Improved detection suggests all Merkel cell carcinomas harbor Merkel polyomavirus

Academic Article

Abstract

  • A human polyomavirus was recently discovered in Merkel cell carcinoma (MCC) specimens. The Merkel cell polyomavirus (MCPyV) genome undergoes clonal integration into the host cell chromosomes of MCC tumors and expresses small T antigen and truncated large T antigen. Previous studies have consistently reported that MCPyV can be detected in approximately 80% of all MCC tumors. We sought to increase the sensitivity of detection of MCPyV in MCC by developing antibodies capable of detecting large T antigen by immunohistochemistry. In addition, we expanded the repertoire of quantitative PCR primers specific for MCPyV to improve the detection of viral DNA in MCC. Here we report that a novel monoclonal antibody detected MCPyV large T antigen expression in 56 of 58 (97%) unique MCC tumors. PCR analysis specifically detected viral DNA in all 60 unique MCC tumors tested. We also detected inactivating point substitution mutations of TP53 in the two MCC specimens that lacked large T antigen expression and in only 1 of 56 tumors positive for large T antigen. These results indicate that MCPyV is present in MCC tumors more frequently than previously reported and that mutations in TP53 tend to occur in MCC tumors that fail to express MCPyV large T antigen.

    • Authors

  • Rodig, Scott J
  • Cheng, Jingwei
  • Wardzala, Jacek
  • DoRosario, Andrew
  • Scanlon, Jessica J
  • Laga, Alvaro C
  • Martinez-Fernandez, Alejandro
  • Barletta, Justine A
  • Bellizzi, Andrew M
  • Sadasivam, Subhashini
  • Holloway, Dustin T
  • Cooper, Dylan J
  • Kupper, Thomas S
  • Wang, Linda C
  • DeCaprio, James A

    • Status

    Publication Date

  • December 3, 2012

    • Has Subject Area

    Published In

    Keywords

  • Aged Aged, 80 and over Antibodies, Viral/immunology Antigens, Polyomavirus Transforming/immunology/metabolism Carcinoma, Merkel Cell/diagnosis/metabolism/*virology Cell Line, Tumor DNA Mutational Analysis Female Gene Dosage Genes, Tumor Suppressor Genotype Humans Immunohistochemistry Male Merkel cell polyomavirus/genetics/immunology/*metabolism Middle Aged Molecular Diagnostic Techniques Oncogenes Polyomavirus Infections/diagnosis/metabolism/*virology Real-Time Polymerase Chain Reaction Tumor Virus Infections/diagnosis/metabolism/*virology

    • Digital Object Identifier (doi)

    Start Page

  • 4645

    • End Page

  • 4653

    • Volume

  • 122

    • Issue

  • 12