为研究肝癌基因组中乙型肝炎病毒（HBV）的整合情况，我们对81名HBV阳性及7名HBV阴性的肝细胞癌（HCCs）患者的肝癌组织及临近正常组织进行了平行测序。结果发现肿瘤组织中HBV的整合（86.4%）较临近正常组织（30.7%）更常见。在可能引起染色体不稳定的HBV断裂位点拷贝数变异（CNVs）显著增多。HBV基因组中大约40%的断裂位点位于包含病毒增强子、X基因及核心基因的一段1 800bp的区域内。我们也通过RNA测序及Sanger法测序确认，复发的HBV基因整合（多于4例HCCs）位点位于已知区域及可能与癌症相关的TERT、MLL4及CCNE1基因区，因为这3个基因在肿瘤组织中比正常组织表达更高。我们的研究还提示HBV的整合数与患者生存率相关。

　　　To survey hepatitis B virus (HBV) integration in liver cancer genomes, we conducted massively parallel sequencing of 81 HBV-positive and 7 HBV-negative hepatocellular carcinomas (HCCs) and adjacent normal tissues. We found that HBV integration is observed more frequently in the tumors(86.4%) than in adjacent liver tissues(30.7%). Copy-number variations (CNVs) were significantly increased at HBV breakpoint locations where chromosomal instability was likely induced. Approximately 40% of HBV breakpoints within the HBV genome were located within a 1,800-bp region where the viral enhancer, X gene and core gene are located. We also identified recurrent HBV integration events (in ≥4 HCCs) that were validated by RNA sequencing (RNA-seq) and Sanger sequencing at the known and putative cancer-related TERT, MLL4 and CCNE1 genes, which showed upregulated gene expression in tumor versus normal tissue. We also report evidence that suggests that the number of HBV integrations is associated with patient survival.　　　

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