Skin contains both pigmented melanocytes and rare, poorly-pigmented LNM cells. Upon Braf activation, both populations expand, but melanocytes arrest as nevi, unless loss-of-function mutation in tumor suppressor gene Pten allows them to develop rapidly into pigmented melanomas (Pathway 1). Otherwise, Braf -activated LNM cells can undergo rare, stochastic transitions to produce scantly pigmented melanomas (Pathway 2). The probability of such transitions depends on host pigmentation status, Sox2 expression, and whether both alleles of Pten have become inactivated. LNM cells persist in both types of tumor. Created in BioRender. Shiu, J. (2025) https://BioRender.com/pf330qi .
