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Published Online January 17, 2008
Science DOI: 10.1126/science.1152586

Reports

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{dagger}*, Patrick S. Moore 1{dagger}*

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

{dagger}These authors contributed equally to this work.

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 six 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.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)