Recurrent targeted genes of hepatitis B virus in the liver cancer genomes identified by a next-generation sequencing-based approach.
Integration of the viral DNA into host chromosomes was found in most of the hepatitis B virus (HBV)-related hepatocellular carcinomas (HCCs). Here we devised a massive anchored parallel sequencing (MAPS) method using next-generation sequencing to isolate and sequence HBV integrants. Applying MAPS to...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003065&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850189797412306944 |
|---|---|
| author | Dong Ding Xiaoyan Lou Dasong Hua Wei Yu Lisha Li Jun Wang Feng Gao Na Zhao Guoping Ren Lanjuan Li Biaoyang Lin |
| author_facet | Dong Ding Xiaoyan Lou Dasong Hua Wei Yu Lisha Li Jun Wang Feng Gao Na Zhao Guoping Ren Lanjuan Li Biaoyang Lin |
| author_sort | Dong Ding |
| collection | DOAJ |
| description | Integration of the viral DNA into host chromosomes was found in most of the hepatitis B virus (HBV)-related hepatocellular carcinomas (HCCs). Here we devised a massive anchored parallel sequencing (MAPS) method using next-generation sequencing to isolate and sequence HBV integrants. Applying MAPS to 40 pairs of HBV-related HCC tissues (cancer and adjacent tissues), we identified 296 HBV integration events corresponding to 286 unique integration sites (UISs) with precise HBV-Human DNA junctions. HBV integration favored chromosome 17 and preferentially integrated into human transcript units. HBV targeted genes were enriched in GO terms: cAMP metabolic processes, T cell differentiation and activation, TGF beta receptor pathway, ncRNA catabolic process, and dsRNA fragmentation and cellular response to dsRNA. The HBV targeted genes include 7 genes (PTPRJ, CNTN6, IL12B, MYOM1, FNDC3B, LRFN2, FN1) containing IPR003961 (Fibronectin, type III domain), 7 genes (NRG3, MASP2, NELL1, LRP1B, ADAM21, NRXN1, FN1) containing IPR013032 (EGF-like region, conserved site), and three genes (PDE7A, PDE4B, PDE11A) containing IPR002073 (3', 5'-cyclic-nucleotide phosphodiesterase). Enriched pathways include hsa04512 (ECM-receptor interaction), hsa04510 (Focal adhesion), and hsa04012 (ErbB signaling pathway). Fewer integration events were found in cancers compared to cancer-adjacent tissues, suggesting a clonal expansion model in HCC development. Finally, we identified 8 genes that were recurrent target genes by HBV integration including fibronectin 1 (FN1) and telomerase reverse transcriptase (TERT1), two known recurrent target genes, and additional novel target genes such as SMAD family member 5 (SMAD5), phosphatase and actin regulator 4 (PHACTR4), and RNA binding protein fox-1 homolog (C. elegans) 1 (RBFOX1). Integrating analysis with recently published whole-genome sequencing analysis, we identified 14 additional recurrent HBV target genes, greatly expanding the HBV recurrent target list. This global survey of HBV integration events, together with recently published whole-genome sequencing analyses, furthered our understanding of the HBV-related HCC. |
| format | Article |
| id | doaj-art-1222e2cb822e42cb8a1ba9d3cb4b2558 |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-1222e2cb822e42cb8a1ba9d3cb4b25582025-08-20T02:15:30ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042012-01-01812e100306510.1371/journal.pgen.1003065Recurrent targeted genes of hepatitis B virus in the liver cancer genomes identified by a next-generation sequencing-based approach.Dong DingXiaoyan LouDasong HuaWei YuLisha LiJun WangFeng GaoNa ZhaoGuoping RenLanjuan LiBiaoyang LinIntegration of the viral DNA into host chromosomes was found in most of the hepatitis B virus (HBV)-related hepatocellular carcinomas (HCCs). Here we devised a massive anchored parallel sequencing (MAPS) method using next-generation sequencing to isolate and sequence HBV integrants. Applying MAPS to 40 pairs of HBV-related HCC tissues (cancer and adjacent tissues), we identified 296 HBV integration events corresponding to 286 unique integration sites (UISs) with precise HBV-Human DNA junctions. HBV integration favored chromosome 17 and preferentially integrated into human transcript units. HBV targeted genes were enriched in GO terms: cAMP metabolic processes, T cell differentiation and activation, TGF beta receptor pathway, ncRNA catabolic process, and dsRNA fragmentation and cellular response to dsRNA. The HBV targeted genes include 7 genes (PTPRJ, CNTN6, IL12B, MYOM1, FNDC3B, LRFN2, FN1) containing IPR003961 (Fibronectin, type III domain), 7 genes (NRG3, MASP2, NELL1, LRP1B, ADAM21, NRXN1, FN1) containing IPR013032 (EGF-like region, conserved site), and three genes (PDE7A, PDE4B, PDE11A) containing IPR002073 (3', 5'-cyclic-nucleotide phosphodiesterase). Enriched pathways include hsa04512 (ECM-receptor interaction), hsa04510 (Focal adhesion), and hsa04012 (ErbB signaling pathway). Fewer integration events were found in cancers compared to cancer-adjacent tissues, suggesting a clonal expansion model in HCC development. Finally, we identified 8 genes that were recurrent target genes by HBV integration including fibronectin 1 (FN1) and telomerase reverse transcriptase (TERT1), two known recurrent target genes, and additional novel target genes such as SMAD family member 5 (SMAD5), phosphatase and actin regulator 4 (PHACTR4), and RNA binding protein fox-1 homolog (C. elegans) 1 (RBFOX1). Integrating analysis with recently published whole-genome sequencing analysis, we identified 14 additional recurrent HBV target genes, greatly expanding the HBV recurrent target list. This global survey of HBV integration events, together with recently published whole-genome sequencing analyses, furthered our understanding of the HBV-related HCC.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003065&type=printable |
| spellingShingle | Dong Ding Xiaoyan Lou Dasong Hua Wei Yu Lisha Li Jun Wang Feng Gao Na Zhao Guoping Ren Lanjuan Li Biaoyang Lin Recurrent targeted genes of hepatitis B virus in the liver cancer genomes identified by a next-generation sequencing-based approach. PLoS Genetics |
| title | Recurrent targeted genes of hepatitis B virus in the liver cancer genomes identified by a next-generation sequencing-based approach. |
| title_full | Recurrent targeted genes of hepatitis B virus in the liver cancer genomes identified by a next-generation sequencing-based approach. |
| title_fullStr | Recurrent targeted genes of hepatitis B virus in the liver cancer genomes identified by a next-generation sequencing-based approach. |
| title_full_unstemmed | Recurrent targeted genes of hepatitis B virus in the liver cancer genomes identified by a next-generation sequencing-based approach. |
| title_short | Recurrent targeted genes of hepatitis B virus in the liver cancer genomes identified by a next-generation sequencing-based approach. |
| title_sort | recurrent targeted genes of hepatitis b virus in the liver cancer genomes identified by a next generation sequencing based approach |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003065&type=printable |
| work_keys_str_mv | AT dongding recurrenttargetedgenesofhepatitisbvirusinthelivercancergenomesidentifiedbyanextgenerationsequencingbasedapproach AT xiaoyanlou recurrenttargetedgenesofhepatitisbvirusinthelivercancergenomesidentifiedbyanextgenerationsequencingbasedapproach AT dasonghua recurrenttargetedgenesofhepatitisbvirusinthelivercancergenomesidentifiedbyanextgenerationsequencingbasedapproach AT weiyu recurrenttargetedgenesofhepatitisbvirusinthelivercancergenomesidentifiedbyanextgenerationsequencingbasedapproach AT lishali recurrenttargetedgenesofhepatitisbvirusinthelivercancergenomesidentifiedbyanextgenerationsequencingbasedapproach AT junwang recurrenttargetedgenesofhepatitisbvirusinthelivercancergenomesidentifiedbyanextgenerationsequencingbasedapproach AT fenggao recurrenttargetedgenesofhepatitisbvirusinthelivercancergenomesidentifiedbyanextgenerationsequencingbasedapproach AT nazhao recurrenttargetedgenesofhepatitisbvirusinthelivercancergenomesidentifiedbyanextgenerationsequencingbasedapproach AT guopingren recurrenttargetedgenesofhepatitisbvirusinthelivercancergenomesidentifiedbyanextgenerationsequencingbasedapproach AT lanjuanli recurrenttargetedgenesofhepatitisbvirusinthelivercancergenomesidentifiedbyanextgenerationsequencingbasedapproach AT biaoyanglin recurrenttargetedgenesofhepatitisbvirusinthelivercancergenomesidentifiedbyanextgenerationsequencingbasedapproach |