Abstract
Hereditary cutaneous melanoma is associated with mutations in the high-risk CDKN2A gene in about 40% of melanoma-prone families. Mutations in the CDK4 gene are the cause in only a few pedigrees. In this study, we analyzed 20 Latvian familial melanoma probands and carried out a comprehensive analysis of CDKN2A including sequencing of its promoter/intronic regions and deletion screening. We also analyzed the critical second exon of the CDK4 gene. One novel intronic variant (IVS2+82C>T) of the CDKN2A gene and a small deletion (c.-20677-20682delGTACGC) in its promoter region were found. Genotyping of the novel variants in larger melanoma and control groups indicated that the deletion increases the risk of melanoma (odds ratio=6.353, 95% confidence interval: 1.34-30.22, P=0.0168). The CDK4 gene analysis showed a Latvian melanoma family with the mutation R24H carried on the same haplotype as in two previously described Latvian CDK4-positive families. Our study suggests that the main risk gene in Latvian families with a strong family history of melanoma is CDK4 and that most of the other cases analyzed could be sporadic or associated with low-penetrance risk genes.
Original language | English |
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Pages (from-to) | 221-226 |
Number of pages | 6 |
Journal | Melanoma Research |
Volume | 23 |
Issue number | 3 |
DOIs | |
Publication status | Published - Jun 2013 |
Keywords*
- 9p21 locus
- CDK4
- CDKN2A
- CDKN2A promoter
- deletion analysis
- familial melanoma
- high-risk genes
- intronic polymorphisms
- multiple ligation-dependent probe amplification
Field of Science*
- 3.2 Clinical medicine
Publication Type*
- 1.1. Scientific article indexed in Web of Science and/or Scopus database