title: Absence of XMRV and closely related viruses in primary prostate cancer tissues used to derive the XMRV-infected cell line 22Rv1.
abstract: The 22Rv1 cell line is widely used for prostate cancer research and other studies throughout the world. These cells were established from a human prostate tumor, CWR22, that was serially passaged in nude mice and selected for androgen independence. The 22Rv1 cells are known to produce high titers of xenotropic murine leukemia virus-related virus (XMRV). Recent studies suggested that XMRV was inadvertently created in the 1990's when two murine leukemia virus (MLV) genomes (pre-XMRV1 and pre-XMRV-2) recombined during passaging of the CWR22 tumor in mice. The conclusion that XMRV originated from mice and not the patient was based partly on the failure to detect XMRV in early CWR22 xenografts. While that deduction is certainly justified, we examined the possibility that a closely related virus could have been present in primary tumor tissue. Here we report that we have located the original prostate tumor tissue excised from patient CWR22 and have assayed the corresponding DNA by PCR and the tissue sections by fluorescence in situ hybridization for the presence of XMRV or a similar virus. The primary tumor tissues lacked mouse DNA as determined by PCR for intracisternal A type particle DNA, thus avoiding one of the limitations of studying xenografts. We show that neither XMRV nor a closely related virus was present in primary prostate tissue of patient CWR22. Our findings confirm and reinforce the conclusion that XMRV is a recombinant laboratory-generated mouse virus that is highly adapted for human prostate cancer cells.
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Jaydip
authors.initials: J
authors.lastname: Das Gupta
authors.forename: Ka-Cheung
authors.initials: KC
authors.lastname: Luk
authors.forename: Ning
authors.initials: N
authors.lastname: Tang
authors.forename: Christina
authors.initials: C
authors.lastname: Gaughan
authors.forename: Eric A
authors.initials: EA
authors.lastname: Klein
authors.forename: Eugene S
authors.initials: ES
authors.lastname: Kandel
authors.forename: John
authors.initials: J
authors.lastname: Hackett
authors.forename: Robert H
authors.initials: RH
authors.lastname: Silverman
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D004279:DNA, Viral / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000473:pathology / Q000821:virology*; D060888:Real-Time Polymerase Chain Reaction; D058008:Xenotropic murine leukemia virus-related virus / Q000235:genetics / Q000302:isolation & purification*
chemical_list: D017931:DNA Primers; D004279:DNA, Viral