Abstract

Abstract A novel gammaretrovirus named xenotropic MuLV-related retrovirus (XMRV) has been recently identified with 40 % prevalence in prostate tumor samples from US American patients carrying a homozygous R462Q mutation in the RNASEL gene. This mutation impairs the function of the innate antiviral type I interferon pathway and is a known susceptibility factor for prostate cancer. In subsequent studies, analyzing small European cohorts of prostate cancer patients a less significant prevalence and correlation of the QQ-phenotype with XMRV has been found or even a complete absence of viral traces was reported. A second independent report from the US found XMRV DNA in 6% and XMRV protein expression in 23% of prostate cancers. Contrary to the initial report the XMRV infection was not associated with this common variant of RNASEL and predominantly observed in malignant epithelial cells. We aimed to determine the prevalence of XMRV in prostate cancer patients who had undergone radical prostatectomy at the Charité hospital in Berlin, Germany between 2000 and 2006. To validate the association of the XMRV infection with the R462Q polymorphism, we first genotyped our 589 prostate tumour samples for the G-to-A transition at nt1385 of the RNASEL gene. Using nested PCR and RT-PCR approaches, DNA and RNA samples of prostate cancer (PCa) patients with varying degrees of malignancy were screened for the presence of XMRV specific gag sequences. Furthermore 146 sera samples from PCa patients were tested for XMRV Gag and Env antibodies with a newly developed ELISA assay. Genotyping our patients revealed the presence of the minor allele (QQ genotype) in 76 samples (12.9 %). Although using highly sensitive PCR-based detection methods we could not detect XMRV specific sequences either at the DNA or RNA level. Consistent with this result, all analysed sera from prostate cancer patients did not contain XMRV specific antibodies. Our results indicate a complete absence or at least a much lower prevalence of XMRV in prostate tumour patients in Germany. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4675.

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