Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma
Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma
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DOI：
10.1038/ng.2295
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发表时间：
2012-07-01
期刊：
影响因子：
30.8
通讯作者：
Luk, John M.
中科院分区：
文献类型：
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作者：
Sung, Wing-Kin;Zheng, Hancheng;Luk, John M.
为了调查乙型肝炎病毒 (HBV) 在肝癌基因组中的整合情况，我们对 81 个 HBV 阳性和 7 个 HBV 阴性肝细胞癌 (HCC) 和邻近正常组织进行了大规模平行测序。我们发现 HBV 整合在肿瘤 (86.4%) 中比在邻近肝组织 (30.7%) 中更频繁地观察到。在可能诱发染色体不稳定的 HBV 断点位置，拷贝数变异 (CNV) 显着增加。 HBV 基因组内大约 40% 的 HBV 断点位于病毒增强子、X 基因和核心基因所在的 1,800 bp 区域内。我们还发现了复发性 HBV 整合事件（在 >= 4 个 HCC 中），这些事件通过 RNA 测序 (RNA-seq) 和 Sanger 测序对已知和推定的癌症相关 TERT、MLL4 和 CCNE1 基因进行了验证，这些基因显示与正常组织相比，肿瘤中的基因表达上调。我们还报告了表明 HBV 整合数量与患者生存相关的证据。
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.