No evidence of XMRV in prostate cancer cohorts in the Midwestern United States

Toshie Sakuma, Stéphane Hué, Karen A. Squillace, Jason M. Tonne, Patrick R. Blackburn, Seiga Ohmine, Tayaramma Thatava, Greg J. Towers, Yasuhiro H Ikeda

Research output: Contribution to journalArticle

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Abstract

Background: Xenotropic murine leukemia virus (MLV)-related virus (XMRV) was initially identified in prostate cancer (PCa) tissue, particularly in the prostatic stromal fibroblasts, of patients homozygous for the RNASEL R462Q mutation. A subsequent study reported XMRV antigens in malignant prostatic epithelium and association of XMRV infection with PCa, especially higher-grade tumors, independently of the RNASEL polymorphism. Further studies showed high prevalence of XMRV or related MLV sequences in chronic fatigue syndrome patients (CFS), while others found no, or low, prevalence of XMRV in a variety of diseases including PCa or CFS. Thus, the etiological link between XMRV and human disease remains elusive. To address the association between XMRV infection and PCa, we have tested prostate tissues and human sera for the presence of viral DNA, viral antigens and anti-XMRV antibodies.Results: Real-time PCR analysis of 110 PCa (Gleason scores >4) and 40 benign and normal prostate tissues identified six positive samples (5 PCa and 1 non-PCa). No statistical link was observed between the presence of proviral DNA and PCa, PCa grades, and the RNASEL R462Q mutation. The amplified viral sequences were distantly related to XMRV, but nearly identical to endogenous MLV sequences in mice. The PCR positive samples were also positive for mouse mitochondrial DNA by nested PCR, suggesting contamination of the samples with mouse DNA. Immuno-histochemistry (IHC) with an anti-XMRV antibody, but not an anti-MLV antibody that recognizes XMRV, sporadically identified antigen-positive cells in prostatic epithelium, irrespectively of the status of viral DNA detection. No serum (159 PCa and 201 age-matched controls) showed strong neutralization of XMRV infection at 1:10 dilution.Conclusion: The lack of XMRV sequences or strong anti-XMRV neutralizing antibodies indicates no or very low prevalence of XMRV in our cohorts. We conclude that real-time PCR- and IHC-positive samples were due to laboratory contamination and non-specific immune reactions, respectively.

Original languageEnglish (US)
Article number23
JournalRetrovirology
Volume8
DOIs
StatePublished - Mar 29 2011

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Midwestern United States
Prostatic Neoplasms
Murine Leukemia Viruses
Chronic Fatigue Syndrome
Viral DNA
Xenotropic murine leukemia virus-related virus
Real-Time Polymerase Chain Reaction
Prostate
Anti-Idiotypic Antibodies
Epithelium
Infection
Antigens
Polymerase Chain Reaction
Mutation
Viral Antigens
Neoplasm Grading
DNA
Neutralizing Antibodies
Serum
Mitochondrial DNA

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Sakuma, T., Hué, S., Squillace, K. A., Tonne, J. M., Blackburn, P. R., Ohmine, S., ... Ikeda, Y. H. (2011). No evidence of XMRV in prostate cancer cohorts in the Midwestern United States. Retrovirology, 8, [23]. https://doi.org/10.1186/1742-4690-8-23

No evidence of XMRV in prostate cancer cohorts in the Midwestern United States. / Sakuma, Toshie; Hué, Stéphane; Squillace, Karen A.; Tonne, Jason M.; Blackburn, Patrick R.; Ohmine, Seiga; Thatava, Tayaramma; Towers, Greg J.; Ikeda, Yasuhiro H.

In: Retrovirology, Vol. 8, 23, 29.03.2011.

Research output: Contribution to journalArticle

Sakuma, T, Hué, S, Squillace, KA, Tonne, JM, Blackburn, PR, Ohmine, S, Thatava, T, Towers, GJ & Ikeda, YH 2011, 'No evidence of XMRV in prostate cancer cohorts in the Midwestern United States', Retrovirology, vol. 8, 23. https://doi.org/10.1186/1742-4690-8-23
Sakuma T, Hué S, Squillace KA, Tonne JM, Blackburn PR, Ohmine S et al. No evidence of XMRV in prostate cancer cohorts in the Midwestern United States. Retrovirology. 2011 Mar 29;8. 23. https://doi.org/10.1186/1742-4690-8-23
Sakuma, Toshie ; Hué, Stéphane ; Squillace, Karen A. ; Tonne, Jason M. ; Blackburn, Patrick R. ; Ohmine, Seiga ; Thatava, Tayaramma ; Towers, Greg J. ; Ikeda, Yasuhiro H. / No evidence of XMRV in prostate cancer cohorts in the Midwestern United States. In: Retrovirology. 2011 ; Vol. 8.
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abstract = "Background: Xenotropic murine leukemia virus (MLV)-related virus (XMRV) was initially identified in prostate cancer (PCa) tissue, particularly in the prostatic stromal fibroblasts, of patients homozygous for the RNASEL R462Q mutation. A subsequent study reported XMRV antigens in malignant prostatic epithelium and association of XMRV infection with PCa, especially higher-grade tumors, independently of the RNASEL polymorphism. Further studies showed high prevalence of XMRV or related MLV sequences in chronic fatigue syndrome patients (CFS), while others found no, or low, prevalence of XMRV in a variety of diseases including PCa or CFS. Thus, the etiological link between XMRV and human disease remains elusive. To address the association between XMRV infection and PCa, we have tested prostate tissues and human sera for the presence of viral DNA, viral antigens and anti-XMRV antibodies.Results: Real-time PCR analysis of 110 PCa (Gleason scores >4) and 40 benign and normal prostate tissues identified six positive samples (5 PCa and 1 non-PCa). No statistical link was observed between the presence of proviral DNA and PCa, PCa grades, and the RNASEL R462Q mutation. The amplified viral sequences were distantly related to XMRV, but nearly identical to endogenous MLV sequences in mice. The PCR positive samples were also positive for mouse mitochondrial DNA by nested PCR, suggesting contamination of the samples with mouse DNA. Immuno-histochemistry (IHC) with an anti-XMRV antibody, but not an anti-MLV antibody that recognizes XMRV, sporadically identified antigen-positive cells in prostatic epithelium, irrespectively of the status of viral DNA detection. No serum (159 PCa and 201 age-matched controls) showed strong neutralization of XMRV infection at 1:10 dilution.Conclusion: The lack of XMRV sequences or strong anti-XMRV neutralizing antibodies indicates no or very low prevalence of XMRV in our cohorts. We conclude that real-time PCR- and IHC-positive samples were due to laboratory contamination and non-specific immune reactions, respectively.",
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AU - Sakuma, Toshie

AU - Hué, Stéphane

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AU - Blackburn, Patrick R.

AU - Ohmine, Seiga

AU - Thatava, Tayaramma

AU - Towers, Greg J.

AU - Ikeda, Yasuhiro H

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N2 - Background: Xenotropic murine leukemia virus (MLV)-related virus (XMRV) was initially identified in prostate cancer (PCa) tissue, particularly in the prostatic stromal fibroblasts, of patients homozygous for the RNASEL R462Q mutation. A subsequent study reported XMRV antigens in malignant prostatic epithelium and association of XMRV infection with PCa, especially higher-grade tumors, independently of the RNASEL polymorphism. Further studies showed high prevalence of XMRV or related MLV sequences in chronic fatigue syndrome patients (CFS), while others found no, or low, prevalence of XMRV in a variety of diseases including PCa or CFS. Thus, the etiological link between XMRV and human disease remains elusive. To address the association between XMRV infection and PCa, we have tested prostate tissues and human sera for the presence of viral DNA, viral antigens and anti-XMRV antibodies.Results: Real-time PCR analysis of 110 PCa (Gleason scores >4) and 40 benign and normal prostate tissues identified six positive samples (5 PCa and 1 non-PCa). No statistical link was observed between the presence of proviral DNA and PCa, PCa grades, and the RNASEL R462Q mutation. The amplified viral sequences were distantly related to XMRV, but nearly identical to endogenous MLV sequences in mice. The PCR positive samples were also positive for mouse mitochondrial DNA by nested PCR, suggesting contamination of the samples with mouse DNA. Immuno-histochemistry (IHC) with an anti-XMRV antibody, but not an anti-MLV antibody that recognizes XMRV, sporadically identified antigen-positive cells in prostatic epithelium, irrespectively of the status of viral DNA detection. No serum (159 PCa and 201 age-matched controls) showed strong neutralization of XMRV infection at 1:10 dilution.Conclusion: The lack of XMRV sequences or strong anti-XMRV neutralizing antibodies indicates no or very low prevalence of XMRV in our cohorts. We conclude that real-time PCR- and IHC-positive samples were due to laboratory contamination and non-specific immune reactions, respectively.

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