RGD Reference Report - Epigenetic changes in Basal Cell Carcinoma affect SHH and WNT signaling components. - Rat Genome Database

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

Authors: Brinkhuizen, Tjinta  van den Hurk, Karin  Winnepenninckx, Véronique J L  de Hoon, Joep P  van Marion, Ariënne M  Veeck, Jürgen  van Engeland, Manon  van Steensel, Maurice A M 
Citation: Brinkhuizen T, etal., PLoS One. 2012;7(12):e51710. doi: 10.1371/journal.pone.0051710. Epub 2012 Dec 17.
RGD ID: 12801452
Pubmed: PMID:23284750   (View Abstract at PubMed)
PMCID: PMC3524166   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0051710   (Journal Full-text)


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.
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.
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 ß-catenin staining, showing nuclear ß-catenin in only 28/101 (27.7%) of BCC. Absence of nuclear ß-catenin in some samples may be due to high levels of membranous E-cadherin (in 94.1% of the samples).
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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
basal cell carcinoma  IDA 12801452DNA more ...RGD 
basal cell carcinoma  ISOSHH (Homo sapiens)12801452; 12801452DNA more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Shh  (sonic hedgehog signaling molecule)

Genes (Mus musculus)
Shh  (sonic hedgehog)

Genes (Homo sapiens)
SHH  (sonic hedgehog signaling molecule)


Additional Information