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Arnold, R. S. et al. XMRV infection in prostate cancer patients: novel serologic assay and correlation with PCR and FISH. Urology 75, 755-761

Department of Chemistry, Emory University, Atlanta, Georgia, United States
Urology (Impact Factor: 2.13). 04/2010; 75(4):755-61. DOI: 10.1016/j.urology.2010.01.038
Source: PubMed

ABSTRACT To develop a serum-based assay to detect neutralizing antibodies to the xenotropic murine leukemia virus-related virus (XMRV) retrovirus and to use this assay with polymerase chain reaction and fluorescence in situ hybridization to identify patients with prostate cancer previously exposed to XMRV infection and those who carry XMRV viral sequences in their prostate.
Patients who had undergone radical prostatectomy were enrolled, and biologic specimens were obtained at surgery. The patients were genotyped for the R462Q RNASEL variant using a TaqMan genotyping assay on DNA from the peripheral blood. A serum assay that detects XMRV neutralizing antibodies was developed and used to determine which patients had serologic evidence of previous infection with XMRV virus. Some of these patients were also tested for the presence of XMRV nucleotide sequences in their prostate using polymerase chain reaction and fluorescence in situ hybridization analysis.
At a serum dilution of 1:150, our assay detected 11 (27.5%) of 40 patients with XMRV neutralizing antibodies, including 8 (40%) of 20 with the RNASEL genotype QQ and 3 (15%) of 20 with either the RQ or RR genotype. These results were in complete concordance with 2 other assays (polymerase chain reaction and fluorescence in situ hybridization), which were designed to detect XMRV infection.
XMRV infects some patients with prostate cancer. Neutralizing antibodies against XMRV correlated with 2 independent methods of detecting the virus in the prostate. The antibody response suggests that with clinical serologic assay development, it might be possible to screen patients for XMRV infection. The cases presented in the present report provided biologic samples that can be used for the development of a clinically relevant assay.

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    • "PCR assays described herein detected MLV provirus env sequences present in mouse genomic DNA (YAC-1 cells) agrees with result of other studies (Danielson et al., 2010; Tang et al., 2012; Rezaei et al., 2013). A high prevalence of XMRV has been reported in patients with prostate cancer and chronic fatigue syndrome (CFS) in the USA (Urisman et al., 2006; Schlaberg et al., 2009; Arnold et al., 2010). But, in Europe (Fischer et al., 2008; Hohn et al., 2009; Verhaegh et al., 2011), the USA, and recent study in Australia detection of XMRV in prostate (Aloia et al., 2010; Switzer et al., 2010; Rezaei et al., 2013), and breast cancer tissues (Khan et al., 2012) have been failed. "
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    ABSTRACT: Background: Multiple etiologies have been hypothesized for prostate cancer, including genetic defects and infectious agents. A recently reported gamaretrovirus, xenotropic murine leukemia virus-related virus (XMRV) has been reported to be detected in prostate cancer. However, this virus has not been detected in similar groups of patients in other studies. Herein, we sought to detect XMRV in prostate cancers and benign controls in Sanandaj, west of Iran. Materials and Methods: In a case-control study, genomic DNA was extracted from formalin fixed and paraffin embedded prostate tissues from a total of 163 Iranian patients. We developed a conventional and a nested PCR assay using primers targeting to an env specific sequence of XMRV. PCR assays were carried out on 63 prostate cancers and 100 benign prostate hyperplasias. Results: Beta-actin sequences were successfully detected in the DNA extracts from all prostate tissues, confirming DNA extraction integrity. We did not detect XMRV in samples either from prostate cancers or benign prostate hyperplasias using XMRV specific primers. Conclusions: We conclude that in our population XMRV does not play a role in genesis of prostate cancer.
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    • "The first of these is a gammaretrovirus, termed xenotropic murine leukaemia virusrelated virus (XMRV) discovered in human prostate carcinomas from patients who were homozygous for the anti-viral enzyme, ribonuclease L (Urisman et al, 2006). If confirmed, XMRV will become the fourth member of the retroviridae family to infect humans and the second to be associated with a human malignancy (Schlaberg et al, 2009; Knouf et al, 2009; Arnold et al, 2010). "
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    • "Findings from previous studies reporting higher prevalence for XMRV in similar cohorts [2] [11] [12] typically involved testing of prostate tumors. None of these studies reported the detection of XMRV in blood samples or the isolation of infectious virus from clinical specimens, and only one measured the presence of reactive antibodies through a virus neutralization assay [10]. Detection of antibody responses to specific viral proteins by ELISA or by reactivity to XMRV immunoblots was not assessed. "
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