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Mutations of the core gene sequence of HCV from patients with hepatocellular carcinoma in China and Japan

中国和日本肝癌患者HCV核心基因序列突变

基本信息

批准号：
11695087
负责人：
ITO Susumu
金额：
$ 1.47万
依托单位：
University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

Firstly, we investigated the association between hepatocellular carcinoma(HCC)and the genomic characteristics of the hepatitis C virus(HCV)isolated from residents of the inshore region of the Yangtze River. That area of China has one of the highest incidences of HCC.Our data revealed that nucleotide substitutions are unevenly scattered along the HCV genome, with a cluster of missense mutations in the region encoding the second hydrophilic domain of the core protein, and that the number of these mutations in the clustering variable region(CVR)is significantly higher in isolates from HCC patients than in those from individuals with chronic hepatitis. Secondly, we determined the sequence divergence of the CVR in HCV isolates from cancerous and noncancerous liver tissues in Japanese patients with HCC.The number of nucleotide substitutions giving rise to changes in amino acid residues in the CVR was significantly greater in liver tissues than in sera from HCC patients. The number of amino acid residues in the CVR that differed from the representative clone from cancerous liver portions was significantly higher than the number differing from noncancerous portions in each patient. An amino acid alteration from Gly to Ser at core codon 45 in the CVR was dominant in noncancerous portions rather than in cancerous portions and sera from HCC patients. These findings suggest that a large number of mutations, including biologically important amino acid sequence changes in the HCV core gene from liver tissue, might be related to hepatocarcinogenesis.

首先，我们研究了从长江沿岸地区居民分离的丙型肝炎病毒（HCV）基因组特征与肝细胞癌（HCC）之间的关系。中国的该地区是 HCC 发病率最高的地区之一。我们的数据显示，核苷酸取代在 HCV 基因组中分布不均匀，在编码核心蛋白第二亲水结构域的区域存在一簇错义突变，并且来自 HCC 患者的分离株中的聚集可变区 (CVR) 中的这些突变数量明显高于来自慢性肝炎个体的分离株。其次，我们确定了日本 HCC 患者癌性和非癌性肝组织中 HCV 分离株的 CVR 序列差异。导致 CVR 氨基酸残基变化的核苷酸取代数量在肝组织中显着高于 HCC 患者血清。 CVR 中与癌性肝脏部分的代表性克隆不同的氨基酸残基数量显着高于每位患者与非癌性部分的差异数量。 CVR 中核心密码子 45 处从 Gly 到 Ser 的氨基酸变化在非癌性部分中占主导地位，而不是在癌性部分和来自 HCC 患者的血清中占主导地位。这些发现表明，大量突变，包括肝组织中 HCV 核心基因中生物学上重要的氨基酸序列变化，可能与肝癌发生有关。