Merkel Cell Polyomavirus in Merkel Cell Carcinoma: Integration Sites and Involvement of the KMT2D Tumor Suppressor Gene

Viruses. 2020 Aug 31;12(9):966. doi: 10.3390/v12090966.


Merkel cell carcinoma (MCC) is an uncommon, lethal cancer of the skin caused by either Merkel cell polyomavirus (MCPyV) or UV-linked mutations. MCPyV is found integrated into MCC tumor genomes, accompanied by truncation mutations that render the MCPyV large T antigen replication incompetent. We used the open access HPV Detector/Cancer-virus Detector tool to determine MCPyV integration sites in whole-exome sequencing data from five MCC cases, thereby adding to the limited published MCPyV integration site junction data. We also systematically reviewed published data on integration for MCPyV in the human genome, presenting a collation of 123 MCC cases and their linked chromosomal sites. We confirmed that there were no highly recurrent specific sites of integration. We found that chromosome 5 was most frequently involved in MCPyV integration and that integration sites were significantly enriched for genes with binding sites for oncogenic transcription factors such as LEF1 and ZEB1, suggesting the possibility of increased open chromatin in these gene sets. Additionally, in one case we found, for the first time, integration involving the tumor suppressor gene KMT2D, adding to previous reports of rare MCPyV integration into host tumor suppressor genes in MCC.

Keywords: KMT2D; Merkel cell carcinoma; Merkel cell polyomavirus; viral integration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Merkel Cell / genetics
  • Carcinoma, Merkel Cell / metabolism*
  • Carcinoma, Merkel Cell / virology
  • Cell Line, Tumor
  • Chromosomes, Human, Pair 5 / genetics
  • Chromosomes, Human, Pair 5 / metabolism
  • Chromosomes, Human, Pair 5 / virology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Genes, Tumor Suppressor
  • Humans
  • Merkel cell polyomavirus / genetics
  • Merkel cell polyomavirus / physiology*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Polyomavirus Infections / genetics
  • Polyomavirus Infections / metabolism*
  • Polyomavirus Infections / virology
  • Tumor Virus Infections / genetics
  • Tumor Virus Infections / metabolism*
  • Tumor Virus Infections / virology
  • Virus Integration
  • Zinc Finger E-box-Binding Homeobox 1 / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism


  • DNA-Binding Proteins
  • KMT2D protein, human
  • Neoplasm Proteins
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1