B de Unamuno Bustos1, R Murria Estal2, G Pérez Simó2, J Simarro Farinos2, C Pujol Marco1, M Navarro Mira1, V Alegre de Miquel3, R Ballester Sánchez4, V Sabater Marco5, M Llavador Ros6, S Palanca Suela2, R Botella Estrada1. 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.
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 melanomaformalin-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.
Authors: Kathleen Conway; Yihsuan S Tsai; Sharon N Edmiston; Joel S Parker; Eloise A Parrish; Honglin Hao; Pei Fen Kuan; Glynis A Scott; Jill S Frank; Paul Googe; David W Ollila; Nancy E Thomas Journal: J Invest Dermatol Date: 2021-11-27 Impact factor: 7.590
Authors: Flávia E Rius; Debora D Papaiz; Hatylas F Z Azevedo; Ana Luísa P Ayub; Diogo O Pessoa; Tiago F Oliveira; Ana Paula M Loureiro; Fernando Andrade; André Fujita; Eduardo M Reis; Christopher E Mason; Miriam G Jasiulionis Journal: Clin Epigenetics Date: 2022-05-23 Impact factor: 7.259
Authors: Dinesh Pradhan; George Jour; Denái Milton; Varshini Vasudevaraja; Michael T Tetzlaff; Priyadharsini Nagarajan; Jonathan L Curry; Doina Ivan; Lihong Long; Yingwen Ding; Ravesanker Ezhilarasan; Erik P Sulman; Adi Diab; Wen-Jen Hwu; Victor G Prieto; Carlos Antonio Torres-Cabala; Phyu P Aung Journal: Cancers (Basel) Date: 2019-12-16 Impact factor: 6.639