The curious case of Merkel cell carcinoma: epigenetic youth and lack of pluripotency

Epigenetics. 2020 Dec;15(12):1319-1324. doi: 10.1080/15592294.2020.1773096. Epub 2020 May 30.

Abstract

Merkel cell carcinoma (MCC) is a very rare, but highly aggressive skin cancer which occurs mainly in elderly patients. MCC cells show an expression pattern of three cell lineages: epithelial, neuroendocrine, and B-cell progenitor. This trilinear expression pattern suggests stemness activity in MCC. The etiopathogenesis of MCC is either linked to the Merkel cell polyomavirus (MCPyV) or in a smaller proportion (20%) to high levels of UV-induced somatic mutations. Both viral presence and accumulation of mutations have been shown to be associated with accelerated DNA methylation Age (DNAmAge) compared to chronological age. The MCC DNAmAge was significantly lower compared to the chronological age, which was irrespective of the viral presence or mutational burden. Although these features indicate some aspects of stemness in MCC cells, gene-expression-based pluripotency testing did not provide evidence for pluripotency of MCC cells.

Keywords: DNA methylation age; Horvath’s epigenetic clock; Merkel cell carcinoma; Merkel cell polyomavirus; pluritest.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Merkel Cell / genetics*
  • Carcinoma, Merkel Cell / pathology
  • Carcinoma, Merkel Cell / virology
  • Cellular Senescence*
  • DNA Methylation
  • Epigenesis, Genetic*
  • Female
  • Humans
  • Male
  • Merkel cell polyomavirus / pathogenicity
  • Middle Aged
  • Mutation Accumulation*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / physiology