Scientists Discover Virus Linked To Deadly Skin CancerFeatured Article
Main Category: Cancer / Oncology
Also Included In: Infectious Diseases / Bacteria / Viruses; Genetics; Dermatology
Article Date: 18 Jan 2008 - 12:00 PDT
Scientists Discover Virus Linked To Deadly Skin Cancer
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A new way of searching for human viruses has helped scientists at the University of Pittsburgh Cancer Institute in the US find a previously unknown one that is linked to a deadly form of skin cancer called Merkel cell carcinoma (MCC).
The discovery is published as a paper in this week's publication ahead of print issue of Science and is the result of work by a husband and wife team that had already discovered another virus linked to another incurable skin cancer, Kaposi's sarcoma.
The University of Pittsburgh Cancer Institute (UPCI) researchers and authors of the paper, Drs Huichen Feng, Masahiro Shuda, and husband and wife, Drs Patrick Moore and Yuan Chang, describe their 10 year programme to perfect the sequencing technology for hunting the virus, which they have named the Merkel cell polyomavirus (MCV).
Their work has not established a causal link between MCV and Merkel cell carcinoma (MCC), but if their results can be confirmed, then they are likely to lead to new treatment and prevention approaches.
Moore, who is professor of microbiology and molecular genetics at the University of Pittsburgh School of Medicine and leader of the molecular virology program at UPCI, said in a prepapared statement that:
"This is the first polyomavirus to be strongly associated with a particular type of human tumor."
Although scientists have known for the last 50 years that polyomaviruses can cause cancer in animals, more work is needed to establish if there are any links to cancer in humans, he explained.
The researchers analyzed nearly 400,000 sequences of messenger RNA taken from four tissue samples of MCC tumours using a technique called digital transcriptome subtraction (DTS). The team had developed the DTS method themselves.
The DTS system allowed them to compare the tumour gene sequences to those already mapped by the Human Genome Project, so conducting a massive "subtraction" exercise, which left at the end of it, a group of genetic transcripts that were not present in the human genome and could therefore reasonably be assumed to have come from a foreign organism, like a virus.
The researchers then mapped the left over genetic transcripts against known viruses and found there was one unknown but distinct sequence. Using this mystery pattern they showed it belonged to a new polyomavirus that was in 80 per cent of the Merkel cell tumours they tested, but only present in 8 per cent of control tissues from various body sites and 16 per cent of control tissues taken from skin.
"If these findings are confirmed, we can look at how this new virus contributes to a very bad cancer with high mortality, and, just as importantly, use it as a model to understand how cancers occur and the cell pathways that are targeted."
Chang, who is professor of pathology at UPCI drew parallels with vaccines that are now available against the human papillomavirus (HPV) to prevent cervical cancer.
"MCV is another model that may increase our understanding of how cancers arise, with possibly important implications for non-viral cancers like prostate or breast cancer," she explained.
MCV is similar to HPV in other ways too, because both viruses have a habit of invading the genome of tumour cells but not the genome of healthy cells. The way they invade the genome, by integrating with it, means they lose their ability to replicate normally, which could be how MCC develops.
Merkel cell carcinoma (MCC) is rare but extremely aggressive. It affects about 1.500 Americans a year, and the rate has tripled in the last 20 years. It is more prevalent among AIDS and transplant patients with immune system weakened by treatment with immunosuppressants.
MCC starts in subcutaneous cells associated with the sense of touch. It occurs mostly in the face, head and neck and spreads rapidly into other tissues and organs.
The life expectancy of a person with MCC is not long. About two thirds of MCC patients die within five years, and about half with the advanced form of the cancer live only nine months or less.
MCV can also be found in healthy people and not just in Merkel cell tumours. As already explained, it behaves like HPV in that it invades and integrates with the DNA of the host cell, and does this before the cell become cancerous.
The UPCI team found that 6 of the 8 MCV-positive tumors had DNA patterns that showed viral DNA had integrated with the tumour genome in a way typical of MCV, a monoclonal pattern. This was taken as a strong sign that infection by MCV was the trigger for tumours to start. The researchers repeated these results with other specimens.
There could be a link between MCV and an as yet undiscovered human equivalent of a monkey virus called African green monkey virus. The genetic structure of MCV is similar to the monkey version of the virus which was found in Germany in the 1970s, wrote the researchers.
There is evidence to suggest around 15 to 25 per cent of adults could be infected with the human version of the monkey virus, and if this turns out to be MCV said the researchers then more than 1 billion people around the globe could already be infected.
However, not wishing to cause undue alarm, Moore drew another parallel with HPV:
"Although up to 50 percent of sexually active young women are infected with HPV, a small proportion may actually get cervical cancer."
And Chang said it was very likely the virus was just part of a much larger picture, as yet unknown.
"Now we need to find out how it works," said Chang.
"Once the virus integrates, it could express an oncoprotein, or it could knock out a gene that suppresses tumor growth. Either way, the results are bound to be interesting," she added.
"Clonal Integration of a Polyomavirus in Human Merkel Cell Carcinoma."
Huichen Feng, Masahiro Shuda, Yuan Chang, and Patrick S. Moore.
Science, Published ahead of print, 17 January 2008.
Click here for Abstract.
Sources: journal abstract, University of Pittsburgh Schools of the Health Sciences press release.
Written by: Catharine Paddock
Copyright: Medical News Today
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