title: Genome-wide Analysis of Epstein-Barr Virus (EBV) Integration and Strain in C666-1 and Raji Cells.
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.
authors.affiliation: 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.
authors.forename: Kai
authors.initials: K
authors.lastname: Xiao
authors.affiliation: 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.
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Yu
authors.affiliation: 3. Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China.
authors.forename: Xiayu
authors.initials: X
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Ke
authors.initials: K
authors.lastname: Tang
authors.affiliation: 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.
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Tu
authors.affiliation: 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.
authors.forename: Peng
authors.initials: P
authors.lastname: Qi
authors.affiliation: 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.
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Liao
authors.affiliation: 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.
authors.forename: Pan
authors.initials: P
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: 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.
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
keywords: Burkitt lymphoma (BL); C666-1; Epstein-Barr Virus (EBV); Nasopharyngeal carcinoma (NPC); Raji; Whole genome sequencing
references.citation: Tumour Biol. 2016 Mar;37(3):3683-95
references.pmid: 26462838
references.citation: Tumour Biol. 2015 Feb;36(2):675-83
references.pmid: 25286756
references.citation: Sci China Life Sci. 2014 Mar;57(3):315-26
references.pmid: 24532457
references.citation: J Natl Cancer Inst. 1966 Oct;37(4):547-59
references.pmid: 4288580
references.citation: J Virol. 1991 Mar;65(3):1245-54
references.pmid: 1847452
references.citation: Int J Cancer. 2013 Apr 15;132(8):1781-9
references.pmid: 22987500
references.citation: J Virol. 2013 Jan;87(2):1172-82
references.pmid: 23152513
references.citation: Mol Biol Evol. 2011 Oct;28(10):2731-9
references.pmid: 21546353
references.citation: Nat Methods. 2011 Jun 12;8(8):652-4
references.pmid: 21666668
references.citation: Genome Res. 2012 Apr;22(4):593-601
references.pmid: 22267523
references.citation: Sci China Life Sci. 2015 Aug;58(8):778-86
references.pmid: 26117827
references.citation: J Virol. 2014 Sep;88(18):10662-72
references.pmid: 24991008
references.citation: FEBS J. 2014 Nov;281(21):4815-29
references.pmid: 25161098
references.citation: Virology. 2006 Jun 20;350(1):164-70
references.pmid: 16490228
references.citation: Sci China Life Sci. 2014 Nov;57(11):1140-8
references.pmid: 25326069
references.citation: BMC Genomics. 2013 Nov 19;14:804
references.pmid: 24252203
references.citation: Bioinformatics. 2009 Aug 15;25(16):2078-9
references.pmid: 19505943
references.citation: Nucleic Acids Res. 2002 Jul 15;30(14):3059-66
references.pmid: 12136088
references.citation: J Virol. 1997 Jul;71(7):5688-91
references.pmid: 9188650
references.citation: Sci China Life Sci. 2011 Oct;54(10):966-75
references.pmid: 22038010
references.citation: Clin Transl Oncol. 2016 Feb;18(2):206-11
references.pmid: 26260913
references.citation: Int J Cancer. 1999 Sep 24;83(1):121-6
references.pmid: 10449618
references.citation: J Mol Histol. 2012 Jun;43(3):297-306
references.pmid: 22391627
references.citation: PLoS One. 2014 Nov 25;9(11):e110674
references.pmid: 25422887
references.citation: Sci China Life Sci. 2014 Jul;57(7):737-8
references.pmid: 24969704
references.citation: J Virol Methods. 2006 Sep;136(1-2):193-9
references.pmid: 16806502
references.citation: Sci China Life Sci. 2015 Aug;58(8):818-20
references.pmid: 26199186
references.citation: Cell. 2012 Jul 20;150(2):402-12
references.pmid: 22817899
references.citation: J Mol Histol. 2013 Oct;44(5):545-54
references.pmid: 23529758
references.citation: Cell. 2012 Mar 2;148(5):873-85
references.pmid: 22385957
references.citation: Sci China Life Sci. 2015 May;58(5):515-6
references.pmid: 25929972
references.citation: PLoS One. 2012;7(5):e36939
references.pmid: 22590638
references.citation: Nature. 2012 Apr 15;485(7397):260-3
references.pmid: 22504184
references.citation: Mol Cell Biochem. 2016 Jan;411(1-2):57-71
references.pmid: 26407966
references.citation: Genome Res. 2009 Jun;19(6):1124-32
references.pmid: 19420381
references.citation: PLoS One. 2013 May 01;8(5):e62869
references.pmid: 23650533
references.citation: Nature. 1984 Jul 19-25;310(5974):207-11
references.pmid: 6087149
references.citation: J Virol. 2011 Nov;85(21):11291-9
references.pmid: 21880770
references.citation: Sci China Life Sci. 2015 Jun;58(6):619-20
references.pmid: 25951934
references.citation: PLoS Genet. 2013;9(1):e1003147
references.pmid: 23326239
references.citation: Oncotarget. 2015 Dec 8;6(39):41766-82
references.pmid: 26497204
references.citation: Blood. 2013 May 2;121(18):3541-2
references.pmid: 23640993
references.citation: Nat Methods. 2009 Jan;6(1):99-103
references.pmid: 19043412
references.citation: Bioinformatics. 2009 Jul 15;25(14):1754-60
references.pmid: 19451168
references.citation: Oncotarget. 2015 Aug 21;6(24):20404-18
references.pmid: 26246469
references.citation: Oncogene. 2014 Apr 17;33(16):2098-109
references.pmid: 23708661
references.citation: Am J Pathol. 2004 Mar;164(3):967-74
references.pmid: 14982850
references.citation: Ann Oncol. 1997;8 Suppl 2:131-5
references.pmid: 9209656
references.citation: Virus Res. 1989 Jan;12(1):53-9
references.pmid: 2541582
references.citation: Cancer Res. 2004 Mar 15;64(6):1972-4
references.pmid: 15026332
references.citation: Nucleic Acids Res. 2010 Sep;38(16):e164
references.pmid: 20601685
references.citation: Tumour Biol. 2016 Jan;37(1):729-37
references.pmid: 26245991
references.citation: J Virol. 2005 Dec;79(24):15323-30
references.pmid: 16306603
references.citation: Genet Med. 2006 Mar;8(3):156-60
references.pmid: 16540749
references.citation: Genome Res. 2010 Feb;20(2):265-72
references.pmid: 20019144