The Skin Molecular Ecosystem Holds the Key to Nevogenesis and Melanomagenesis

Early detection of melanoma is critical to good patient outcomes, but we still know little about the mechanisms of early melanoma development. Normal epidermis has many of the sequence variants and genetic architecture disruptions found in both benign nevi, melanomas, and other skin cancers, yet continues to behave more or less normally. One hypothesis is that many melanocytes in this context are "tumor competent" but are regulated by the microenvironment provided by the surrounding keratinocytes to inhibit progress to nevi or melanoma. There is evidence of accumulating disorder in several measures of the genomic and epigenomic landscape from normal skin through nevi to melanoma that may be key to promoting nevogenesis and melanomagenesis.