Hino O, Shows T B, Rogler C E
Proc Natl Acad Sci U S A. 1986 Nov;83(21):8338-42. doi: 10.1073/pnas.83.21.8338.
Integrated hepatitis B virus (HBV) DNA is almost invariably found in hepatocellular carcinomas (HCC) which develop in HBV carriers. Integrated HBV DNAs from two single-integration HCCs (C3 and C4) have been cloned, and the cellular integration sites have been analyzed. Integrated HBV DNA of C3 is present in chromosome 6 and contains a nearly complete linear HBV genome. The HBV DNA integration in tumor C3 was not associated with major rearrangements of cellular DNA. In contrast, the integrated HBV DNA in C4 contains a large inverted repeat of HBV DNA, in which each repeat consists of a linear HBV DNA segment similar to that present in C3. The C4 integration was also accompanied by a cellular DNA translocation at the HBV integration site. The translocation occurred between chromosomes 17 and 18, along with a deletion of at least 1.3 kilobases of chromosome 18 DNA at the translocation site. Our data support a model in which postintegration rearrangement of integrated HBV and cellular DNA results in the generation of chromosomal aberrations. These chromosomal aberrations may function in a multistage mechanism leading to fully malignant HCC.
在乙肝病毒（HBV）携带者所发生的肝细胞癌（HCC）中几乎总能发现整合型乙肝病毒DNA。已克隆了来自两个单整合型肝癌（C3和C4）的整合型HBV DNA，并分析了细胞整合位点。C3的整合型HBV DNA存在于6号染色体中，包含一个近乎完整的线性HBV基因组。肿瘤C3中的HBV DNA整合与细胞DNA的重大重排无关。相比之下，C4中的整合型HBV DNA包含一个HBV DNA的大反向重复序列，其中每个重复序列由一个类似于C3中存在的线性HBV DNA片段组成。C4整合还伴随着在HBV整合位点处的细胞DNA易位。易位发生在17号和18号染色体之间，同时在易位位点处18号染色体DNA至少缺失了1.3千碱基。我们的数据支持一种模型，即整合型HBV和细胞DNA的整合后重排导致染色体畸变的产生。这些染色体畸变可能在导致完全恶性的HCC的多阶段机制中发挥作用。
