In-depth investigation of archival and prospectively collected samples reveals no evidence for XMRV infection in prostate cancer.
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In-depth investigation of archival and prospectively collected samples reveals no evidence for XMRV infection in prostate cancer. / Lee, Deanna; Jaydip, Das Gupta; Gaughan, Christina; Steffen, Imke; Tang, Ning; Luk, Ka-Cheung; Qiu, Xiaoxing; Urisman, Anatoly; Fischer, Nicole; Molinaro, Ross; Broz, Miranda; Schochetman, Gerald; Klein, Eric A; Ganem, Don; Derisi, Joseph L; Simmons, Graham; Hackett, John; Silverman, Robert H; Chiu, Charles Y.
In: PLOS ONE, Vol. 7, No. 9, 9, 2012, p. 44954.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - In-depth investigation of archival and prospectively collected samples reveals no evidence for XMRV infection in prostate cancer.
AU - Lee, Deanna
AU - Jaydip, Das Gupta
AU - Gaughan, Christina
AU - Steffen, Imke
AU - Tang, Ning
AU - Luk, Ka-Cheung
AU - Qiu, Xiaoxing
AU - Urisman, Anatoly
AU - Fischer, Nicole
AU - Molinaro, Ross
AU - Broz, Miranda
AU - Schochetman, Gerald
AU - Klein, Eric A
AU - Ganem, Don
AU - Derisi, Joseph L
AU - Simmons, Graham
AU - Hackett, John
AU - Silverman, Robert H
AU - Chiu, Charles Y
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Animals
KW - Humans
KW - Male
KW - Prospective Studies
KW - Cohort Studies
KW - Mice
KW - Cell Line, Tumor
KW - Polymorphism, Single Nucleotide
KW - Databases, Factual
KW - Prostatectomy
KW - Mitochondria/genetics
KW - Genome, Viral/genetics
KW - Prostatic Neoplasms/blood/pathology/surgery/virology
KW - RNA/genetics
KW - Specimen Handling/methods
KW - Xenotropic murine leukemia virus-related virus/genetics/isolation & purification
KW - Animals
KW - Humans
KW - Male
KW - Prospective Studies
KW - Cohort Studies
KW - Mice
KW - Cell Line, Tumor
KW - Polymorphism, Single Nucleotide
KW - Databases, Factual
KW - Prostatectomy
KW - Mitochondria/genetics
KW - Genome, Viral/genetics
KW - Prostatic Neoplasms/blood/pathology/surgery/virology
KW - RNA/genetics
KW - Specimen Handling/methods
KW - Xenotropic murine leukemia virus-related virus/genetics/isolation & purification
U2 - 10.1371/journal.pone.0044954
DO - 10.1371/journal.pone.0044954
M3 - SCORING: Journal article
VL - 7
SP - 44954
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 9
M1 - 9
ER -
