乙型肝炎病毒的早发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 andShuhan Sun1,*
    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 article.

*Address reprint requests to: Shuhan Sun, M.D., Ph.D., Department of Medical Genetics, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China. E-mail: [email protected]; fax: +86-21-81871053.
Article first published online: 18 MAR 2015

DOI: 10.1002/hep.27722

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

I
Hepatology

Volume 61, Issue 6, pages 1821–1831, June 2015


    This work was funded by the National Natural Science Foundation of China (No. 30801328, 81472770), Science Fund for Creative Research Groups (No. 81221061, 81201940), Shanghai Pujiang Project, and New Excellent Youth Plan (XYQ2013074) for financial support.

Early-onset hepatocellular carcinoma (HCC) accounts for 15%-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 of HBV subgenotypes and integration in early- (≤30) and late-onset (≥70) HBV-associated HCC using a novel high-throughput viral integration detection 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 plasmocytoma variant translocation 1 (PVT1), which was detected in 12.4% (14 of 113) of early-onset HCCs, but only 1.4% (2 of 145) in late-onset HCCs. HBV integrating this site results in c-MYC, PVT1, and microRNA-1204 overexpression in tumors, thereby potentially contributing to the development of early-onset HCC. Conclusion: HBV genotype and integration patterns may be distinct in early-onset HCC. 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. (Hepatology 2015;61:1821-1831)

StephenW

乙型肝炎病毒的早发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，张卫平Zhou2 andShuhan SUN1，*
    医学遗传学，第二军医大学，上海，中国1系
    2肝手术，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，中国的3系

    †这些作者同等贡献这篇文章。

*地址转载请：蜀汉太阳，医学博士，医学遗传学系，第二军医大学，翔殷路800号，上海200433，中国。电子信箱：[email protected];传真：+ 86-21-81871053。
文章首次在线发表：2015年3月18日

DOI：10.1002 / hep.27722

©2015年肝病研究的美国协会

我
肝病

第61卷，第6期，页1821至1831年，2015年6月


    这一工作是由中国国家自然科学基金（编号30801328，81472770），自然科学基金创新研究群体（编号81221061，81201940），上海浦江项目，以及新优秀青年计划（XYQ2013074）的资金支持。

早发肝细胞癌（HCC）占15％的总HCC病例在亚洲的-20％，并且发病率正在增加。肝硬化和早发性肝癌预后差的低频表明，其机制可能与晚发性肝癌。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，我们报告乙肝病毒亚型和融合的早发（≤30）使用一种新型高通量病毒整合检测方法进行了比较研究和迟发性（≥70）乙肝相关肝癌。我们报告说，乙肝病毒B2存在于早发性肝癌主要。 HBV整合是一个普遍的现象，无论是在早期和晚期肝癌发病，这有利于融入人类的重复区域。此外，我们发现了一个断点位于8q24上的c-Myc和浆细胞瘤变异易位1（PVT1），这是在早发肝癌12.4％（113 14）检测的，但只有1.4％（2 145）晚-onset肝癌。 HBV整合在肿瘤中，此网站的结果中的c-MYC，PVT1，和微小RNA-1204过表达，从而可能造成的早发性肝癌的发展。结论：HBV基因型和集成模式可能是不同的早发性肝癌。我们的研究结果可以揭示在年轻的乙肝病毒携带者肝癌的危险因素光。还需要进一步的研究来阐明其时在肿瘤发展这种整合事件发生，无论它在肝癌或发展一个重要的致病作用。 （2015年肝病; 61：1821年至1831年）