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.

在该项目中，我们分析了肝炎病毒（HBV）DNA复制模式和整合模式，与肝组织不同部分和肝细胞癌（HCC）组织之间的宿主基因组中的整合模式。在一项研究中，我们分析了三种肝细胞癌结节（HCCN）的HBV DNA整合模式，该模式通过Southern印迹杂交感染了HBV患者的肝脏中。我们发现一个HCCN的HBV DNA积分模式与其他两个人完全不同。我们认为这表明在这种情况下，HCC的克隆起源不同，即多中心起源。我们认为，这是分子水平上HCC多中心起源的首次确认。在下一项研究中，我们分析了肝肝硬化（LC）结节中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，在LC和HCC的结节中未发现共同的整合模式。这些结果表明：1）HBV DNA相对于限制性酶切割位点积分到宿主基因组和整合位点与一种肝硬化结节（LCN）不同，而另一个细胞之间可能不同。 2）在某些LCN中，其中一些具有集成HBV DNA的细胞在克隆上生长。 3）在LCN中，HBV DNA的复制不是均匀的，一个小标本（例如活检材料）不能代表肝硬化肝脏的每个区域。应牢记这种现象，以解释活检材料为患者病毒复制状态的指标。