A non-invasive method for whole genome skin methylome profiling
Cristiana Banila, Daniel Green, Dimitris Katsanos, Joana Viana, Alice Osmaston, Angel Menendez Vazquez, Magnus Lynch, Shakiba Kaveh- Dermatology
Abstract
Background
Both aging, disease and malignant transformation of the skin are associated with changes in DNA methylation. So far mostly invasive methodologies such as biopsies have been applied towards collecting DNA methylation signatures. Tape-stripping offers a non-invasive option for skin diagnostics. It enables the easy but robust capture biological material, in large numbers of participants without the need for specialized medical personnel.
Objectives
To design and validate a methodology for non-invasive skin sample collection using tape-stripping for subsequent DNA methylation analysis.
Methods
A total of 175 participants were recruited and provided tape-stripping samples from a sun-exposed area, 92 of those provided matched tape-stripping samples from a sun-protected area, and an additional 5 provided matched skin-shave biopsies from the same area. Using enzymatic conversion and whole genome Illumina sequencing, we generated genome-wide DNA methylation profiles which we used to evaluate the feasibility of non-invasive data acquisition, to compare with established sampling approaches and to investigate biomarker identification for age and UV exposure.
Results
We found that tape-stripping samples show strong concordance in their global DNA methylation landscapes with those of conventional invasive biopsies. Moreover, we show sample reproducibility and consistent global methylation profiles in skin tape-stripping samples collected from different parts of the body. Using matched samples from sun-protected and sun-exposed areas of the body we were able to validate the capacity of our method to capture the effects of environmental changes and aging from a cohort covering various ages, ethnicities, and skin types. We present DNA methylation changes on the skin resulting from UV exposure and identify a significant age-related hypermethylation of CpG islands, with a pronounced peak effect at 50–55 years of age, including methylation changes in well-described markers of aging.
Conclusion
These data demonstrate the feasibility of using tape-stripping combined with whole genome sequencing as a non-invasive approach to measure DNA methylation changes in the skin. In addition, they outline a viable experimental framework for the use of skin tape-stripping, particularly when that is performed in large cohorts of patients to identify biomarkers of skin aging, UV damage, and possibly to track treatment response to therapeutic interventions.