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.
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.
Kumar
R
R
Department of Biosciences, Center for Nutrition and Toxicology, Karolinska Institute, Novum, Huddinge, Sweden. rajiv.kumar@cnt.ki.se
Smeds
J
J
Berggren
P
P
Straume
O
O
Rozell
B L
BL
Akslen
L A
LA
Hemminki
K
K
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*
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