Analysis of Germline and Somatic Mutation in Patients With Developmental Odontogenic Cysts Using Targeted Gene Panel.

Background: Odontogenic keratocyst (OKC) is a partial manifestation of Gorlin syndrome (GS), resulting from the abnormal activation of the hedgehog signaling pathway. OKC predominantly occurs in young adults and is mostly asymptomatic at the time of initial diagnosis. As OKC is asymptomatic, GS can be challenging to diagnose in certain instances. In this study, we attempted to identify asymptomatic GS from sporadic OKC cases using a previously developed gene panel for GS.

Methods: Genomic DNA was extracted from patient samples. These DNA samples were analyzed using the AmpliSeq Custom DNA Panel (Illumina), which was specifically designed to target four previously established genes (PTCH1, PTCH2, SMO, and SUFU). Mutations from patients were predicted using tools, such as MutationTaster, CADD, and Polyphen-2.

Results: Thirty-one patients with OKC were included: 22 sporadic, 9 syndromic, 14 cases with dentigerous cysts, and 3 patients with orthokeratinized odontogenic cysts. One patient with sporadic OKC carried 50% genetic mutation in the cyst and blood, indicative of GS. PTCH1 mutations were found in one of the 14 patients with dentigerous cysts, 3 of the 17 first-time sporadic cases, and all four recurrent cases. Resected OKC tissues revealed a PTCH1 mutation.

Conclusions: We found one patient with GS from those diagnosed with sporadic OKC. Our findings suggest that PTCH1 mutations are associated with postoperative recurrence of OKC, implying that hedgehog-related gene variations may contribute to jaw cyst development and improve the prognosis of OKC.