PTCH1 alterations are frequent but other genetic alterations are rare in sporadic odontogenic keratocysts

Abstract

Objective: Odontogenic keratocysts (OKCs) are benign jaw lesions with high growth potential and propensity for recurrence. Our previous study revealed that PTCH1 mutations, which were frequently detected in sporadic OKCs, might be underestimated due to the masking effect of the stromal components within the tested tissues. We aimed to confirm these results in larger scale and further present the unbiased view of the genomic basis of sporadic OKCs except PTCH1.

Materials and methods: We analyzed PTCH1 mutations in additional 19 samples. Using whole-exome sequencing (WES), we further characterized the mutational landscape of five sporadic OKC samples lacking PTCH1 mutation and loss of heterozygosity (LOH).

Results: Combined with our previously reported 19 cases, thirty of 38 (79%) cases harbored PTCH1 mutations. Through whole-exome sequencing and integrative analysis, 22 novel mutations were confirmed among five PTCH1-negative samples. No recurrent mutations were identified in the WES samples and validation cohort of 10 OKCs.

Conclusions: Our data further confirmed the frequent PTCH1 mutation and other rare genetic alterations in sporadic OKCs, highlighting the central role of SHH signaling pathway. In PTCH1-negative cases, other rare mutations scattered in a subset of OKCs were independent of the SHH pathway. These results suggested that an SHH inhibitor may be effective to treat the majority of OKCs.

Keywords: PTCH1 mutation; odontogenic keratocysts; whole-exome sequencing.