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Involvement of PTCH gene in various noninflammatory cysts
S Levanat1, B Pavelić, I Crnić
1Division of Molecular Medicine, Ruder Bosković Institute, Zagreb, Croatia. levanat@rudjer.irb.hr
Abstract:
Constitutional hemizygous inactivation of PTCH, the Shh signaling pathway gene that moderates the signal, manifests itself as nevoid basal cell carcinoma syndrome or Gorlin syndrome, a condition variably characterized by a number of developmental disorders and malformations, and by predisposition to some malignancies, basal cell carcinoma in particular. Loss of heterozygosity for the PTCH region was found several years ago in the epithelial lining of odontogenic keratocysts, the cyst type with highly increased incidence in nevoid basal cell carcinoma syndrome. This finding confirmed the expectations that the gene responsible for the syndrome would have a decisive role in the genesis of these cysts even when they are not syndrome related. Suggestive temporal distribution of Shh signaling, recently observed during tooth development, lead us to investigate PTCH association with dentigerous cysts, the other major noninflammatory cyst of odontogenic origin. We report here that PTCH appears to be inactivated in dentigerous cysts, suggesting that it is responsible for their genesis as well. More generally, if our similar observations of incomplete heterozygosity in this region for dermoid cysts can be interpreted as loss of heterozygosity, PTCH alterations may prove to be a necessary, and perhaps the initiating event, in formation and growth of various noninflammatory cysts. This would be consistent with our view that local PTCH inactivation can, under favorable circumstances, lead to persistent though not by itself truly aggressive cell proliferation.
Insights
PTCH gene inactivation is linked to Gorlin syndrome and odontogenic cysts. This study finds PTCH alterations in dentigerous cysts, suggesting its role in their development, similar to other non-inflammatory cysts.
Area of Science:
- Oncology
- Developmental Biology
- Genetics
Background:
- Nevoid basal cell carcinoma syndrome (Gorlin syndrome) results from PTCH gene inactivation, leading to developmental abnormalities and cancer predisposition.
- Loss of heterozygosity in the PTCH gene region is observed in odontogenic keratocysts, implicating PTCH in cystogenesis.
- The Shh signaling pathway, moderated by PTCH, plays a role in tooth development.
Purpose of the Study:
- To investigate the association of PTCH gene alterations with dentigerous cysts, a common non-inflammatory odontogenic cyst.
- To explore the potential role of PTCH inactivation in the genesis of dentigerous cysts.
Main Methods:
- Analysis of PTCH gene status in the epithelial lining of dentigerous cysts.
- Comparison of PTCH alterations in dentigerous cysts with findings in odontogenic keratocysts and Gorlin syndrome.
Main Results:
- PTCH gene inactivation was observed in dentigerous cysts.
- These findings suggest PTCH alterations are involved in the development of dentigerous cysts.
- PTCH alterations may be a key event in the formation of various non-inflammatory cysts.
Conclusions:
- PTCH gene inactivation is implicated in the pathogenesis of dentigerous cysts.
- Alterations in PTCH may be a necessary initiating event for the development of non-inflammatory cysts.
- Local PTCH inactivation can promote persistent cell proliferation, contributing to cyst formation.