title: PTCH mutations: distribution and analyses.
abstract: Mutations in the PTCH (PTCH1) gene are the underlying cause of nevoid basal cell carcinoma syndrome (NBCCS), and are also found in many different sporadic tumors in which PTCH is thought to act as a tumor suppressor gene. To investigate the distribution pattern of these mutations in tumors and NBCCS, we analyzed 284 mutations and 48 SNPs located in the PTCH gene that were compiled from our PTCH mutation database. We found that the PTCH mutations were mainly clustered into the predicted two large extracellular loops and the large intracellular loop. The SNPs appeared to be clustered around the sterol sensing domain and the second half of the protein. The NBCCS cases and each class of tumor analyzed revealed a different distribution of the mutations in the various PTCH domains. Moreover, the types of mutations were also unique for the different groups. Finally, the PTCH gene harbors mutational hot spot residues and regions, including a slippage-sensitive sequence in the N-terminus.
authors.affiliation: Karolinska Institute, Department of Biosciences, NOVUM, Huddinge, Sweden. E.Lindstrom@csb.ki.se
authors.forename: Erika
authors.initials: E
authors.lastname: Lindström
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimokawa
authors.forename: Rune
authors.initials: R
authors.lastname: Toftgård
authors.forename: Peter G
authors.initials: PG
authors.lastname: Zaphiropoulos
mesh_terms: D001478:Basal Cell Nevus Syndrome / Q000235:genetics*; D030541:Databases, Genetic; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D020641:Polymorphism, Single Nucleotide; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface