Mutations within the hepatitis B virus genome among chronic hepatitis B patients with hepatocellular carcinoma
Mutations within the hepatitis B virus genome among chronic hepatitis B patients with hepatocellular carcinoma
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DOI：
10.1002/jmv.10458
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发表时间：
2003-09-01
影响因子：
12.7
通讯作者：
Kidd-Ljunggren, K
中科院分区：
文献类型：
--
作者：
Bläckberg, J;Kidd-Ljunggren, K
慢性B型肝炎感染是肝细胞癌（HCC）的主要原因。癌变的发病机制尚未完全清楚。病毒蛋白如X蛋白和截短的中间S蛋白被认为是反式激活因子。为了研究B型肝炎病毒（HBV）基因组相关部分的突变是否与HCC的发生相关，研究了16株慢性HBV携带者HCC的HBV基因组。血清样本进行PCR和HBV DNA测序。代表基因型A-D。序列分析显示，与慢性HBV感染的对照组21%（CI 95%，3-39%）相比，HCC患者中携带HBV突变体的比例特别高，为50%（CI 95%，25-75%），这些突变体在前S2区的N-末端一半缺失或插入，或在前S2的起始密码子中具有点突变。在核心启动子区的1762（A，T）和/或1764（G -> A）位置也有很高比例（69%）的突变，但核心启动子突变的比例与无HCC的HBV携带者对照组（68%）没有差异。涉及免疫原性区域缺失的pre-S2变体可能具有生存优势，因为它们大多存在于长期HBV感染中。在编码X蛋白的区域内没有发现其他突变。(C)2003 Wiley-Liss，Inc.
Chronic hepatitis B infection is a major cause of hepatocellular cancer (HCC). The pathogenesis of the carcinogenesis is not fully understood. Viral proteins such as the X protein and the truncated middle S protein have been implicated to be transactivators. In order to investigate whether any mutations within relevant parts of the hepatitis B virus (HBV) genome could be associated with the development of HCC, the genomes of 16 HBV strains from chronic HBV carriers with HCC were studied. Serum samples were subjected to PCR and the HBV DNA sequenced subsequently. Genotypes A-D were represented. The sequence analysis showed that an especially high proportion, 50% (CI 95%, 25-75%), of the patients with HCC carried HBV mutants with deletions or insertions in the N-terminal half of the pre-S2 region or had a point mutation in the start codon of pre-S2 compared with controls with chronic HBV infection, 21% (CI 95%, 3-39%). A high proportion (69%) also had mutations at position 1762 (A, T) and/or 1764 (G --> A) in the core promoter region, but the proportion of core promoter mutations was no different from what was found in a control group of HBV carriers without HCC (68%). The pre-S2 variants, which involve deletions of immunogenic regions, may have a survival advantage as they are mostly found in long-standing HBV infection. There were no other mutations found frequently within the region coding for the X protein. (C) 2003 Wiley-Liss, Inc.