Distribution and difference of APOBEC-induced mutations in the TpCpW context of HBV DNA between HCC and non-HCC
Distribution and difference of APOBEC-induced mutations in the TpCpW context of HBV DNA between HCC and non-HCC
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APOBEC 诱导的 HCC 和非 HCC HBV DNA TpCpW 背景突变的分布和差异。
DOI：
10.1002/jmv.25572
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发表时间：
2019-08-29
影响因子：
12.7
通讯作者：
Guo, YanHai
中科院分区：
文献类型：
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作者：
Ren, FengLing;Li, WeiNa;Guo, YanHai
乙型肝炎病毒(HBVDNA)DNA容易被人载脂蛋白B(ApoB)mRNA编辑酶催化多肽样(APOBEC)胞苷脱氨酶编辑。然而，APOBEC诱导的HBVDNA突变的分布还没有得到很好的描述。为此，我们从NCBI数据库中获得了有肝细胞癌和无肝细胞癌的乙肝病毒感染者的HBVDNA序列，并计算了APOBEC诱导的TpCpW->；TpKpW突变在HBVDNA中的发生率。结果表明，APOBEC诱导的突变主要分布在非肝癌来源的HBVDNA的负链(r(Apo)=2.04)，而正链的突变较弱(r(Apo)=0.99)。HBVDNA1~1000个核苷酸(NTS)负链和1000~1500个核苷酸(NTS)正链有较高的APOBEC诱变区，1~1000NTS区突变以TpCpW-GT、TpTpW突变为主(总T/G：111/18)，错义/同义突变(P基因35/94，S基因17/15，X基因5/10)。肝细胞癌患者外周血中HBVdna负链与正链载脂蛋白的差值(Apo)(1.96)大于非肝细胞癌组(1.05)。肝癌来源的HBVDNA 1000~1500和1500~2000 nts区域的负链r(Apo)也高于非肝癌来源的相同区域(r(Apo)=1.2和1.1)。最后，用负链与正链r的比值(Apo)来区分肝癌来源的HBVDNA和非肝癌来源的HBVDNA。本研究揭示了APOBEC诱导的肝细胞癌和非肝细胞癌标本中HBVDNA双链突变的分布特征。我们的发现将有助于了解APOBEC对HBVDNA的作用机制，并可能为肝癌的筛查提供重要的启示。
Hepatitis B virus (HBV) DNA is vulnerable to editing by human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) cytidine deaminases. However, the distribution of APOBEC-induced mutations on HBV DNA is not well characterized. To this end, we obtained the HBV DNA sequence of HBV-infected individuals with and without hepatocellular carcinoma (HCC and non-HCC groups, respectively) from NCBI database and calculated the r(apo) values of APOBEC-induced TpCpW -> TpKpW mutation prevalence in HBV DNA. The results showed that the APOBEC-induced mutations were mainly distributed in the minus strand of non-HCC-derived HBV DNA (r(apo) = 2.04), while the mutation on the plus-strand was weaker (r(apo) = 0.99). There were high APOBEC-induced mutation regions in the minus strand of HBV DNA 1 to 1000 nucleotides (nts) region and in the plus-strand of HBV DNA 1000 to 1500 nts region; the mutations in the 1 to 1000 nts region were mainly TpCpW -> TpTpW mutation types (total T/G: 111/18) and a number of these were missense mutations (missense/synonymous: 35/94 in P gene, 17/15 in S gene, and 5/10 in X gene). The difference between minus to plus-strand r(apo) of HCC-derived HBV DNA (1.96) was greater than that of the non-HCC group (1.05). The minus-strand r(apo) of HCC-derived HBV DNA regions 1000 to1500nts and 1500 to 2000 nts (r(apo )=( )4.2 and 4.2) was also higher than that of the same regions of non-HCC-derived HBV DNA (r(apo) = 1.2 and 1.1). Finally, the ratio of minus to plus-strand r(apo) was used to distinguish HCC-derived HBV DNA from non-HCC-derived HBV DNA. This study unraveled the distribution characteristics of APOBEC-induced mutations on double strands of HBV DNA from HCC and non-HCC samples. Our findings would help understand the mechanism of APOBECs on HBV DNA and may provide important insights for the screening of HCC.