Quantitative evaluation of genomic instability as a possible predictor for development of hepatocellular carcinoma: Comparison of loss of heterozygosity and replication error
Quantitative evaluation of genomic instability as a possible predictor for development of hepatocellular carcinoma: Comparison of loss of heterozygosity and replication error
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DOI：
10.1053/jhep.2000.7298
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发表时间：
2000-06-01
期刊：
影响因子：
13.5
通讯作者：
Asakura, H
中科院分区：
文献类型：
--
作者：
Kawai, H;Suda, T;Asakura, H
杂合性丢失（洛）和复制错误（RER）被认为是基因组不稳定性的表型。为了揭示基因组不稳定性在肝癌发生中的作用，我们同时检测了15例肝细胞癌（HCC）及其癌旁肝组织（SL）中洛和RER的频率，和13例慢性病毒性肝炎无癌肝组织（NC），采用18个分布于全基因组的微卫星标记参照相应供体的外周血白细胞（PBL）。洛在肝癌中的发生率显著高于SL和NC（分别为P = 0.005和P = 0.0003），并在特定的微卫星位点D1S204、D2S123、D8S1106、D9S266、D16S748和D19S601上优先观察到。尽管肝癌患者RER的患病率也显著高于NC（P = 0.03），但在大多数情况下，在非常低的频率和随机位点检测到错误。洛缺失和粗面内质网缺失在SL中的发生率均高于NC。B型肝炎病毒（HBV）感染者的洛缺失率高于丙型肝炎病毒（HCV）感染者，尤其是肝癌（HCC）（P = 0.03）。当参考SL而不是PBL时，HCC中的洛杂合性缺失和粗面缺失的患病率显着降低（分别为P = 0.02和P = 0.03）。这些结果表明：洛缺失与多步肝癌发生密切相关，尤其是在HBV感染的情况下，而粗面内质网缺失与多步肝癌发生的关系不大。参考外周血淋巴细胞定量评估洛性缺失的频率可能是慢性肝病中HCC发生的一个有用的预测因素。
Both loss of heterozygosity (LOH) and replication error (RER) are considered to be phenotypes of genomic instability To unveil the role of the genomic instability in hepatocarcinogenesis, frequencies of LOH and RER were simultaneously determined in 15 hepatocellular carcinomas (HCCs), surrounding nontumorous liver tissues (SL), and 13 liver tissues with chronic viral hepatitis void of cancer (NC) by referencing peripheral blood leukocytes (PBLs) from the corresponding donor using 18 microsatellite markers spread throughout the genome. LOH was significantly frequent in HCC compared with that in SL or NC (P = .005, P = .0003, respectively) and observed preferentially at particular microsatellite loci, D1S204, D2S123, D8S1106, D9S266, D16S748, and D19S601. Although the higher prevalence of RER was also significant in HCC compared with that in NC (P = .03), in most cases the errors were detected at very low frequencies and random loci. Both LOH and RER tended to appear more prevalently in SL than in NC. The occurrence rate of LOH was higher in the tissues associated with hepatitis B virus (HBV) than with hepatitis C virus (HCV) infection especially in HCC (P = .03). When referencing SL instead of PBLs, the prevalence of LOH and RER in HCC significantly decreased (P = .02 and P = .03, respectively). These results suggest that: LOH is closely associated with multistep hepatocarcinogenesis especially under HBV infection, but RER is imperceptibly associated. The quantitative evaluation of the frequency of LOH by referencing PBLs may be a useful predictor for HCC development in chronic liver diseases.