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

作者：Veinalde Ruta^*; Ozola Aija; Azarjana Kristine; Molven Anders; Akslen Lars A; Donina Simona; Proboka Guna; Cema Ingrida; Baginskis Ainars; Pjanova Dace

来源：Melanoma Research, 2013, 23(3): 221-226.

DOI：10.1097/CMR.0b013e3283608695

• 9p21 locus
• CDK4
• CDKN2A
• CDKN2A promoter
• deletion analysis
• familial melanoma
• high-risk genes
• intronic polymorphisms
• multiple ligation-dependent probe amplification

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 %26gt; 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.

• 出版日期2013-6