OPRPN and metastatic melanoma: 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).