Genetics and epigenetics of the skin meet deep sequence

Rapid advances in next-generation sequencing technology are revolutionizing approaches to genomic and epigenomic studies of skin. Deep sequencing of cutaneous malignancies reveals heavily mutagenized genomes with large numbers of low-prevalence mutations and multiple resistance mechanisms to targeted therapies. Next-generation sequencing approaches have already paid rich dividends in identifying the genetic causes of dermatologic disease, both in heritable mutations and the somatic aberrations that underlie cutaneous mosaicism. Although epigenetic alterations clearly influence tumorigenesis, pluripotent stem cell biology, and epidermal cell lineage decisions, labor and cost-intensive approaches long delayed a genome-scale perspective. New insights into epigenomic mechanisms in skin disease should arise from the accelerating assessment of histone modification, DNA methylation, and related gene expression signatures.