Download
s41388-021-02064-1.pdf 2,47MB
WeightNameValue
1000 Titel
  • DNA-methylation patterns imply a common cellular origin of virus- and UV-associated Merkel cell carcinoma
1000 Autor/in
  1. Gravemeyer, Jan |
  2. Spassova, Ivelina |
  3. Verhaegen, Monique |
  4. Dlugosz, Andrzej |
  5. Hoffmann, Daniel |
  6. , Anja |
  7. Becker, Jürgen |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-10-19
1000 Erschienen in
1000 Quellenangabe
  • 41(1):37-45
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1038/s41388-021-02064-1 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724008/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Merkel cell carcinoma (MCC) is a neuroendocrine tumor either induced by integration of the Merkel cell polyomavirus into the cell genome or by accumulation of UV-light-associated mutations (VP-MCC and UV-MCC). Whether VP- and UV-MCC have the same or different cellular origins is unclear; with mesenchymal or epidermal origins discussed. DNA-methylation patterns have a proven utility in determining cellular origins of cancers. Therefore, we used this approach to uncover evidence regarding the cell of origin of classical VP- and UV-MCC cell lines, i.e., cell lines with a neuroendocrine growth pattern (n = 9 and n = 4, respectively). Surprisingly, we observed high global similarities in the DNA-methylation of UV- and VP-MCC cell lines. CpGs of lower methylation in VP-MCC cell lines were associated with neuroendocrine marker genes such as SOX2 and INSM1, or linked to binding sites of EZH2 and SUZ12 of the polycomb repressive complex 2, i.e., genes with an impact on carcinogenesis and differentiation of neuroendocrine cancers. Thus, the observed differences appear to be rooted in viral compared to mutation-driven carcinogenesis rather than distinct cells of origin. To test this hypothesis, we used principal component analysis, to compare DNA-methylation data from different epithelial and non-epithelial neuroendocrine cancers and established a scoring model for epithelial and neuroendocrine characteristics. Subsequently, we applied this scoring model to the DNA-methylation data of the VP- and UV-MCC cell lines, revealing that both clearly scored as epithelial cancers. In summary, our comprehensive analysis of DNA-methylation suggests a common epithelial origin of UV- and VP-MCC cell lines.
1000 Sacherschließung
lokal Carcinoma, Merkel Cell/genetics [MeSH]
lokal DNA Methylation/genetics [MeSH]
lokal Cancer of unknown primary
lokal Article
lokal High-Throughput Screening Assays/methods [MeSH]
lokal Humans [MeSH]
lokal Tumor Virus Infections/genetics [MeSH]
lokal High-throughput screening
lokal Cancer genomics
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0003-4181-7685|https://orcid.org/0000-0003-4663-7966|https://orcid.org/0000-0003-0229-5917|https://orcid.org/0000-0002-9791-3257|https://orcid.org/0000-0003-2973-7869|https://orcid.org/0000-0002-6529-0606|https://orcid.org/0000-0001-9183-653X
1000 Hinweis
  • DeepGreen-ID: 7e67ad51e08c47e2b1310369deea6d7e ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
1000 Label
1000 Dateien
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6443672.rdf
1000 Erstellt am 2023-04-27T10:17:40.511+0200
1000 Erstellt von 322
1000 beschreibt frl:6443672
1000 Zuletzt bearbeitet 2023-10-19T15:21:29.887+0200
1000 Objekt bearb. Thu Oct 19 15:21:29 CEST 2023
1000 Vgl. frl:6443672
1000 Oai Id
  1. oai:frl.publisso.de:frl:6443672 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

View source