Fig. 7: A model of the genomic evolution of acral melanoma.
The progression cascade begins with field cells, i.e., histopathologically normal acral melanocytes distributed along the basilar epidermis at normal density but already harboring hailstorms as demonstrated by prior FISH studies37,38. As cell density increases, the nascent tumor becomes histopathological and clinically manifest as melanoma in situ, which later develops foci of dermal invasion with genetically heterogeneous subclones that can seed metastases. Activation of TERT arises before canonical driver mutations of melanoma, which activate the MAP-kinase pathway, override the G1/S checkpoint, and further disrupt other pathways.
