Division of Structural and Functional Genomics, Center for Genome Science, National Institute of Health, Chungcheongbuk-do 363-951, Korea.
BMB Rep. 2012 Jun;45(6):365-70. doi: 10.5483/bmbrep.2012.45.6.279.
Hepatitis B virus (HBV) DNA is often integrated into hepatocellular carcinoma (HCC). Although the relationship between HBV integration and HCC development has been widely studied, the role of HBV integration in HCC development is still not completely understood. In the present study, we constructed a pooled BAC library of 9 established cell lines derived from HCC patients with HBV infections. By amplifying viral genes and superpooling of BAC clones, we identified 2 clones harboring integrated HBV DNA. Screening of host-virus junctions by repeated sequencing revealed an HBV DNA integration site on chromosome 11q13 in the SNU-886 cell line. The structure and rearrangement of integrated HBV DNA were extensively analyzed. An inverted duplicated structure, with fusion of at least 2 HBV DNA molecules in opposite orientations, was identified in the region. The gene expression of cancer-related genes increased near the viral integration site in HCC cell line SNU-886.
乙型肝炎病毒 (HBV) DNA 常整合到肝细胞癌 (HCC) 中。尽管 HBV 整合与 HCC 发展之间的关系已被广泛研究，但 HBV 整合在 HCC 发展中的作用仍不完全清楚。在本研究中，我们构建了一个由 9 株来自 HBV 感染 HCC 患者的已建立细胞系组成的 pooled BAC 文库。通过扩增病毒基因和 BAC 克隆的超级池化，我们鉴定出 2 个含有整合 HBV DNA 的克隆。通过重复测序筛选宿主-病毒连接点，我们在 SNU-886 细胞系中发现了一个位于 11q13 染色体上的 HBV DNA 整合位点。我们对整合 HBV DNA 的结构和重排进行了广泛分析。在该区域中鉴定出至少有 2 个 HBV DNA 分子以相反方向融合的倒置重复结构。在 HCC 细胞系 SNU-886 中，病毒整合位点附近的癌症相关基因表达增加。
