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Aberrant DNA methylation is associated with aggressive clinicopathological features and poor survival in cutaneous melanoma
Author(s) -
Unamuno Bustos B.,
Murria Estal R.,
Pérez Simó G.,
Simarro Farinos J.,
Pujol Marco C.,
Navarro Mira M.,
Miquel V.,
Ballester Sánchez R.,
Sabater Marco V.,
Llavador Ros M.,
Palanca Suela S.,
Botella Estrada R.
Publication year - 2018
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.16254
Subject(s) - cdkn2a , methylation , dna methylation , epigenetics , melanoma , cancer research , biology , cdkn2b , cancer , cpg site , survival analysis , oncology , medicine , gene , genetics , gene expression
Summary Background Promoter methylation of tumour suppressor genes ( TSG s) has recently been implicated in the pathogenesis of several types of cancer. Regarding melanoma, over 100 genes that contribute to its pathogenesis have been identified to be aberrantly hypermethylated. Objectives This is a retrospective observational study that aims to analyse the prevalence of CpG island methylation in a series of primary melanomas, to identify the associations with the main clinicopathological features, and to explore the prognostic significance of methylation in melanoma survival. Materials and methods DNA methylation was analysed using methylation‐specific multiplex ligation‐dependent probe amplification in a series of 170 melanoma formalin‐fixed paraffin‐embedded tumour 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. Results 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%, CDH 13 16%, ESR 1 14%, CDKN 2A 6% and RASSF 1 5%. An association between aberrant methylation and aggressive clinicopathological features was observed (older age, increased Breslow thickness, 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 OS . Conclusions Aberrant methylation of TSG s is a frequent event in melanoma. It is associated with aggressive clinicopathological features and poorer survival. Epigenetic alterations may represent a significant prognostic marker with utility in routine practice.