Back to Search
Start Over
Epigenetic changes in Basal Cell Carcinoma affect SHH and WNT signaling components.
- Source :
-
PloS one [PLoS One] 2012; Vol. 7 (12), pp. e51710. Date of Electronic Publication: 2012 Dec 17. - Publication Year :
- 2012
-
Abstract
- Background: 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.<br />Objective: 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.<br />Results: 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).<br />Conclusions: 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.
- Subjects :
- Aged
Case-Control Studies
Female
Gene Expression Regulation, Neoplastic
Humans
Male
Promoter Regions, Genetic genetics
Tumor Cells, Cultured
Tumor Suppressor Proteins genetics
Carcinoma, Basal Cell genetics
DNA Methylation
Epigenesis, Genetic
Hedgehog Proteins genetics
Skin metabolism
Skin Neoplasms genetics
Wnt Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 7
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23284750
- Full Text :
- https://doi.org/10.1371/journal.pone.0051710