PTCH1 isoforms in odontogenic keratocysts

Odontogenic keratocyst (OKC) is an aggressive benign odontogenic neoplasm associated with PTCH1 alteration. PTCH1 has several isoforms generated by use of different first exon (1b, 1d and 1e). These isoforms code for proteins with different functions, expression profiles and transcriptional regulation. The aim of the present study was to investigate the expression of PTCH1 first exons in OKC tumors to shed light on scenery whereby PTCH1 coordinates OKC tumorigenesis. Forty OKC, including 12 sporadic and 28 associated with Nevoid Basal Cell Carcinoma Syndrome (NBCCS), were included in the study. The variants 1b, 1d and 1e were investigated by RT-PCR. The exon 1b was detected in 90% of OKC and none of the dental follicle (control). Most of the OKC, sporadic and syndromic, and all of the samples of dental follicles demonstrated the expression of 1d mRNA. All primary OKC had 1b mRNA while 4 (24%) lesions marsupialized lost 1b expression. In addition, the pattern of exon 1 expression observed in oral mucosa adjacent to the OKC was similar to the OKC tumor. In conclusion, this report showed overactivity of Hedgehog (HH) pathway in OKC lesion and at adjacent oral mucosa. We also demonstrated that marsupialization could alter PTCH1 variants profiling in some OKC cases.