title: Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome.
abstract: The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by multiple basal cell carcinomas (BCCs), pits of the palms and soles, jaw keratocysts, a variety of other tumors, and developmental abnormalities. NBCCS maps to chromosome 9q22.3. Familial and sporadic BCCs display loss of heterozygosity in this region, consistent with the gene being a tumor suppressor. A human sequence (PTC) with strong homology to the Drosophila segment polarity gene, patched, was isolated from a YAC and cosmid contig of the NBCCS region. Mutation analysis revealed alterations of PTC in NBCCS patients and in related tumors. We propose that a reduction in expression of the patched gene can lead to the developmental abnormalities observed in the syndrome and that complete loss of patched function contributes to transformation of certain cell types.
authors.affiliation: Centre for Molecular and Cell Biology, University of Queensland, St. Lucia, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Hahn
authors.forename: C
authors.initials: C
authors.lastname: Wicking
authors.forename: P G
authors.initials: PG
authors.lastname: Zaphiropoulous
authors.forename: M R
authors.initials: MR
authors.lastname: Gailani
authors.forename: S
authors.initials: S
authors.lastname: Shanley
authors.forename: A
authors.initials: A
authors.lastname: Chidambaram
authors.forename: I
authors.initials: I
authors.lastname: Vorechovsky
authors.forename: E
authors.initials: E
authors.lastname: Holmberg
authors.forename: A B
authors.initials: AB
authors.lastname: Unden
authors.forename: S
authors.initials: S
authors.lastname: Gillies
authors.forename: K
authors.initials: K
authors.lastname: Negus
authors.forename: I
authors.initials: I
authors.lastname: Smyth
authors.forename: C
authors.initials: C
authors.lastname: Pressman
authors.forename: D J
authors.initials: DJ
authors.lastname: Leffell
authors.forename: B
authors.initials: B
authors.lastname: Gerrard
authors.forename: A M
authors.initials: AM
authors.lastname: Goldstein
authors.forename: M
authors.initials: M
authors.lastname: Dean
authors.forename: R
authors.initials: R
authors.lastname: Toftgard
authors.forename: G
authors.initials: G
authors.lastname: Chenevix-Trench
authors.forename: B
authors.initials: B
authors.lastname: Wainwright
authors.forename: A E
authors.initials: AE
authors.lastname: Bale
mesh_terms: D000483:Alleles; D000818:Animals; D001478:Basal Cell Nevus Syndrome / Q000235:genetics*; D001483:Base Sequence; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D007301:Insect Hormones / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D011956:Receptors, Cell Surface; D012689:Sequence Homology, Nucleic Acid
chemical_list: D018076:DNA, Complementary; D029721:Drosophila Proteins; D007301:Insect Hormones; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; C070844:ptc protein, Drosophila