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In addition, the recent identification of the presence of shared genomic abnormalities between some melanomas and associated nevi has provided support for a potential role of some nevi ( - Pathway 1: the vast majority of acquired nevi possess single driver mutations of either BRAF V600E or NRAS Q61R/L ( - Pathway 4: some Spitz nevi harbor HRAS mutation or translocations with kinase gene fusions involving ALK , ROS , RET , MET , and NTRK ( - Pathway 7: NRAS mutation is most frequently observed in congenital melanocytic nevi ( - Pathway 8: some blue nevi harbor the GNAQ or GNA11 mutation ( In contrast to melanomas, which acquire additional driver mutations, nevi usually enter a suppressive state of replicative senescence which is regulated by the tumor suppressor gene CDKN2A via its proteins, p14 and p16, and various transcriptional controls of the cell cycle ( in situ ) as well as papulonodular tumorigenic dermal proliferations (melanocytomas), and both categories are subclassified into low-grade and high-grade ( BRAF or NRAS ( TERT promoter and, sometimes, hemizygous loss of CDKN2A are involved in the morphological progression to a classical (superficial spreading) melanoma in situ ( Many melanocytomas are instead dermal-based, thick, combined melanocytic tumors in which an activating mutation of BRAF (or, much less commonly, NRAS ) is followed by a second genetic hit with expansion of a morphologically peculiar (non-classical) clone of melanocytes
