Here, we constructed an isogenic PTCH1<sup>R135X/+</sup> cellular model of PTCH1 inactivation by introducing a heterozygous mutation, namely, c.403C>T (p.R135X), which has been identified in OKC patients, into a human embryonic stem cell line using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system.
Mutations in the patched 1 (PTCH1) gene are the main genetic alteration reported in sporadic and nevoid basal cell carcinoma-associated odontogenic keratocyst (OKC).
While various genetic alterations, such as PTCH1 mutation and loss of heterozygosity in tumor suppressor genes, have been reported, the molecular background of OKC is not well-understood.
It is known that some sporadic OKCs harbor PTCH1 mutations, and via the dissection of cyst epithelium, these mutations were demonstrated to occur much more frequently than previously thought.
The immunoprofile of odontogenic keratocyst (keratocystic odontogenic tumor) that includes expression of PTCH, SMO, GLI-1 and bcl-2 is similar to ameloblastoma but different from odontogenic cysts.
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.
This report describes PTCH mutations in both non-syndromic and Gorlin-syndrome-related odontogenic keratocysts in Chinese patients, and suggests that defects of PTCH are associated with the pathogenesis of syndromic as well as a subset of non-syndromic keratocysts.
Our data showed allelic loss of microsatellite markers in close vicinity to the PTCH1 locus in both odontogenic keratocysts and dentigerous cysts as well as in ovarian dermoid cysts (ODC).
Motivated by the evidence that odontogenic keratocysts are associated with genetic alterations, we examined the possibility that development of other odontogenic cysts can be attributed to gene malfunctioning, in particular to the PTCH gene.
Loss of heterozygosity for the PTCH region was found several years ago in the epithelial lining of odontogenic keratocysts, the cyst type with highly increased incidence in nevoid basal cell carcinoma syndrome.
This retrospective study aims to investigate the prognostic relevance of various clinicopathological features as well as immunoexpression of COX-2, bcl-2, PCNA, and p53 in sporadic OKC.
Eighty-three OKC samples (29 cases associated with nevoid basal cell carcinoma syndrome, 29 solitary non-recurrent cases 20 solitary recurrent cases, and 5 chondroid keratocysts) were studied by immunohistochemistry to detect p53 protein (PAb 244) and Ki-67 (MIB-1) expression, and by PCR to detect HPV DNA.
In conclusion, the finding of cyclin D1 and p53 overexpression in odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome could be considered a hallmark of a mutated cellular phenotype, thus leading to the hypothesis that their aggressive clinical behavior could be due to a dysregulation of the expression of cyclin D1 and p53 proteins, involved in a check-point control of cellular proliferation.
Ten were recurrences and five were associated with the basal-cell naevus syndrome (Gorlin-Goltz syndrome). p53 protein was found in 50% (15/30) of the odontogenic keratocysts, in 53.3% (8/15) of non-recurrent cysts, in 40% (4/10) of recurrent cysts and in 60% (3/5) of those associated with the basal-cell naevus syndrome.