Polyomavirus and Human Merkel Cell Carcinoma
It has been known for over 50 years that Polyomaviruses can cause cancers in animals, but until now, there has been no scientific evidence that these viruses cause human cancers. Merkel cell polyomavirus (MCV) was discovered by the husband-and-wife team who found the cause of Kaposi’s sarcoma using a new strategy to hunt for human viruses. The research team analyzed nearly 400,000 messenger RNA genetic sequences from four samples of tumor tissue using a technique 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 80% of Merkel cell tumors they tested but in only 8% of control tissues from various body sites and 16% of control skin tissues. So 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. While the research team emphasizes that their 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.
Clonal Integration of a Polyomavirus in Human Merkel Cell Carcinoma. Science, January 17, 2008
Merkel cell carcinoma (MCC) is a rare but aggressive human skin cancer that typically affects elderly and immunosuppressed individuals, a feature suggestive of an infectious origin. We studied MCC samples by digital transcriptome subtraction (DTS) and detected a fusion transcript between a previously undescribed virus T antigen and a human receptor tyrosine phosphatase. Further investigation led to discovery and sequence analysis of the 5387-base-pair genome of a new polyomavirus that we call Merkel cell polyomavirus (MCV or MCPyV). MCV sequences were detected in 8 of 10 (80%) MCC tumors but in only 5 of 59 (8%) control tissues from various body sites and 4 of 25 (16%) control skin tissues. In 6 of 8 MCV-positive MCCs, viral DNA was integrated within the tumor genome in a pattern suggesting that MCV infection/integration preceded clonal expansion of the tumor cells. Thus, MCV may be a contributing factor in the pathogenesis of MCC.
Tags: Biology, Genetics, Health, Medicine, Microbiology, Science, Virology
