The Patched gene is epigenetically regulated in ovarian dermoids and fibromas, but not in basocellular carcinomas.
The Hedgehog/Patched signaling pathway plays a prominent role during mammalian development but it is also involved in oncogenic transformation. We investigated the methylation status of the Patched promotor in a set of basocellular carcinomas of the skin and ovarian tumors as an alternative to mutational causes of the pathway deregulation. Our aim was to define a possible role of genetic and/or epigenetic mechanisms of Hedgehog/Patched signal transduction in the development of these tumors. Bisulfite-converted DNA from tumors and from matched healthy tissue was amplified by a specific PCR and the CpG-rich regions of the Patched promoter were sequenced. Two promoter regions showed statistically significant hypermethylation compared to healthy controls in ovarian tumors; more significantly in the region in the vicinity of Gli1-binding sites and less significantly in the region containing the ATG codon. But, in basocellular carcinomas of the skin we observed no difference in methylation, suggesting different mechanisms of neoplasia in these tumors.
Cretnik
Maja
M
Division of Molecular Medicine, Rudjer Boskovic Institute, HR 10002 Zagreb, Croatia.
Musani
Vesna
V
Oreskovic
Slavko
S
Leovic
Dinko
D
Levanat
Sonja
S
D001483:Base Sequence; D001665:Binding Sites; D002280:Basal Cell Carcinoma / Q000235:genetics*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D003884:Dermoid Cyst / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D005350:Fibroma / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics*; D000072079:Patched Receptors; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
C400551:GLI1 protein, human; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1