乙型肝炎病毒的早期和晚发肝细胞癌的基因型和集成模式的

StephenW

Characterization of the genotype and integration patterns of hepatitis B virus in early- and late-onset hepatocellular carcinoma

    Hongli Yan1,3,†,
    Yuan Yang2,†,
    Ling Zhang1,
    Guannan Tang1,
    YuZhao Wang1,
    Geng Xue1,
    Weiping Zhou2 and
    Shuhan Sun1,*

DOI: 10.1002/hep.27722

© 2015 by the American Association for the Study of Liver Diseases

Vol. 61 Issue 2
Hepatology

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)


Author Information

    1    Department of Medical Genetics, Second Military Medical University, Shanghai, China
    2    The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
    3    Department of Laboratory Medicine, Changhai Hospital, The Second Military Medical University, Shanghai, China

    †    These authors contributed equally to this paper

*Corresponding author. E-mail: [email protected]

ABSTRACT

Early-onset hepatocellular carcinoma (HCC) accounts for 15 to 20% of total HCC cases in Asia, and the incidence is increasing. The low frequency of cirrhosis and poor prognosis of early-onset HCC suggests that its mechanisms may differ from late-onset HCC. Although hepatitis B virus (HBV) infection is epidemiologically associated with HCC, the role of HBV in early-onset HCC remains poorly understood. Here, we report a comparative study on HBV subgenotypes and integration in early- (≤30) and late-onset (≥70) HBV-associated HCC using a novel high-throughput viral integration detection (HIVID) method. We report that HBV B2 is predominantly present in early-onset HCC. HBV integration is a common phenomenon both in early- and late-onset HCC, which favors integrating into human repeat regions. Moreover, we found a breakpoint in 8q24 located between c-Myc and PVT1 which was detected in 12.4% (14/113) of early-onset HCCs, but only 1.4% (2/145) in late-onset HCCs. HBV integrating this site results in c-MYC, PVT1 and miR-1204 over-expression in tumors, thereby potentially contributing to the development of early-onset HCC. Conclusion: To the best of our knowledge, this is the first systematic investigation of HBV genotype and integration in early-onset HCC, and our results may shed light on HCC risk factors in young HBV carriers. Further studies are needed to elucidate at which time in tumor development this integration event occurs and whether it plays an important, causative role in HCC development or progression. This article is protected by copyright. All rights reserved.

StephenW

乙型肝炎病毒的早期和晚发肝细胞癌的基因型和集成模式的表征

    宏利Yan1,3，†，
    袁Yang2，†，
    凌Zhang1，
    灌南县Tang1，
    YuZhao旺1，
    耿雪1，
    卫平Zhou2和
    蜀汉SUN1，*

DOI：10.1002/ hep.27722

©2015年肝病研究的美国协会

第一卷。 61第2期
肝病

接受第（接受，未经编辑的文章在网上和引述的公布，最终编辑和记录排版本将出现在未来。）


作者信息

    医学遗传学，第二军医大学，上海，中国1系
    2肝脏外科，东方肝胆外科医院，第二军医大学，上海，中国的第三部门
    检验医学，长海医院，第二军医大学，上海，中国3系

    †这些作者同等贡献本文

*通讯作者。电子邮件：[email protected]

摘要

早发肝细胞癌（HCC）占15至20％的总HCC病例在亚洲，与发病率正在增加。肝硬化和早发性肝癌预后不良的低频表明，其机制可能与晚发HCC。虽然乙型肝炎病毒（HBV）感染是流行病学与肝癌相关，乙肝病毒在早发性肝癌的作用仍然知之甚少。在这里，我们报告HBV基因亚型和整合早发（≤30）采用了一种新的高通量病毒整合检测（HIVID）方法进行了比较研究和迟发性（≥70）HBV相关HCC。我们报告说，乙肝病毒B2存在于早发性肝癌主要。 HBV整合是在早期和晚发HCC，这有利于融入人类的重复区域的普遍现象。此外，我们发现8q24上位于c-myc和PVT1之间的迟发性肝癌断点这是在早发性肝癌12.4％（113分之14）检测，但只有1.4％（一百四十五分之二）。 HBV整合此网站导致的c-MYC，PVT1和miR-1204过表达在肿瘤中，由此可能造成的早发性肝癌的发展。结论：要尽我们所知，这是HBV基因型和整合早发性肝癌的第一次系统的调查，我们的结果可能揭示在年轻的乙肝病毒携带者HCC危险因素光。还需要进一步的研究来阐明其时在肿瘤的发生发展这种整合事件发生时，是否发挥在肝癌发生或发展的重要致病作用。这篇文章是受版权保护的。版权所有。

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