BRADFORD SCHOLARS

    • Sign in
    View Item 
    •   Bradford Scholars
    • Life Sciences
    • Life Sciences Publications
    • View Item
    •   Bradford Scholars
    • Life Sciences
    • Life Sciences Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of Bradford ScholarsCommunitiesAuthorsTitlesSubjectsPublication DateThis CollectionAuthorsTitlesSubjectsPublication Date

    My Account

    Sign in

    HELP

    Bradford Scholars FAQsCopyright Fact SheetPolicies Fact SheetDeposit Terms and ConditionsDigital Preservation Policy

    Statistics

    Display statistics

    Frequent p16-independent inactivation of p14ARF in human melanoma

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Publication date
    2008
    Author
    Freedberg, D.E.
    Rigas, S.H.
    Russak, J.
    Gai, W.
    Kaplow, M.
    Osman, I.
    Turner, F.
    Randerson-Moor, J.A.
    Houghton, A.
    Busam, K.
    Bishop, D.T.
    Bastian, B.C.
    Newton-Bishop, J.A.
    Polsky, D.
    Keyword
    Animals
    ; Cell line; Tumor
    ; Chromosomes; Pair 9
    ; DNA methylation
    ; Gene deletion
    ; Gene silencing
    ; Genes; p16
    ; Humans
    ; Immunoblotting
    ; Immunohistochemistry
    ; Melanoma; Genetics; Pathology
    ; Mice
    ; Microsatellite repeats
    ; Mutation
    ; Neoplasm proteins
    ; Polymerase chain reaction
    ; Promoter regions
    ; Tumor suppressor protein p14ARF
    ; REF 2014
    
    Metadata
    Show full item record
    Abstract
    BACKGROUND: The tumor suppressors p14(ARF) (ARF) and p16(INK4A) (p16) are encoded by overlapping reading frames at the CDKN2A/INK4A locus on chromosome 9p21. In human melanoma, the accumulated evidence has suggested that the predominant tumor suppressor at 9p21 is p16, not ARF. However, recent observations from melanoma-prone families and murine melanoma models suggest a p16-independent tumor suppressor role for ARF. We analyzed a group of melanoma metastases and cell lines to investigate directly whether somatic alterations to the ARF gene support its role as a p16-independent tumor suppressor in human melanoma, assuming that two alterations (genetic and/or epigenetic) would be required to inactivate a gene. METHODS: We examined the p16/ARF locus in 60 melanoma metastases from 58 patients and in 9 human melanoma cell lines using multiplex ligation-dependent probe amplification and multiplex polymerase chain reaction (PCR) to detect deletions, methylation-specific PCR to detect promoter methylation, direct sequencing to detect mutations affecting ARF and p16, and, in a subset of 20 tumors, immunohistochemistry to determine the effect of these alterations on p16 protein expression. All statistical tests were two-sided. RESULTS: We observed two or more alterations to the ARF gene in 26/60 (43%) metastases. The p16 gene sustained two or more alterations in 13/60 (22%) metastases (P = .03). Inactivation of ARF in the presence of wild-type p16 was seen in 18/60 (30%) metastases. CONCLUSION: Genetic and epigenetic analyses of the human 9p21 locus indicate that modifications of ARF occur independently of p16 inactivation in human melanoma and suggest that ARF is more frequently inactivated than p16.
    URI
    http://hdl.handle.net/10454/5973
    Citation
    Freedberg DE, Rigas SH, Russak J et al (2008) Frequent p16-independent inactivation of p14ARF in human melanoma. Journal of the National Cancer Institute. 100(11): 784-795.
    Link to publisher’s version
    http://dx.doi.org/10.1093/jnci/djn157
    Type
    Article
    Collections
    Life Sciences Publications

    entitlement

     
    DSpace software (copyright © 2002 - 2019)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.