PTCH Gene Mutations in Odontogenic Keratocysts

Abstract

An odontogenic keratocyst (OKC) is a benign cystic lesion of the jaws that occurs sporadically or in association with nevoid basal cell carcinoma syndrome (NBCCS). Recently, the gene for NBCCS was cloned and shown to be the human homologue of the Drosophila segment polarity gene Patched (PTCH), a tumor suppressor gene. The PTCH gene encodes a transmembrane protein that acts in opposition to the Hedgehog signaling protein, controlling cell fates, patterning, and growth in numerous tissues, including tooth. We investigated three cases of sporadic odontogenic keratocysts and three other cases associated with NBCCS, looking for mutations of the PTCH gene. Non-radioactive single-strand conformational polymorphism and direct sequencing of PCR products revealed a deletion of 5 base pairs (bp) in exon 3 (518delAAGCG) in one sporadic cyst as well as mutations in two cysts associated with NBCCS, a nonsense (C2760A) and a missense (G3499A) alteration. This report is the first to describe a somatic mutation of PTCH in sporadic odontogenic keratocysts as well as two novel mutations in cysts associated with NBCCS, indicating a similar pathogenesis in a subset of sporadic keratocysts.

Novel PTCH1 mutations in Japanese Nevoid basal cell carcinoma syndrome patients: two familial and three sporadic cases including the first Japanese patient with medulloblastoma

“…The mutations in families 1, 2, 4 and 5 were novel, and the mutation in family 3 was previously reported in a KCOT sample from a Brazilian NBCCS patient. 16 We found a mutation at a PTCH1 splice donor site in patient NS11, therefore, we analyzed PTCH1 mRNA using cells derived from a KCOT from NS11. Sequence analysis of DNA derived from KCOT cells and peripheral blood of NS11 showed identical patterns.…”

Odontogenic Tumors, WHO 2005: Where Do We Go from Here?

“…However, the original references on mutations were all on syndromic patients and the 6 WHO references on non-syndromic cases included syndromic patients. There were numerous subsequent papers dealing with PTCH mutations in syndromic and nonsyndromic OKCs, which have shown mutations in approximately 85 % of syndromic cases and 30 % of non-syndromic cases [26][27][28][29][30][31][32].…”

Nevoid basal cell carcinoma (Gorlin) syndrome

“…In the syndrome, various tumors and hamartomas (basal cell carcinomas, odontogenic keratocysts, meningiomas, ovarian fibromas) exhibit loss of heterozygosity 62,63 but other lesions do not, for example, palmar pits. 64 Loss of heterozygosity in the Patched locus has been observed in almost 90% of hereditary basal cell carcinomas.…”