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Int J Clin Exp Pathol 2013;6(12):2943-2948

Original Article
Transposable hypomethylation is associated with metastatic capacity of primary
melanomas

Szilvia I Ecsedi, Hector Hernandez-Vargas, Sheila C Lima, Zdenko Herceg, Roza Adany, Margit Balazs

Department of Preventive Medicine, Faculty of Public Health, Medical and Health Science Centre, University of Debrecen, Hungary; Public
Health Research Group of The Hungarian Academy of Sciences, University of Debrecen, Hungary; International Agency for Research on
Cancer, Epigenetics Group, Lyon, France

Received September 25, 2013; Accepted October 13, 2013; Epub November 15, 2013; Published December 1, 2013

Abstract: 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. (IJCEP1309070).

Keywords: Melanoma progression, epigenetics, DNA methylation, global hypomethylation, LINE1

Address correspondence to: Margit Balazs, Department of Preventive Medicine, Faculty of Public Health, Medical and Health Science Centre,
University of Debrecen, Debrecen 4028 Kassai út 26/b, Hungary. E-mail: balazs.margit@sph.unideb.hu