In January, 2008, a group of researchers at the University of Pittsburgh Medical School reported that a rare skin cancer may be cause by a newly discovered polyoma virus.

Merkel cell carcinoma (MCC) is a rare but extremely aggressive cancer that spreads rapidly into other tissues and organs, develops from specialized nerve cells that respond to touch or pressure. The incidence of MCC has tripled over the past 20 years to about 1,500 cases a year, especially among people whose immune systems are compromised by AIDS or transplant-related immunosuppressant drugs. About half of patients with advanced MCC live nine months or less, and some two-thirds of MCC patients die within five years.

Like, human papillomavirus (HPV), which is known to cause cervical cancer, MCV is integrated into the tumor cell genome but not the genome of healthy cells. This integration destroys the virus’s ability to replicate normally and may be the first critical step in MCC development.

The Pittsburgh team analyzed nearly 400,000 messenger RNA genetic sequences from four samples of MCC tumor tissue using a technique refined in their lab called digital transcriptome subtraction (DTS). Comparing the sequences expressed by the tumor genome to gene sequences mapped by the Human Genome Project, the researchers systematically subtracted known human sequences, leaving a group of genetic transcripts that might be from a foreign organism.

One sequence was similar to but distinct from all known viruses. The team went on to show that this sequence belonged to a new polyomavirus present in eight of 10 (80 percent) Merkel cell tumors they tested but only five of 59 (8 percent) control tissues from various body sites and four of 25 (16 percent) control skin tissues.

Although MCV is most commonly found in Merkel cell tumors, it also can be found in healthy people. The most important distinguishing feature is that MCV integrates into tumor cells in what is known as a monoclonal pattern, indicating that it infects the cell before the cell becomes cancerous. Tests on six of the eight MCV-positive tumors confirmed that viral DNA was integrated within the tumor genome in this monoclonal pattern, suggesting that infection with MCV could be a trigger for tumor formation. The Pittsburgh team subsequently has confirmed these results with additional tumor specimens.

Clues from elsewhere in the biomedical literature point to the existence of MCV, which has a genetic structure that is closely related to an African green monkey virus found in Germany in the 1970s. Researchers have found antibody evidence from blood tests that indicates some 15 percent to 25 percent of adults are infected with the still undiscovered human relative of this monkey virus. If MCV turns out to be this long-sought infection, then more than 1 billion people worldwide could already be infected. However, not very infected person will develop cancer. In the case of HPV, although up to 50 percent of sexually active young women are infected with HPV, a small proportion may actually get cervical cancer.

Even if MCV is proven to play a role in MCC, the virus is likely to be just a part of a much larger picture. 

This is the second tumor-associated virus discovered by the same research team. They also discovered Kaposi’s sarcoma-associated herpesvirus (KSHV) in 1993. KSHV, which causes Kaposi’s sarcoma, is the most common malignancy in AIDS patients and the most common cancer in Africa. To find KSHV, the researchers used a different method to physically subtract human genetic sequences from Kaposi’s sarcoma tumors, leaving fragments of viral DNA.

Viruses, and some bacteria and parasites, are estimated to cause at least 20 percent of cancers worldwide. Over the past 40 years, few cancer-causing viruses have been confirmed in humans, including KSHV. Most of these viruses express cancer-causing proteins, called oncoproteins, in infected cells. Polyomaviruses, including MCV, possess an oncoprotein that has been shown to cause cancer after infection in animals. If MCV is confirmed to play a role in human cancer, it will be the eighth human tumor virus discovered.

 Adapted from media release from University of Pittsburgh

http://www.upmc.com/Communications/MediaRelations/NewsReleaseArchives/2008/January/MCVScience.htm

This work was published in Science