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ReportsClonal Integration of a Polyomavirus in Human Merkel Cell CarcinomaMerkel 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 and detected a fusion transcript between a previously undescribed virus T antigen and a human receptor tyrosine phosphatase. Further investigation led to identification and sequence analysis of the 5387–base-pair genome of a previously unknown polyomavirus that we call Merkel cell polyomavirus (MCV or MCPyV). MCV sequences were detected in 8 of 10 (80%) MCC tumors but only 5 of 59 (8%) control tissues from various body sites and 4 of 25 (16%) control skin tissues. In six of eight MCV-positive MCCs, viral DNA was integrated within the tumor genome in a clonal pattern, suggesting that MCV infection and integration preceded clonal expansion of the tumor cells. Thus, MCV may be a contributing factor in the pathogenesis of MCC. Molecular Virology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, 5117 Centre Avenue, Suite 1.8, Pittsburgh, PA 15213, USA. * These authors contributed equally to this work. To whom correspondence should be addressed. E-mail: yc70{at}pitt.edu (Y.C.); psm9{at}pitt.edu (P.S.M.)
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