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J Cancer 2016; 7(2):214-224. doi:10.7150/jca.13150 This issue Cite

Research Paper

Genome-wide Analysis of Epstein-Barr Virus (EBV) Integration and Strain in C666-1 and Raji Cells

Kai Xiao^1,2,3, Zhengyuan Yu², Xiayu Li³, Xiaoling Li^1,2,3, Ke Tang², Chaofeng Tu², Peng Qi², Qianjin Liao^1,2, Pan Chen^1,2, Zhaoyang Zeng^1,2,3, Guiyuan Li^1,2,3, Wei Xiong^1,2,3✉

1. Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410013, China.
2. Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, 410078, China.
3. Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China.

✉ Corresponding author: Wei Xiong, Cancer Research Institute and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha, Hunan, 410013, China. Telephone: +86-731-8480-5446. Fax: +86-731-8480-5383. Email: xiongweiedu.cn More

Abstract

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.

Keywords: Epstein-Barr Virus (EBV), Whole genome sequencing, Raji, C666-1, Nasopharyngeal carcinoma (NPC), Burkitt lymphoma (BL)

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