Editing Melanoma (section)

=== '''Pathogenesis''' ===

** Genotypic
*** The highest mutational burden of any malignancy studied in humans
*** Mutations generally exert effects via MAPK signalling pathway, which modulates gene expression in the nucleus. Alterations can result in unchecked cellular growth.
**** BRAF and RAS are gain-of-function mutations, while NF1 is loss of inhibition
*** Other affected pathway is the PI3/AKT pathway, which can potentially be altered in all four genomic subtypes
** Cellular
*** Proliferates in the basal layer of the skin
*** Radial growth phase: expands radially in the epidermis and superficial dermal layer 
*** Vertical growth phase: invasion into deeper layers of the skin, and the skin lesion may become palpable. May ultimately develop metastatic potential by invasion of blood vessels and lymphatic channels.