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.

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The human patched gene (PTCH) functions in both embryologic development and tumor suppression. PTCH mutations have been found in odontogenic keratocysts. However, the expression and localization of the protein product of the gene have not been determined in odontogenic tumors and cysts. We investigated 68 odontogenic lesions by immunohistochemistry, and compared their PTCH expression with that in basal cell carcinomas. All odontogenic lesions, including two keratocysts with truncating mutations, were positive for PTCH. Different types of lesions had different amounts of staining. Lack of staining was noted in the majority of basal cell carcinomas. Taken together, these data suggest that odontogenic keratocysts arise with heterozygous mutations of the PTCH gene.