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A novel mutation of the PTCH1 gene activates the Shh/Gli signaling pathway in a Chinese family with nevoid basal cell carcinoma syndrome.

Authors: Zhang, Tingting  Chen, Mingjie  Lü, Yan  Xing, Qinghe  Chen, Wantao 
Citation: Zhang T, etal., Biochem Biophys Res Commun. 2011 Jun 3;409(2):166-70. doi: 10.1016/j.bbrc.2011.04.047. Epub 2011 Apr 13.
Pubmed: (View Article at PubMed) PMID:21514272
DOI: Full-text: DOI:10.1016/j.bbrc.2011.04.047


OBJECTIVE: Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by a predisposition to neoplasms and developmental abnormalities. Mutation of the PTCH1 gene, which is considered to be responsible for NBCCS, was investigated in a Chinese NBCCS family in this study.
METHODS: Genomic DNA was isolated from blood samples of all eight living individuals in this family. Mutation analysis of PTCH1 was done by amplified polymerase chain reaction and direct sequencing. Biophysical predictions of the altered protein were made using various bioinformatics tools. To determine the action of the mutated protein, the expression of Gli1 and Gli2 was investigated by immunohistochemistry.
RESULTS: A novel PTCH1 mutation at 897G->A in exon4 was identified in all four affected members. This mutation was not found in any unaffected members of this family or in 100 unrelated healthy Chinese people. The mutation causes amino acid replacement 237E->K in the first large extracellular loop of the PTCH1 protein which is required for Sonic Hedgehog (Shh) binding. This mutation changes the protein's biochemical properties and protein activity, resulting in subsequent activation of transcription factors, Gli1 and Gli2, in the Shh/Gli signaling pathway. Immunohistochemistry showed overexpression of Gli1 and Gli2 in the keratocystic odontogenic tumor (KCOT) tissues.

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CRRD Object Information
CRRD ID: 12801422
Created: 2017-03-29
Species: All species
Last Modified: 2017-03-29
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.