Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma

Ling Hao Zhao; Xiao Liu; He Xin Yan; Wei Yang Li; Xi Zeng; Yuan Yang; Jie Zhao; Shi Ping Liu; Xue Han Zhuang; Chuan Lin; Chen Jie Qin; Yi Zhao; Ze Ya Pan; Gang Huang; Hui Liu; Jin Zhang; Ruo Yu Wang; Yun Yang; Wen Wen; Gui Shuai Lv; Hui Lu Zhang; Han Wu; Shuai Huang; Ming Da Wang; Liang Tang; Hong Zhi Cao; Ling Wang; T. P. Lee; Hui Jiang; Ye Xiong Tan; Sheng Xian Yuan; Guo Jun Hou; Qi Fei Tao; Qin Guo Xu; Xiu Qing Zhang; Meng Chao Wu; Xun Xu; Jun Wang; Huan Ming Yang; Wei Ping Zhou; Hong Yang Wang

doi:10.1038/ncomms12992

Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma

Ling Hao Zhao
, Xiao Liu
, He Xin Yan
, Wei Yang Li
, Xi Zeng
, Yuan Yang
, Jie Zhao
, Shi Ping Liu
, Xue Han Zhuang
, Chuan Lin
, Chen Jie Qin
, Yi Zhao
, Ze Ya Pan
, Gang Huang
, Hui Liu
, Jin Zhang
, Ruo Yu Wang
, Yun Yang
, Wen Wen
, Gui Shuai Lv

Hui Lu Zhang, Han Wu, Shuai Huang, Ming Da Wang, Liang Tang, Hong Zhi Cao, Ling Wang, T. P. Lee, Hui Jiang, Ye Xiong Tan, Sheng Xian Yuan, Guo Jun Hou, Qi Fei Tao, Qin Guo Xu, Xiu Qing Zhang, Meng Chao Wu, Xun Xu, Jun Wang, Huan Ming Yang, Wei Ping Zhou, Hong Yang Wang

Naval Medical University
National Center for Liver Cancer
BGI-Shenzhen
South China University of Technology
Chinese University of Hong Kong
Xijing Hospital
University of Copenhagen
Shanghai Jiao Tong University

Research output: Contribution to journal › Article › peer-review

290 Scopus citations

Abstract

Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation.

Original language	English
Article number	12992
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms12992
State	Published - 5 Oct 2016
Externally published	Yes

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/ncomms12992

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Zhao, L. H., Liu, X., Yan, H. X., Li, W. Y., Zeng, X., Yang, Y., Zhao, J., Liu, S. P., Zhuang, X. H., Lin, C., Qin, C. J., Zhao, Y., Pan, Z. Y., Huang, G., Liu, H., Zhang, J., Wang, R. Y., Yang, Y., Wen, W., ... Wang, H. Y. (2016). Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma. Nature Communications, 7, Article 12992. https://doi.org/10.1038/ncomms12992

@article{2a14c9a0c3cc4f638b35420720c69a3f,

title = "Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma",

abstract = "Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation.",

author = "Zhao, \{Ling Hao\} and Xiao Liu and Yan, \{He Xin\} and Li, \{Wei Yang\} and Xi Zeng and Yuan Yang and Jie Zhao and Liu, \{Shi Ping\} and Zhuang, \{Xue Han\} and Chuan Lin and Qin, \{Chen Jie\} and Yi Zhao and Pan, \{Ze Ya\} and Gang Huang and Hui Liu and Jin Zhang and Wang, \{Ruo Yu\} and Yun Yang and Wen Wen and Lv, \{Gui Shuai\} and Zhang, \{Hui Lu\} and Han Wu and Shuai Huang and Wang, \{Ming Da\} and Liang Tang and Cao, \{Hong Zhi\} and Ling Wang and Lee, \{T. P.\} and Hui Jiang and Tan, \{Ye Xiong\} and Yuan, \{Sheng Xian\} and Hou, \{Guo Jun\} and Tao, \{Qi Fei\} and Xu, \{Qin Guo\} and Zhang, \{Xiu Qing\} and Wu, \{Meng Chao\} and Xun Xu and Jun Wang and Yang, \{Huan Ming\} and Zhou, \{Wei Ping\} and Wang, \{Hong Yang\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2016.",

year = "2016",

month = oct,

day = "5",

doi = "10.1038/ncomms12992",

language = "英语",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

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Zhao, LH, Liu, X, Yan, HX, Li, WY, Zeng, X, Yang, Y, Zhao, J, Liu, SP, Zhuang, XH, Lin, C, Qin, CJ, Zhao, Y, Pan, ZY, Huang, G, Liu, H, Zhang, J, Wang, RY, Yang, Y, Wen, W, Lv, GS, Zhang, HL, Wu, H, Huang, S, Wang, MD, Tang, L, Cao, HZ, Wang, L, Lee, TP, Jiang, H, Tan, YX, Yuan, SX, Hou, GJ, Tao, QF, Xu, QG, Zhang, XQ, Wu, MC, Xu, X, Wang, J, Yang, HM, Zhou, WP & Wang, HY 2016, 'Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma', Nature Communications, vol. 7, 12992. https://doi.org/10.1038/ncomms12992

TY - JOUR

T1 - Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma

AU - Zhao, Ling Hao

AU - Liu, Xiao

AU - Yan, He Xin

AU - Li, Wei Yang

AU - Zeng, Xi

AU - Yang, Yuan

AU - Zhao, Jie

AU - Liu, Shi Ping

AU - Zhuang, Xue Han

AU - Lin, Chuan

AU - Qin, Chen Jie

AU - Zhao, Yi

AU - Pan, Ze Ya

AU - Huang, Gang

AU - Liu, Hui

AU - Zhang, Jin

AU - Wang, Ruo Yu

AU - Yang, Yun

AU - Wen, Wen

AU - Lv, Gui Shuai

AU - Zhang, Hui Lu

AU - Wu, Han

AU - Huang, Shuai

AU - Wang, Ming Da

AU - Tang, Liang

AU - Cao, Hong Zhi

AU - Wang, Ling

AU - Lee, T. P.

AU - Jiang, Hui

AU - Tan, Ye Xiong

AU - Yuan, Sheng Xian

AU - Hou, Guo Jun

AU - Tao, Qi Fei

AU - Xu, Qin Guo

AU - Zhang, Xiu Qing

AU - Wu, Meng Chao

AU - Xu, Xun

AU - Wang, Jun

AU - Yang, Huan Ming

AU - Zhou, Wei Ping

AU - Wang, Hong Yang

PY - 2016/10/5

Y1 - 2016/10/5

N2 - Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation.

AB - Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation.

UR - https://www.scopus.com/pages/publications/84990922469

U2 - 10.1038/ncomms12992

DO - 10.1038/ncomms12992

M3 - 文章

C2 - 27703150

AN - SCOPUS:84990922469

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 12992

ER -

Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma

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