title: In-depth investigation of archival and prospectively collected samples reveals no evidence for XMRV infection in prostate cancer.
abstract: XMRV, or xenotropic murine leukemia virus (MLV)-related virus, is a novel gammaretrovirus originally identified in studies that analyzed tissue from prostate cancer patients in 2006 and blood from patients with chronic fatigue syndrome (CFS) in 2009. However, a large number of subsequent studies failed to confirm a link between XMRV infection and CFS or prostate cancer. On the contrary, recent evidence indicates that XMRV is a contaminant originating from the recombination of two mouse endogenous retroviruses during passaging of a prostate tumor xenograft (CWR22) in mice, generating laboratory-derived cell lines that are XMRV-infected. To confirm or refute an association between XMRV and prostate cancer, we analyzed prostate cancer tissues and plasma from a prospectively collected cohort of 39 patients as well as archival RNA and prostate tissue from the original 2006 study. Despite comprehensive microarray, PCR, FISH, and serological testing, XMRV was not detected in any of the newly collected samples or in archival tissue, although archival RNA remained XMRV-positive. Notably, archival VP62 prostate tissue, from which the prototype XMRV strain was derived, tested negative for XMRV on re-analysis. Analysis of viral genomic and human mitochondrial sequences revealed that all previously characterized XMRV strains are identical and that the archival RNA had been contaminated by an XMRV-infected laboratory cell line. These findings reveal no association between XMRV and prostate cancer, and underscore the conclusion that XMRV is not a naturally acquired human infection.
authors.affiliation: Department of Laboratory Medicine, University of San Francisco, San Francisco, California, United States of America.
authors.forename: Deanna
authors.initials: D
authors.lastname: Lee
authors.forename: Jaydip
authors.initials: J
authors.lastname: Das Gupta
authors.forename: Christina
authors.initials: C
authors.lastname: Gaughan
authors.forename: Imke
authors.initials: I
authors.lastname: Steffen
authors.forename: Ning
authors.initials: N
authors.lastname: Tang
authors.forename: Ka-Cheung
authors.initials: KC
authors.lastname: Luk
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Qiu
authors.forename: Anatoly
authors.initials: A
authors.lastname: Urisman
authors.forename: Nicole
authors.initials: N
authors.lastname: Fischer
authors.forename: Ross
authors.initials: R
authors.lastname: Molinaro
authors.forename: Miranda
authors.initials: M
authors.lastname: Broz
authors.forename: Gerald
authors.initials: G
authors.lastname: Schochetman
authors.forename: Eric A
authors.initials: EA
authors.lastname: Klein
authors.forename: Don
authors.initials: D
authors.lastname: Ganem
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Derisi
authors.forename: Graham
authors.initials: G
authors.lastname: Simmons
authors.forename: John
authors.initials: J
authors.lastname: Hackett
authors.forename: Robert H
authors.initials: RH
authors.lastname: Silverman
authors.forename: Charles Y
authors.initials: CY
authors.lastname: Chiu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015331:Cohort Studies; D016208:Databases, Factual; D016679:Genome, Viral / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology / Q000601:surgery / Q000821:virology*; D012313:RNA / Q000235:genetics; D013048:Specimen Handling / Q000379:methods*; D058008:Xenotropic murine leukemia virus-related virus / Q000235:genetics / Q000302:isolation & purification*
chemical_list: D012313:RNA