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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
Author(s) -
Kumar Rajiv,
Smeds Johanna,
Berggren Petra,
Straume Oddbjørn,
Rozell Barbro Lundh,
Akslen Lars A.,
Hemminki Kari
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20011120)95:6<388::aid-ijc1069>3.0.co;2-6
Subject(s) - cdkn2a , cdkn2b , exon , biology , genetics , genotype , allele , gene , genotyping , microbiology and biotechnology , untranslated region , single nucleotide polymorphism , polymorphism (computer science) , messenger rna
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; χ 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 (χ 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 ∼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. © 2001 Wiley‐Liss, Inc.