The most common histological subtypes of cutaneous melanoma include superficial spreading and nodular melanoma. However, the spectrum of somatic mutations developed in those lesions and all potential druggable targets have not yet been fully elucidated. We present the results of a sequence capture NGS analysis of 114 primary nodular and superficial spreading melanomas identifying driver mutations using biostatistical, immunohistochemical and/or functional approach. The spectrum and frequency of pathogenic or likely pathogenic variants were identified across 54 evaluated genes, including 59 novel mutations, and the newly identified TP53 loss-of-function mutations p.(L194P) and p.(R280K). Frequently mutated genes most commonly affected the MAPK pathway, followed by chromatin remodeling, and cell cycle regulation. Frequent aberrations were also detected in the genes coding for proteins involved in DNA repair and the regulation and modification of cellular tight junctions. Furthermore, relatively frequent mutations were described in KDR and MET, which represent potential clinically important targets. Those results suggest that with the development of new therapeutic possibilities, not only BRAF testing, but complex molecular testing of cutaneous melanoma may become an integral part of the decision process concerning the treatment of patients with melanoma.

• MeSH
• Cell Cycle genetics   MeSH
• Adult MeSH
• Gene Frequency genetics   MeSH
• Genetic Predisposition to Disease genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Melanoma, Cutaneous Malignant MeSH
• MAP Kinase Signaling System genetics   MeSH
• Melanoma genetics   pathology   MeSH
• Young Adult MeSH
• Loss of Function Mutation genetics   MeSH
• Biomarkers, Tumor genetics   MeSH
• Tumor Suppressor Protein p53 genetics   MeSH
• Skin Neoplasms genetics   pathology   MeSH
• DNA Repair genetics   MeSH
• Proto-Oncogene Proteins B-raf genetics   MeSH
• Chromatin Assembly and Disassembly genetics   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Tight Junctions genetics   MeSH
• High-Throughput Nucleotide Sequencing MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biomarkers, Tumor MeSH
• Tumor Suppressor Protein p53 MeSH
• Proto-Oncogene Proteins B-raf MeSH
• TP53 protein, human MeSH Browser