The effects of hepatitis B virus integration into the genomes of hepatocellular carcinoma patients
The effects of hepatitis B virus integration into the genomes of hepatocellular carcinoma patients
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DOI：
10.1101/gr.133926.111
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发表时间：
2012-04-01
期刊：
影响因子：
7
通讯作者：
Zhang, Zemin
中科院分区：
文献类型：
--
作者：
Jiang, Zhaoshi;Jhunjhunwala, Suchit;Zhang, Zemin
B型肝炎病毒（HBV）感染是肝细胞癌（HCC）的主要危险因素。HBV整合到宿主基因组中已有报道，但其规模、影响和对HCC发展的贡献尚不清楚。在这里，我们对4名HCC患者的肿瘤和非肿瘤基因组（> 80倍覆盖率）和转录组进行了测序，并确定了255个HBV整合位点。将测序增加到240 x覆盖率揭示了成比例地更高数量的整合位点。HBV整合的肝细胞的克隆性扩增在肿瘤样品中特异性地发现。我们观察到病毒整合位点附近的基因组扰动的多样性，包括直接基因破坏，病毒启动子驱动的人类转录，病毒-人类转录融合，和DNA拷贝数改变。因此，我们报告了肝细胞癌患者中HBV整合的最全面表征。这种广泛的随机病毒整合可能会增加HBV感染者的致癌机会。
Hepatitis B virus (HBV) infection is a leading risk factor for hepatocellular carcinoma (HCC). HBV integration into the host genome has been reported, but its scale, impact and contribution to HCC development is not clear. Here, we sequenced the tumor and nontumor genomes (>80x coverage) and transcriptomes of four HCC patients and identified 255 HBV integration sites. Increased sequencing to 240x coverage revealed a proportionally higher number of integration sites. Clonal expansion of HBV-integrated hepatocytes was found specifically in tumor samples. We observe a diverse collection of genomic perturbations near viral integration sites, including direct gene disruption, viral promoter-driven human transcription, viral-human transcript fusion, and DNA copy number alteration. Thus, we report the most comprehensive characterization of HBV integration in hepatocellular carcinoma patients. Such widespread random viral integration will likely increase carcinogenic opportunities in HBV-infected individuals.