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Updated: Feb 14, 2026

Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
Methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin
Manuel Rodríguez-Paredes1, Felix Bormann1, Günter Raddatz1
1Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120, Heidelberg, Germany.
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.
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