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