title: Gene copy number variations in the leukocyte genome of hepatocellular carcinoma patients with integrated hepatitis B virus DNA.
abstract: Integration of hepatitis B virus (HBV) DNA into the human liver cell genome is believed to promote HBV-related carcinogenesis. This study aimed to quantify the integration of HBV DNA into the leukocyte genome in hepatocellular carcinoma (HCC) patients in order to identify potential biomarkers for HBV-related diseases. Whole-genome comparative genomic hybridization (CGH) chip array analyses were performed to screen gene copy number variations (CNV) in the leukocyte genome, and the results were confirmed by quantitative polymerase chain reaction (qPCR). The commonly detected regions included chromosome arms 19p, 5q, 1q and 15p, where 200 copy number gain events and 270 copy number loss events were noted. In particular, gains were observed in 5q35.3 (OR4F3) and 19p13.3 (OR4F17) in 90% of the samples. Successful homologous recombination of OR4F3 and the HBV P gene was demonstrated, and the amplification at 5q35.3 is potentially associated with the integration of HBV P gene into natural killer cells isolated from peripheral blood mononuclear cells (PBMCs). Receiver operating characteristic (ROC) curve analysis indicated that the combination of OR4F3 and OR4F17 a novel potential biomarker of HBV-related diseases.
authors.affiliation: Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Pang
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Weixing
authors.initials: W
authors.lastname: Guo
authors.affiliation: Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Wang
authors.affiliation: Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Guixia
authors.initials: G
authors.lastname: Xu
authors.affiliation: Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Cheng
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, China.
authors.forename: Guangwen
authors.initials: G
authors.lastname: Cao
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Mengchao
authors.initials: M
authors.lastname: Wu
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Shuqun
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Shanrong
authors.initials: S
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000821:virology; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D006509:Hepatitis B / Q000150:complications* / Q000235:genetics / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000235:genetics*; D016662:Virus Integration / Q000235:genetics
chemical_list: D004279:DNA, Viral; D012333:RNA, Messenger; D014764:Viral Proteins
keywords: CGH; HBV-HCC; biomarker; integration