Mouse DNA contamination in human tissue tested for XMRV

Area of Science:

• Virology
• Oncology
• Molecular Biology

Background:

• Xenotropic murine leukemia virus-related virus (XMRV) association with human diseases, including prostate cancer, is controversial.
• Previous XMRV identification in US patients contrasts with limited European findings.
• Concerns exist regarding sample contamination in retroviral studies.

Purpose of the Study:

• To investigate the prevalence of XMRV genetic sequences in human prostate cancer tissues.
• To assess the extent of mouse DNA contamination in these samples using sensitive assays.

Main Methods:

• PCR-based detection of XMRV sequences in formalin-fixed paraffin-embedded prostate tissues.
• Control assays for mouse mitochondrial DNA (mtDNA) and intracisternal A particle (IAP) DNA to detect contamination.
• Analysis of XMRV, IAP, and mtDNA sequences in prostate cancer samples.

Main Results:

• XMRV-like sequences were detected in 4.8% of prostate cancers, aligning with US prevalence.
• A significant percentage of samples, including XMRV-negative ones, tested positive for IAP sequences (21.5%).
• Many samples also showed positivity for mouse mtDNA, indicating widespread contamination.

Conclusions:

• Mouse DNA contamination is prevalent in laboratory specimens and detectable by sensitive assays like IAP PCR.
• Less sensitive assays, such as murine mtDNA PCR, may not reliably detect contamination.
• This study emphasizes the need for rigorous validation to prevent false associations between murine retroviruses and human diseases.