title: Mutations of the CDKN2/p16INK4 gene in Australian melanoma kindreds.
abstract: The cyclin dependent kinase inhibitor 2 (CDKN2) gene on chromosome 9p21 is potentially involved in the genesis of many cancers and is currently under intense investigation as a possible melanoma susceptibility locus. We have analyzed 18 Australian melanoma kindreds for mutations within the coding and neighboring splice junction portions of the CDKN2 gene. In seven kindreds (including our six largest), CDKN2 mutations were found to segregate with the putative melanoma chromosome previously assigned by 9p haplotype analysis. These changes included the duplication of a 24 bp repeat, a deleted C residue resulting in the introduction of a premature stop codon, and four single basepair changes causing amino acid substitutions. Mutations segregated to 46 of 51 affected individuals in these seven kindreds, with three apparent sporadic cases in one family and one in each of another two families. Penetrance was variable (55-100%) among the different mutations. These data provide additional strong support that the CDKN2 gene is the chromosome 9p21 familial melanoma locus.
authors.affiliation: University of Southern California, Department of Biochemistry and Molecular Biology, Los Angeles 90033, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Walker
authors.forename: C J
authors.initials: CJ
authors.lastname: Hussussian
authors.forename: J F
authors.initials: JF
authors.lastname: Flores
authors.forename: J M
authors.initials: JM
authors.lastname: Glendening
authors.forename: F G
authors.initials: FG
authors.lastname: Haluska
authors.forename: N C
authors.initials: NC
authors.lastname: Dracopoli
authors.forename: N K
authors.initials: NK
authors.lastname: Hayward
authors.forename: J W
authors.initials: JW
authors.lastname: Fountain
mesh_terms: D001315:Australia; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers; D004791:Enzyme Inhibitors; D005091:Exons; D005190:Family; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion
chemical_list: D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers; D004791:Enzyme Inhibitors