A large Norwegian family with inherited malignant melanoma, multiple atypical nevi, and CDK4 mutation

Molven, Anders, Grimstvedt, Magne B., Steine, Solrun J., Harland, Mark, Avril, Marie-Françoise, Hayward, Nicholas K. and Akslen, Lars A. (2005) A large Norwegian family with inherited malignant melanoma, multiple atypical nevi, and CDK4 mutation. Genes, Chromosomes and Cancer, 44 1: 10-18. doi:10.1002/gcc.20202

Author Molven, Anders
Grimstvedt, Magne B.
Steine, Solrun J.
Harland, Mark
Avril, Marie-Françoise
Hayward, Nicholas K.
Akslen, Lars A.
Title A large Norwegian family with inherited malignant melanoma, multiple atypical nevi, and CDK4 mutation
Journal name Genes, Chromosomes and Cancer   Check publisher's open access policy
ISSN 1098-2264
Publication date 2005-09-01
Sub-type Article (original research)
DOI 10.1002/gcc.20202
Open Access Status
Volume 44
Issue 1
Start page 10
End page 18
Total pages 9
Place of publication Hoboken, NJ, United States
Publisher John Wiley and Sons
Language eng
Subject 111201 Cancer Cell Biology
111203 Cancer Genetics
Abstract Mutations in two loci encoding cell-cycle-regulatory proteins have been shown to cause familial malignant melanoma. About 20% of melanoma-prone families bear a mutation in the CDKN2A locus, which encodes two unrelated proteins, p16INK4A and p14ARF. Mutations in the other locus, CDK4, are much rarer and have been linked to the disease in only three families worldwide. In the 1960s, a large Norwegian pedigree with multiple atypical nevi and malignant melanomas was identified. Subsequently, six generations and more than 100 family members were traced and 20 cases of melanoma verified. In this article, we report that CDK4 codon 24 is mutated from CGT to CAT (Arg24His) in this unusually large melanoma kindred. Intriguingly, one of the family members had ocular melanoma, but the CDK4 mutation could not be detected in archival tissue samples from this subject. Thus, the case of ocular melanoma in this family was sporadic, suggesting an etiology different from that of the skin tumors. The CDK4 mutation in the Norwegian family was identical to that in melanoma families in France, Australia, and England. Haplotype analysis using microsatellite markers flanking the CDK4 gene and single-nucleotide polymorphisms within the gene did not support the possibility that there was a common founder, but rather indicated at least two independent mutational events. All CDK4 melanoma families known to date have a substitution of amino acid 24. In addition to resulting from selection pressure, this observation may be explained by the CG dinucleotide of codon 24 representing a mutational hot spot in the CDK4 gene.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
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