title: XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors.
abstract: Xenotropic murine leukemia virus-related virus (XMRV) was recently discovered in human prostate cancers and is the first gammaretrovirus known to infect humans. While gammaretroviruses have well-characterized oncogenic effects in animals, they have not been shown to cause human cancers. We provide experimental evidence that XMRV is indeed a gammaretrovirus with protein composition and particle ultrastructure highly similar to Moloney murine leukemia virus (MoMLV), another gammaretrovirus. We analyzed 334 consecutive prostate resection specimens, using a quantitative PCR assay and immunohistochemistry (IHC) with an anti-XMRV specific antiserum. We found XMRV DNA in 6% and XMRV protein expression in 23% of prostate cancers. XMRV proteins were expressed primarily in malignant epithelial cells, suggesting that retroviral infection may be directly linked to tumorigenesis. XMRV infection was associated with prostate cancer, especially higher-grade cancers. We found XMRV infection to be independent of a common polymorphism in the RNASEL gene, unlike results previously reported. This finding increases the population at risk for XMRV infection from only those homozygous for the RNASEL variant to all individuals. Our observations provide evidence for an association of XMRV with malignant cells and with more aggressive tumors.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, 622 West 168th Street, New York, NY 10032, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Schlaberg
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Choe
authors.forename: Kristy R
authors.initials: KR
authors.lastname: Brown
authors.forename: Harshwardhan M
authors.initials: HM
authors.lastname: Thaker
authors.forename: Ila R
authors.initials: IR
authors.lastname: Singh
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D015153:Blotting, Western; D004279:DNA, Viral / Q000235:genetics; D004722:Endoribonucleases / Q000235:genetics; D004848:Epithelium / Q000473:pathology / Q000821:virology; D017988:Gammaretrovirus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005838:Genotype; D054884:Host-Pathogen Interactions; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000473:pathology / Q000821:virology*; D011471:Prostatic Neoplasms / Q000473:pathology / Q000821:virology*; D012192:Retroviridae Infections / Q000473:pathology / Q000821:virology*; D012689:Sequence Homology, Nucleic Acid; D014412:Tumor Virus Infections / Q000473:pathology / Q000821:virology*; D019562:Viral Load; D014764:Viral Proteins / Q000378:metabolism; D014771:Virion / Q000235:genetics / Q000276:immunology / Q000648:ultrastructure
chemical_list: D004279:DNA, Viral; D014764:Viral Proteins; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease