Virus linked to Merkel cell carcinoma

PITTSBURGH—University of Pittsburgh Cancer Institute researchers have discovered a previously unknown virus strongly associated with Merkel cell carcinoma, a rare but aggressive skin cancer that typically affects elderly and immunosuppressed individuals.

In Science (Feng et al: published online January 17, 2008, DOI: 10.1126/science.1152586), the researchers describe a nearly decade-long effort to identify the virus, which they call Merkel cell polyomavirus (MCV).

"This is the first polyomavirus to be strongly associated with a particular type of human tumor," said Patrick Moore, MD, MPH, leader of the molecular virology program at UPCI.

The researchers analyzed nearly 400,000 mRNA genetic sequences from four samples of Merkel cell tumor tissue using a technique refined in their lab called digital transcriptome subtraction.

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 8 of 10 (80%) Merkel cell tumors they tested but only 5 of 59 (8%) control tissues from various body sites and 4 of 25 (16%) control tissues from skin.

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 a monoclonal pattern, indicating that it infects the cell before it becomes cancerous. In 6 of 8 MCV-positive Merkel cell tumors, viral DNA was integrated within the tumor genome in this pattern.

Dr. Moore said that the findings, if confirmed, could ultimately lead to a blood test for the virus or a vaccine against it, similar to the HPV vaccine model to prevent cervical cancer.