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

Int J Cancer. 2001 Nov 20;95(6):388-93. doi: 10.1002/1097-0215(20011120)95:6<388::aid-ijc1069>3.0.co;2-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions*
  • Alleles
  • Base Sequence
  • Case-Control Studies
  • Cell Cycle Proteins / genetics*
  • Codon
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p18
  • Cyclin-Dependent Kinases / genetics*
  • Enzyme Inhibitors
  • Exons
  • Genes, p16*
  • Genes, p53 / genetics*
  • Heterozygote
  • Homozygote
  • Humans
  • Introns
  • Melanoma / genetics*
  • Molecular Sequence Data
  • Mutation*
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide*
  • Polymorphism, Single-Stranded Conformational
  • Proto-Oncogene Proteins*
  • Tumor Suppressor Proteins / genetics*

Substances

  • 3' Untranslated Regions
  • CDKN2B protein, human
  • CDKN2C protein, human
  • Cell Cycle Proteins
  • Codon
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18
  • Enzyme Inhibitors
  • Proto-Oncogene Proteins
  • Tumor Suppressor Proteins
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases