(1) The underlying melanoma-driving mutations may give rise to specific dermoscopic growth patterns, (2) BRAF/NRAS mutations in early melanomas may not be as common as previously thought, and (3) patients may be predisposed to developing specific driving mutations giving rise to melanomas or nevi of similar growth patterns.
Melanomas without chronic sun-induced damage (Non-CSD) were more likely (P<0.01) to show BRAF mutations while NRAS mutation frequency was unbiased between melanoma subtypes.
Melanoma is a heterogenous disease and can be subclassified based on distinct clinical characteristics, histopathological features and mutation patterns within NRAS and BRAF genes.
Melanomas with NF1 mutations typically occur on chronically sun-exposed skin or in older individuals, show a high mutation burden, and are wild-type for BRAF and NRAS.
Melanoma onset and progression are associated with a high variety of activating mutations in the MAPK-pathway, most frequently involving BRAF (35-45%) and NRAS (15-25%) genes, but also c-KIT and PTEN.
NRAS and CKIT mutant melanoma represent the next oncogene defined melanoma subsets for which initial targeted therapy approaches are being explored, with early evidence suggesting progress with MEK and CKIT inhibitors, respectively.
NRAS mutations were most frequently detected in acral melanomas (9.3 %), followed by melanomas without chronic sun-induced damage (7.0 %) and mucosal melanomas (4.8 %), and were not detected in melanomas with chronic sun-induced damage.
NRAS mutated melanoma were mainly observed in chronic sun-damaged areas and had a negative prognostic value, with shorter time to progression and a high incidence of central nervous system involvement.