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Submitted on November 5, 2007
Accepted on January 8, 2008
Clonal Integration of a Polyomavirus in Human Merkel Cell Carcinoma
Huichen Feng 1,Masahiro Shuda 1,Yuan Chang 1*,Patrick S. Moore 1*
1 Molecular Virology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, 5117 Centre Ave, Suite 1.8, Pittsburgh, PA 15213, USA.
* To whom correspondence should be addressed.
Yuan Chang , E-mail: yc70{at}pitt.edu Patrick S. Moore , E-mail: psm9{at}pitt.edu
These authors contributed equally to this work.
Merkel cell carcinoma (MCC) is a rare but aggressive human skincancer that typically affects elderly and immunosuppressed individuals,a feature suggestive of an infectious origin. We studied MCCsamples by digital transcriptome subtraction (DTS) and detecteda fusion transcript between a previously undescribed virus Tantigen and a human receptor tyrosine phosphatase. Further investigationled to discovery and sequence analysis of the 5387-base-pairgenome 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 variousbody sites and 4 of 25 (16%) control skin tissues. In six of8 MCV-positive MCCs, viral DNA was integrated within the tumorgenome in a pattern suggesting that MCV infection/integrationpreceded clonal expansion of the tumor cells. Thus, MCV maybe a contributing factor in the pathogenesis of MCC.
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