In-depth investigation of archival and prospectively collected samples reveals no evidence for XMRV infection in prostate cancer.

In-depth investigation of archival and prospectively collected samples reveals no evidence for XMRV infection in prostate cancer.
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DOI:
10.1371/journal.pone.0044954
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Chiu CY
Chiu CY
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lee D;Das Gupta J;Gaughan C;Steffen I;Tang N;Luk KC;Qiu X;Urisman A;Fischer N;Molinaro R;Broz M;Schochetman G;Klein EA;Ganem D;Derisi JL;Simmons G;Hackett J Jr;Silverman RH;Chiu CY

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XMRV,或异嗜性小鼠白血病病毒(MLV)相关病毒,是一种新型的γ逆转录病毒,最初在2006年分析前列腺癌患者组织和2009年分析慢性疲劳综合征(CFS)患者血液的研究中发现。然而,随后的大量研究未能证实XMRV感染与CFS或前列腺癌之间的联系。相反,最近的证据表明,XMRV是一种污染物,来源于两种小鼠内源性逆转录病毒在小鼠前列腺肿瘤异种移植物(CWR22)传代过程中的重组,产生实验室来源的细胞系,是XMRV感染。为了证实或反驳XMRV与前列腺癌之间的关联,我们分析了前瞻性收集的39名患者的前列腺癌组织和血浆以及2006年原始研究的存档RNA和前列腺组织。尽管进行了全面的微阵列、PCR、FISH和血清学检测,但在任何新收集的样本或存档组织中均未检测到XMRV,尽管存档RNA仍为XMRV阳性。值得注意的是,衍生原型XMRV毒株的存档VP62前列腺组织在再分析时对XMRV测试为阴性。病毒基因组和人类线粒体序列的分析显示,所有先前表征的XMRV毒株是相同的,并且档案RNA已被XMRV感染的实验室细胞系污染。这些发现揭示了XMRV和前列腺癌之间没有关联,并强调了XMRV不是自然获得的人类感染的结论。
XMRV, or xenotropic murine leukemia virus (MLV)-related virus, is a novel gammaretrovirus originally identified in studies that analyzed tissue from prostate cancer patients in 2006 and blood from patients with chronic fatigue syndrome (CFS) in 2009. However, a large number of subsequent studies failed to confirm a link between XMRV infection and CFS or prostate cancer. On the contrary, recent evidence indicates that XMRV is a contaminant originating from the recombination of two mouse endogenous retroviruses during passaging of a prostate tumor xenograft (CWR22) in mice, generating laboratory-derived cell lines that are XMRV-infected. To confirm or refute an association between XMRV and prostate cancer, we analyzed prostate cancer tissues and plasma from a prospectively collected cohort of 39 patients as well as archival RNA and prostate tissue from the original 2006 study. Despite comprehensive microarray, PCR, FISH, and serological testing, XMRV was not detected in any of the newly collected samples or in archival tissue, although archival RNA remained XMRV-positive. Notably, archival VP62 prostate tissue, from which the prototype XMRV strain was derived, tested negative for XMRV on re-analysis. Analysis of viral genomic and human mitochondrial sequences revealed that all previously characterized XMRV strains are identical and that the archival RNA had been contaminated by an XMRV-infected laboratory cell line. These findings reveal no association between XMRV and prostate cancer, and underscore the conclusion that XMRV is not a naturally acquired human infection.
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