Research Papers:

Gene copy number variations in the leukocyte genome of hepatocellular carcinoma patients with integrated hepatitis B virus DNA

Yanan Pang, Weixing Guo, Jiaqi Wang, Guixia Xu, Kai Cheng, Guangwen Cao, Mengchao Wu, Shuqun Cheng and Shanrong Liu _

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Oncotarget. 2016; 7:8006-8018. https://doi.org/10.18632/oncotarget.6895

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Yanan Pang1,*, Weixing Guo2,*, Jiaqi Wang1,*, Guixia Xu1, Kai Cheng1, Guangwen Cao3, Mengchao Wu2, Shuqun Cheng2, Shanrong Liu1

1Changhai Hospital, Second Military Medical University, Shanghai, China

2Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China

3Department of Epidemiology, Second Military Medical University, Shanghai, China

*These authors have contributed equally to this work

Correspondence to:

Shanrong Liu, e-mail: [email protected]

Shuqun Cheng, e-mail: [email protected]

Keywords: HBV-HCC, CGH, integration, biomarker

Received: July 31, 2015     Accepted: January 01, 2016     Published: January 12, 2016


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.

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