Fig. 3

DNA methylation biomarkers with prognostic value. a Two groups of primary melanomas were observed in the discovery cohort when comparing primary melanomas and benign nevi, with significantly different Breslow thickness and distant metastasis-free survival (left panel); 734 probes displayed significant differences in median DNA methylation values higher than 20% when comparing the DNA methylation profiles of long survivors (>48 months) versus patients dying within this period (<48 months; right panel; primary primary tumor). Note that the vast majority correspond to gain-of-methylation events. b Kaplan–Meier survival curves for pyrosequencing results of three selected markers (PON3, OLIG3, and MEOX2) in validation cohort II (Additional file 1: Table S1) corroborating their prognostic power on overall survival (and progression-free survival, see Additional file 2: Figure S10; UM unmethylated; M methylated; Log-Rank test: P < 0.05). c Kaplan–Meier survival curves for PON3 pyrosequencing results in validation cohort II grouped according Breslow thickness and ulceration status (left and middle panel, respectively; HB high Breslow, LB low Breslow, NU no ulceration, U ulceration; Log-Rank test: P < 0.05). Multivariate analysis for PON3 establishes its value for survival prediction independent of these two prognostic markers (right panel; Cox regression analysis)