Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New study confirms erroneous link between XMRV and prostate cancer-contamination was the cause

19.09.2012
A once-promising discovery linking prostate cancer to an obscure retrovirus derived from mice was the result of an inadvertent laboratory contamination, a forensic analysis of tissue samples and lab experiments – some dating back nearly a decade – has confirmed.

The connection, which scientists have questioned repeatedly over the last couple years, was first proposed more than six years ago, when the telltale signature of the virus, known as XMRV, was detected in genetic material derived from tissue samples taken from men with prostate cancer.

Later studies failed to find the same signature, and researchers reported that while XMRV is a real, previously-undiscovered virus with interesting and useful properties, it is an infection of human prostate cancer cells in laboratories and not of prostate cancer patients.

Now, an analysis by a team of scientists led by researchers from the University of California, San Francisco (UCSF), Cleveland Clinic and Abbott has uncovered the complete story behind this contamination.

As described this week in the open-access journal PLOS ONE, the original association between XMRV and prostate cancer resulted from traces of XMRV that appear to have found their way into the prostate samples from other cells being handled in the same laboratory in 2003. These cells were also contaminated with the retrovirus.

"Everything arose from this presumed contamination event," said Charles Chiu, MD, PhD, an assistant professor of laboratory medicine at UCSF and director of the UCSF-Abbott Viral Diagnostics and Discovery Center.

Anatomy of a Contamination

XMRV became a focus of research after its genetic signature was first found in prostate cancer samples in 2006. Similar studies in 2009 also detected the virus among samples taken from people with Chronic Fatigue Syndrome – though both discoveries have now been called into question. The original publication related to Chronic Fatigue Syndrome has since been retracted.

When the prostate connection first emerged, there was a lot of excitement in the field, said Chiu, because of the lesson from human papillomavirus, a virus known to cause cervical cancer in women. HPV taught doctors that a cancer caused by a virus could be prevented by giving people a vaccine.

For people with Chronic Fatigue Syndrome, the 2009 news offered hope because it promised new tests that could definitively diagnose their condition – and possibly lead to treatment with antiviral drugs that block XMRV.

But the connection between the virus and both diseases began to unravel after a number of follow-up studies in several different laboratories failed to detect XMRV in tissue samples taken from men with prostate cancer and people with Chronic Fatigue Syndrome. Other studies added to the doubt by providing strong evidence that XMRV may have arisen simply from laboratory contamination.

Working with the original groups that made the 2006 discovery, Chiu and his colleagues sought to definitively uncover how this contamination occurred.

They first repeated the 2006 experiments in an unbiased way by using a variety of methods to examine new samples taken from a cohort of 39 men with prostate cancer. Failing to detect any trace of XMRV in these samples, they went back to the original material described in the 2006 paper and retraced its route through the laboratory step by step.

Quickly, they determined that the virus detected in these samples was essentially identical in each – which suggested contamination rather than natural infection. Viruses like XMRV readily mutate, and if the different men who had donated prostate tissues had truly been infected, there likely would have been more than one strain present.

Looking further, the scientists found that while the virus was present in genetic extracts made from the samples – and analyzed in the 2006 study – it was not present in the original prostate tissues themselves, samples of which were fixed in waxy paraffin immediately after they were first surgically removed.

That discovery suggested that XMRV was introduced as a contaminant at some point when the tissue was being manipulated in the laboratory that processed the prostate tissue samples, prior to them being sent to UCSF for analysis.

Searching for a possible culprit, the team found a completely different cell line that was not used in the study but had been used in the same laboratory at the same time. They found frozen samples of these cells, called "LNCaP," which had been packed away in a lab freezer since 2003. The virus was in these cells.

Using a sophisticated new technique called mitochondrial RNA profiling, the researchers showed that these cells were indeed the source of the virus detected in the prostate samples.

But how did the LNCaP cells themselves become contaminated? Looking further, the scientists found that the source was another type of cell, called the 22Rv1 cell line, which was developed at Case Western Reserve University and is used extensively in prostate cancer research. Prior research by other scientists showed that this virus appears to have been created accidentally in the laboratory in the 1990s in a "recombination event" in which two viruses combined to form XMRV. This event occurred while scientists were working with mice and a prostate cancer tumor to make the 22Rv1 cell line.

"These findings underscore the importance of rapidly evolving new technologies such as deep sequencing and a novel application of this technology, mitochondrial RNA profiling," said John Hackett Jr., PhD, senior research fellow of Emerging Pathogens and Virus Discovery at Abbott. If these scientific tools were available when XMRV was first discovered, contamination would likely have been identified far sooner. The most important contribution of our study to the scientific community may well be the demonstration of how these technologies can be applied in future studies."

The whole affair is something of a cautionary tale, Chiu said. "This is basically the nature of science – fallible and not necessarily error-free, yet ultimately self-correcting."

"It's been known for over a year that XMRV was the result of lab contamination. I couldn't rest until we figured out how it happened. It felt like the right thing to do was to collaborate with Dr. Chiu and the others to get the answers," said Robert Silverman, PhD, interim chair of Cancer Biology at the Cleveland Clinic and one of the authors of the original study. "I'm gratified that we finally got to the bottom of the story."

The article, "In-Depth Investigation of Archival and Prospectively Collected Samples Reveals No Evidence for XMRV Infection in Prostate Cancer," by Deanna Lee, Jaydip Das Gupta, Christina Gaughan, Imke Steffen, Ning Tang, Ka-Cheung Luk, Xiaoxing Qiu, Anatoly Urisman, Nicole Fischer, Ross Molinaro, Miranda Broz, Gerald Schochetman, Eric A. Klein, Don Ganem, Joseph L. DeRisi, Graham Simmons, John Hackett Jr., Robert H. Silverman and Charles Y. Chiu, appears in the journal PLOS ONE on Sept. 18. See: http://dx.plos.org/10.1371/journal.ppat.1002924

In addition to UCSF, authors on this study are affiliated with the University of San Francisco, Cleveland Clinic, Blood Systems Research Institute in San Francisco, Abbott in Abbott Park, Ill., University Medical Center Hamburg-Eppendorf in Germany, Emory University School of Medicine in Atlanta, Novartis Institutes for Biomedical Research in Emeryville, Calif.

This work was funded by the National Institutes of Health (grant #CA103943, #1R21HL109761, #R56-AI08953 and #R01-HL105704), the Charlotte Geyer Foundation, the Maltz Family Foundation, Abbott and the Howard Hughes Medical Institute.

Several authors on the study not affiliated with UCSF are included as inventors on one or more patent applications, which include either the Cleveland Clinic, Abbott Laboratories, or both. Abbott is the sole assignee of issued U.S. Patent No. 8,183,349 relating to XMRV.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

Jason Socrates Bardi | EurekAlert!
Further information:
http://www.ucsf.edu

More articles from Studies and Analyses:

nachricht Antarctic Ice Sheet mass loss has increased
14.06.2018 | Technische Universität Dresden

nachricht WAKE-UP provides new treatment option for stroke patients | International study led by UKE
17.05.2018 | Universitätsklinikum Hamburg-Eppendorf

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Better model of water under extreme conditions could aid understanding of Earth's mantle

21.06.2018 | Earth Sciences

What are the effects of coral reef marine protected areas?

21.06.2018 | Life Sciences

The Janus head of the South Asian monsoon

21.06.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>