Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma

被引：714

作者：

Sung, Wing-Kin ^{[2
,3
,4
,5
]}

Zheng, Hancheng ^{[6
]}

Li, Shuyu ^{[1
]}

Chen, Ronghua ^{[8
]}

Liu, Xiao ^{[6
]}

Li, Yingrui ^{[6
]}

Lee, Nikki P. ^{[2
]}

Lee, Wah H. ^{[5
]}

Ariyaratne, Pramila N. ^{[5
]}

Tennakoon, Chandana ^{[3
,4
]}

Mulawadi, Fabianus H. ^{[5
]}

Wong, Kwong F. ^{[2
,7
,9
,10
]}

Liu, Angela M. ^{[2
,7
,9
,10
]}

Poon, Ronnie T. ^{[2
]}

Fan, Sheung Tat ^{[2
]}

Chan, Kwong L. ^{[2
]}

Gong, Zhuolin ^{[6
]}

Hu, Yujie ^{[6
]}

Lin, Zhao ^{[6
]}

Wang, Guan ^{[6
]}

Zhang, Qinghui ^{[6
]}

Barber, Thomas D. ^{[1
]}

Chou, Wen-Chi ^{[1
]}

Aggarwal, Amit ^{[1
]}

Hao, Ke

Zhou, Wei ^{[8
]}

Zhang, Chunsheng ^{[8
]}

Hardwick, James ^{[8
,11
]}

Buser, Carolyn

Xu, Jiangchun ^{[8
,12
]}

Kan, Zhengyan ^{[12
]}

Dai, Hongyue ^{[8
,12
]}

Mao, Mao ^{[11
]}

Reinhard, Christoph ^{[1
]}

Wang, Jun ^{[6
,13
,14
]}

Luk, John M. ^{[2
,7
,9
,10
]}

机构：

[1] Eli Lilly & Co, Indianapolis, IN 46285 USA

[2] Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China

[3] Natl Univ Singapore, Sch Comp, Singapore 117548, Singapore

[4] Natl Univ Singapore, NUS Grad Sch Integrat Sci & Engn, Singapore 117548, Singapore

[5] Genome Inst Singapore, Dept Computat & Syst Biol, Singapore, Singapore

[6] Beijing Genom Inst, Shenzhen, Peoples R China

[7] NUS, Canc Sci Inst, Singapore, Singapore

[8] Merck Res Labs, Boston, MA USA

[9] NUS, Dept Pharmacol, Singapore, Singapore

[10] NUS, Dept Surg, Singapore, Singapore

[11] Asian Canc Res Grp Inc, Wilmington, DE USA

[12] Pfizer Oncol, San Diego, CA USA

[13] Univ Copenhagen, Dept Biol, Copenhagen, Denmark

[14] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark

来源：

NATURE GENETICS | 2012年 / 44卷 / 07期

关键词：

B-VIRUS-DNA; CLINICAL-FEATURES; YOUNG-PATIENTS; CELL-LINE; RNA-SEQ; HEPATITIS; LIVER; GENE; IDENTIFICATION; MUTATIONS;

D O I：

10.1038/ng.2295

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

To survey hepatitis B virus (HBV) integration in liver cancer genomes, we conducted massively parallel sequencing of 81 HBV-positive and 7 HBV-negative hepatocellular carcinomas (HCCs) and adjacent normal tissues. We found that HBV integration is observed more frequently in the tumors (86.4%) than in adjacent liver tissues (30.7%). Copy-number variations (CNVs) were significantly increased at HBV breakpoint locations where chromosomal instability was likely induced. Approximately 40% of HBV breakpoints within the HBV genome were located within a 1,800-bp region where the viral enhancer, X gene and core gene are located. We also identified recurrent HBV integration events (in >= 4 HCCs) that were validated by RNA sequencing (RNA-seq) and Sanger sequencing at the known and putative cancer-related TERT, MLL4 and CCNE1 genes, which showed upregulated gene expression in tumor versus normal tissue. We also report evidence that suggests that the number of HBV integrations is associated with patient survival.

引用

页码：765 / U188

页数：6

共 30 条

[1] PRESENCE OF INTEGRATED HEPATITIS-B VIRUS-DNA SEQUENCES IN CELLULAR DNA OF HUMAN HEPATOCELLULAR-CARCINOMA [J].