Promoter methylation of tumor suppressor genes (TSGs) has recently been implicated in the pathogenesis of several types of cancer. Regarding melanoma, over a hundred genes that contribute to its pathogenesis have been identified to be aberrantly hypermethylated. This is a retrospective observational study that aims to analyze the prevalence of CpG island methylation in a series of primary melanoma, to identify the associations with the main clinicopathological features, and to explore the prognostic significance of methylation in melanoma survival.

DNA methylation was analyzed using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in a series of 170 melanoma formalin-fixed paraffin embedded (FFPE) tumor samples. The relationship between the methylation status, known somatic mutations and clinicopathological features was evaluated. Disease-free survival (DFS) and overall survival (OS) were displayed by the Kaplan-Meier method.

In the entire cohort, one or more genes were detected to be methylated in 55% of the patients. The most prevalent methylated genes were RARB 31%, PTEN 24%, APC 16%, CDH13 16%, ESR1 14%, CDKN2A 6%, and RASSF1 5%. An association between aberrant methylation and aggressive clinicopathological features was observed (older age, increased Breslow, presence of mitosis and ulceration, fast-growing melanomas, advancing stage, and TERT mutations). Furthermore, Kaplan-Meier survival analysis showed a correlation of methylation and poorer DFS and overall survival OS.

Aberrant methylation of TSGs is a frequent event in melanoma. It is associated to aggressive clinicopathological features and poorer survival. Epigenetic alterations may represent a significant prognostic marker with utility in routine practice. This article is protected by copyright. All rights reserved.