Hepatitis B virus integration site in hepatocellular carcinoma at chromosome 17;18 translocation.
Hepatitis B virus integration site in hepatocellular carcinoma at chromosome 17;18 translocation.
复制标题
肝细胞癌中乙型肝炎病毒整合位点位于染色体 17;18 易位处。
DOI：
10.1073/pnas.83.21.8338
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发表时间：
1986
影响因子：
11.1
通讯作者：
Rogler,CE
中科院分区：
文献类型：
--
作者：
Hino,O;Shows,TB;Rogler,CE
整合乙型肝炎病毒（HBV） DNA几乎总是在HBV携带者发生的肝细胞癌（HCC）中发现。从两个单整合的hcc （C3和C4）中克隆了整合的HBV dna，并分析了细胞整合位点。C3的整合HBV DNA存在于6号染色体上，包含一个几乎完整的线性HBV基因组。肿瘤C3中HBV DNA整合与细胞DNA重排无关。相比之下，C4中整合的HBV DNA包含一个大的HBV DNA倒置重复序列，其中每个重复序列由一个线性HBV DNA片段组成，类似于C3中存在的HBV DNA片段。C4整合还伴随着HBV整合位点的细胞DNA易位。易位发生在17号和18号染色体之间，同时在易位位点有至少1.3千碱基的18号染色体DNA缺失。我们的数据支持一个模型，即整合后HBV和细胞DNA的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HCC的多阶段机制中起作用。
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.