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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.

Laake, Kirsten
; 
Launonen, Virpi
; 
Niederacher, Dieter
; 
Gudlaugsdottir, Sigfridur
; 
Seitz, Susanne
; 
Rio, Pascale
; 
Champème, Marie-Helene
; 
Bièche, Ivan
; 
Birnbaum, Daniel
; 
White, Gavin R M
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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.
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
Affiliation
Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo.
Description
Date
1999-07
Publisher
Collections
All Paterson Institute for Cancer Research
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Keywords
Type
Article
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 Title
Journal ISSN
Volume Title
URI
http://hdl.handle.net/10541/90795
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