Epigenetic changes in Basal Cell Carcinoma affect SHH and WNT signaling components.

<h4>Background</h4>The genetic background of Basal Cell Carcinoma (BCC) has been studied extensively, while its epigenetic makeup has received comparatively little attention. Epigenetic alterations such as promoter hypermethylation silence tumor suppressor genes (TSG) in several malignan...

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Autores principales:	Tjinta Brinkhuizen, Karin van den Hurk, Véronique J L Winnepenninckx, Joep P de Hoon, Ariënne M van Marion, Jürgen Veeck, Manon van Engeland, Maurice A M van Steensel
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c538522c95144ee4a3d887164b480cdd
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spelling	oai:doaj.org-article:c538522c95144ee4a3d887164b480cdd2021-11-18T08:04:49ZEpigenetic changes in Basal Cell Carcinoma affect SHH and WNT signaling components.1932-620310.1371/journal.pone.0051710https://doaj.org/article/c538522c95144ee4a3d887164b480cdd2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23284750/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The genetic background of Basal Cell Carcinoma (BCC) has been studied extensively, while its epigenetic makeup has received comparatively little attention. Epigenetic alterations such as promoter hypermethylation silence tumor suppressor genes (TSG) in several malignancies.<h4>Objective</h4>We sought to analyze the promoter methylation status of ten putative (tumor suppressor) genes that are associated with Sonic Hedgehog (SHH), WNT signaling and (hair follicle) tumors in a large series of 112 BCC and 124 healthy control samples by methylation-specific PCR.<h4>Results</h4>Gene promoters of SHH (P = 0.016), adenomatous polyposis coli (APC) (P = 0.003), secreted frizzled-related protein 5 (SFRP5) (P = 0.004) and Ras association domain family 1A (RASSF1A) (P = 0.023) showed significantly more methylation in BCC versus normal skin. mRNA levels of these four genes were reduced for APC and SFRP5 in BCC (n = 6) vs normal skin (n = 6). Down regulation of SHH, APC and RASSF1A could be confirmed on protein level as well (P<0.001 for all genes) by immunohistochemical staining. Increased canonical WNT activity was visualized by β-catenin staining, showing nuclear β-catenin in only 28/101 (27.7%) of BCC. Absence of nuclear β-catenin in some samples may be due to high levels of membranous E-cadherin (in 94.1% of the samples).<h4>Conclusions</h4>We provide evidence that promoter hypermethylation of key players within the SHH and WNT pathways is frequent in BCC, consistent with their known constitutive activation in BCC. Epigenetic gene silencing putatively contributes to BCC tumorigenesis, indicating new venues for treatment.Tjinta BrinkhuizenKarin van den HurkVéronique J L WinnepenninckxJoep P de HoonAriënne M van MarionJürgen VeeckManon van EngelandMaurice A M van SteenselPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e51710 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tjinta Brinkhuizen Karin van den Hurk Véronique J L Winnepenninckx Joep P de Hoon Ariënne M van Marion Jürgen Veeck Manon van Engeland Maurice A M van Steensel Epigenetic changes in Basal Cell Carcinoma affect SHH and WNT signaling components.
description	<h4>Background</h4>The genetic background of Basal Cell Carcinoma (BCC) has been studied extensively, while its epigenetic makeup has received comparatively little attention. Epigenetic alterations such as promoter hypermethylation silence tumor suppressor genes (TSG) in several malignancies.<h4>Objective</h4>We sought to analyze the promoter methylation status of ten putative (tumor suppressor) genes that are associated with Sonic Hedgehog (SHH), WNT signaling and (hair follicle) tumors in a large series of 112 BCC and 124 healthy control samples by methylation-specific PCR.<h4>Results</h4>Gene promoters of SHH (P = 0.016), adenomatous polyposis coli (APC) (P = 0.003), secreted frizzled-related protein 5 (SFRP5) (P = 0.004) and Ras association domain family 1A (RASSF1A) (P = 0.023) showed significantly more methylation in BCC versus normal skin. mRNA levels of these four genes were reduced for APC and SFRP5 in BCC (n = 6) vs normal skin (n = 6). Down regulation of SHH, APC and RASSF1A could be confirmed on protein level as well (P<0.001 for all genes) by immunohistochemical staining. Increased canonical WNT activity was visualized by β-catenin staining, showing nuclear β-catenin in only 28/101 (27.7%) of BCC. Absence of nuclear β-catenin in some samples may be due to high levels of membranous E-cadherin (in 94.1% of the samples).<h4>Conclusions</h4>We provide evidence that promoter hypermethylation of key players within the SHH and WNT pathways is frequent in BCC, consistent with their known constitutive activation in BCC. Epigenetic gene silencing putatively contributes to BCC tumorigenesis, indicating new venues for treatment.
format	article
author	Tjinta Brinkhuizen Karin van den Hurk Véronique J L Winnepenninckx Joep P de Hoon Ariënne M van Marion Jürgen Veeck Manon van Engeland Maurice A M van Steensel
author_facet	Tjinta Brinkhuizen Karin van den Hurk Véronique J L Winnepenninckx Joep P de Hoon Ariënne M van Marion Jürgen Veeck Manon van Engeland Maurice A M van Steensel
author_sort	Tjinta Brinkhuizen
title	Epigenetic changes in Basal Cell Carcinoma affect SHH and WNT signaling components.
title_short	Epigenetic changes in Basal Cell Carcinoma affect SHH and WNT signaling components.
title_full	Epigenetic changes in Basal Cell Carcinoma affect SHH and WNT signaling components.
title_fullStr	Epigenetic changes in Basal Cell Carcinoma affect SHH and WNT signaling components.
title_full_unstemmed	Epigenetic changes in Basal Cell Carcinoma affect SHH and WNT signaling components.
title_sort	epigenetic changes in basal cell carcinoma affect shh and wnt signaling components.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/c538522c95144ee4a3d887164b480cdd
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Epigenetic changes in Basal Cell Carcinoma affect SHH and WNT signaling components.

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