Loss of heterozygosity at 11q23.1 and survival in breast cancer

Results of a large European study

Kirsten Laake, Virpi Launonen, Dieter Niederacher, Sigfridur Gudlaugsdottir, Susanne Seitz, Pascale Rio, Marie Hélène Champème, Ivan Bièche, Daniel Birnbaum, Gavin White, Marianna Sztan, Natasa Sever, Sarah Plummer, Ana Osorio, Annegien Broeks, Pia Huusko, Nigel Spurr, Åke Borg, Anne Marie Cleton-Jansen, Laura Van't Veer & 14 others Javier Benitez, Graham Casey, Borut Peterlin, E. Oláh, Jenny Varley, Yves Jean Bignon, Siegfried Scherneck, Valgerdur Sigurdardottir, Rosette Lidereau, Jorunn Eyfjord, Matthias Wilhelm Beckmann, Robert Winqvist, Eva Skovlund, Anne Lise Børresen-Dale

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 (CI 1.2-2.8, P = 0.010) and 2.1 (CI 1.4-3.0, 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.

Original languageEnglish
Pages (from-to)212-221
Number of pages10
JournalGenes Chromosomes and Cancer
Volume25
Issue number3
DOIs
Publication statusPublished - Jul 1999

Fingerprint

Loss of Heterozygosity
Breast Neoplasms
Survival
Genes
Neoplasms
Ataxia Telangiectasia
Heterozygote
Survival Analysis
Microsatellite Repeats
Multicenter Studies

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Laake, K., Launonen, V., Niederacher, D., Gudlaugsdottir, S., Seitz, S., Rio, P., ... Børresen-Dale, A. L. (1999). Loss of heterozygosity at 11q23.1 and survival in breast cancer: Results of a large European study. Genes Chromosomes and Cancer, 25(3), 212-221. https://doi.org/10.1002/(SICI)1098-2264(199907)25:3<212::AID-GCC3>3.0.CO;2-G

Loss of heterozygosity at 11q23.1 and survival in breast cancer : Results of a large European study. / Laake, Kirsten; Launonen, Virpi; Niederacher, Dieter; Gudlaugsdottir, Sigfridur; Seitz, Susanne; Rio, Pascale; Champème, Marie Hélène; Bièche, Ivan; Birnbaum, Daniel; White, Gavin; Sztan, Marianna; Sever, Natasa; Plummer, Sarah; Osorio, Ana; Broeks, Annegien; Huusko, Pia; Spurr, Nigel; Borg, Åke; Cleton-Jansen, Anne Marie; Van't Veer, Laura; Benitez, Javier; Casey, Graham; Peterlin, Borut; Oláh, E.; Varley, Jenny; Bignon, Yves Jean; Scherneck, Siegfried; Sigurdardottir, Valgerdur; Lidereau, Rosette; Eyfjord, Jorunn; Beckmann, Matthias Wilhelm; Winqvist, Robert; Skovlund, Eva; Børresen-Dale, Anne Lise.

In: Genes Chromosomes and Cancer, Vol. 25, No. 3, 07.1999, p. 212-221.

Research output: Contribution to journalArticle

Laake, K, Launonen, V, Niederacher, D, Gudlaugsdottir, S, Seitz, S, Rio, P, Champème, MH, Bièche, I, Birnbaum, D, White, G, Sztan, M, Sever, N, Plummer, S, Osorio, A, Broeks, A, Huusko, P, Spurr, N, Borg, Å, Cleton-Jansen, AM, Van't Veer, L, Benitez, J, Casey, G, Peterlin, B, Oláh, E, Varley, J, Bignon, YJ, Scherneck, S, Sigurdardottir, V, Lidereau, R, Eyfjord, J, Beckmann, MW, Winqvist, R, Skovlund, E & Børresen-Dale, AL 1999, 'Loss of heterozygosity at 11q23.1 and survival in breast cancer: Results of a large European study', Genes Chromosomes and Cancer, vol. 25, no. 3, pp. 212-221. https://doi.org/10.1002/(SICI)1098-2264(199907)25:3<212::AID-GCC3>3.0.CO;2-G
Laake, Kirsten ; Launonen, Virpi ; Niederacher, Dieter ; Gudlaugsdottir, Sigfridur ; Seitz, Susanne ; Rio, Pascale ; Champème, Marie Hélène ; Bièche, Ivan ; Birnbaum, Daniel ; White, Gavin ; Sztan, Marianna ; Sever, Natasa ; Plummer, Sarah ; Osorio, Ana ; Broeks, Annegien ; Huusko, Pia ; Spurr, Nigel ; Borg, Åke ; Cleton-Jansen, Anne Marie ; Van't Veer, Laura ; Benitez, Javier ; Casey, Graham ; Peterlin, Borut ; Oláh, E. ; Varley, Jenny ; Bignon, Yves Jean ; Scherneck, Siegfried ; Sigurdardottir, Valgerdur ; Lidereau, Rosette ; Eyfjord, Jorunn ; Beckmann, Matthias Wilhelm ; Winqvist, Robert ; Skovlund, Eva ; Børresen-Dale, Anne Lise. / Loss of heterozygosity at 11q23.1 and survival in breast cancer : Results of a large European study. In: Genes Chromosomes and Cancer. 1999 ; Vol. 25, No. 3. pp. 212-221.
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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 (CI 1.2-2.8, P = 0.010) and 2.1 (CI 1.4-3.0, 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.",
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AU - Seitz, Susanne

AU - Rio, Pascale

AU - Champème, Marie Hélène

AU - Bièche, Ivan

AU - Birnbaum, Daniel

AU - White, Gavin

AU - Sztan, Marianna

AU - Sever, Natasa

AU - Plummer, Sarah

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AU - Spurr, Nigel

AU - Borg, Åke

AU - Cleton-Jansen, Anne Marie

AU - Van't Veer, Laura

AU - Benitez, Javier

AU - Casey, Graham

AU - Peterlin, Borut

AU - Oláh, E.

AU - Varley, Jenny

AU - Bignon, Yves Jean

AU - Scherneck, Siegfried

AU - Sigurdardottir, Valgerdur

AU - Lidereau, Rosette

AU - Eyfjord, Jorunn

AU - Beckmann, Matthias Wilhelm

AU - Winqvist, Robert

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N2 - 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 (CI 1.2-2.8, P = 0.010) and 2.1 (CI 1.4-3.0, 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.

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