Genomic DNA was extracted from the biopsies using QIAamp DNA Mini Kit (Qiagen). A total of 500 ng of DNA were used for bisulfite treatment, using the EZ DNA Methylation Kit (Zymo). We hybridized 200 ng in 4 μl to the Infinium Human Methylation450 BeadChip array.

Bisulphite converted DNA was amplified, fragmented and hybridised to Illumina Infinium Human Methylation450 Beadchip using standard Illumina protocol

Arrays were imaged using BeadArray Reader using standard recommended Illumina scanner setting

Raw intensities for methylated (M) and unmethylated (U) signal were extracted from Illumina’s GenomeStudio. Beta-values were calculated as M/(M+U). A total of 496 missing values (melanomas) were imputed using k-nearest neighbor imputation (k=10). For each sample we performed a peak-based correction of Illumina I and II chemical assays. For both assays we smoothed the beta values (Epanechnikov smoothing kernel) to estimate unmethylated and methylated peaks, respectively; and the unmethylated peak was moved to 0 and the methylated peak to 1 using linear scaling, with beta-values in between stretched accordingly. Beta-values below 0 were set back to 0 and values above 1 were set to 1.