Abstract

XMRV is a gammaretrovirus associated in some studies with human prostate cancer and chronic fatigue syndrome. Central to the hypothesis of XMRV as a human pathogen is the description of integration sites in DNA from prostate tumour tissues. Here we demonstrate that 2 of 14 patient-derived sites are identical to sites cloned in the same laboratory from experimentally infected DU145 cells. Identical integration sites have never previously been described in any retrovirus infection. We propose that the patient-derived sites are the result of PCR contamination. This observation further undermines the notion that XMRV is a genuine human pathogen.

Highlights

  • XMRV was originally described in 2006 in the tumour tissue of patients with a familial form of prostate cancer associated with mutations that impair the function of the antiviral defence protein RNase L [1]

  • Current knowledge based on the analysis of several thousand retroviral integration sites suggests that target site selection is not primarily sequence-specific, different classes of retrovirus exhibit distinct genome location biases [10]

  • HIV-1 for example appears to favour integration into transcription units whereas MLV tends to integrate near transcription start sites and CpG islands

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Summary

Introduction

XMRV was originally described in 2006 in the tumour tissue of patients with a familial form of prostate cancer associated with mutations that impair the function of the antiviral defence protein RNase L [1]. The considerable potential for false positives arising from minute traces of murine DNA contaminating test samples or reagents has been clearly demonstrated as has the risk of erroneous results due to contamination from human tumour cell lines infected with XMRV (e.g. 22Rv1) or other xenotropic MLVs acquired by xenografting in mice [6].

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