title: Novel mutations in the p16/CDKN2A binding region of the cyclin-dependent kinase-4 gene.
abstract: Mutations in genes that lie in the retinoblastoma pathway have been implicated in the pathogenesis of many tumor types. Two critical components that determine progression from G1 to S include p16/CDKN2A and CDK4. Alterations in p16/CDKN2A have been well documented in multiple cancers, including melanoma. However, changes in CDK4 are apparently more rare. Only two alterations, both at codon 24, have been identified in CDK4: an activating arginine-to-cysteine transition and a germ-line arginine-to-histidine substitution in one French kindred. In a survey of 20 neuroblastomas, 17 uncultured metastatic melanomas, 33 uncultured primary uveal melanomas, 8 colon cancer cell lines, and 20 primary colon cancer samples, we found no evidence of mutations in exon 2 of CDK4. From our cell lines derived from metastatic melanomas, we detected two alterations in the functionally critical exon 2 of CDK4: a lysine-to-glutamine transition at codon 22 and the arginine-to-histidine mutation at codon 24. These findings document several novel changes in the p16-binding region of CDK4.
authors.affiliation: Department of Dermatology, Massachusetts General Hospital and Dana-Farber/Partner Cancer Care, Boston 02114, USA.
authors.forename: H
authors.initials: H
authors.lastname: Tsao
authors.forename: E
authors.initials: E
authors.lastname: Benoit
authors.forename: A J
authors.initials: AJ
authors.lastname: Sober
authors.forename: C
authors.initials: C
authors.lastname: Thiele
authors.forename: F G
authors.initials: FG
authors.lastname: Haluska
mesh_terms: D001665:Binding Sites / Q000235:genetics; D003062:Codon / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics; D051358:Cyclin-Dependent Kinase 4; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D005091:Exons / Q000235:genetics; D018095:Germ-Line Mutation; D006801:Humans; D008545:Melanoma / Q000235:genetics; D009447:Neuroblastoma / Q000235:genetics; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured
chemical_list: D003062:Codon; D019941:Cyclin-Dependent Kinase Inhibitor p16; D011518:Proto-Oncogene Proteins; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases