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Re-evaluation of the carcinogenic significance of hepatitis B virus integration in hepatocarcinogenesis
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Jiang, Suzhen, Yang, Ziwei, Li, Weijie, Li, Xiaojun, Wang, Yongfeng, Zhang, Jiangbo, Xu, Chunhui, Chen, Pei-Jer, Hou, Jinlin, McCrae, Malcolm A., Chen, Xiangmei, Zhuang, Hui and Lu, Fengmin (2012) Re-evaluation of the carcinogenic significance of hepatitis B virus integration in hepatocarcinogenesis. PLoS One, Vol.7 (No.9). e40363. doi:10.1371/journal.pone.0040363 ISSN 1932-6203.
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Official URL: http://dx.doi.org/10.1371/journal.pone.0040363
Abstract
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.
Item Type: | Journal Article | ||||
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Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) > Biological Sciences ( -2010) Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) |
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Library of Congress Subject Headings (LCSH): | Hepatitis B virus, Liver -- Cancer, Carcinogenesis | ||||
Journal or Publication Title: | PLoS One | ||||
Publisher: | Public Library of Science | ||||
ISSN: | 1932-6203 | ||||
Official Date: | 4 September 2012 | ||||
Dates: |
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Volume: | Vol.7 | ||||
Number: | No.9 | ||||
Page Range: | e40363 | ||||
DOI: | 10.1371/journal.pone.0040363 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Open Access (Creative Commons) | ||||
Date of first compliant deposit: | 23 December 2015 | ||||
Date of first compliant Open Access: | 23 December 2015 | ||||
Funder: | Institut Pasteur of Shanghai | ||||
Grant number: | 2012ZX10004-904 (IPS), 2012ZX10002-007 (IPS) |
Data sourced from Thomson Reuters' Web of Knowledge
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