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: 2.19).
04/2010; 75(4):755-61. DOI: 10.1016/j.urology.2010.01.038
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.
Available from: Mazaher Khodabandehloo
- "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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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.
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.
We conclude that in our population XMRV does not play a role in genesis of prostate cancer.
Available from: Simin Rezaei
- "A gammaretrovirus named xenotropic murine leukemia virus-related virus (XMRV) was identified in cDNA samples from seven of 11 R462Q homozygous (QQ) cases using a novel DNA microarray (Virochip) containing oligonucleotides comprising conserved sequences from known viral genomes . However, the association of XMRV with the QQ RNASEL variant was observed in some  but not all studies [4,5]. XMRV was reportedly linked with higher-grade PC cancers suggesting that its presence may be a useful biomarker for severe disease . "
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Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus reported to be associated with prostate cancer (PC) and chronic fatigue syndrome (CFS). While the association of XMRV with CFS and PC has recently been discredited, no studies have been performed in Australian patients to investigate the association between PC and XMRV or related murine leukemia virus (MLV) in matched PC and normal tissue.
Genomic DNA (gDNA) was purified from matched normal and cancer formalin-fixed paraffin-embedded (FFPE) prostate tissue from 35 Australian PC patients with Gleason scores ranging from 7 – 10. The presence of the ribonuclease L (RNase L) polymorphism R462Q was determined by allele specific PCR. Samples were screened for XMRV and related murine leukemia virus (MLV) variants by qPCR. Contaminating mouse DNA was detected using qPCR targeting mouse intracisternal A particle long terminal repeat DNA.
gDNA was successfully purified from 94% (66/70) of normal and cancer FFPE prostate tissues. RNase L typing revealed 8% were homozygous (QQ), 60% were heterozygous (RQ) and 32% were wild-type (RR) for the RNase L mutation. None of the 66 samples tested were positive for XMRV or related MLV sequences using broad MLV or XMRV specific primers with detection sensitivities of 1 viral copy of MLV/XMRV and XMRV DNA, respectively.
Using highly sensitive qPCR we found no evidence of XMRV or related gammaretroviruses in prostate tissues from 35 Australian PC patients. Our findings are consistent with other studies demonstrating that XMRV is a laboratory contaminant that has no role in the aetiology of PC.
Available from: Harriet C T Groom
- "However, this serum was from a low PSA control individual and therefore there was no association with PC. This neutralisation assay was similar to that used by Arnold et al., except that the pseudotyped virus-like particles used were based on MLV rather than HIV . This conceivably represents a false positive result due to epitope cross-reactivity. "
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ABSTRACT: The prevalence of specific infections in UK prostate cancer patients was investigated. Serum from 84 patients and 62 controls was tested for neutralisation of xenotropic murine leukaemia virus-related virus (XMRV) Envelope. No reactivity was found in the patient samples. In addition, a further 100 prostate DNA samples were tested for XMRV, BK virus, Trichomonas vaginalis and human papilloma viruses by nucleic acid detection techniques. Despite demonstrating DNA integrity and assay sensitivity, we failed to detect the presence of any of these agents in DNA samples, bar one sample that was weakly positive for HPV16. Therefore we conclude that these infections are absent in this typical cohort of men with prostate cancer.
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