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Identification and characterization of a prevalent hepatitis B virus X protein mutant in Taiwanese patients with hepatocellular carcinoma

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Abstract

The aim of this study was to investigate whether there was a particular hepatitis B virus (HBV) X protein (HBx) mutant associated with Taiwanese patients with hepatocellular carcinoma (HCC). Initially, the entire coding region of HBx gene from the serum samples of 14 Taiwanese patients were sequenced. A novel mutant, HBx-A31, was preferentially found in patients with HCC. Sera from 67 patients with HCC and 100 patients with chronic hepatitis B were thus subjected for codon 31 analysis using a dual amplification created restriction site method. HBx-A31 was detected more frequently in patients with HCC (52% versus 12%; P<0.001) and in patients with liver cirrhosis (44% versus 6%; P<0.001). Site directed mutagenesis experiment revealed that HBx-A31 was less effective in transactivating HBV enhancer I-X promoter complex, less efficient in supporting HBV replication, and less potent in enhancing TNF-α induced increment of CPP32/caspase 3 activities in HepG2 cells. In conclusion, a prevalent HBx mutant was identified in Taiwanese patients with hepatocellular carcinoma. Development of this mutant might represent a strategy of the virus to escape immune surveillance and thus contribute to the process of multiple-step hepatocarcinogenesis.

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Acknowledgements

This study is supported by grants from Chang Gung Medical Research Council (CMRP 605/996) and National Science Council, Taiwan (NSC 89-2315-B-182-003).

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Authors and Affiliations

  1. Liver Research Unit, Chang Gung Memorial Hospital, 199 Tung Hwa North Road, Taipei, 105, Taiwan

    Chau-Ting Yeh, Chien-Hong Shen, Dar-In Tai, Chia-Ming Chu & Yun-Fan Liaw

  2. Chang Gung University School of Medicine, Taipei, 105, Taiwan

    Chau-Ting Yeh, Chien-Hong Shen, Dar-In Tai, Chia-Ming Chu & Yun-Fan Liaw

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  1. Chau-Ting Yeh
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  2. Chien-Hong Shen
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Yeh, CT., Shen, CH., Tai, DI. et al. Identification and characterization of a prevalent hepatitis B virus X protein mutant in Taiwanese patients with hepatocellular carcinoma. Oncogene 19, 5213–5220 (2000). https://doi.org/10.1038/sj.onc.1203903

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