Clonal integration of a polyomavirus in human Merkel cell carcinoma

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 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.