title: Identification of the familial cylindromatosis tumour-suppressor gene.
abstract: Familial cylindromatosis is an autosomal dominant genetic predisposition to multiple tumours of the skin appendages. The susceptibility gene (CYLD) has previously been localized to chromosome 16q and has the genetic attributes of a tumour-suppressor gene (recessive oncogene). Here we have identified CYLD by detecting germline mutations in 21 cylindromatosis families and somatic mutations in 1 sporadic and 5 familial cylindromas. All mutations predict truncation or absence of the encoded protein. CYLD encodes three cytoskeletal-associated-protein-glycine-conserved (CAP-GLY) domains, which are found in proteins that coordinate the attachment of organelles to microtubules. CYLD also has sequence homology to the catalytic domain of ubiquitin carboxy-terminal hydrolases (UCH).
authors.affiliation: [1] Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: G R
authors.initials: GR
authors.lastname: Bignell
authors.forename: W
authors.initials: W
authors.lastname: Warren
authors.forename: S
authors.initials: S
authors.lastname: Seal
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: E
authors.initials: E
authors.lastname: Rapley
authors.forename: R
authors.initials: R
authors.lastname: Barfoot
authors.forename: H
authors.initials: H
authors.lastname: Green
authors.forename: C
authors.initials: C
authors.lastname: Brown
authors.forename: P J
authors.initials: PJ
authors.lastname: Biggs
authors.forename: S R
authors.initials: SR
authors.lastname: Lakhani
authors.forename: C
authors.initials: C
authors.lastname: Jones
authors.forename: J
authors.initials: J
authors.lastname: Hansen
authors.forename: E
authors.initials: E
authors.lastname: Blair
authors.forename: B
authors.initials: B
authors.lastname: Hofmann
authors.forename: R
authors.initials: R
authors.lastname: Siebert
authors.forename: G
authors.initials: G
authors.lastname: Turner
authors.forename: D G
authors.initials: DG
authors.lastname: Evans
authors.forename: C
authors.initials: C
authors.lastname: Schrander-Stumpel
authors.forename: F A
authors.initials: FA
authors.lastname: Beemer
authors.forename: A
authors.initials: A
authors.lastname: van Den Ouweland
authors.forename: D
authors.initials: D
authors.lastname: Halley
authors.forename: B
authors.initials: B
authors.lastname: Delpech
authors.forename: M G
authors.initials: MG
authors.lastname: Cleveland
authors.forename: I
authors.initials: I
authors.lastname: Leigh
authors.forename: J
authors.initials: J
authors.lastname: Leisti
authors.forename: S
authors.initials: S
authors.lastname: Rasmussen
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D003001:Cloning, Molecular; D020451:Contig Mapping; D000074749:Deubiquitinating Enzyme CYLD; D005091:Exons / Q000235:genetics; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic / Q000235:genetics; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D016324:Sequence Tagged Sites; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D013869:Thiolester Hydrolases / Q000737:chemistry; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase
chemical_list: D011506:Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D013869:Thiolester Hydrolases; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD; D043222:Ubiquitin Thiolesterase