title: Lack of germline CDK6 mutations in familial melanoma.
abstract: Germline mutations in genes encoding several components of the retinoblastoma pathway have been linked with inherited predisposition to melanoma. Most commonly, such mutations involve CDKN2A, a cyclin-dependent kinase inhibitor of two kinases, CDK4 and CDK6, which phosphorylate the retinoblastoma protein (pRB) and thereby promote passage through the G1/S cell-cycle restriction point. Less frequently, germline mutations in the CDK4 gene have also been linked with an increased risk of melanoma. Despite the sequence and functional homology between CDK4 and CDK6, the role of germline mutations in CDK6 in melanoma predisposition is unknown. We detected no CDK6 mutations within the p16 (CDKN2A) binding domain in index cases from 60 melanoma-prone kindreds that lacked germline mutations in the coding regions of either CDKN2A or within the entire CDK4 coding region. We conclude that germline mutations in CDK6 do not make a significant contribution to melanoma predisposition.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: M G
authors.initials: MG
authors.lastname: Shennan
authors.forename: A C
authors.initials: AC
authors.lastname: Badin
authors.forename: S
authors.initials: S
authors.lastname: Walsh
authors.forename: A
authors.initials: A
authors.lastname: Summers
authors.forename: L
authors.initials: L
authors.lastname: From
authors.forename: M
authors.initials: M
authors.lastname: McKenzie
authors.forename: A M
authors.initials: AM
authors.lastname: Goldstein
authors.forename: M A
authors.initials: MA
authors.lastname: Tucker
authors.forename: D
authors.initials: D
authors.lastname: Hogg
authors.forename: N
authors.initials: N
authors.lastname: Lassam
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D030342:Genetic Diseases, Inborn / Q000235:genetics; D018095:Germ-Line Mutation; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; C495900:CDK4 protein, human; C495911:CDK6 protein, human; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases