RGD Reference Report - Melanoma development in relation to non-functional p16/INK4A protein and dysplastic naevus syndrome in Swedish melanoma kindreds. - Rat Genome Database

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Melanoma development in relation to non-functional p16/INK4A protein and dysplastic naevus syndrome in Swedish melanoma kindreds.

Authors: Hashemi, J  Linder, S  Platz, A  Hansson, J 
Citation: Hashemi J, etal., Melanoma Res. 1999 Feb;9(1):21-30.
RGD ID: 8552302
Pubmed: (View Article at PubMed) PMID:10338331

The CDKN2A gene encodes the cell cycle inhibitor p16/ INK4A, which is involved in familial cutaneous melanoma. We have studied five Swedish familial melanoma kindreds characterized by germline mutations in CDKN2A and dysplastic naevus syndrome (DNS). We found significant correlations between germline CDKN2A mutations and melanoma and between DNS phenotype and melanoma, respectively. There was also a correlation between mutation status and the presence of DNS. In CDKN2A mutation carriers, all cases of early-onset melanoma occurred in DNS individuals, and the mean age at melanoma diagnosis was significantly lower in individuals with DNS than in those without a confirmed DNS phenotype. In one family where the proband had a P48L mutation in CDKN2A exon 1, the DNS phenotype was studied in detail. In vitro binding experiments established that the P48L mutant protein does not bind to cdk4 or cdk6 and thus is functionally abnormal. Furthermore, we demonstrated loss of heterozygosity at markers on chromosome 9p flanking the CDKN2A locus in a primary melanoma and a metastasis from the proband. Our results are consistent with the hypothesis that germline CDKN2A mutations and DNS both contribute to the predisposition to melanoma and may lead to the development of early-onset melanoma when present in the same individual.

Annotation

Disease Annotations    

Phenotype Annotations    

Human Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Cdkn2a  (cyclin-dependent kinase inhibitor 2A)

Genes (Mus musculus)
Cdkn2a  (cyclin dependent kinase inhibitor 2A)

Genes (Homo sapiens)
CDKN2A  (cyclin dependent kinase inhibitor 2A)


Additional Information