Analysis of Latvian familial melanoma patients shows novel variants in the noncoding regions of CDKN2A and that the CDK4 mutation R24H is a founder mutation

Ruta Veinalde, Aija Ozola, Kristine Azarjana, Anders Molven, Lars A. Akslen, Simona Doniņa, Guna Proboka, Ingrida Čema, Ainars Baginskis, Dace Pjanova

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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 languageEnglish
Pages (from-to)221-226
Number of pages6
JournalMelanoma Research
Volume23
Issue number3
DOIs
Publication statusPublished - 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

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