Detection of PTCH mutations in odontogenic keratocysts by direct sequencing

Objectives: The aim of this study was to investigate the frequency, type and distribution of PTCH mutations in odontogenic keratocysts (OKC) and to analyze the molecular pathological relationship between sporadic OKC and OKC associated with nevoid basal cell carcinoma syndrome (NBCCS). Methods: Genomic DNA was extracted from 8 cases of OKC lesions (4 sporadic OKCs and 4 NBCCS-related OKCs). PTCH gene mutations were detected by PCR-direct sequencing. Results: Six novel PTCH mutations were identified in 6 out of 8 cases (2 sporadic and 4 NBCCS-related OKCs). Two of these were missense mutations (317T>G, 1939A>T) leading to substitution of an amino acid residue respectively. The other 4 mutations were identified as insertion or deletion ranging from one single base to 7 bases(331 del G, 361 ins GAGC, 3074 ins GCCTCCG, 3300 ins CACGTT). Three of which caused frame-shift leading to premature truncation of PTCH protein and one resulted in an insertion of 2 amino acid residues. All of these identified mutations were novel and have not been previously described. In addition, four previously reported polymorphisms in PTCH were also detected in 5 cases. Conclusion: PTCH gene mutation is a common event in NBCCS-related OKCs and could also be detected in some sporadic OKCs. Abnormalities of PTCH gene may be involved in the pathogenesis of OKC.