Abstract
BackgroundXenotropic 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.MethodsGenomic 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.ResultsgDNA 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.ConclusionsUsing 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.
Highlights
Prostate cancer (PC) is one of the most commonly diagnosed cancers in men resulting in approximately 3,300 deaths in Australia per year
Human vesicle-associated membrane protein 2 (VAMP2) quantitative PCR (qPCR) confirms integrity of DNA purified from formalin-fixed paraffin-embedded (FFPE) samples DNA derived from FFPE samples is expected to be fragmented due to the fixation process and may contain substances that are inhibitory for PCR amplification
The Blood Xenotropic murine leukemia virus-related virus (XMRV) Scientific Working Group’s findings, along with the discovery that XMRV is a virus generated by a rare recombination event in the laboratory has provided irrefutable evidence that XMRV or related murine leukemia virus (MLV) are not associated with chronic fatigue syndrome (CFS) [27,36,37]
Summary
Prostate cancer (PC) is one of the most commonly diagnosed cancers in men resulting in approximately 3,300 deaths in Australia per year. A gammaretrovirus named xenotropic murine leukemia virus-related virus (XMRV) was identified in cDNA samples from seven of 11 R462Q. XMRV is highly related to murine leukemia virus (MLV) sharing. In addition to PC, XMRV was associated with chronic fatigue syndrome (CFS) [6], which was remarkable since no other gammaretroviruses have been described that infect humans. 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
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