Re-evaluation of the carcinogenic significance of hepatitis B virus integration in hepatocarcinogenesis.

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...

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Autores principales:	Suzhen Jiang, Ziwei Yang, Weijie Li, Xiaojun Li, Yongfeng Wang, Jiangbo Zhang, Chunhui Xu, Pei-Jer Chen, Jinlin Hou, Malcolm A McCrae, Xiangmei Chen, Hui Zhuang, Fengmin Lu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e5184ca8ed9443239bb89c3c9977faeb
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spelling	oai:doaj.org-article:e5184ca8ed9443239bb89c3c9977faeb2021-11-18T07:06:46ZRe-evaluation of the carcinogenic significance of hepatitis B virus integration in hepatocarcinogenesis.1932-620310.1371/journal.pone.0040363https://doaj.org/article/e5184ca8ed9443239bb89c3c9977faeb2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22962577/?tool=EBIhttps://doaj.org/toc/1932-6203To 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.Suzhen JiangZiwei YangWeijie LiXiaojun LiYongfeng WangJiangbo ZhangChunhui XuPei-Jer ChenJinlin HouMalcolm A McCraeXiangmei ChenHui ZhuangFengmin LuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e40363 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Suzhen Jiang Ziwei Yang Weijie Li Xiaojun Li Yongfeng Wang Jiangbo Zhang Chunhui Xu Pei-Jer Chen Jinlin Hou Malcolm A McCrae Xiangmei Chen Hui Zhuang Fengmin Lu Re-evaluation of the carcinogenic significance of hepatitis B virus integration in hepatocarcinogenesis.
description	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.
format	article
author	Suzhen Jiang Ziwei Yang Weijie Li Xiaojun Li Yongfeng Wang Jiangbo Zhang Chunhui Xu Pei-Jer Chen Jinlin Hou Malcolm A McCrae Xiangmei Chen Hui Zhuang Fengmin Lu
author_facet	Suzhen Jiang Ziwei Yang Weijie Li Xiaojun Li Yongfeng Wang Jiangbo Zhang Chunhui Xu Pei-Jer Chen Jinlin Hou Malcolm A McCrae Xiangmei Chen Hui Zhuang Fengmin Lu
author_sort	Suzhen Jiang
title	Re-evaluation of the carcinogenic significance of hepatitis B virus integration in hepatocarcinogenesis.
title_short	Re-evaluation of the carcinogenic significance of hepatitis B virus integration in hepatocarcinogenesis.
title_full	Re-evaluation of the carcinogenic significance of hepatitis B virus integration in hepatocarcinogenesis.
title_fullStr	Re-evaluation of the carcinogenic significance of hepatitis B virus integration in hepatocarcinogenesis.
title_full_unstemmed	Re-evaluation of the carcinogenic significance of hepatitis B virus integration in hepatocarcinogenesis.
title_sort	re-evaluation of the carcinogenic significance of hepatitis b virus integration in hepatocarcinogenesis.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/e5184ca8ed9443239bb89c3c9977faeb
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Re-evaluation of the carcinogenic significance of hepatitis B virus integration in hepatocarcinogenesis.

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