Sonic Hedgehog and Other Molecular Pathways in Odontogenic Cysts and Tumours: A Review Based on WHO 2022 Classification

Nur Syahirah Binti Mohd Nazar; Vinesh Raj.S

doi:10.5327/2525-5711.454

Autores/as

Nur Syahirah Binti Mohd Nazar Department of Oral and Maxillofacial Surgery, Medicine and Pathology, Faculty of Dentistry, Universiti Sains Islam Malaysia, Kuala Lumpur, Malaysia. https://orcid.org/0000-0002-3789-1981
Vinesh Raj.S Centre of Oral & Maxillofacial Diagnostics & Medicine Studies, Faculty of Dentistry, Universiti Technology MARA, Sungai Buloh, Selangor, Malaysia. https://orcid.org/0000-0003-1335-4070

DOI:

https://doi.org/10.5327/2525-5711.454

Palabras clave:

Sonic Hedgehog pathway, Molecular signalling pathways, Odontogenic cysts and tumours, WHO 2022 classification

Resumen

Molecular signalling pathways, including Sonic Hedgehog (SHH), MAPK/ERK, Wnt/β-catenin, and PI3K/mTOR, play critical role in embryonic development and odontogenesis, and its dysregulation contributes to the development of certain odontogenic cysts and tumours. A review of current evidence, aligned with the WHO 2022 classification, shows that aberrant SHH activity is particularly prominent in odontogenic keratocysts and ameloblastomas, where it promotes epithelial proliferation, survival, and lesion expansion. In contrast, other developmental cysts such as dentigerous, glandular, and orthokeratinized cysts demonstrate minimal SHH involvement, with their pathogenesis more strongly linked to mechanical, inflammatory, or differentiation-related factors. Benign odontogenic tumours exhibit distinct molecular profiles, with MAPK/ERK signalling common in mixed epithelial–mesenchymal lesions, Wnt/β-catenin alterations in adenoid ameloblastoma and odontomas, and PI3K/mTOR activation in mesenchymal tumours. Overall, SHH plays a lesion-specific role, within a broader network of molecular pathways and most significant in odontogenic keratocysts and ameloblastomas, and integrating these molecular insights with the WHO 2022 framework improves understanding of pathogenesis, diagnostic accuracy, and identification of potential therapeutic targets.

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