JBS Science, Inc., Doylestown, PA 18902, USA.
The Baruch S. Blumberg Research Institute, Doylestown, PA 18902, USA.
Cells. 2021 May 23;10(6):1294. doi: 10.3390/cells10061294.
Chronic hepatitis B virus (HBV) infection is the major etiology of hepatocellular carcinoma (HCC), frequently with HBV integrating into the host genome. HBV integration, found in 85% of HBV-associated HCC (HBV-HCC) tissue samples, has been suggested to be oncogenic. Here, we investigated the potential of HBV-HCC driver identification via the characterization of recurrently targeted genes (RTGs). A total of 18,596 HBV integration sites from our in-house study and others were analyzed. RTGs were identified by applying three criteria: at least two HCC subjects, reported by at least two studies, and the number of reporting studies. A total of 396 RTGs were identified. Among the 28 most frequent RTGs, defined as affected in at least 10 HCC patients, 23 (82%) were associated with carcinogenesis and 5 (18%) had no known function. Available breakpoint positions from the three most frequent RTGs, , , and , were analyzed. Mutual exclusivity of TERT promoter mutation and HBV integration into TERT was observed. We present an RTG consensus through comprehensive analysis to enable the potential identification and discovery of HCC drivers for drug development and disease management.
慢性乙型肝炎病毒（HBV）感染是肝细胞癌（HCC）的主要病因，常伴有 HBV 整合到宿主基因组中。HBV 整合，在 85%的 HBV 相关 HCC（HBV-HCC）组织样本中发现，被认为具有致癌性。在这里，我们通过对反复靶向基因（RTGs）的特征分析，研究了 HBV-HCC 驱动基因鉴定的潜力。我们分析了来自内部研究和其他研究的总共 18596 个 HBV 整合位点。通过应用三个标准来识别 RTGs：至少有两个 HCC 患者，至少有两个研究报道，以及报道研究的数量。共鉴定出 396 个 RTGs。在 28 个最常见的 RTGs 中，定义为至少 10 个 HCC 患者受影响，其中 23 个（82%）与致癌作用有关，5 个（18%）具有未知功能。对三个最常见的 RTGs ， ， 和 ，的可用断点位置进行了分析。TERT 启动子突变和 HBV 整合到 TERT 之间存在互斥性。我们通过综合分析提出了一个 RTG 共识，以实现 HCC 驱动基因的潜在识别和发现，从而为药物开发和疾病管理提供帮助。
