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确定HBV整合在染色体上的精确位置。结果在40例乙肝表面抗原阳性的肝癌组织中,有34例(85%)存在HBV整合现象。每份标本中的病毒整合拷贝数为1～5个不等,因此共获得了68个病毒整合位点。从病毒基因分析,整合可发生于X基因的任何长度,并不集中于通常认为的HBVDR1和DR2区,但在96%(65/68)的整合中,X基因均以截短形式插入宿主细胞DNA;从宿主基因分析,HBV偏好插入于基因的内含子和上游调控区,未见外显子中的插入。这些基因80%已被报道与肿瘤有关,它们的产物大多与细胞基本生存和死亡密切相关,可在各个细胞调控环节上促进肿瘤生成。十分有意义的是,在总共26个基因中即有3个基因(myeloid/lymphoidormixed lineageleukemia4,G proteinalphatransducingactivity polypeptide1和fibronectin1)发现被HBV重复整合。结论HBV在肝癌细胞染色体上的整合并不呈均衡分布,病毒对宿主细胞的“插入诱变”及整合子中持续表达的“截短型X蛋白”可能在病毒的致癌过程中起重要作用。
Determine the precise location of HBV integration on the chromosome. Results Of the 40 cases of hepatocellular carcinoma with HBsAg positive, 34 cases (85%) had HBV integration. The number of virus-integrated copies per sample ranged from 1 to 5, resulting in a total of 68 virus integration sites. From viral genomic analysis, integration can occur at any length of the X gene and is not centered on what is commonly thought to be the HBVDRl and DR2 regions, but in 96% (65/68) of the integrants, the X genes are all truncated into the host cell DNA; From host gene analysis, HBV preference was inserted into the introns and upstream regulatory regions of the gene, with no insertion in exons. About 80% of these genes have been reported to be tumor-related, most of their products are closely related to the basic survival and death of cells, and can promote tumorigenesis in various cell regulatory processes. Significantly, 3 genes out of a total of 26 genes (myeloid / lymphoidormixed lineageleukemia4, G proteinalphatransducingactivity polypeptide1 and fibronectin1) were found to be repeatedly integrated by HBV. Conclusion The integration of HBV on the chromosomes of hepatocellular carcinoma cells is not evenly distributed. The “intercalation mutation” of host cells and the expression of “truncated X protein” in the integron may play an important role in the carcinogenesis of the virus.