title: 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.
authors.affiliation: Department of Clinics, Universidade Federal de Minas Gerais, Brazil.
authors.forename: D C
authors.initials: DC
authors.lastname: Barreto
authors.forename: R S
authors.initials: RS
authors.lastname: Gomez
authors.forename: A E
authors.initials: AE
authors.lastname: Bale
authors.forename: W L
authors.initials: WL
authors.lastname: Boson
authors.forename: L
authors.initials: L
authors.lastname: De Marco
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D001478:Basal Cell Nevus Syndrome / Q000235:genetics; D020029:Base Pairing / Q000235:genetics; D018389:Codon, Nonsense / Q000235:genetics; D004627:Embryonic Induction / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor / Q000235:genetics; D053823:Hedgehog Proteins; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D009807:Odontogenic Cysts / Q000235:genetics*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics; D011956:Receptors, Cell Surface; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators
chemical_list: D018389:Codon, Nonsense; D053823:Hedgehog Proteins; D008565:Membrane Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011506:Proteins; D011956:Receptors, Cell Surface; D015534:Trans-Activators