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Interestingly, the relationship between survival and tumor driven mutational status has been extensively investigated: BRAF -mutated melanoma has been associated with a shorter survival in patients with both metastatic ( BRAF -mutated melanoma receiving BRAF inhibitors, a worse prognosis has been also associated with alterations in the thrombophilic status, such as high D-dimer levels at baseline ( NRAS mutations did not display any effect on the survival if measured in the primary tumor ( NRAS mutations were associated with improved survival ( NRAS -mutated melanoma data on survival result conflicting: some studies report no difference in patients survival ( NRAS mutations were associated with improved survival in metastatic disease ( According to the TCGA Pan-Cancer Atlas data set, 65% of melanomas that have BRAF , NRAS , NF1 , or KIT as driver mutation co-occur with mutations in at least one other pathway, most frequently affecting PTEN , Cyclin-Dependent Kinase Inhibitor 2A ( CDKN2A ), and TP53 ( Regarding somatic CNVs assessment, deletions have been identified most frequently in the tumor suppressors PTEN, PPP6C , and CDKN2A genes, while amplifications occur repeatedly in KIT , Epidermal Growth Factor Receptor (EGFR) , and Cyclin-Dependent Kinase 4 ( CDK4 ) oncogenes

10.3390/ijms22126403 93

Recurrence may occur due to invasion of the tumor edge into the bone, difficulty in complete resection due to a tumor with no envelope (15) or multicenter growth