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

Emil Chteinberg, Julia Vogt, Julia Kolarova, Felix Bormann, Joost van den Oord, Ernst Jan Speel, Veronique Winnepenninckx, Anna Kordelia Kurz, Martin Zenke, Reiner Siebert, Axel zur Hausen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)1319-1324
Number of pages6
JournalEpigenetics
Volume15
Issue number12
Early online date1 Jun 2020
DOIs
Publication statusPublished - 1 Dec 2020

Keywords

  • Horvath's epigenetic clock
  • Merkel cell carcinoma
  • Merkel cell polyomavirus
  • pluritest
  • DNA methylation age

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