Germline mutations of the CDKN2 gene in UK melanoma families
| Autor: | D. Timothy Bishop, Julia A. Newton Bishop, Gordon Peters, Elizabeth Pinney, Anna-Marie Frischauf, Mark Harland, Nelleke A. Gruis, Peter Selby, Rolando Meloni, Veronique Bataille, Nigel K. Spurr, Sharon Brookes, Jack Cuzick |
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| Rok vydání: | 1997 |
| Předmět: |
Adult
Male Mutant DNA Mutational Analysis Biology medicine.disease_cause Exon Germline mutation Genetics medicine Humans neoplasms Molecular Biology Gene Melanoma Genetics (clinical) Germ-Line Mutation Aged Aged 80 and over Mutation Polymorphism Genetic Genes p16 Genetic Variation General Medicine Sequence Analysis DNA Middle Aged medicine.disease Penetrance United Kingdom Pedigree biology.protein Cancer research Female Cyclin-dependent kinase 6 Disease Susceptibility Protein Binding |
| Zdroj: | Human molecular genetics. 6(12) |
| ISSN: | 0964-6906 |
| Popis: | Germline mutations in CDKN2 on chromosome 9p21, which codes for the cyclin D kinase inhibitor p16, and more rarely, mutations in the gene coding for CDK4, the protein to which p16 binds, underlie susceptibility in some melanoma families. We have sequenced all exons of CDKN2 and analysed the CDK4 gene for mutations in 27 UK families showing evidence of predisposition to melanoma. Five different germline mutations in CDKN2 were found in six families. Three of the mutations (Met53IIe, Arg24Pro and 23ins24) have been reported previously. We have identified two novel CDKN2 mutations (88delG and Ala118Thr) which are likely to be associated with the development of melanoma, because of their co-segregation with the disease and their likely functional effect on the CDKN2 protein. In binding assays the protein expressed from the previously described mutation, Met53IIe, did not bind to CDK4/CDK6, confirming its role as a causal mutation in the development of melanoma. Ala118Thr appeared to be functional in this assay. Arg24Pro appeared to bind to CDK6, but not to CDK4. No mutations were detected in exon 2 of CDK4, suggesting that causal mutations in this gene are uncommon. The penetrance of these mutant CDKN2 genes is not yet established, nor is the risk of non-melanoma cancer to gene carriers. |
| Databáze: | OpenAIRE |
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