On the basis of the mutational signature activity in each patient with melanoma (eFigure 8 in the Supplement), we observed significant associations of UV light–related signature 7 (median contribution, 0.71 vs 0.15; difference, 0.56; 95% CI, 0.3-0.68; P < .001, Mann-Whitney U test) and alkylating agents-related signature 11 (median contribution, 0.21 vs 0.11; difference, 0.10; 95% CI, 0.02-0.19; P < .001, Mann-Whitney U test) with MUC16 mutation (eFigure 9 in the Supplement). Here, MUC16 is linked to melanoma.