Cutaneous malignant melanoma is the most fatal
skin cancer and although improved comprehension of its pathogenic pathways allowed to realize some effective
molecular targeted therapies, novel targets and drugs are still needed. Aiming to add genetic information potentially useful for novel targets discovery, we performed an extensive genomic characterization by whole-exome sequencing and SNP array profiling of six cutaneous
melanoma cell lines derived from metastatic patients. We obtained a total of 3,325 novel coding single
nucleotide variants, including 2,172 non-synonymous variants. We catalogued the coding mutations according to Sanger COSMIC database and to a manually curated list including genes involved in
melanoma pathways identified by mining recent literature. Besides confirming the presence of known
melanoma driver mutations (BRAF(V600E), NRAS(Q61R) ), we identified novel mutated genes involved in signalling pathways crucial for
melanoma pathogenesis and already addressed by current targeted
therapies (such as MAPK and
glutamate pathways). We also identified mutations in four genes (MUC19, PAICS, RBMXL1, KIF23) never reported in
melanoma, which might deserve further investigations. All data are available to the entire research community in our
Melanoma Exome Database (at https://155.253.6.64/MExDB/). In summary, these cell lines are valuable
biological tools to improve the genetic comprehension of this complex
cancer disease and to study functional relevance of individual mutational events, and these findings could provide insights potentially useful for identification of novel therapeutic targets for
cutaneous malignant melanoma.