Clonal integration of a polyomavirus in human Merkel cell carcinoma

Science. 2008 Feb 22;319(5866):1096-100. doi: 10.1126/science.1152586. Epub 2008 Jan 17.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Polyomavirus Transforming / genetics
  • Carcinoma, Merkel Cell / genetics
  • Carcinoma, Merkel Cell / virology*
  • Gene Library
  • Genetic Techniques
  • Genome, Viral
  • Humans
  • Polyomavirus / genetics*
  • Polyomavirus / isolation & purification
  • Polyomavirus / pathogenicity
  • Polyomavirus / physiology
  • Polyomavirus Infections / genetics
  • Polyomavirus Infections / virology*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / genetics
  • Skin Neoplasms / genetics
  • Skin Neoplasms / virology*
  • Tumor Virus Infections / genetics
  • Tumor Virus Infections / virology*
  • Virus Integration*

Substances

  • Antigens, Polyomavirus Transforming
  • PTPRG protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5