title: A single nucleotide polymorphism in the 3'untranslated region of the CDKN2A gene is common in sporadic primary melanomas but mutations in the CDKN2B, CDKN2C, CDK4 and p53 genes are rare.
abstract: In this report we present the results of mutational analysis of the CDKN2B, CDKN2C, CDK4, p53 genes and 5'UTR of the CDKN2A gene in a set of 44 sporadic primary melanomas, which had been earlier analysed for mutations in the CDKN2A (p16/p14(ARF)) gene. No tumour-associated mutations were detected except in 1 melanoma where we found a CC>T* deletion-mutation in the codon 151-152 (exon 5) of the p53 gene. On the basis of our preliminary results, we did extended genotyping of the 500 C>G and 540 C>T polymorphisms in the 3'UTR of the CDKN2A gene in 229 melanoma cases and 235 controls. The T-allele frequency (for 540 C>T polymorphism) in melanomas was significantly higher than in controls (0.14 vs. 0.08; chi(2) = 5.95, p = 0.01; OR = 1.71, 95%CI = 1.11-2.66). The heterozygote frequency for this polymorphism was 0.26 (59/229) in melanomas compared to 0.13 (30/235) in healthy controls (chi(2) = 11.4; p = 0.0007; OR = 2.34, 95% CI = 1.40-3.92). The frequency of the 500 C>G polymorphism in the 3'UTR in the CDKN2A gene was not significantly higher in melanomas compared to healthy controls. The 500 C>G polymorphism, however, was in linkage disequilibrium with approximately 50 kb apart the C>A intronic polymorphism in the CDKN2B gene (determined in 44 melanomas and 90 controls; Fisher exact test, p<0.0001). Finally, the sequence analysis of genomic DNA isolated from T cell lymphocytes of healthy individuals exhibited that the codon reported as last of exon 2 of the CDKN2C gene is rather the first codon of exon 3.
authors.affiliation: Department of Biosciences, Center for Nutrition and Toxicology, Karolinska Institute, Novum, Huddinge, Sweden. rajiv.kumar@cnt.ki.se
authors.forename: R
authors.initials: R
authors.lastname: Kumar
authors.forename: J
authors.initials: J
authors.lastname: Smeds
authors.forename: P
authors.initials: P
authors.lastname: Berggren
authors.forename: O
authors.initials: O
authors.lastname: Straume
authors.forename: B L
authors.initials: BL
authors.lastname: Rozell
authors.forename: L A
authors.initials: LA
authors.lastname: Akslen
authors.forename: K
authors.initials: K
authors.lastname: Hemminki
mesh_terms: D020413:3' Untranslated Regions; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D003062:Codon; D051358:Cyclin-Dependent Kinase 4; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D050763:Cyclin-Dependent Kinase Inhibitor p18; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D004791:Enzyme Inhibitors; D005091:Exons; D019942:Genes, p16; D016158:Genes, p53 / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007438:Introns; D008545:Melanoma / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C493966:CDKN2B protein, human; C493971:CDKN2C protein, human; D018797:Cell Cycle Proteins; D003062:Codon; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases