The second patient had stage III BRAFV600R mutant melanoma that was treated with pembrolizumab and dabrafenib, and also developed a regressed melanocytic nevus.
They were ulcerated (p = 0.0001), they were associated with neurotropism (p = 0.0001), they lacked the BRAF mutation (p = 0.03), and they less often coexisted with a preceding melanocytic nevus (p = 0.0001).
Both drug resistance and inherent transition from melanocytic nevi to malignant melanoma involve the overexpression of histone deacetylases (HDACs) and a B-Raf proto-oncogene (BRAF) mutation.
RhoJ deletion in BRAF mutant melanocytes modulates the expression of the pro-apoptotic protein BAD as well as genes involved in cellular metabolism, impairing nevus formation, cellular transformation, and metastasis.
Mutations of the β-catenin pathway change the phenotype of a common nevus with BRAF mutation into that of DPN, with increased pigmentation, cell volume and nuclear cyclin D1 levels.
BRAF mutations were more frequent in males, in young patients, and in tumours with a sun-exposed tumour location (bulbar conjunctiva or caruncle), with a mixed or non-pigmented colour, with absence of primary acquired melanosis, and with origin in a nevus.
BRAF mutations were associated with T1 stage (p = 0.007), young age (p = 0.001), male gender (p = 0.02), sun-exposed location (p = 0.01), mixed/non-pigmented tumour colour (p = 0.02) and nevus origin (p = 0.005), but did not associate with prognosis.
In the present study, the frequency of BRAFV600E mutation was evaluated in Russian patients with melanocytic lesions, of which 41.25% were primary melanoma and 60% were melanocytic nevi.
In contrast, only 21% of the primary melanomas unassociated with naevi were BRAF(V600E) mutant (p = 0.009).Our results suggest that melanomas with associated naevi have a higher frequency of BRAF(V600E) mutations than melanomas unassociated with naevi.