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

Autor: Evgeniya Denisova, Katrin Schmidt, Carlota Lucena-Porcel, Horst Wenck, Lars Feuerbach, Florian Köhler, Ingo Nindl, Elisabeth Wurzer, Julian Gutekunst, Marc Winnefeld, Esther Herpel, Manuel Rodríguez-Paredes, Joachim Röwert-Huber, Thomas G. Hofmann, Benedikt Brors, Günter Raddatz, Frank Lyko, Jeongbin Park, Felix Bormann, Stefan Gallinat
Rok vydání: 2018
Předmět:
Adult
Keratinocytes
Male
0301 basic medicine
Skin Neoplasms
Keratosis
Science
Cellular differentiation
General Physics and Astronomy
Biology
600 Technik
Medizin
angewandte Wissenschaften::610 Medizin und Gesundheit
600 Technik
Medizin
angewandte Wissenschaften::610 Medizin und Gesundheit::616 Krankheiten
Article
General Biochemistry
Genetics and Molecular Biology
Young Adult
03 medical and health sciences
Squamous cell carcinoma
medicine
Humans
lcsh:Science
Aged
Aged
80 and over
Regulation of gene expression
Multidisciplinary
Epidermis (botany)
Actinic keratosis
Cancer
Cell Differentiation
General Chemistry
Methylation
DNA Methylation
Middle Aged
medicine.disease
Gene Expression Regulation
Neoplastic
Keratosis
Actinic
030104 developmental biology
Case-Control Studies
DNA methylation
Carcinoma
Squamous Cell
Cancer research
Female
lcsh:Q
Zdroj: Nature Communications, Vol 9, Iss 1, Pp 1-9 (2018)
Nature Communications
ISSN: 2041-1723
DOI: 10.1038/s41467-018-03025-1
Popis: 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.
Cutaneous squamous cell carcinoma (cSCC) is a skin cancer that normally progresses from UV-induced actinic keratosis (AK). Here, the authors investigate the epigenomics of cSCC and highlight two distinct subclasses of AK and cSCC originating from distinct keratinocyte differentiation stages.
Databáze: OpenAIRE
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