Integrative genomics identifies gene signature associated with melanoma ulceration.

<h4>Background</h4>Despite the extensive research approaches applied to characterise malignant melanoma, no specific molecular markers are available that are clearly related to the progression of this disease. In this study, our aims were to define a gene expression signature associated...

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Autores principales:	Zsuzsa Rakosy, Szilvia Ecsedi, Reka Toth, Laura Vizkeleti, Hector Hernandez-Vargas, Viktoria Lazar, Gabriella Emri, Istvan Szatmari, Zdenko Herceg, Roza Adany, Margit Balazs
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8cb75d8a2eba4bbba0df6ab1fb33a61a
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spelling	oai:doaj.org-article:8cb75d8a2eba4bbba0df6ab1fb33a61a2021-11-18T07:59:29ZIntegrative genomics identifies gene signature associated with melanoma ulceration.1932-620310.1371/journal.pone.0054958https://doaj.org/article/8cb75d8a2eba4bbba0df6ab1fb33a61a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23383013/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Despite the extensive research approaches applied to characterise malignant melanoma, no specific molecular markers are available that are clearly related to the progression of this disease. In this study, our aims were to define a gene expression signature associated with the clinical outcome of melanoma patients and to provide an integrative interpretation of the gene expression -, copy number alterations -, and promoter methylation patterns that contribute to clinically relevant molecular functional alterations.<h4>Methods</h4>Gene expression profiles were determined using the Affymetrix U133 Plus2.0 array. The NimbleGen Human CGH Whole-Genome Tiling array was used to define CNAs, and the Illumina GoldenGate Methylation platform was applied to characterise the methylation patterns of overlapping genes.<h4>Results</h4>WE IDENTIFIED TWO SUBCLASSES OF PRIMARY MELANOMA: one representing patients with better prognoses and the other being characteristic of patients with unfavourable outcomes. We assigned 1,080 genes as being significantly correlated with ulceration, 987 genes were downregulated and significantly enriched in the p53, Nf-kappaB, and WNT/beta-catenin pathways. Through integrated genome analysis, we defined 150 downregulated genes whose expression correlated with copy number losses in ulcerated samples. These genes were significantly enriched on chromosome 6q and 10q, which contained a total of 36 genes. Ten of these genes were downregulated and involved in cell-cell and cell-matrix adhesion or apoptosis. The expression and methylation patterns of additional genes exhibited an inverse correlation, suggesting that transcriptional silencing of these genes is driven by epigenetic events.<h4>Conclusion</h4>Using an integrative genomic approach, we were able to identify functionally relevant molecular hotspots characterised by copy number losses and promoter hypermethylation in distinct molecular subtypes of melanoma that contribute to specific transcriptomic silencing and might indicate a poor clinical outcome of melanoma.Zsuzsa RakosySzilvia EcsediReka TothLaura VizkeletiHector Hernandez-VargasViktoria LazarGabriella EmriIstvan SzatmariZdenko HercegRoza AdanyMargit BalazsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e54958 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zsuzsa Rakosy Szilvia Ecsedi Reka Toth Laura Vizkeleti Hector Hernandez-Vargas Viktoria Lazar Gabriella Emri Istvan Szatmari Zdenko Herceg Roza Adany Margit Balazs Integrative genomics identifies gene signature associated with melanoma ulceration.
description	<h4>Background</h4>Despite the extensive research approaches applied to characterise malignant melanoma, no specific molecular markers are available that are clearly related to the progression of this disease. In this study, our aims were to define a gene expression signature associated with the clinical outcome of melanoma patients and to provide an integrative interpretation of the gene expression -, copy number alterations -, and promoter methylation patterns that contribute to clinically relevant molecular functional alterations.<h4>Methods</h4>Gene expression profiles were determined using the Affymetrix U133 Plus2.0 array. The NimbleGen Human CGH Whole-Genome Tiling array was used to define CNAs, and the Illumina GoldenGate Methylation platform was applied to characterise the methylation patterns of overlapping genes.<h4>Results</h4>WE IDENTIFIED TWO SUBCLASSES OF PRIMARY MELANOMA: one representing patients with better prognoses and the other being characteristic of patients with unfavourable outcomes. We assigned 1,080 genes as being significantly correlated with ulceration, 987 genes were downregulated and significantly enriched in the p53, Nf-kappaB, and WNT/beta-catenin pathways. Through integrated genome analysis, we defined 150 downregulated genes whose expression correlated with copy number losses in ulcerated samples. These genes were significantly enriched on chromosome 6q and 10q, which contained a total of 36 genes. Ten of these genes were downregulated and involved in cell-cell and cell-matrix adhesion or apoptosis. The expression and methylation patterns of additional genes exhibited an inverse correlation, suggesting that transcriptional silencing of these genes is driven by epigenetic events.<h4>Conclusion</h4>Using an integrative genomic approach, we were able to identify functionally relevant molecular hotspots characterised by copy number losses and promoter hypermethylation in distinct molecular subtypes of melanoma that contribute to specific transcriptomic silencing and might indicate a poor clinical outcome of melanoma.
format	article
author	Zsuzsa Rakosy Szilvia Ecsedi Reka Toth Laura Vizkeleti Hector Hernandez-Vargas Viktoria Lazar Gabriella Emri Istvan Szatmari Zdenko Herceg Roza Adany Margit Balazs
author_facet	Zsuzsa Rakosy Szilvia Ecsedi Reka Toth Laura Vizkeleti Hector Hernandez-Vargas Viktoria Lazar Gabriella Emri Istvan Szatmari Zdenko Herceg Roza Adany Margit Balazs
author_sort	Zsuzsa Rakosy
title	Integrative genomics identifies gene signature associated with melanoma ulceration.
title_short	Integrative genomics identifies gene signature associated with melanoma ulceration.
title_full	Integrative genomics identifies gene signature associated with melanoma ulceration.
title_fullStr	Integrative genomics identifies gene signature associated with melanoma ulceration.
title_full_unstemmed	Integrative genomics identifies gene signature associated with melanoma ulceration.
title_sort	integrative genomics identifies gene signature associated with melanoma ulceration.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/8cb75d8a2eba4bbba0df6ab1fb33a61a
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_version_	1718422680611323904

Integrative genomics identifies gene signature associated with melanoma ulceration.

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