Non-invasive epidermis sampling for DNA methylation-based prediction of skin cancer phenotypes

The epidermis is uniquely exposed to the effects of environmental factors, such as ultraviolet radiation, which induce progressive genetic and epigenetic modifications contributing to aging and the onset of keratinocyte carcinomas. DNA methylation is the best-characterized epigenetic modification and a valuable biomarker for assessing epidermal health. However, broad screening approaches have been hindered by the limited quantity and quality of the genomic DNA obtained from the epidermis and the resulting need for invasive sampling methods. Here we describe an integrated method that enables the non-invasive sampling of epidermal DNA for subsequent analysis by DNA methylation microarrays. This procedure combines a gel-based adhesive tape for keratinocyte collection, a robust gDNA extraction protocol and a curated selection of microarray probes optimized for low-input DNA conditions. Analysis of >100 corresponding methylomes demonstrates that our approach can be used for both the training of epigenetic clocks capable of predicting epidermal age with high accuracy, as well as the investigation of various DNA methylation-based biomarkers relevant to keratinocyte cancer development. These findings underscore the potential of our method for broad and non-invasive skin health assessment and cancer prevention strategies.