Wednesday, September 19, 2012

Another XMRV shoe drops: PLoS Pathogens study linking prostate ...

Less than 24 hours after the publication of a study showing no link between XMRV, aka xenotropic murine leukemia-related virus, and chronic fatigue syndrome (CFS), the authors of a a study claiming a link between the virus and prostate cancer have has been retractedit. The move comes along with the publication of a new study showing that no such link exists.

Here?s the notice, from PLoS Pathogens:

Retraction: Urisman A, Molinaro RJ, Fischer N, Plummer SJ, Casey G, et al. (2006) Identification of a Novel Gammaretrovirus in Prostate Tumors of Patients Homozygous for R462Q RNASEL Variant. PLoS Pathog 2(3): e25. doi:10.1371/journal.ppat.0020025

In light of the findings from a recent study ?In-Depth Investigation of Archival and Prospectively Collected Samples Reveals No Evidence for XMRV Infection in Prostate Cancer? and others in the field, the editors of PLOS Pathogens have issued a retraction of this study. The association of XMRV with prostate cancer has now been thoroughly refuted. Although the original finding of a novel gammaretrovirus, XMRV, with the use of a pan-viral detection microarray is valid, and sequencing and phylogenetic characterization of the virus still stands, the editors agree that it is clear that XMRV found in this study is laboratory-derived and there is no association of XMRV with prostate cancer. As a result the paper was retracted from PLOS Pathogens on September 18th, 2012.

The ?recent study? to which the authors refer is quite recent, in fact: It was published yesterday, September 18, in PLoS ONE. It shares a number of authors with the now-retracted PLoS Pathogens paper, which has been cited 346 times, according to Thomson Scientific?s Web of Knowledge. One of the authors of both papers ? the Cleveland Clinic?s Robert Silverman ?? also co-authored the now-retracted Science paper linking XMRV to chronic fatigue syndrome.

In a blog post accompanying the study, a PLoS ONE editor, Gilda Tachedjian, explains why this is the ?final chapter? in the story alleging a link between XMRV and prostate cancer:

Despite the controversies in the CFS field, at that time the XMRV prostate cancer story remained an open question. ?Fast forward to early 2012 ? and over a 100 publications later ? XMRV was accepted by the majority of the scientific community to be a contaminant with no role in causing prostate cancer. This was due to several studies published in late 2010 and early 2011 demonstrating that XMRV was a laboratory-generated virus (Paprotka et al 2011) and that highly sensitive nucleic acid detection assays were not detecting a bone fide infection of XMRV or related viruses in humans, but instead contamination from a variety of sources including mouse DNA, XMRV plasmid DNA, and XMRV from infected cell lines (see reviews by Sfanos et al 2012 and Groom and Bishop 2012).

Why was the new PLoS ONE study important? Tachedjian continues:

In the context of these findings, this study in PLOS ONE by Lee and colleagues is significant because it has allowed the authors who originally reported the association of XMRV with prostate cancer to set the record straight.? Using careful molecular detective work, they found that the original archived prostate cancer tissue was negative for XMRV although the archival extracted RNA from the original study was positive for XMRV.? They also failed to demonstrate the presence of XMRV in new prostate cancer samples. In addition, they discovered that the source of XMRV contamination in the archival extracted RNA was from an XMRV-infected cell line used in the laboratory.? The inability to confirm their original findings published in PLOS Pathogens represents the final chapter that closes the book on XMRV and its role as a naturally acquired human infection associated with prostate cancer. The PLOS Pathogens paper is retracted today.

Update, 10:45 a.m. Eastern, 9/19/12: As a commenter notes, the notice refers only to the editors, not the authors. We?ve contacted the corresponding authors ? many of whom, as we point out, are also authors of the PLoS ONE study overturning their findings ? and the editor of PLOS Pathogens, to ask whether the authors agreed to this retraction, and will update with anything we find out.

Update, 4:30 p.m. Eastern, 9/19/12: This article has been updated to include information from a nice story by Martin Enserink at Science. It turns out the retraction caught the authors by surprise and was not at their request. Neither the authors nor the journal have responded to our request for comment.

Update, 5:45 pm Eastern, 9/19/12: Kasturi Haldar, the editor of PLoS Pathogens, tells us the journal acted after not hearing back from the authors:

PLOS Pathogens is a member of the Committee on Publication Ethics (COPE: http://publicationethics.org) and we follow their guidelines in reviewing any situation in which the literature may need to be corrected. The decision to retract the original 2006 paper was made in consultation with a large group of PLOS Pathogens? senior editors. The authors were contacted by email on August 27th regarding our decision, and were asked to comment on the retraction text and suggest changes. We did not receive a reply, and decided to move forward with the retraction in conjunction with the PLOS ONE publication yesterday, September 18th.

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Source: http://retractionwatch.wordpress.com/2012/09/19/another-xmrv-shoe-drops-plos-pathogens-prostate-cancer-study-retracted/

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