According to a study by A. Hunter Shain, PhD, Assistant Professor, Department of Dermatology Risk, University of California – San Francisco, and colleagues, melanoma can be predicted long before any suspicious moles are detected thanks to the identification of DNA mutations in individual skin cells (Nature. 2020 Oct 7. Epub ahead of print).

“Every cell in the human body has a unique set of somatic mutations, but it remains difficult to comprehensively genotype an individual cell. Here we describe ways to overcome this obstacle in the context of normal human skin, thus offering a glimpse into the genomic landscapes of individual melanocytes from human skin,” Dr Shain and colleagues wrote.

Although skin damage from the sun is not always obvious to the naked eye, the sun's ultraviolet rays damage the DNA in skin cells, and this damage can in turn be measured.

The methods by which skin damage are probed the study by Dr Shain et al could help predict baseline melanoma risk for individuals in the general population, and guide how often cancer screenings should be conducted by a dermatologist.

“As expected, sun-shielded melanocytes had fewer mutations than sun-exposed melanocytes. However, melanocytes from chronically sun-exposed skin (for example, the face) had a lower mutation burden than melanocytes from intermittently sun-exposed skin (for example, the back),” the researchers reported.

Of note, melanocytes from bodily areas bordering a skin cancer had higher mutation burdens than melanocytes from donors without skin cancer, suggesting that mutations to normal skin can be used to measure cumulative sun damage and the risk for skin cancer.

Healthy skin melanocytes were frequently found to harbor pathogenic mutations, although these mutations were often weakly oncogenic (a possible cause for why they did not lead to discernible lesions).

According to phylogenetic analyses that revealed groups of related melanocytes, Dr Shain and co-investigators deduce that melanocytes spread throughout skin as fields of clonally related cells invisible to the human eye.

“Overall, our results uncover the genomic landscapes of individual melanocytes, providing key insights into the causes and origins of melanoma,” they concluded.—Hina Porcelli