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.
Feng
Huichen
H
Molecular Virology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, 5117 Centre Avenue, Suite 1.8, Pittsburgh, PA 15213, USA.
Shuda
Masahiro
M
Chang
Yuan
Y
Moore
Patrick S
PS
D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D015266:Carcinoma, Merkel Cell / Q000235:genetics / Q000821:virology*; D015723:Gene Library; D005821:Genetic Techniques; D016679:Genome, Viral; D006801:Humans; D011120:Polyomavirus / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity / Q000502:physiology; D027601:Polyomavirus Infections / Q000235:genetics / Q000821:virology*; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics / Q000821:virology*; D014412:Tumor Virus Infections / Q000235:genetics / Q000821:virology*; D016662:Virus Integration
D000952:Antigens, Polyomavirus Transforming; C516850:PTPRG protein, human; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5