Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma

Sung, Wing-Kin; Zheng, Hancheng; Li, Shuyu; Chen, Ronghua; Liu, Xiao; Li, Yingrui; Lee, Nikki P; Lee, Wah H; Ariyaratne, Pramila N; Tennakoon, Chandana; Mulawadi, Fabianus H; Wong, Kwong F; Liu, Angela M; Poon, Ronnie T; Fan, Sheung Tat; Chan, Kwong L; Gong, Zhuolin; Hu, Yujie; Lin, Zhao; Wang, Guan
July 2012
Nature Genetics;Jul2012, Vol. 44 Issue 7, p765
Academic Journal
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.


Related Articles

  • Temporal relationship between hepatitis B virus enhancer II/basal core promoter sequence variation and risk of hepatocellular carcinoma. Chou, Y-C; Yu, M-W; Wu, C-F; Yang, S-Y; Lin, C-L; Liu, C-J; Shih, W-L; Chen, P-J; Liaw, Y-F; Chen, C-J // Gut;Jan2008, Vol. 57 Issue 1, p91 

    Background and aims: To investigate the temporal relationship between sequence variation in the enhancer II (EnhII), basal core promoter (BCP), and precore regions of hepatitis B virus (HBV) and the risk of hepatocellular carcinoma (HCC), we conducted a nested case-control study within a cohort...

  • Simultaneous Detection of Precore/Basal Core Promoter Mutations in Hepatitis B Virus Using Arrayed Primer Extension. Wai-Yan Ha; Chi-Chiu Lau; Yue, Patrick Y. K.; Hung, Kaman K. M.; Chan, Kelvin; Siu-Hon Chui; Chui, Albert K. K.; Wing-Cheong Yam; Wong, Ricky N. S. // Molecular Diagnosis & Therapy;Mar2006, Vol. 10 Issue 2, p125 

    Background: Hepatitis B is a major disease that causes serious public health problems worldwide. The loss of HBeAg expression due to point mutations or single nucleotide polymorphisms (SNPs) in the precore/basal core promoter region of the hepatitis B virus (HBV) is associated with...

  • Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma. Li, Meng; Zhao, Hong; Zhang, Xiaosong; Wood, Laura D.; Anders, Robert A.; Choti, Michael A.; Pawlik, Timothy M.; Daniel, Hubert D.; Kannangai, Rajesh; Offerhaus, G Johan A.; Velculescu, Victor E.; Wang, Linfang; Zhou, Shibin; Vogelstein, Bert; Hruban, Ralph H; Papadopoulos, Nick; Cai, Jianqiang; Torbenson, Michael S.; Kinzler, Kenneth W. // Nature Genetics;Sep2011, Vol. 43 Issue 9, p828 

    Through exomic sequencing of ten hepatitis C virus (HCV)-associated hepatocellular carcinomas (HCC) and subsequent evaluation of additional affected individuals, we discovered novel inactivating mutations of ARID2 in four major subtypes of HCC (HCV-associated HCC, hepatitis B virus...

  • Deep sequencing of the hepatitis B virus in hepatocellular carcinoma patients reveals enriched integration events, structural alterations and sequence variations. Toh, Soo Ting; Jin, Yu; Liu, Lizhen; Wang, Jingbo; Babrzadeh, Farbod; Gharizadeh, Baback; Ronaghi, Mostafa; Toh, Han Chong; Chow, Pierce Kah-Hoe; Chung, Alexander Y-F.; Ooi, London L-P-J.; Lee, Caroline G-L. // Carcinogenesis;Apr2013, Vol. 34 Issue 4, p787 

    Chronic hepatitis B virus (HBV) infection is epidemiologically associated with hepatocellular carcinoma (HCC), but its role in HCC remains poorly understood due to technological limitations. In this study, we systematically characterize HBV in HCC patients. HBV sequences were enriched from 48...

  • Effects of Hepatitis B Virus Mutations on its Replication and Liver Disease Severity. Hakami, Abdulrahim; Ali, Abdelwahid; Hakami, Ahmed // Open Virology Journal;2013, Vol. 7, p12 

    Hepatitis B virus (HBV), nowadays, is o n e o f th e major human pathogens worldwide. Approximately, 400 million people worldwide have chronic HBV infection. Only 5% of persons infected during adulthood develop chronic infection. The reverse is true for those infected at birth or in early...

  • Association of Hepatitis B Virus Pre-S Deletions with the Development of Hepatocellular Carcinoma in Qidong, China. Qu, Li-Shuai; Liu, Jin-Xia; Liu, Tao-Tao; Shen, Xi-Zhong; Chen, Tao-Yang; Ni, Zheng-Pin; Lu, Cui-Hua // PLoS ONE;May2014, Vol. 9 Issue 5, p1 

    Background/Aim: To investigate the roles of mutations in pre-S and S regions of hepatitis B virus (HBV) on the progression of hepatocellular carcinoma (HCC) in Qidong, China. Methods: We conducted an age matched case-control study within a cohort of 2387 male HBV carriers who were recruited from...

  • The Characteristic Changes in Hepatitis B Virus X Region for Hepatocellular Carcinoma: A Comprehensive Analysis Based on Global Data. Li, Wenwen; Goto, Kaku; Matsubara, Yasuo; Ito, Sayaka; Muroyama, Ryosuke; Li, Qiang; Kato, Naoya // PLoS ONE;May2015, Vol. 10 Issue 5, p1 

    Objectives: Mutations in hepatitis B virus (HBV) X region (HBx) play important roles in hepatocarcinogenesis while the results remain controversial. We sought to clarify potential hepatocellular carcinoma (HCC)-characteristic mutations in HBx from HBV genotype C-infected patients and the...

  • Profiling of Exome Mutations Associated with Progression of HBV-Related Hepatocellular Carcinoma. Woo, Hyun Goo; Kim, Soon Sun; Cho, Hyunwoo; Kwon, So Mee; Cho, Hyo Jung; Ahn, Seun Joo; Park, Eun Sung; Lee, Ju-Seog; Cho, Sung Won; Cheong, Jae Youn // PLoS ONE;Dec2014, Vol. 9 Issue 12, p1 

    Recent advances in sequencing technology have allowed us to profile genome-wide mutations of various cancer types, revealing huge heterogeneity of cancer genome variations. However, its heterogeneous landscape of somatic mutations according to liver cancer progression is not fully understood....

  • The influence of hepatitis B DNA level and antiviral therapy on recurrence after initial curative treatment in patients with hepatocellular carcinoma. Chuma, Makoto; Hige, Shuhei; Kamiyama, Toshiya; Meguro, Takashi; Nagasaka, Atsushi; Nakanishi, Kazuaki; Yamamoto, Yoshiya; Nakanishi, Mitsuru; Kohara, Toshihisa; Sho, Takuya; Yamamoto, Keiko; Horimoto, Hiromasa; Kobayashi, Tomoe; Yokoo, Hideki; Matsushita, Michiaki; Todo, Satoru; Asaka, Masahiro // Journal of Gastroenterology;2009, Vol. 44 Issue 9, p991 

    Prediction and prevention of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) recurrence is an important clinical issue. We investigated whether HBV DNA level and antiviral therapy are associated with HCC recurrence. This retrospective study involved 103 patients who underwent...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics