Takada S, Gotoh Y, Hayashi S, Kobayashi M, Koike K
Department of Gene Research, Cancer Institute, Tokyo, Japan.
Gastroenterol Jpn. 1990 Sep;25 Suppl 2:31-7. doi: 10.1007/BF02779925.
Cellular DNAs of chronically hepatitis B virus (HBV)-infected human livers were analysed by Southern blot hybridization for the presence of integrated HBV DNA. In 15 out of 16 tissue samples, random HBV DNA integration was evident. By molecular cloning and structural analyses of 19 integrants from 3 chronic hepatitis tissues, rearrangement of HBV DNA with inverted duplication or translocation of cellular flanking DNA at the virus-cell junction was noted. Thus, the rearrangement of HBV DNA or cellular flanking DNA not to be a specific incident of HCC formation. Analyses of various integrants bearing HBV DNA rearrangement and their cellular counterpart DNAs failed to indicate any gross structural alteration in cellular DNA except for a small deletion at the integration sites, indicating HBV DNA rearrangement with inverted duplication to possibly occur prior to integration. Based on nucleotide sequencing analyses of virus-virus junctions, a mechanism of this inverted duplication of HBV DNA is proposed, in which an illegitimate recombination may take place by means of a patchy homology on one side of adjoining viral sequences.
通过Southern印迹杂交分析慢性乙型肝炎病毒（HBV）感染的人肝脏细胞DNA中是否存在整合的HBV DNA。在16个组织样本中的15个中，明显存在随机的HBV DNA整合。通过对来自3个慢性肝炎组织的19个整合体进行分子克隆和结构分析，发现在病毒-细胞连接处HBV DNA发生重排，伴有细胞侧翼DNA的反向重复或易位。因此，HBV DNA或细胞侧翼DNA的重排并非是肝癌形成的特定事件。对携带HBV DNA重排的各种整合体及其细胞对应DNA的分析未能表明细胞DNA有任何明显的结构改变，除了整合位点处有一个小的缺失，这表明带有反向重复的HBV DNA重排可能在整合之前发生。基于病毒-病毒连接处的核苷酸序列分析，提出了这种HBV DNA反向重复的机制，即相邻病毒序列一侧的局部同源性可能导致非法重组。
