Integration Site Preference of Xenotropic Murine Leukemia Virus-Related Virus, a New Human Retrovirus Associated with Prostate Cancer

被引：84

作者：

Kim, Sanggu ^{[1
]}

Kim, Namshin ^{[3
]}

Dong, Beihua ^{[5
]}

Boren, David ^{[2
]}

Lee, Serena A. ^{[2
]}

Das Gupta, Jaydip ^{[5
]}

Gaughan, Christina ^{[5
]}

Klein, Eric A. ^{[6
]}

Lee, Christopher ^{[3
]}

Silverman, Robert H. ^{[5
]}

Chow, Samson A. ^{[1
,2
,3
,4
]}

机构：

[1] Univ Calif Los Angeles, Sch Med, Biomed Engn Interdept Program, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Sch Med, Inst Mol Biol, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Sch Med, UCLA AIDS Inst, Los Angeles, CA 90095 USA

[5] Cleveland Clin, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA

[6] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44195 USA

来源：

JOURNAL OF VIROLOGY | 2008年 / 82卷 / 20期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1128/JVI.01299-08

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Xenotropic murine leukemia virus-related virus (XMRV) is a new human gammaretrovirus identified in prostate cancer tissue from patients homozygous for a reduced-activity variant of the antiviral enzyme RNase L. Neither a casual relationship between XMRV infection and prostate cancer nor a mechanism of tumorigenesis has been established. To determine the integration site preferences of XMRV and the potential risk of proviral insertional mutagenesis, we carried out a genome-wide analysis of viral integration sites in the prostate cell line DU145 after an acute XMRV infection and compared the integration site pattern of XMRV with those found for murine leukemia virus and two human retroviruses, human immunodeficiency virus type 1 and human T-cell leukemia virus type 1. Among all retroviruses analyzed, XMRV has the strongest preference for transcription start sites, CpG islands, DNase-hypersensitive sites, and gene-dense regions; all are features frequently associated with structurally open transcription regulatory regions of a chromosome. Analyses of XMRV integration sites in tissues from prostate cancer patients found a similar preference for the aforementioned chromosomal features. Additionally, XMRV integration sites in cancer tissues were associated with cancer breakpoints, common fragile sites, microRNA, and cancer-related genes, suggesting a selection process that favors certain chromosomal integration sites. In both acutely infected cells and cancer tissues, no common integration site was detected within or near proto-oncogenes or tumor suppressor genes. These results are consistent with a model in which XMRV may contribute to tumorigenicity via a paracrine mechanism.

引用

页码：9964 / 9977

页数：14

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