Large scaled analysis of hepatitis B virus (HBV) DNA integration in HBV related hepatocellular carcinomas
Large scaled analysis of hepatitis B virus (HBV) DNA integration in HBV related hepatocellular carcinomas
复制标题
DOI：
10.1136/gut.2004.054452
复制
发表时间：
2005-08-01
期刊：
影响因子：
24.5
通讯作者：
Paterlini-Bréchot, P
中科院分区：
文献类型：
--
作者：
Murakami, Y;Saigo, K;Paterlini-Bréchot, P
背景和目的：乙型肝炎病毒（HBV） DNA整合或接近细胞基因在HBV阳性肝细胞癌（HCC）中经常检测到。我们之前已经证明病毒整合可导致靶基因转录异常。在这项研究中，我们试图探讨肝癌发生的常见途径。方法：采用改进的铝聚合酶链反应方法，我们分析了50例hcc和10例先前发表的病例。结果：共获得68个细胞侧翼序列（7个重复或未知序列，42个细胞基因，19个可能编码未知蛋白的序列）。鉴定出15个肿瘤相关基因和25个细胞基因。HBV整合反复靶向人类端粒酶逆转录酶基因（3例）和属于不同途径的基因：钙信号相关基因、60s核糖体蛋白编码基因、血小板衍生生长因子和混合谱系白血病编码基因。在整合位点还发现了两个肿瘤抑制基因和五个参与细胞凋亡控制的基因。结论：在61/68（89.7%）的病例中，HBV DNA被整合到细胞基因中，可能为细胞生长提供优势。将复发病毒整合位点鉴定为同一家族的基因，可以识别在肝癌发生中激活的常见细胞信号通路。
Background and aims: Hepatitis B virus (HBV) DNA integration into or close to cellular genes is frequently detected in HBV positive hepatocellular carcinomas (HCC). We have previously shown that viral integration can lead to aberrant target gene transcription. In this study, we attempted to investigate common pathways to hepatocarcinogenesis.Methods: By using a modified Alu-polymerase chain reaction approach, we analysed 50 HCCs along with 10 previously published cases.Results: Sixty eight cellular flanking sequences ( seven repetitive or unidentified sequences, 42 cellular genes, and 19 sequences potentially coding for unknown proteins) were obtained. Fifteen cancer related genes and 25 cellular genes were identified. HBV integration recurrently targeted the human telomerase reverse transcriptase gene ( three cases) and genes belonging to distinct pathways: calcium signalling related genes, 60s ribosomal protein encoding genes, and platelet derived growth factor and mixed lineage leukaemia encoding genes. Two tumour suppressor genes and five genes involved in the control of apoptosis were also found at the integration site. The viral insertion site was distributed over all chromosomes except 13, X, and Y.Conclusions: In 61/68 (89.7%) cases, HBV DNA was integrated into cellular genes potentially providing cell growth advantage. Identification of recurrent viral integration sites into genes of the same family allows recognition of common cell signalling pathways activated in hepatocarcinogenesis.