Our data suggest that the mutational status of BRAF-V600 and NRAS-Q61 did not vary among geographical regions and altitudes of residence. Regression analysis confirmed that mutational burden was an independent variable that was not influenced by altitude of residence but by some clinical characteristics of CM [39,40,41] and patients’ demographics. Contrary to previous studies [42,43], in our cohort, BRAFV600 mutations were more frequently detected in men. This result is likely due to our selection criteria as CMs of male patients were analyzed from the trunk, which has already been reported as a preferential anatomical site associated with BRAF mutation [44]. Patient age showed a clear influence on the documented BRAF mutation rate in this study, with younger patients prevailing in the BRAF-mutated group in comparison with NRAS-mutated as well as BRAF/NRAS wild-type ones. BRAF-mutated melanomas are indeed characterized by a young age at diagnosis, absence of chronic sun damage of the skin, and melanoma occurrence on the trunk [45], which closely reflect the features of our BRAF-mutated patients. NRAS mutations were frequently recorded in CMs located on the lower limbs (7.7%, n = 22 of 287) in our dataset, in agreement with others [44,46]. The trunk is commonly considered a site of intermittent sun exposure, while the lower limbs a chronic sun-damaged skin area (CSD). Therefore, our data confirm that the type of UV exposure is a determinant influencing the mutational burden of BRAF V600 and NRAS Q61 [44,46].
