摘要
目的:探讨肝细胞癌(HCC)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10个微卫星的杂合性缺失(loss of heterozygosity,LOH)、微卫星不稳定性(microsatillite instability,MSI)和等位基因失衡(allelic imbalance,AI)3种变异特征进行检测。结果:56例HCC中,76.8％(43/56)出现LOH,其中以RIZ[76.7％(23/30)]和D4S426[61.0％(25/41)]最高;EdmondsonⅢ、Ⅳ级肿瘤D4S426的LOH明显高于Edmondson Ⅰ、Ⅱ级[76.7％(23/30)vs 18.2％(2/11),P<0.01];血清HBsAg阳性患者中D8S277的LOH发生率明显高于阴性患者[72.7％(16/22)vs12.5％(2/16),P<0.01]。MSI的发生率为32.1％(18/56),其中以BAT-26[24.3％(9/37)]和D13S170[21.9％(7/32)]最高,HBsAg阳性者MSI发生频率显著高于HBsAg阴性者(P<0.01)。AI的发生率为35.7％(20/56)。结论:HCC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。
Objective: To study the features of microsatellite alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC). Methods: Ten high-polymorphic microsateliite markers were detected for loss of heterozygosity (LOH), microsateliite instability (MSI) and allelic imbalance (AI) in 56 HCC using MegaBACE 500 automatic DNA analysis system. Results: LOH was found in 43 of 56 HCC (76. 8%) on at least 1 locus, the top 2 loci were RIZ (76. 7%) and D4S426 (61. 0%). LOH on D4S426 was more frequent in Edmondson grade Ⅲ and Ⅳ tumors than in grade I and 11 tumors (P<0. 01). LOH on D8S277 was more frequently found in HBsAg-positive carriers than in HBsAg-negative group (76. 7% vs 18. 2%, P<0. 01). MSI was found in 32. 1% cases, the top 2 loci were BAT-26 (24. 3%) and D13S170 (21. 9%) MSI rates were significantly higher in cases with positive HBsAg than in those with negative HBsAg(P<0. 01). AI was found in 35. 7% of all cases examined. Conclusion: Frequent microsateliite alterations exist in HCC. LOH, which represents tumor suppressor gene pathway, plays a more important role in hepatocarcinogenesis; MSI representing mismatch repair gene pathway ranks next.
出处
《第二军医大学学报》
CAS
CSCD
北大核心
2003年第4期364-368,共5页
Academic Journal of Second Military Medical University
基金
上海市卫生系统百名跨世纪优秀学科带头人培养计划(98BR007).
关键词
肝细胞癌
微卫星变异
研究
杂合性缺失
自动化DNA分析系统
carcinoma, hepatocellular i loss of heterozygosity
microsatellite instability
allelic imbalance
