),D8S1721(52.5%)and D8S1771(52.5%).LOH frequency on D8S277 was significantly higher in cases positive for serum HBsAg than in those negative for HBsAg(P<0.01). Similarly,LOH on D8S261,D8S298 and D8S1733 occurred more frequently in patients with negative HB- sAg than those with positive HBsAg(P<0.01).LOH on D8S298 and D8S1771 was more frequent in those tumors larger than 3 cm in size(P<0.05 or P<0.01).LOH frequencies of D8S1721 were significantly higher in the patients with absent or not intact tumor capsule than in those with intact tumor capsule(P<0.05). LOH on D8S298 and D8S1771 was more frequently detected in tumors with intrahepatic metastasis than in those without intrahepatic metastasis(P<0.01).MSI was found in 12.5%(7/56)cases,and AI was found in 19.6%(11/56),no correlation was found between MSI and AI and clinicopathological character- istics of HCC.Conclusion:Frequent microsatellite alterations on chromosome 8 existed in HCC.LOH, which represents tumor suppressor gene pathway,plays a more important role in hepatocarcinogenesis; MSI representing mismatch repair gene pathway ranks next.LOH at a particula locus is associated with the clinicopathological parameters of human HCC.