Molecular biological study on the relationship between hepatitis B virus and hepatocellular carcinoma

乙型肝炎病毒与肝癌关系的分子生物学研究

基本信息

批准号：
59570129
负责人：
SAKAI Masaharu
金额：
$ 1.09万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1984
资助国家：
日本
起止时间：
1984 至 1986
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-59570129/
关键词：
Hepatitis B virus (HBV)DNA HBV DNA integration Hepatocellular carcinoma Liver cirrhosis Multicentric origin of hepatocellular carcinoma 肝細胞増生クローン

项目摘要

In this project, we analyzed hepatitis B virus (HBV) DNA replication patterns and integration patterns into the host genome among different part of the liver tissues and hepatocellular carcinoma (HCC) tissues. In one investigation, we analyzed HBV DNA integration patterns of three hepatocellular carcinoma nodules (HCCN) in the liver of a HBV infected patient by Southern blot hybridization. We found HBV DNA integration pattern of one HCCN was completely different from those of other two. We think this indicates different clonal origin, i.e. multicentric origin, of HCC in this case. We believe this is the first confirmation of multicentric origin of HCC at molecular level. In the next investigation, we analyzed the difference of HBV DNA replication patterns and integration patterns among the nodules of the liver cirrhosis (LC). In this investigation, we found the HBV DNA replication patterns are heterogeneous among the nodules of LC. We also found HBV DNA integration patterns among the nodules of LC are heterogeneous and no common integration patterns are found among the nodules of LC and HCC. These results indicate: 1) HBV DNA integrates into the host genome and integration sites relative to the restriction enzyme cutting sites are different from one liver cirrhosis nodules (LCN) to another and probably different from one cell to another. 2) In some LCN, some of these cells with integrated HBV DNA grow clonally. 3) Replication of HBV DNA is not homogeneous among LCN and one small specimen such as biopsy materials cannot represent every areas of the cirrhotic liver. This phenomenon should be kept in mind in the interpretation of the biopsy material as an indicator of virus replication state of a patient.

在这个项目中，我们分析了乙型肝炎病毒（HBV）DNA复制模式以及在肝组织和肝细胞癌（HCC）组织的不同部分之间与宿主基因组的整合模式。在一项研究中，我们通过 Southern blot 杂交分析了 HBV 感染患者肝脏中三个肝细胞癌结节 (HCCN) 的 HBV DNA 整合模式。我们发现一种 HCCN 的 HBV DNA 整合模式与其他两种完全不同。我们认为这表明本例中 HCC 具有不同的克隆起源，即多中心起源。我们相信这是在分子水平上首次证实肝癌的多中心起源。在接下来的研究中，我们分析了肝硬化（LC）结节之间 HBV DNA 复制模式和整合模式的差异。在这项研究中，我们发现 LC 结节中的 HBV DNA 复制模式是异质的。我们还发现 LC 结节中的 HBV DNA 整合模式是异质的，并且 LC 和 HCC 结节中没有发现共同的整合模式。这些结果表明：1) HBV DNA 整合到宿主基因组中，并且相对于限制性内切酶切割位点的整合位点在肝硬化结节 (LCN) 中与另一种肝硬化结节 (LCN) 不同，而且在一个细胞与另一个细胞之间可能也不同。 2) 在一些 LCN 中，一些整合了 HBV DNA 的细胞进行克隆生长。 3) HBV DNA的复制在LCN中并不均匀，并且诸如活检材料之类的小样本不能代表肝硬化肝脏的每个区域。在将活检材料解释为患者病毒复制状态的指标时，应牢记这种现象。