Aberrant methylated key genes of methyl group metabolism within the molecular etiology of urothelial carcinogenesis

Abstract Urothelial carcinoma (UC), the most common cancer of the urinary bladder causes severe morbidity and mortality, e.g. about 40.000 deaths in the EU annually, and incurs considerable costs for the health system due to the need for prolonged treatments and long-term monitoring. Extensive aberr...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Lars Erichsen, Foued Ghanjati, Agnes Beermann, Cedric Poyet, Thomas Hermanns, Wolfgang A. Schulz, Hans-Helge Seifert, Peter J. Wild, Lorenz Buser, Alexander Kröning, Stefan Braunstein, Martin Anlauf, Silvia Jankowiak, Mohamed Hassan, Marcelo L. Bendhack, Marcos J. Araúzo-Bravo, Simeon Santourlidis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2c7f1dd5e43c455492ff4ecacd90cfcf
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2c7f1dd5e43c455492ff4ecacd90cfcf
record_format	dspace
spelling	oai:doaj.org-article:2c7f1dd5e43c455492ff4ecacd90cfcf2021-12-02T15:09:02ZAberrant methylated key genes of methyl group metabolism within the molecular etiology of urothelial carcinogenesis10.1038/s41598-018-21932-72045-2322https://doaj.org/article/2c7f1dd5e43c455492ff4ecacd90cfcf2018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21932-7https://doaj.org/toc/2045-2322Abstract Urothelial carcinoma (UC), the most common cancer of the urinary bladder causes severe morbidity and mortality, e.g. about 40.000 deaths in the EU annually, and incurs considerable costs for the health system due to the need for prolonged treatments and long-term monitoring. Extensive aberrant DNA methylation is described to prevail in urothelial carcinoma and is thought to contribute to genetic instability, altered gene expression and tumor progression. However, it is unknown how this epigenetic alteration arises during carcinogenesis. Intact methyl group metabolism is required to ensure maintenance of cell-type specific methylomes and thereby genetic integrity and proper cellular function. Here, using two independent techniques for detecting DNA methylation, we observed DNA hypermethylation of the 5′-regulatory regions of the key methyl group metabolism genes ODC1, AHCY and MTHFR in early urothelial carcinoma. These hypermethylation events are associated with genome-wide DNA hypomethylation which is commonly associated with genetic instability. We therefore infer that hypermethylation of methyl group metabolism genes acts in a feed-forward cycle to promote additional DNA methylation changes and suggest a new hypothesis on the molecular etiology of urothelial carcinoma.Lars ErichsenFoued GhanjatiAgnes BeermannCedric PoyetThomas HermannsWolfgang A. SchulzHans-Helge SeifertPeter J. WildLorenz BuserAlexander KröningStefan BraunsteinMartin AnlaufSilvia JankowiakMohamed HassanMarcelo L. BendhackMarcos J. Araúzo-BravoSimeon SantourlidisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lars Erichsen Foued Ghanjati Agnes Beermann Cedric Poyet Thomas Hermanns Wolfgang A. Schulz Hans-Helge Seifert Peter J. Wild Lorenz Buser Alexander Kröning Stefan Braunstein Martin Anlauf Silvia Jankowiak Mohamed Hassan Marcelo L. Bendhack Marcos J. Araúzo-Bravo Simeon Santourlidis Aberrant methylated key genes of methyl group metabolism within the molecular etiology of urothelial carcinogenesis
description	Abstract Urothelial carcinoma (UC), the most common cancer of the urinary bladder causes severe morbidity and mortality, e.g. about 40.000 deaths in the EU annually, and incurs considerable costs for the health system due to the need for prolonged treatments and long-term monitoring. Extensive aberrant DNA methylation is described to prevail in urothelial carcinoma and is thought to contribute to genetic instability, altered gene expression and tumor progression. However, it is unknown how this epigenetic alteration arises during carcinogenesis. Intact methyl group metabolism is required to ensure maintenance of cell-type specific methylomes and thereby genetic integrity and proper cellular function. Here, using two independent techniques for detecting DNA methylation, we observed DNA hypermethylation of the 5′-regulatory regions of the key methyl group metabolism genes ODC1, AHCY and MTHFR in early urothelial carcinoma. These hypermethylation events are associated with genome-wide DNA hypomethylation which is commonly associated with genetic instability. We therefore infer that hypermethylation of methyl group metabolism genes acts in a feed-forward cycle to promote additional DNA methylation changes and suggest a new hypothesis on the molecular etiology of urothelial carcinoma.
format	article
author	Lars Erichsen Foued Ghanjati Agnes Beermann Cedric Poyet Thomas Hermanns Wolfgang A. Schulz Hans-Helge Seifert Peter J. Wild Lorenz Buser Alexander Kröning Stefan Braunstein Martin Anlauf Silvia Jankowiak Mohamed Hassan Marcelo L. Bendhack Marcos J. Araúzo-Bravo Simeon Santourlidis
author_facet	Lars Erichsen Foued Ghanjati Agnes Beermann Cedric Poyet Thomas Hermanns Wolfgang A. Schulz Hans-Helge Seifert Peter J. Wild Lorenz Buser Alexander Kröning Stefan Braunstein Martin Anlauf Silvia Jankowiak Mohamed Hassan Marcelo L. Bendhack Marcos J. Araúzo-Bravo Simeon Santourlidis
author_sort	Lars Erichsen
title	Aberrant methylated key genes of methyl group metabolism within the molecular etiology of urothelial carcinogenesis
title_short	Aberrant methylated key genes of methyl group metabolism within the molecular etiology of urothelial carcinogenesis
title_full	Aberrant methylated key genes of methyl group metabolism within the molecular etiology of urothelial carcinogenesis
title_fullStr	Aberrant methylated key genes of methyl group metabolism within the molecular etiology of urothelial carcinogenesis
title_full_unstemmed	Aberrant methylated key genes of methyl group metabolism within the molecular etiology of urothelial carcinogenesis
title_sort	aberrant methylated key genes of methyl group metabolism within the molecular etiology of urothelial carcinogenesis
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/2c7f1dd5e43c455492ff4ecacd90cfcf
work_keys_str_mv	AT larserichsen aberrantmethylatedkeygenesofmethylgroupmetabolismwithinthemolecularetiologyofurothelialcarcinogenesis AT fouedghanjati aberrantmethylatedkeygenesofmethylgroupmetabolismwithinthemolecularetiologyofurothelialcarcinogenesis AT agnesbeermann aberrantmethylatedkeygenesofmethylgroupmetabolismwithinthemolecularetiologyofurothelialcarcinogenesis AT cedricpoyet aberrantmethylatedkeygenesofmethylgroupmetabolismwithinthemolecularetiologyofurothelialcarcinogenesis AT thomashermanns aberrantmethylatedkeygenesofmethylgroupmetabolismwithinthemolecularetiologyofurothelialcarcinogenesis AT wolfgangaschulz aberrantmethylatedkeygenesofmethylgroupmetabolismwithinthemolecularetiologyofurothelialcarcinogenesis AT hanshelgeseifert aberrantmethylatedkeygenesofmethylgroupmetabolismwithinthemolecularetiologyofurothelialcarcinogenesis AT peterjwild aberrantmethylatedkeygenesofmethylgroupmetabolismwithinthemolecularetiologyofurothelialcarcinogenesis AT lorenzbuser aberrantmethylatedkeygenesofmethylgroupmetabolismwithinthemolecularetiologyofurothelialcarcinogenesis AT alexanderkroning aberrantmethylatedkeygenesofmethylgroupmetabolismwithinthemolecularetiologyofurothelialcarcinogenesis AT stefanbraunstein aberrantmethylatedkeygenesofmethylgroupmetabolismwithinthemolecularetiologyofurothelialcarcinogenesis AT martinanlauf aberrantmethylatedkeygenesofmethylgroupmetabolismwithinthemolecularetiologyofurothelialcarcinogenesis AT silviajankowiak aberrantmethylatedkeygenesofmethylgroupmetabolismwithinthemolecularetiologyofurothelialcarcinogenesis AT mohamedhassan aberrantmethylatedkeygenesofmethylgroupmetabolismwithinthemolecularetiologyofurothelialcarcinogenesis AT marcelolbendhack aberrantmethylatedkeygenesofmethylgroupmetabolismwithinthemolecularetiologyofurothelialcarcinogenesis AT marcosjarauzobravo aberrantmethylatedkeygenesofmethylgroupmetabolismwithinthemolecularetiologyofurothelialcarcinogenesis AT simeonsantourlidis aberrantmethylatedkeygenesofmethylgroupmetabolismwithinthemolecularetiologyofurothelialcarcinogenesis
_version_	1718387927933779968

Aberrant methylated key genes of methyl group metabolism within the molecular etiology of urothelial carcinogenesis

Ejemplares similares