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Basic Characteristics of Mutations
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Mutation Site
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S42P |
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Mutation Site Sentence
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Furthermore, mutations across the HBV X gene, such as the amino acid (aa) alterations of V5M, S42P, V88F, H94Y, V/I127D/N, K130M and V131I, displayed a significant upward trend associated with liver disease progression to HCC. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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X |
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Standardized Encoding Gene
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X
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Genotype/Subtype
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D;B;C |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Carcinoma, Hepatocellular
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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China |
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Literature Information
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PMID
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36102940
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Title
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Compartmentalisation of Hepatitis B virus X gene evolution in hepatocellular carcinoma microenvironment and the genotype-phenotype correlation of tumorigenicity in HBV-related patients with hepatocellular carcinoma
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Author
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Fu Y,Fang F,Guo H,Xiao X,Hu Y,Zeng Y,Chen T,Wu S,Lin N,Huang J,Jiang L,Ou Q,Liu C
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Journal
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Emerging microbes & infections
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Journal Info
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2022 Dec;11(1):2486-2501
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Abstract
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Hepatitis B virus (HBV) exists as quasispecies (QS). However, the evolutionary characteristics of haplotypes of HBV X gene in the hepatocellular carcinoma (HCC) microenvironment remain unclear. Mutations across X gene are essential for the tumorigenicity of HBV X protein (HBx). However, the functional phenotypes of many mutant HBx remain unknown. This study aims to compare the characteristics of X gene evolution between tumour and non-tumour tissues in HCC patients and investigate the tumorigenic phenotype of HBx harbouring mutation T81P/S101P/L123S. This study included 24 HCC patients. Molecular cloning of X gene was performed to analyse characteristics of haplotypes in liver tissues. HCC cell lines stably expressing wild-type or mutant HBx and subcutaneous tumour xenograft mouse model were used to assess HBx-T81P/S101P/L123S tumorigenicity. The mean heterogeneity of HBV QS across X gene in tumour tissues was lower than that in non-tumour tissues. A location bias was observed in X gene clones with genotype C or D in tumour tissues compared to those with genotype B. Mutations in genotype-C or - D clones were mainly clustered in the dimerization region and aa110-aa140 within the transactivation region. A novel mutation combination at residues 81, 101 and 123 was identified in tumour tissues. Further, HBx-T81P/S101P/L123S promotes cell proliferation and increases genomic instability, which was mediated by MYC. This study elucidates the compartmentalized evolution patterns of HBV X gene between intra tumour and non-tumour tissues in HCC patients and provides a new mechanism underlying HBV-driven hepatocarcinogenesis, suggesting a potential viral marker for monitoring HCC.
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Sequence Data
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-
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