title: Mutation testing in melanoma families: INK4A, CDK4 and INK4D.
abstract: The INK4A gene which codes for the cyclin-dependent kinase (CDK) inhibitor INK4A or p16 underlies susceptibility to melanoma in some families. Germline mutations in the gene that codes for the target protein of p16, CDK4, underlie susceptibility in very rare families. We report mutation screening of the INK4A and CDK4 genes in 42 UK families. A total of nine families were identified with INK4A mutations and none with CDK4 exon 2 mutations. These mutations were in 8/22 (35%) families with three or more cases of melanoma and 1/20 (5%) families with only two cases. In one of these nine families a novel single base pair substitution was identified, Gly67Arg. In an attempt to identify another melanoma susceptibility gene, a member of the INK4 family, the p19 INK4D gene has been studied. The p19 gene was sequenced in DNA from the 42 UK families and six additional US families. No mutations were identified.
authors.affiliation: ICRF Cancer Medicine Research Unit, St James's University Hospital, Leeds, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Newton Bishop
authors.forename: M
authors.initials: M
authors.lastname: Harland
authors.forename: D C
authors.initials: DC
authors.lastname: Bennett
authors.forename: V
authors.initials: V
authors.lastname: Bataille
authors.forename: A M
authors.initials: AM
authors.lastname: Goldstein
authors.forename: M A
authors.initials: MA
authors.lastname: Tucker
authors.forename: B A
authors.initials: BA
authors.lastname: Ponder
authors.forename: J
authors.initials: J
authors.lastname: Cuzick
authors.forename: P
authors.initials: P
authors.lastname: Selby
authors.forename: D T
authors.initials: DT
authors.lastname: Bishop
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D051358:Cyclin-Dependent Kinase 4; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D050764:Cyclin-Dependent Kinase Inhibitor p19; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D011518:Proto-Oncogene Proteins
chemical_list: C493974:CDKN2D protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050764:Cyclin-Dependent Kinase Inhibitor p19; D011518:Proto-Oncogene Proteins; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases