Whole Exome Sequencing of SMO, BRAF, PTCH1 and GNAS in Odontogenic Diseases

Abstract

Background/Aim: Odontogenic diseases are diagnosed based on clinical course, imaging, and histopathology. However, a definitive diagnosis is not always possible. Patients and Methods: We analyzed whole exons of SMO, BRAF, PTCH1 and GNAS using next-generation sequencing (NGS) in 18 patients. Results: Of the 6 patients with ameloblastoma, 2 patients had the same missense mutation in BRAF, and 1 patient with peripheral ameloblastoma had a missense mutation in PTCH1. Of the 7 patients with odontogenic keratocyst, 4 patients had a missense mutation in PTCH1, 2 patients had missense mutations in BRAF, and 1 patient had a missense mutation in SMO. The patient with odontoma had missense mutations in SMO, BRAF and PTCH1. One patient with cementosseous dysplasia had missense mutations in SMO and PTCH1. The patient with adenomatoid odontogenic tumor had missense mutations in SMO. Conclusion: Whole exome sequencing of the above genes by NGS would be useful for the differential diagnosis of odontogenic diseases.Odontogenic diseases (tumors, cysts and dysplasias) are diagnosed based on clinical course, several X-ray images, and histopathological findings, but a definitive diagnosis is not always possible (1). Odontogenic tumors derive from cells involved in tooth development, and in many cases, it is difficult 3233 This article is freely accessible online.

Genetic Profile of Adenomatoid Odontogenic Tumor and Ameloblastoma. A Systematic Review

“…Among the remaining three studies, one article worked with a Targeted NGS panel assessing specifically mutations in SMO, BRAF, PTCH1 , and GNAS [ 25 ]. Only one AOT was included and showed two missense mutations in SMO (Y394S and p.Y399S).…”

“…Only one AOT was included and showed two missense mutations in SMO (Y394S and p.Y399S). No mutations affecting BRAF or PTCH1 were reported [ 25 ].…”

“…A total of 680 tumors were assessed using small-to large-scale and “omics” techniques. Two studies performed whole-exome sequencing (WES) [ 13 , 15 ], eight used targeted NGS panels [ 6 , 8 , 10 , 12 , 14 , 16 , 20 , 25 ], and the remaining 26 performed either TaqMan-allele specific probes or direct sequencing ( Table 3 ).…”

“…Six articles reported mutations in AOT [4,[22][23][24][25][26]. A total of 59 AOTs were assessed under different genomic techniques, such as direct sequencing, targeted NGS panels, and TaqMan allele-specific qPCR (Table 1).…”

“…Only one AOT was included and showed two missense mutations in SMO (Y394S and p.Y399S). No mutations affecting BRAF or PTCH1 were reported [25]. By direct sequencing, one study identified one heterozygous missense mutation affecting AMBN, leading to a R90W substitution [26].…”