1Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, No.600 Tianhe Road, Guangzhou 510630, PR China.
2Genetic Testing Lab, Guangdong Provincial Hospital of Chinese Medicine, No. 111 Dade Road, Guangzhou 510120, PR China.
J Med Microbiol. 2018 Nov;67(11):1614-1627. doi: 10.1099/jmm.0.000839. Epub 2018 Sep 21.
About 10 % of gastric carcinoma worldwide is associated with EBV, which is defined as EBV-associated gastric carcinoma (EBVaGC). To date, EBV sequence data from EBVaGC in Guangdong, China, an endemic area of nasopharyngeal carcinoma (NPC), are not available. In the present study, two EBV genomes from EBVaGC specimens from Guangdong (designated as GDGC1 and GDGC2) were determined by next-generation sequencing, de novo assembly and joining of contigs by Sanger sequencing. In addition, we sequenced EBV from two Korean EBVaGC cell lines, YCCEL1 and SNU-719. Genomic diversity, including single nucleotide polymorphisms (SNPs) and insertions and deletions (indels), phylogenetic analysis and rates of protein evolution, was performed using bioinformatics software. The four gastric carcinoma-derived EBV (GC-EBV) were all type I. Compared with the reference EBV genome, a total of 1815 SNPs (146 indels), 1519 SNPs (106 indels), 1812 SNPs (126 indels) and 1484 SNPs (106 indels) were found in GDGC1, GDGC2, YCCEL1 and SNU-719, respectively. These variations were distributed across the entire genome, especially in latent genes. In contrast, the sequences of promoters and non-coding RNAs were strictly conserved. Phylogenetic analyses suggested the presence of at least two parental lineages of EBV among the GC-EBV genomes. Rates of protein evolution analyses showed that lytic genes were under purifying selection; in contrast, latency genes were under positive selection. In conclusion, this study determined the EBV genomes in EBVaGC from Guangdong and performed a detailed genome-wide analysis of GC-EBV, which would be helpful for further understanding of the relationship between EBV genomic variation and EBVaGC carcinogenesis.
全世界约有 10%的胃癌与 EBV 相关,被定义为 EBV 相关胃癌(EBVaGC)。迄今为止,中国广东鼻咽癌高发地区(NPC)的 EBVaGC 的 EBV 序列数据尚不可用。在本研究中,通过下一代测序、从头组装和 Sanger 测序拼接 contigs 确定了来自广东的 2 个 EBVaGC 标本中的 2 个 EBV 基因组(命名为 GDGC1 和 GDGC2)。此外,我们还对来自韩国的 2 个 EBVaGC 细胞系 YCCEL1 和 SNU-719 的 EBV 进行了测序。使用生物信息学软件对基因组多样性,包括单核苷酸多态性(SNP)和插入/缺失(indel)、系统发育分析和蛋白质进化率进行了分析。这 4 种胃癌衍生的 EBV(GC-EBV)均为 I 型。与参考 EBV 基因组相比,GDGC1、GDGC2、YCCEL1 和 SNU-719 中分别发现了 1815 个 SNPs(146 个 indels)、1519 个 SNPs(106 个 indels)、1812 个 SNPs(126 个 indels)和 1484 个 SNPs(106 个 indels)。这些变异分布在整个基因组中,尤其是在潜伏基因中。相比之下,启动子和非编码 RNA 的序列是严格保守的。系统发育分析表明,GC-EBV 基因组中至少存在 2 个 EBV 亲本谱系。蛋白质进化率分析表明,裂解基因受到纯化选择;相反,潜伏基因受到正选择。总之,本研究确定了广东 EBVaGC 中的 EBV 基因组,并对 GC-EBV 进行了详细的全基因组分析,这将有助于进一步了解 EBV 基因组变异与 EBVaGC 癌变之间的关系。