IR@PKUHSC  > 北京大学基础医学院  > 病原生物学系
学科主题基础医学
Re-evaluation of the Carcinogenic Significance of Hepatitis B Virus Integration in Hepatocarcinogenesis
Jiang, Suzhen1,2,3; Yang, Ziwei1; Li, Weijie1; Li, Xiaojun1; Wang, Yongfeng1; Zhang, Jiangbo1; Xu, Chunhui1; Chen, Pei-Jer4; Hou, Jinlin2; McCrae, Malcolm A.5; Chen, Xiangmei1,6; Zhuang, Hui1,6; Lu, Fengmin1,6
刊名PLOS ONE
2012-09-04
DOI10.1371/journal.pone.0040363
7期:9
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
资助者National S & ; T Major Project for Infectious Diseases ; National S & ; T Major Project for Infectious Diseases
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]HUMAN HEPATOCELLULAR-CARCINOMA ; WOODCHUCK HEPATITIS ; GENE ; DNA ; ACTIVATION ; MECHANISMS ; EXPRESSION ; MUTANTS ; TUMORS ; CHINA
英文摘要

To examine the role of hepatitis B virus (HBV) integration in hepatocarcinogenesis, a systematic comparative study of both tumor and their corresponding non-tumor derived tissue has been conducted in a cohort of 60 HBV associated hepatocellular carcinoma (HCC) patients. By using Alu-polymerase chain reaction (PCR) and ligation-mediated PCR, 233 viral-host junctions mapped across all human chromosomes at random, no difference between tumor and non-tumor tissue was observed, with the exception of fragile sites (P = 0.0070). HBV insertions in close proximity to cancer related genes such as hTERT were found in this study, however overall they were rare events. No direct correlation between chromosome aberrations and the number of HBV integration events was found using a sensitive array-based comparative genomic hybridization (aCGH) assay. However, a positive correlation was observed between the status of several tumor suppressor genes (TP53, RB1, CDNK2A and TP73) and the number of chromosome aberrations (r = 0.6625, P = 0.0003). Examination of the viral genome revealed that 43% of inserts were in the preC/C region and 57% were in the HBV X gene. Strikingly, approximately 24% of the integrations examined had a breakpoint in a short 15 nt viral genome region (1820-1834 nt). As a consequence, all of the confirmed X gene insertions were C-terminal truncated, losing their growth-suppressive domain. However, the same pattern of X gene C-terminal truncation was found in both tumor and non-tumor derived samples. Furthermore, the integrated viral sequences in both groups had a similar low frequency of C1653T, T1753V and A1762T/G1764A mutations. The frequency and patterns of HBV insertions were similar between tumor and their adjacent non-tumor samples indicating that the majority of HBV DNA integration events are not associated with hepatocarcinogenesis.

语种英语
所属项目编号2012ZX10004-904 ; 2012ZX10002-007
资助者National S & ; T Major Project for Infectious Diseases ; National S & ; T Major Project for Infectious Diseases
WOS记录号WOS:000308577600004
引用统计
被引频次:37[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54457
专题北京大学基础医学院_病原生物学系
作者单位1.Linyi Peoples Hosp, Dept Infect Dis, Linyi, Shandong, Peoples R China
2.Peking Univ, Ctr Infect Dis, Beijing 100871, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Dept Microbiol, Sch Basic Med Sci, Beijing 100871, Peoples R China
4.So Med Univ, Nanfang Hosp, Dept Infect Dis, Guangzhou, Guangdong, Peoples R China
5.Natl Taiwan Univ & Hosp, Hepatitis Res Ctr, Taipei, Taiwan
6.Univ Warwick, Dept Biol Sci, Coventry CV4 7AL, W Midlands, England
推荐引用方式
GB/T 7714
Jiang, Suzhen,Yang, Ziwei,Li, Weijie,et al. Re-evaluation of the Carcinogenic Significance of Hepatitis B Virus Integration in Hepatocarcinogenesis[J]. PLOS ONE,2012,7(9).
APA Jiang, Suzhen.,Yang, Ziwei.,Li, Weijie.,Li, Xiaojun.,Wang, Yongfeng.,...&Lu, Fengmin.(2012).Re-evaluation of the Carcinogenic Significance of Hepatitis B Virus Integration in Hepatocarcinogenesis.PLOS ONE,7(9).
MLA Jiang, Suzhen,et al."Re-evaluation of the Carcinogenic Significance of Hepatitis B Virus Integration in Hepatocarcinogenesis".PLOS ONE 7.9(2012).
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