Clonal Integration of a Polyomavirus in Human Merkel Cell Carcinoma

American Association for the Advancement of Science (AAAS) - Tập 319 Số 5866 - Trang 1096-1100 - 2008
Huichen Feng1, Masahiro Shuda1, Yuan Chang1, Patrick S. Moore1
1Molecular Virology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, 5117 Centre Avenue, Suite 1.8, Pittsburgh, PA 15213, USA.

Tóm tắt

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.

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We thank the National Cancer Institute–supported Cooperative Human Tissue Network for tissues used in this study M. Aquafondata for tissue staining P. S. Schnable for sharing cDNA data sets used in DTS pilot testing O. Gjoerup and R. D. Wood for helpful comments and J. Zawinul for help with the manuscript. Supported in part by funds from NIH R33CA120726 and the Pennsylvania Department of Health. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses interpretations or conclusions.

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American Association for the Advancement of Science (AAAS)

Tập 319 Số 5866

1096-1100

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