DNA methylation characteristics of primary melanomas with distinct biological behaviour.

In melanoma, the presence of promoter related hypermethylation has previously been reported, however, no methylation-based distinction has been drawn among the diverse melanoma subtypes. Here, we investigated DNA methylation changes associated with melanoma progression and links between methylation...

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Autores principales:	Szilvia Ecsedi, Hector Hernandez-Vargas, Sheila C Lima, Laura Vizkeleti, Reka Toth, Viktoria Lazar, Viktoria Koroknai, Timea Kiss, Gabriella Emri, Zdenko Herceg, Roza Adany, Margit Balazs
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2866978865b0486cbaff03d6096a3f44
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spelling	oai:doaj.org-article:2866978865b0486cbaff03d6096a3f442021-11-18T08:19:01ZDNA methylation characteristics of primary melanomas with distinct biological behaviour.1932-620310.1371/journal.pone.0096612https://doaj.org/article/2866978865b0486cbaff03d6096a3f442014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24832207/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203In melanoma, the presence of promoter related hypermethylation has previously been reported, however, no methylation-based distinction has been drawn among the diverse melanoma subtypes. Here, we investigated DNA methylation changes associated with melanoma progression and links between methylation patterns and other types of somatic alterations, including the most frequent mutations and DNA copy number changes. Our results revealed that the methylome, presenting in early stage samples and associated with the BRAF(V600E) mutation, gradually decreased in the medium and late stages of the disease. An inverse relationship among the other predefined groups and promoter methylation was also revealed except for histologic subtype, whereas the more aggressive, nodular subtype melanomas exhibited hypermethylation as well. The Breslow thickness, which is a continuous variable, allowed for the most precise insight into how promoter methylation decreases from stage to stage. Integrating our methylation results with a high-throughput copy number alteration dataset, local correlations were detected in the MYB and EYA4 genes. With regard to the effects of DNA hypermethylation on melanoma patients' survival, correcting for clinical cofounders, only the KIT gene was associated with a lower overall survival rate. In this study, we demonstrate the strong influence of promoter localized DNA methylation changes on melanoma initiation and show how hypermethylation decreases in melanomas associated with less favourable clinical outcomes. Furthermore, we establish the methylation pattern as part of an integrated apparatus of somatic DNA alterations.Szilvia EcsediHector Hernandez-VargasSheila C LimaLaura VizkeletiReka TothViktoria LazarViktoria KoroknaiTimea KissGabriella EmriZdenko HercegRoza AdanyMargit BalazsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 5, p e96612 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Szilvia Ecsedi Hector Hernandez-Vargas Sheila C Lima Laura Vizkeleti Reka Toth Viktoria Lazar Viktoria Koroknai Timea Kiss Gabriella Emri Zdenko Herceg Roza Adany Margit Balazs DNA methylation characteristics of primary melanomas with distinct biological behaviour.
description	In melanoma, the presence of promoter related hypermethylation has previously been reported, however, no methylation-based distinction has been drawn among the diverse melanoma subtypes. Here, we investigated DNA methylation changes associated with melanoma progression and links between methylation patterns and other types of somatic alterations, including the most frequent mutations and DNA copy number changes. Our results revealed that the methylome, presenting in early stage samples and associated with the BRAF(V600E) mutation, gradually decreased in the medium and late stages of the disease. An inverse relationship among the other predefined groups and promoter methylation was also revealed except for histologic subtype, whereas the more aggressive, nodular subtype melanomas exhibited hypermethylation as well. The Breslow thickness, which is a continuous variable, allowed for the most precise insight into how promoter methylation decreases from stage to stage. Integrating our methylation results with a high-throughput copy number alteration dataset, local correlations were detected in the MYB and EYA4 genes. With regard to the effects of DNA hypermethylation on melanoma patients' survival, correcting for clinical cofounders, only the KIT gene was associated with a lower overall survival rate. In this study, we demonstrate the strong influence of promoter localized DNA methylation changes on melanoma initiation and show how hypermethylation decreases in melanomas associated with less favourable clinical outcomes. Furthermore, we establish the methylation pattern as part of an integrated apparatus of somatic DNA alterations.
format	article
author	Szilvia Ecsedi Hector Hernandez-Vargas Sheila C Lima Laura Vizkeleti Reka Toth Viktoria Lazar Viktoria Koroknai Timea Kiss Gabriella Emri Zdenko Herceg Roza Adany Margit Balazs
author_facet	Szilvia Ecsedi Hector Hernandez-Vargas Sheila C Lima Laura Vizkeleti Reka Toth Viktoria Lazar Viktoria Koroknai Timea Kiss Gabriella Emri Zdenko Herceg Roza Adany Margit Balazs
author_sort	Szilvia Ecsedi
title	DNA methylation characteristics of primary melanomas with distinct biological behaviour.
title_short	DNA methylation characteristics of primary melanomas with distinct biological behaviour.
title_full	DNA methylation characteristics of primary melanomas with distinct biological behaviour.
title_fullStr	DNA methylation characteristics of primary melanomas with distinct biological behaviour.
title_full_unstemmed	DNA methylation characteristics of primary melanomas with distinct biological behaviour.
title_sort	dna methylation characteristics of primary melanomas with distinct biological behaviour.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/2866978865b0486cbaff03d6096a3f44
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DNA methylation characteristics of primary melanomas with distinct biological behaviour.

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