Transposable hypomethylation is associated with metastatic capacity of primary melanomas

Despite the strong progress has been made in the field of melanoma epigenetics, the importance of genome-wide demethylation or hypomethylation remains underestimated. However, this phenomenon might also reflect important epigenetic alterations due to its ability to cause genetic instability. Furthermore, no methylation-based distinction has been drawn among the diverse primary melanoma subtypes. To assess global methylation we measured the methylation level on the 6 CpG sites of LINE1 sequences in 46 primary melanomas in association with patients' survivals and the clinicopathological characteristics of specimens. We demonstrate that LINE1 hypomethylation is accompanied by the shortened relapse-free survival of melanoma patients; however, Cox regression analysis shows a direct relationship between the overall loss of 5-methylcytosine and metastatic potential of primary melanomas, which is confirmed by Kruskal-Wallis tests with Dunn's Multiple Comparison Post-test showing that not only the presence but the number of metastases during the 5-year follow-up period is associated with the transposon demethylation. In this study, we demonstrate the strong influence of global DNA demethylation in the metastatic formation of primary melanomas during the follow-up period.