Methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin

Manuel Rodríguez-Paredes, Felix Bormann, Günter Raddatz, Julian Gutekunst, Carlota Lucena-Porcel, Florian Köhler, Elisabeth Wurzer, Katrin Schmidt, Stefan Gallinat, Horst Wenck, Joachim Röwert-Huber, Evgeniya Denisova, Lars Feuerbach, Jeongbin Park, Benedikt Brors, Esther Herpel, Ingo Nindl, Thomas G. Hofmann, Marc Winnefeld and Frank Lyko ()
Additional contact information
Manuel Rodríguez-Paredes: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center
Felix Bormann: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center
Günter Raddatz: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center
Julian Gutekunst: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center
Carlota Lucena-Porcel: Heidelberg University
Florian Köhler: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center
Elisabeth Wurzer: Research & Development, Beiersdorf AG
Katrin Schmidt: Research & Development, Beiersdorf AG
Stefan Gallinat: Research & Development, Beiersdorf AG
Horst Wenck: Research & Development, Beiersdorf AG
Joachim Röwert-Huber: University Hospital
Evgeniya Denisova: Division of Applied Bioinformatics, German Cancer Research Center (DKFZ)
Lars Feuerbach: Division of Applied Bioinformatics, German Cancer Research Center (DKFZ)
Jeongbin Park: Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ)
Benedikt Brors: Division of Applied Bioinformatics, German Cancer Research Center (DKFZ)
Esther Herpel: Heidelberg University
Ingo Nindl: University Hospital
Thomas G. Hofmann: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center
Marc Winnefeld: Research & Development, Beiersdorf AG
Frank Lyko: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-03025-1

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