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Methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and usually progresses from a UV-induced precancerous lesion termed actinic keratosis (AK). Despite various efforts to characterize these lesions molecularly, the etiology of AK and its progression to cSCC remain partiall...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805678/ https://www.ncbi.nlm.nih.gov/pubmed/29422656 http://dx.doi.org/10.1038/s41467-018-03025-1 |
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author | Rodríguez-Paredes, Manuel Bormann, Felix Raddatz, Günter Gutekunst, Julian Lucena-Porcel, Carlota Köhler, Florian Wurzer, Elisabeth Schmidt, Katrin Gallinat, Stefan Wenck, Horst Röwert-Huber, Joachim Denisova, Evgeniya Feuerbach, Lars Park, Jeongbin Brors, Benedikt Herpel, Esther Nindl, Ingo Hofmann, Thomas G. Winnefeld, Marc Lyko, Frank |
author_facet | Rodríguez-Paredes, Manuel Bormann, Felix Raddatz, Günter Gutekunst, Julian Lucena-Porcel, Carlota Köhler, Florian Wurzer, Elisabeth Schmidt, Katrin Gallinat, Stefan Wenck, Horst Röwert-Huber, Joachim Denisova, Evgeniya Feuerbach, Lars Park, Jeongbin Brors, Benedikt Herpel, Esther Nindl, Ingo Hofmann, Thomas G. Winnefeld, Marc Lyko, Frank |
author_sort | Rodríguez-Paredes, Manuel |
collection | PubMed |
description | Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and usually progresses from a UV-induced precancerous lesion termed actinic keratosis (AK). Despite various efforts to characterize these lesions molecularly, the etiology of AK and its progression to cSCC remain partially understood. Here, we use Infinium MethylationEPIC BeadChips to interrogate the DNA methylation status in healthy, AK and cSCC epidermis samples. Importantly, we show that AK methylation patterns already display classical features of cancer methylomes and are highly similar to cSCC profiles. Further analysis identifies typical features of stem cell methylomes, such as reduced DNA methylation age, non-CpG methylation, and stem cell-related keratin and enhancer methylation patterns. Interestingly, this signature is detected only in half of the samples, while the other half shows patterns more closely related to healthy epidermis. These findings suggest the existence of two subclasses of AK and cSCC emerging from distinct keratinocyte differentiation stages. |
format | Online Article Text |
id | pubmed-5805678 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58056782018-02-12 Methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin Rodríguez-Paredes, Manuel Bormann, Felix Raddatz, Günter Gutekunst, Julian Lucena-Porcel, Carlota Köhler, Florian Wurzer, Elisabeth Schmidt, Katrin Gallinat, Stefan Wenck, Horst Röwert-Huber, Joachim Denisova, Evgeniya Feuerbach, Lars Park, Jeongbin Brors, Benedikt Herpel, Esther Nindl, Ingo Hofmann, Thomas G. Winnefeld, Marc Lyko, Frank Nat Commun Article Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and usually progresses from a UV-induced precancerous lesion termed actinic keratosis (AK). Despite various efforts to characterize these lesions molecularly, the etiology of AK and its progression to cSCC remain partially understood. Here, we use Infinium MethylationEPIC BeadChips to interrogate the DNA methylation status in healthy, AK and cSCC epidermis samples. Importantly, we show that AK methylation patterns already display classical features of cancer methylomes and are highly similar to cSCC profiles. Further analysis identifies typical features of stem cell methylomes, such as reduced DNA methylation age, non-CpG methylation, and stem cell-related keratin and enhancer methylation patterns. Interestingly, this signature is detected only in half of the samples, while the other half shows patterns more closely related to healthy epidermis. These findings suggest the existence of two subclasses of AK and cSCC emerging from distinct keratinocyte differentiation stages. Nature Publishing Group UK 2018-02-08 /pmc/articles/PMC5805678/ /pubmed/29422656 http://dx.doi.org/10.1038/s41467-018-03025-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Rodríguez-Paredes, Manuel Bormann, Felix Raddatz, Günter Gutekunst, Julian Lucena-Porcel, Carlota Köhler, Florian Wurzer, Elisabeth Schmidt, Katrin Gallinat, Stefan Wenck, Horst Röwert-Huber, Joachim Denisova, Evgeniya Feuerbach, Lars Park, Jeongbin Brors, Benedikt Herpel, Esther Nindl, Ingo Hofmann, Thomas G. Winnefeld, Marc Lyko, Frank Methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin |
title | Methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin |
title_full | Methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin |
title_fullStr | Methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin |
title_full_unstemmed | Methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin |
title_short | Methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin |
title_sort | methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805678/ https://www.ncbi.nlm.nih.gov/pubmed/29422656 http://dx.doi.org/10.1038/s41467-018-03025-1 |
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