|
DVID
|
1007047 |
|
VISID
|
TVIS10015613 |
|
Chromosome
|
chr2 |
|
GRCh38 Location
|
212144709 |
|
Disease
|
Carcinoma, Hepatocellular |
|
Sample
|
Adjacent tissue |
|
Virus Reference Genome
|
AY800389.1;AY800390.1;AY800391.1;AY800392.1 |
|
Target Gene
|
ERBB4 |
Literature Information
|
PubMed PMID
|
23236287
|
|
Year
|
2012;8(12):e1003065 |
|
Journal
|
PLoS genetics |
|
Title
|
Recurrent targeted genes of hepatitis B virus in the liver cancer genomes identified by a next-generation sequencing-based approach. |
|
Author
|
Ding D,Lou X,Hua D,Yu W,Li L,Wang J,Gao F,Zhao N,Ren G,Li L,Lin B |
|
Evidence
|
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.
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HBV VIS Detail Information
