Comparative Analysis of Molecular Profiles of Sporadic Odontogenic Keratocyst and Bilateral Odontogenic Keratocyst: A Next Generation Sequencing Study

Abstract

Aim:

To comparatively analyse and interpret the molecular profiles of sporadic odontogenic keratocysts (OKC) with bilateral non-syndromic odontogenic keratocysts employing next-generation sequencing (NGS).

Materials and Methods:

All histopathologically confirmed cases were processed for 50 hotspot gene panel using NGS, followed by protein-protein analysis using the STRING Consortium 2023.

Results:

Except for 1 case, which was seen in the maxilla in a female patient, all included cases affected the mandible in males. In sporadic cases, a missense mutation was frequently found with either gain/ loss of function (GOF/LOF). TP53 showed a missense mutation with LOF at exon 5 and a nonsense mutation with LOF at exon 10. Other mutations were noted in the MET gene exon 19 and BRAF gene exon 11. Contrariwise, an identical mutation was seen in the left and right lesions of bilateral OKC, which was a mutation of TP53 with LOF at exon 8. Additionally OKC of the right side showed a gain-of-function (missense mutation) of the NRAS gene at exon 3.

Conclusion:

The TP53 gene mutation plays a significant role in the pathogenesis of OKC and supports its neoplastic nature. Bilateral OKC showed additional NRAS mutation, and sporadic cases demonstrated MET and BRAF mutations.