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R esearchers at the University of Pittsburgh Cancer Institute (UPCI), employing a new strategy to hunt for human viruses, have discovered a previously unknown virus strongly associated with a rare but deadly skin cancer called Merkel cell carcinoma. The strategy was described in a recent issue of the journal Science by UPCI’s Yuan Chang, Patrick Moore, Huichen Feng, and Masahiro Shuda. This is the second tumorassociated virus discovered by Moore and Chang, a husband-and-wife research team who also discovered the cause of Kaposi’s sarcoma, another rare and deadly skin cancer. The Science article explains a nearly decade-long effort to harness the sequencing technology to identify the new virus, which the researchers call Merkel cell polyomavirus (MCV). While the research team emphasizes that its work does not prove MCV to be the cause of Merkel cell carcinoma, if the findings are confirmed, they may lead to new cancer treatment and prevention options. “This is the first polyomavirus to be strongly associated with a particular type of human tumor,” said Moore, professor of microbiology and molecular genetics in Pitt’s School of Medicine and leader of the molecular virology program at UPCI. “Although polyomaviruses have been studied in relation to cancer development for years, the weight of scientific evidence had been leaning toward the view that these viruses do not cause human cancers.” Polyomaviruses are a group of viruses that have been shown to cause cancers in animals for more than 50 years. But Moore noted that additional research is needed to determine what role, if any, MCV plays in human cancer development. A rare but extremely aggressive cancer that spreads rapidly into other tissues and organs, Merkel cell carcinoma (MCC) 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. “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,” added Moore. “Information that we gain could possibly lead to a blood test or vaccine that improves disease management and aids in prevention.” For example, vaccines are now available against human papillomavirus (HPV) to prevent cervical cancer, noted Chang, professor of pathology. “MCV is another model that may increase our understanding of how cancers arise, possibly with important implications for nonviral cancers like prostate or breast cancer.” MCV has additional similarities to HPV since both viruses integrate 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. 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 UPCI Researchers Discover Virus Linked to Deadly Skin Cancer