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    Genomic alterations associated with loss of heterozygosity for TP53 in Li-Fraumeni syndrome fibroblasts.

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    Authors
    Burt, E C
    James, Louise A
    Greaves, Martin J
    Birch, Jillian M
    Boyle, John M
    Varley, Jennifer
    Affiliation
    CRC Cancer Genetics Group, Patterson Institute for Cancer Research, Manchester.
    Issue Date
    2000-08
    
    Metadata
    Show full item record
    Abstract
    Studies of Li-Fraumeni syndrome fibroblasts heterozygous for germline TP53 mutations have shown that loss of heterozygosity (LOH) occurs during passaging and is associated with genomic instability, such as chromosomal aberrations and aneuploidy to investigate the genomic changes associated with LOH in Li-Fraumeni (LF) fibroblasts, we have analysed cell strains at increasing population doublings (PD) using Comparative Genomic Hybridization (CGH). We have looked at three groups of cell strains: LF mutation-carrying strains which showed LOH for TP53, LF mutation-carrying strains which did not show LOH, and strains from normal individuals. Using CGH, we have detected loss of distinct chromosomal regions associated with LOH in 4 out of 5 mutation-carrying strains. In particular we have found loss of chromosomal regions containing genes involved in cell cycle control or senescence, including loss of 9p and 17p in these strains. Other recurrent changes included loss of chromosomes 4q and 6q, regions shown to contain one or more tumour suppressor genes. No genomic alterations were detected at cumulative PD in the normal strains or in the LF mutation-carrying strains which did not show LOH for TP53. We have also analysed the three groups of strains for microsatellite instability and somatic TP53 mutations, and have found genetic alterations in only one strain.
    Citation
    Genomic alterations associated with loss of heterozygosity for TP53 in Li-Fraumeni syndrome fibroblasts. 2000, 83 (4):467-72 Br. J. Cancer
    Journal
    British Journal of Cancer
    URI
    http://hdl.handle.net/10541/88044
    DOI
    10.1054/bjoc.2000.1292
    PubMed ID
    10945493
    Type
    Article
    Language
    en
    ISSN
    0007-0920
    ae974a485f413a2113503eed53cd6c53
    10.1054/bjoc.2000.1292
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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