Distinct hepatitis B virus integration patterns in hepatocellular carcinoma and adjacent normal liver tissue. Issue 6 (15th March 2017)

• Record Type: Journal Article
• Authors: Yang, Xiaobo; Wu, Liangcai; Lin, Jianzhen; Wang, Anqiang; Wan, Xueshuai; Wu, Yan; Robson, Simon C.; Sang, Xinting; Zhao, Haitao
• Is Part Of: International journal of cancer. Volume 140:Issue 6(2017:Mar. 15)
• Page Start: 1324
• Page End: 1330
• Publication Date: 2017-03-15
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.30547
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Infection by the hepatitis B virus (HBV) is one of the main etiologies of hepatocellular carcinoma (HCC). During chronic infection, HBV DNA can integrate into the human genome, and this has been postulated as a possible mechanism of HBV‐induced HCC. In this study we used 2199 HBV integration sites from Dr.VIS v2.0 and mapped them to the human genome (hg19) to obtain viral integration sites (VIS) related to protein‐coding and non‐protein‐coding genes. In total, we found 1, 377 and 767 VIS within close proximity to protein coding genes and noncoding genes, respectively. Genes affected more than two times included 23.1% of protein‐coding genes and 24.7% of long noncoding RNAs (lncRNA). Only 4.8% of VIS were shared between HCC and non‐tumor tissues. HBV integrations were more common in chromosomes 5, 8, 10, and 19 in HCC tissue and chromosomes 1 and 2 in non‐tumorous tissue. The number of integration sites on each chromosome correlated with the number of fragile sites in non‐tumorous tissue but not in HCC tissue. Functional enrichment analysis of the protein‐coding genes containing or in close proximity to HBV integration sites in HCC tissue showed an enrichment of cancer related gene ontology terms. Additionally, the most frequently associated lncRNA genes were related to telomere maintenance, protein modification processes, and chromosome localization. Thus, HBV may have preferred integration sites in the human genome that serve a critical role in HCC development. These results show that HCC treatment may benefit from the development of next generation anti‐viral therapies. Abstract : What's new? During chronic infection, the hepatitis B virus (HBV) can integrate into chromosomal DNA, possibly inducing hepatocellular carcinoma (HCC). In this study, the authors found that the HBV‐integration pattern in chromosomes of HCC cells was distinctly different than that in normal liver tissue. For example, in HCC cells, the virus had often integrated close to genes that regulate important oncogenic pathways. In addition, the study identified several novel HBV‐integration hotspot long noncoding RNAs (lncRNAs), which were related to telomere maintenance and chromosome localization.