Understanding the natural history and molecular characterization of epidermolysis bullosa nevi".

Epidermolysis bullosa (EB) is a rare genodermatosis characterized by skin fragility, blisters and wounds. A characteristic, but poorly understood skin finding is the EB nevus (EBN). EBN are pigmented macules occurring in 10-14% of patients across all EB subtypes. They frequently show clinical and dermoscopic features of melanoma, although they are usually considered benign. The pathogenesis of EBN remains unclear. We hypothesize that EBN are melanocytic nevi carrying BRAF or NRAS mutations, and that atypicality results from basement membrane zone abnormalities. By joining EB populations of Freiburg, Chicago, and the North American EB Clinical Research Consortium, we will accrue a large set of clinical and dermoscopic photographs to trace EBN natural history. From archived biopsies, we will study melanocyte architecture with regard to EB-specific changes in the basal membrane zone. We will sequence BRAF and NRAS hot spots known to occur in melanocytic nevi from extracted DNA of EBN. The risk for Ras-driven nevi to transform to melanoma is age-dependent. As we will likely prolong EB life expectancy through genetic and pharmacologic interventions in the near future, EBN will need careful longitudinal monitoring for possible transformation. Our better understanding of EBN will enable more information and reassurance for families concerned about these potentially alarming pigmented lesions.