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    Loss of heterozygosity at 11q23.1 and survival in breast cancer: results of a large European study. Breast Cancer Somatic Genetics Consortium.

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    Authors
    Laake, Kirsten
    Launonen, Virpi
    Niederacher, Dieter
    Gudlaugsdottir, Sigfridur
    Seitz, Susanne
    Rio, Pascale
    Champème, Marie-Helene
    Bièche, Ivan
    Birnbaum, Daniel
    White, Gavin R M
    Sztan, Marianna
    Sever, Natasa
    Plummer, Sarah
    Osorio, Ana
    Broeks, Annegien
    Huusko, P
    Spurr, Nigel
    Borg, Ake
    Cleton-Jansen, Anne-Marie
    Van't Veer, Laura
    Benitez, Javier
    Casey, Graham
    Peterlin, Borut
    Olah, Edith
    Børresen-Dale, Anne-Lise
    Varley, Jennifer
    Bignon, Yves-Jean
    Scherneck, Siegfried
    Sigurdardottir, Valgerdur
    Lidereau, Rosette
    Eyfjord, Jorunn
    Beckmann, Matthias W
    Winqvist, Robert
    Skovlund, Eva
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    Affiliation
    Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo.
    Issue Date
    1999-07
    
    Metadata
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    Abstract
    Among the chromosomal regions commonly undergoing deletions in breast tumors is 11q23.1. The genes that are targets for loss of heterozygosity (LOH) in this region is not yet established. One of the candidate genes located in this region is ATM, responsible for the rare autosomal recessive disorder ataxia-telangiectasia (A-T). Interestingly, A-T heterozygotes may have an increased risk of cancer, in particular breast cancer, although this is still controversial. A common assumption has been that the target for the LOH at 11q23.1 in breast carcinoma is the ATM gene, but the area studied has been too large, the density of markers too low, and the number of tumors studied has been too small to draw any firm conclusions. The present study is a multicenter study including 918 breast cancer patients with clinical information and survival data available for most of them. Primary breast tumors were investigated for LOH using a high density of microsatellite markers spanning approximately 6 Mb around the ATM gene. Survival analyses showed that there are most likely one or more candidate genes in a 3-4 Mb region between the markers D11S1819 and D11S927 including the ATM gene. Cancer-specific survival was significantly reduced in patients whose tumors exhibited LOH of markers D11S2179 (within the ATM gene), D11S1778, D11S1294, and D11S1818. The highest survival hazard ratios were 1.8(C11.2-2.8, P = 0.010) and 2.1 (C11.4-3.0, P = 0.0004) for markers D11S2179 and D11S1818, respectively. One or more of these markers are therefore most likely to be located close to or within genes associated with breast cancer survival.
    Citation
    Loss of heterozygosity at 11q23.1 and survival in breast cancer: results of a large European study. Breast Cancer Somatic Genetics Consortium. 1999, 25 (3):212-21 Genes Chromosomes Cancer
    Journal
    Genes, Chromosomes & Cancer
    URI
    http://hdl.handle.net/10541/90795
    DOI
    10.1002/(SICI)1098-2264(199907)25:3<212::AID-GCC3>3.0.CO;2-G
    PubMed ID
    10379867
    Type
    Article
    Language
    en
    ISSN
    1045-2257
    ae974a485f413a2113503eed53cd6c53
    10.1002/(SICI)1098-2264(199907)25:3<212::AID-GCC3>3.0.CO;2-G
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