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PTC gene mutations and expression of SHH, PTC, SMO, and GLI-1 in odontogenic keratocysts
K Ohki1, H Kumamoto, R Ichinohasama
1Department of Oral Medicine and Surgery, Division of Maxillofacial Surgery, Graduate School of Dentistry, Tohoku University, Sendai, Japan. k-ohki@mail.tains.tohoku.ac.jp
Abstract:
The Patched (PTC) gene is responsible for basal cell nevus syndrome (BCNS) accompanied by multiple odontogenic keratocysts (OKCs), and its product plays a role in the Sonic hedgehog (SHH) signaling pathway involving smoothened (SMO) and GLI-1. To clarify the role of SHH signaling in OKCs, the expression of SHH, PTC, SMO, and GLI-1 and mutations of PTC were examined in 18 sporadic, 4 BCNS-associated OKCs and 7 control gingivae. SHH, PTC, SMO, and GLI-1 were detected in all OKC and gingiva samples by reverse transcriptase-polymerase chain reaction (RT-PCR). Immunoreactivity for SHH and GLI-1 was markedly higher in epithelial components than in subepithelial cells, while immunoreactivity for PTC and SMO was similar in epithelial components and subepithelial cells in OKCs. The positive rate of PTC and SMO expression in subepithelial cells of OKCs was significantly higher than that in gingivae. The positive rate of GLI-1 expression in subepithelial cells of BCNS-associated OKCs was significantly higher than that in primary OKCs. These results suggest that the SHH signaling might be involved in the pathophysiologic nature of OKCs. While mutations of the PTC gene could not be detected in 4 BCNS-associated OKCs by direct DNA sequencing, 3 of 5 primary and 4 of 4 recurrent OKCs had several mutations of this gene. These results suggest that PTC mutations are probably related not only to BCNS-associated OKCs but also to sporadic OKCs.
Insights
Sonic hedgehog (SHH) signaling and Patched (PTC) gene mutations are implicated in odontogenic keratocysts (OKCs). PTC mutations were found in sporadic and recurrent OKCs, suggesting their role in both BCNS-associated and primary OKC development.
Area of Science:
- Oral pathology
- Molecular biology
- Oncology
Background:
- Basal cell nevus syndrome (BCNS) is linked to the Patched (PTC) gene and Sonic hedgehog (SHH) signaling.
- Odontogenic keratocysts (OKCs) are a common feature of BCNS.
- The role of SHH signaling in OKC pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the expression of SHH signaling pathway components (SHH, PTC, SMO, GLI-1) in OKCs.
- To identify mutations in the PTC gene in sporadic and BCNS-associated OKCs.
- To explore the involvement of SHH signaling in OKC pathophysiology.
Main Methods:
- Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect gene expression.
- Immunohistochemistry was employed to assess protein localization and expression levels.
- Direct DNA sequencing was performed to identify PTC gene mutations.
Main Results:
- SHH, PTC, SMO, and GLI-1 were expressed in all OKC and gingiva samples.
- Elevated PTC and SMO expression in subepithelial cells of OKCs compared to gingiva.
- GLI-1 expression was higher in subepithelial cells of BCNS-associated OKCs than primary OKCs.
- PTC mutations were identified in primary and recurrent sporadic OKCs, but not in BCNS-associated OKCs.
Conclusions:
- SHH signaling pathway components are present in OKCs and may play a role in their development.
- PTC gene mutations are associated with sporadic OKCs, including recurrent forms.
- These findings suggest that PTC mutations contribute to both BCNS-related and sporadic OKC development.
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