CYT-low metastatic melanomas were associated with non-silent mutations in GALNTL5, RGPD4, DNAJC5B, DEFA3, IRF2, COL2A1, VEGFC, WFDC11, PROL1, CD80, ADAM18, APOBEC3H and CSHL1; whereas CYT-high metastatic skin tumors were significantly mutated in PPP6C, DSG1, DEFB112, SPATA16, STARD6, RARRES2 PDE1A, IQCF3, KLK8, CDKN2A, SPANXN5, C16orf90, CD48, TXNDC3 and RAC1 (Fig. 3a). This evidence concerns the gene RARRES2 and metastatic melanoma.