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Clonal Integration of a Polyomavirus in Human Merkel Cell Carcinoma
Huichen Feng,Masahiro Shuda,Yuan Chang,*Patrick S. Moore*
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 and detected afusion transcript between a previously undescribed virus T antigenand a human receptor tyrosine phosphatase. Further investigationled to identification and sequence analysis of the 5387–base-pairgenome of a previously unknown polyomavirus that we call Merkelcell polyomavirus (MCV or MCPyV). MCV sequences were detectedin 8 of 10 (80%) MCC tumors but only 5 of 59 (8%) control tissuesfrom various body sites and 4 of 25 (16%) control skin tissues.In six of eight MCV-positive MCCs, viral DNA was integratedwithin the tumor genome in a clonal pattern, suggesting thatMCV infection and integration preceded clonal expansion of thetumor cells. Thus, MCV may be a contributing factor in the pathogenesisof 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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|Abstract »|Full Text »|PDF »
T antigen mutations are a human tumor-specific signature for Merkel cell polyomavirus.
M. Shuda, H. Feng, H. J. Kwun, S. T. Rosen, O. Gjoerup, P. S. Moore, and Y. Chang (2008)
PNAS
105, 16272-16277
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A specific signature of Merkel cell polyomavirus persistence in human cancer cells.
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N. Engl. J. Med.
359, 1629-1631
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P. A. Swanson II, C. D. Pack, A. Hadley, C.-R. Wang, I. Stroynowski, P. E. Jensen, and A. E. Lukacher (2008)
J. Exp. Med.
205, 1647-1657
|Abstract »|Full Text »|PDF »
Frequent Detection of Merkel Cell Polyomavirus in Human Merkel Cell Carcinomas and Identification of a Unique Deletion in the VP1 Gene.
A. Kassem, A. Schopflin, C. Diaz, W. Weyers, E. Stickeler, M. Werner, and A. zur Hausen (2008)
Cancer Res.
68, 5009-5013
|Abstract »|Full Text »|PDF »
Case 19-2008 -- A 63-Year-Old HIV-Positive Man with Cutaneous Merkel-Cell Carcinoma.
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N. Engl. J. Med.
358, 2717-2723
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