Role of hepatitis B virus DNA integration in human hepatocarcinogenesis
Role of hepatitis B virus DNA integration in human hepatocarcinogenesis
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DOI：
10.3748/wjg.v20.i20.6236
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发表时间：
2014-05-28
影响因子：
4.3
通讯作者：
Kawada, Norifumi
中科院分区：
文献类型：
--
作者：
Hai, Hoang;Tamori, Akihiro;Kawada, Norifumi
肝癌在癌症发病率中排名第六，是全球癌症相关死亡的第三大原因。肝细胞癌（HCC）是最常见的肝癌类型，其起源于肝细胞，约占病例的70%-85%。B型肝炎病毒（HBV）经常引起肝脏炎症、肝损伤和随后的肝硬化。在85%-90%的HBV相关HCC中发现了整合的病毒DNA。它存在于儿童或年轻人的非肝硬化肝脏肿瘤中，进一步支持了病毒DNA整合在肝癌发生中的作用。亚基因组HBV DNA片段整合到宿主DNA的不同位置是慢性HBV感染的一个重要特征。整合有两个潜在的后果：（1）宿主基因组发生改变（“顺式”效应）;和（2）HBV基因组发生改变（“反式”效应）。顺式效应包括插入诱变，其可以潜在地破坏宿主基因功能或改变宿主基因调控。肿瘤进展通常与病毒和宿主序列的重排和部分获得或丢失相关。然而，整合的HBV DNA在肝癌发生中的作用仍存在争议。现代技术为我们进一步了解疾病机制提供了新的范例。本文就HBV DNA整合在人类肿瘤发生中的作用作一综述。(C)2014百世登出版集团股份有限公司All rights reserved.
Liver cancer ranks sixth in cancer incidence, and is the third leading cause of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, which arises from hepatocytes and accounts for approximately 70%-85% of cases. Hepatitis B virus (HBV) frequently causes liver inflammation, hepatic damage and subsequent cirrhosis. Integrated viral DNA is found in 85%-90% of HBV-related HCCs. Its presence in tumors from non-cirrhotic livers of children or young adults further supports the role of viral DNA integration in hepatocarcinogenesis. Integration of subgenomic HBV DNA fragments into different locations within the host DNA is a significant feature of chronic HBV infection. Integration has two potential consequences: (1) the host genome becomes altered ("cis" effect); and (2) the HBV genome becomes altered ("trans" effect). The cis effect includes insertional mutagenesis, which can potentially disrupt host gene function or alter host gene regulation. Tumor progression is frequently associated with rearrangement and partial gain or loss of both viral and host sequences. However, the role of integrated HBV DNA in hepatocarcinogenesis remains controversial. Modern technology has provided a new paradigm to further our understanding of disease mechanisms. This review summarizes the role of HBV DNA integration in human carcinogenesis. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.