Germline mutations of the CDKN2 gene in UK melanoma families.
Hum Mol Genet
; 6(12): 2061-7, 1997 Nov.
Article
de En
| MEDLINE
| ID: mdl-9328469
ABSTRACT
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 (Met53Ile, 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, Met53Ile, 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.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Mutation germinale
/
Gènes p16
/
Mélanome
Limites:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Pays/Région comme sujet:
Europa
Langue:
En
Journal:
Hum Mol Genet
Sujet du journal:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Année:
1997
Type de document:
Article
Pays d'affiliation:
Royaume-Uni