Format

Send to

Choose Destination
Br J Dermatol. 2018 Aug;179(2):394-404. doi: 10.1111/bjd.16254. Epub 2018 May 25.

Aberrant DNA methylation is associated with aggressive clinicopathological features and poor survival in cutaneous melanoma.

Author information

1
Department of Dermatology, Hospital Universitari i Politecnic La Fe, Valencia, Spain.
2
Department of Molecular Biology Laboratory, Service of Clinical Analysis, Hospital Universitari i Politecnic La Fe, Valencia, Spain.
3
Department of Dermatology, Hospital General Universitario de Valencia, Valencia, Spain.
4
Department of Dermatology, La Plana Hospital, Villarreal, Castellón, Spain.
5
Department of Pathology, Hospital General Universitario de Valencia, Valencia, Spain.
6
Department of Pathology, Hospital Universitari i Politecnic La Fe, Valencia, Spain.

Abstract

BACKGROUND:

Promoter methylation of tumour suppressor genes (TSGs) 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%, CDH13 16%, ESR1 14%, CDKN2A 6% and RASSF1 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 TSGs 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.

PMID:
29278418
DOI:
10.1111/bjd.16254

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center