Genome-wide Analysis of Epstein-Barr Virus (EBV) Integration and Strain in C666-1 and Raji Cells.
Genome-wide Analysis of Epstein-Barr Virus (EBV) Integration and Strain in C666-1 and Raji Cells.
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C666-1 和 Raji 细胞中 Epstein-Barr 病毒 (EBV) 整合和菌株的全基因组分析
DOI：
10.7150/jca.13150
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发表时间：
2016
影响因子：
3.9
通讯作者：
Xiong W
中科院分区：
文献类型：
--
作者：
Xiao K;Yu Z;Li X;Li X;Tang K;Tu C;Qi P;Liao Q;Chen P;Zeng Z;Li G;Xiong W
爱泼斯坦 - 巴尔病毒（EBV）是许多恶性疾病的关键风险因素，如鼻咽癌（NPC）和伯基特淋巴瘤（BL）。已有关于EBV整合的报道，但其规模以及对癌症发展的影响仍不明确。C666 - 1（鼻咽癌细胞系）和Raji（伯基特淋巴瘤细胞系）是常用作研究的EBV阳性癌细胞。以往研究通过传统方法仅在Raji细胞中发现极少数EBV整合位点。为深入研究EBV整合情况，我们利用下一代测序（NGS）技术对C666 - 1和Raji细胞的全基因组进行测序，在这两种细胞系中共检测到909个断点。此外，我们观察到整合位点的数量与染色体结构变异（SVs）和拷贝数结构变异（CNVs）的总量呈正相关，且大多数断点位于基因组结构变异区域内部或附近。这表明宿主基因组不稳定性一方面为EBV整合提供了机会，另一方面，EBV整合又加剧了宿主基因组的不稳定性。随后，我们分别组装了C666 - 1和Raji细胞中的EBV毒株，这将为EBV相关研究提供有用资源。因此，我们报告了对NPC细胞和BL细胞中EBV整合最为全面的特征描述，EBV呈现出广泛且随机的整合，从而增加了肿瘤发生的几率。与以往任何研究技术相比，NGS在EBV整合研究方面提供了无与伦比的分辨率水平，同时为获取病毒毒株提供了便捷途径。
EBV is a key risk factor for many malignancy diseases such as nasopharyngeal carcinoma (NPC) and Burkitt lymphoma (BL). EBV integration has been reported, but its scale and impact to cancer development is remains unclear. C666-1 (NPC cell line) and Raji (BL cell line) are commonly studied EBV-positive cancer cells. A rare few EBV integration sites in Raji were found in previous research by traditional methods. To deeply survey EBV integration, we sequenced C666-1 and Raji whole genomes by the next generation sequencing (NGS) technology and a total of 909 breakpoints were detected in the two cell lines. Moreover, we observed that the number of integration sites was positive correlated with the total amount of chromosome structural variations (SVs) and copy number structural variations (CNVs), and most breakpoints located inside or nearby genome structural variations regions. It suggested that host genome instability provided an opportunity for EBV integration on one hand and the integration aggravated host genome instability on the other hand. Then, we respectively assembled the C666-1 and Raji EBV strains which would be useful resources for EBV-relative studies. Thus, we report the most comprehensive characterization of EBV integration in NPC cell and BL cell, and EBV shows the wide range and random integration to increase the tumorigenesis. The NGS provides an incomparable level of resolution on EBV integration and a convenient approach to obtain viral strain compared to any research technology before.