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

Author

Listed:
  • 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
    Tissue Bank of the National Center for Tumor Diseases (NCT))

  • 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)
    National Center for Tumor Diseases (NCT)
    German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Esther Herpel

    (Heidelberg University
    Tissue Bank of the National Center for Tumor Diseases (NCT))

  • 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)

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.

Suggested Citation

  • Manuel Rodríguez-Paredes & Felix Bormann & Günter Raddatz & Julian Gutekunst & Carlota Lucena-Porcel & Florian Köhler & Elisabeth Wurzer & Katrin Schmidt & Stefan Gallinat & Horst Wenck & Joachim Röwe, 2018. "Methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03025-1
    DOI: 10.1038/s41467-018-03025-1
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