QUT ePrints

Analysis of the CDKN2A, CDKN2B and CDK4 genes in 48 Australian melanoma kindreds

Flores, Jose F. , Pollock, Pamela M., Walker, Graeme J. , Glendening, J. Michael , Lin, Amy H-T , Palmer, Jane M. , Walters, Marilyn K. , Hayward, Nicholas K. , & Fountain, Jane W. (1997) Analysis of the CDKN2A, CDKN2B and CDK4 genes in 48 Australian melanoma kindreds. Oncogene, 15(24), pp. 2999-3005.

[img] Published Version (PDF 358kB)
Administrators only | Request a copy from author

    View at publisher

    Abstract

    Germline mutations within the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene and one of its targets, the cyclin dependent kinase 4 (CDK4) gene, have been identified in a proportion of melanoma kindreds. In the case of CDK4, only one specific mutation, resulting in the substitution of a cysteine for an arginine at codon 24 (R24C), has been found to be associated with melanoma. We have previously reported the identification of germline CDKN2A mutations in 7/18 Australian melanoma kindreds and the absence of the R24C CDK4 mutation in 21 families lacking evidence of a CDKN2A mutation. The current study represents an expansion of these efforts and includes a total of 48 melanoma families from Australia. All of these families have now been screened for mutations within CDKN2A and CDK4, as well as for mutations within the CDKN2A homolog and 9p21 neighbor, the CDKN2B gene, and the alternative exon 1 (E1beta) of CDKN2A. Families lacking CDKN2A mutations, but positive for a polymorphism(s) within this gene, were further evaluated to determine if their disease was associated with transcriptional silencing of one CDKN2A allele. Overall, CDKN2A mutations were detected in 3/30 (10%) of the new kindreds. Two of these mutations have been observed previously: a 24 bp duplication at the 5' end of the gene and a G to C transversion in exon 2 resulting in an M531 substitution. A novel G to A transition in exon 2, resulting in a D108N substitution was also detected. Combined with our previous findings, we have now detected germline CDKN2A mutations in 10/48 (21%) of our melanoma kindreds. In none of the 'CDKN2A-negative' families was melanoma found to segregate with either an untranscribed CDKN2A allele, an R24C CDK4 mutation, a CDKN2B mutation, or an E1beta mutation. The last three observations suggest that these other cell cycle control genes (or alternative gene products) are either not involved at all, or to any great extent, in melanoma predisposition.

    Impact and interest:

    63 citations in Scopus
    Search Google Scholar™
    62 citations in Web of Science®

    Citation countsare sourced monthly from Scopus and Web of Science® citation databases.

    These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

    Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

    ID Code: 45810
    Item Type: Journal Article
    Additional URLs:
    Keywords: Alleles, Alternative Splicing, Australia, Cyclin-Dependent Kinases/genetics, DNA Mutational Analysis, Disease Susceptibility, Genes, p16/ genetics, Genetic Linkage, Genetic Markers, Genetic Testing, Haplotypes, Humans, Melanoma/ genetics, Mutation, Pedigree, Polymorphism, Single-Stranded Conformational, Transcription, Genetic
    ISSN: 0950-9232
    Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Cell Biology (111201)
    Divisions: Past > Schools > Cell & Molecular Biosciences
    Past > QUT Faculties & Divisions > Faculty of Science and Technology
    Current > Institutes > Institute of Health and Biomedical Innovation
    Copyright Owner: Copyright 1997 Nature Publishing Group
    Deposited On: 09 Sep 2011 10:49
    Last Modified: 09 Sep 2011 10:49

    Export: EndNote | Dublin Core | BibTeX

    Repository Staff Only: item control page