Tuesday, August 12, 2014

XMRV also retracted for Prostate Cancer


Retraction Watch

Authors retract highly cited XMRV-prostate cancer link paper from PNAS
Written by Ivan Oransky
August 12, 2014 at 8:33 am

Retraction Watch readers may recall that nearly two years ago, an
editor at PLOS declared the scientific story of a link between XMRV,
aka xenotropic murine leukemia-related virus, and prostate cancer
over, saying that a retraction from PLOS Pathogens was the "final
chapter." (That retraction led to an apology from the journal about
how it was handled.)

Perhaps, however, there is an epilogue. This week, a group of authors
who published a highly cited 2009 study in the Proceedings of the
National Academy of Sciences (PNAS) making the same link retracted it.
Here's the notice, signed by all five authors:

"Retraction for "XMRV is present in malignant prostatic epithelium and
is associated with prostate cancer, especially high-grade tumors," by
Robert Schlaberg, Daniel J. Choe, Kristy R. Brown, Harshwardhan M.
Thaker, and Ila R. Singh, which appeared in issue 38, September 22,
2009, of Proc Natl Acad Sci USA (106:16351–16356; first published
September 8, 2009; 10.1073/pnas.0906922106).

The authors wish to note, "Due to work performed in other labs, we now
know that some conclusions from our paper on xenotropic murine
leukemia virus-related virus (XMRV) cannot be true. However, other
findings that we reported in that paper still remain valid.

"XMRV was first described in 2006 as a new retrovirus detected in
prostate cancer tissues (1). We replicated this finding, identifying
XMRV sequences by PCR from an independent set of prostate cancer
samples. Other groups also detected XMRV sequences in prostate cancers
by PCR (2, 3). However, subsequent studies showed that XMRV was in
fact generated by the recombination of two endogenous murine
retroviruses when a prostate cancer was passaged in nude mice to
generate the 22Rv1 cell line (4). The detection of XMRV DNA in various
human tissues by PCR has been attributed to contamination of
commercially available reagents with mouse DNA (5).This explanation is
the most likely for the PCR findings we reported.

"The immunohistochemical staining with anti-XMRV antiserum that we
reported in our PNAS publication was most likely due to
cross-reactivity of our antiserum with a protein present almost
exclusively in malignant prostatic epithelial cells. We are in the
process of identifying this cross-reactive protein.

"We wish to note that other parts of our paper remain valid. We
created a full-length infectious clone that replicated efficiently in
a human prostate cancer cell line. We used transmission electron
microscopy to analyze the XMRV particles produced and showed that
their morphology was identical to type-C retroviruses. Using gel
electrophoresis and Western blotting, we determined the molecular
weights of all the structural and nonstructural proteins of XMRV. Such
detailed characterization of a xenotropic virus, including electron
microscopy, has not, to our knowledge, been performed elsewhere. This
characterization still remains correct and is relevant to the
understanding of other wildtype xenotropic viruses.

"Taking all of this information together, we would like to retract our
paper; specifically, the findings reported in Figs. 2–4 and Fig. S1
are no longer valid and we no longer believe that XMRV is associated
with prostate cancer.""

The paper has been cited 199 times, according to Thomson Scientific's
Web of Knowledge. The first reference in the retraction is to the
retracted 2012 PLOS Pathogens study.

A Science paper claiming a link between XMRV and chronic fatigue
syndrome (CFS) was retracted in 2011.

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