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对从一名人类肝细胞癌患者细胞DNA中克隆出的六个不同的整合型乙型肝炎病毒序列的分析。

Analysis of six distinct integrated hepatitis B virus sequences cloned from the cellular DNA of a human hepatocellular carcinoma.

作者信息

Choo K B, Liu M S, Chang P C, Wu S M, Su M W, Pan C C, Han S H

出版信息

Virology. 1986 Oct 30;154(2):405-8. doi: 10.1016/0042-6822(86)90467-8.

DOI:10.1016/0042-6822(86)90467-8
PMID:3020787
Abstract

Six distinct hepatitis B virus (HBV) integrations and the flanking cellular sequences were cloned from a hepatoma DNA preparation. None of the cloned fragments retains the entire HBV sequences but the surface antigen (HBsAg) gene and the HBV enhancer are retained in three of the six clones. The other three clones carry only short and possibly highly rearranged HBV genomic sequences and seem to contain some GC-rich clusters. Members of the repetitive Alu family are also found in the vicinity of five of the six integration regions which may have contributed to genome instability. In these six clones, the preferred integration sites are shown to lie within the single-strand region of the HBV genome. None of the clones carries in the flanking cellular sequences any of the 17 oncogenes tested, although the possibility still exists that an oncogene may be found on the side of the genome which has not been cloned. This work thus paves the way for detailed sequence analysis of virus-host junctions, for transfection studies of the HBV integration events, and for a search of genes in the flanking cellular sequences which may have been activated by the retained HBV enhancer using the clones described.

摘要

从一份肝癌DNA样本中克隆出了六个不同的乙型肝炎病毒(HBV)整合片段及其侧翼细胞序列。克隆片段均未保留完整的HBV序列,但六个克隆中的三个保留了表面抗原(HBsAg)基因和HBV增强子。另外三个克隆仅携带短的且可能高度重排的HBV基因组序列,并且似乎含有一些富含GC的簇。在六个整合区域中的五个区域附近还发现了重复的Alu家族成员,这可能导致了基因组的不稳定性。在这六个克隆中,发现优先整合位点位于HBV基因组的单链区域内。尽管在尚未克隆的基因组一侧仍有可能发现癌基因,但在侧翼细胞序列中,这六个克隆均未携带所检测的17种癌基因中的任何一种。因此,这项工作为病毒-宿主连接的详细序列分析、HBV整合事件的转染研究以及使用所述克隆寻找侧翼细胞序列中可能被保留的HBV增强子激活的基因铺平了道路。

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