PTCH gene mutations in odontogenic keratocysts

An odontogenic keratocyst (OKC) is a benign cystic lesion of the jaws that occurs sporadically or in association with nevoid basal cell carcinoma synd rome (NBCCS). Recently, the gene for NBCCS was cloned and shown to be the h uman homologue of the Drosophila segment polarity gene Patched (PTCH), a tu mor suppressor gene. The PTCH gene encodes a transmembrane protein that act s in opposition to the Hedgehog signaling protein, controlling cell fates, patterning, and growth in numerous tissues, including tooth. We investigate d three cases of sporadic odontogenic keratocysts and three other cases ass ociated with NBCCS, looking for mutations of the PTCH gene. Non-radioactive single-strand conformational polymorphism and direct sequencing of PCR pro ducts revealed a deletion of 5 base pairs (bp) in exon 3 (518delAAGCG) in o ne sporadic cyst as well as mutations in two cysts associated with NBCCS, a nonsense (C2760A) and a missense (G3499A) alteration. This report is the f irst to describe a somatic mutation of PTCH in sporadic odontogenic keratoc ysts as well as two novel mutations in cysts associated with NBCCS, indicat ing a similar pathogenesis in a subset of sporadic keratocysts.