Identification of a novel polymorphism involving a CGG repeat in the PTCH gene and a genome-wide screening of CGG-containing genes

Regulation of humanPTCH1bexpression by different 5' untranslated regioncis-regulatory elements

“…A functional analysis was conducted by cloning various (CGG) n CAAC constructs downstream of SV40 (Simian vacuolating virus 40) promoter and upstream of luciferase reporter gene (Fluc). 32 The results of luciferase assays, performed 24 h post-transfection in HEK 293T cells, revealed a positive correlation between the CGG-repeat number and the luciferase activity, although statistical analysis of the differences was not provided. Fluc mRNA quantification showed no differences in the reporter gene transcription levels regarding the CGG-repeat number, leading to the conclusion that the increase in luciferase activity with the expansion of CGG repeats is due to the increased efficiency of Firefly luciferase translation.…”

“…47 Even though much is known about the genomic organization of PTCH1 gene, its transcripts and the protein products, much less is known about the transcriptional regulation of PTCH1 transcripts, and even less is known about the role of 5'UTR in the regulation of their expression. In the 5'UTR of PTCH1 transcript 1b a novel polymorphism involving a CGG trinucleotide repeat, separated from main AUG codon only by the CAAC tetranucleotide, was discovered by Nagao et al 32 The major allele contained 7 CGG repeats, while the minor allele contained 8 (rs71366293). In our previous research in patients with different types of ovarian neoplasms and healthy controls, we identified 2 additional alleles -(CGG) 5 , which was found in one healthy control sample, and (CGG) 6 allele, which was found in one ovarian cancer patient.…”

“…20 Up to now, the only studied potential regulatory element has been a (CGG) n repeat polymorphism present immediately upstream the AUG start site, but not clear association between repeat numbers and disease risk was found. 32,33 Here we thoroughly explored cis-element features of the 5'UTR of the PTCH1 transcript 1b applying the methodology previously used for the functional analysis of 5'UTR of the CDKN2A gene. 34 …”

Basal cell carcinoma: biology, morphology and clinical implications

“…8 In most cases, the abnormality represents a mutation in the human homologue of the Drosophila patched gene (PTCH). 25 Perturbation of this tumor suppressor gene on chromosome 9 q22-q31 26,27 results in upregulated cell proliferation. The biology of sporadic BCC and of tumors arising in the setting of nevoid BCC syndrome is discussed in greater detail below.…”

“…It is now recognized that for most patients the abnormality represents a mutation in the human homologue of the PTCH. 25 A tumor suppressor gene, PTCH is sited on chromosome 9 q22-q31. 26 The PTCH gene product functions as a transmembrane receptor for the Sonic hedgehog (shh) protein; when binding of the wild-type protein occurs, the inhibition by PTCH of a second seven-span transmembrane protein termed Smoothened (smo) is downregulated.…”