title: Loss of heterozygosity at 11q23.1 and survival in breast cancer: results of a large European study. Breast Cancer Somatic Genetics Consortium.
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.affiliation: Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo.
authors.forename: K
authors.initials: K
authors.lastname: Laake
authors.forename: V
authors.initials: V
authors.lastname: Launonen
authors.forename: D
authors.initials: D
authors.lastname: Niederacher
authors.forename: S
authors.initials: S
authors.lastname: Gudlaugsdottir
authors.forename: S
authors.initials: S
authors.lastname: Seitz
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authors.initials: P
authors.lastname: Rio
authors.forename: M H
authors.initials: MH
authors.lastname: Champème
authors.forename: I
authors.initials: I
authors.lastname: Bièche
authors.forename: D
authors.initials: D
authors.lastname: Birnbaum
authors.forename: G
authors.initials: G
authors.lastname: White
authors.forename: M
authors.initials: M
authors.lastname: Sztan
authors.forename: N
authors.initials: N
authors.lastname: Sever
authors.forename: S
authors.initials: S
authors.lastname: Plummer
authors.forename: A
authors.initials: A
authors.lastname: Osorio
authors.forename: A
authors.initials: A
authors.lastname: Broeks
authors.forename: P
authors.initials: P
authors.lastname: Huusko
authors.forename: N
authors.initials: N
authors.lastname: Spurr
authors.forename: A
authors.initials: A
authors.lastname: Borg
authors.forename: A M
authors.initials: AM
authors.lastname: Cleton-Jansen
authors.forename: L
authors.initials: L
authors.lastname: van't Veer
authors.forename: J
authors.initials: J
authors.lastname: Benitez
authors.forename: G
authors.initials: G
authors.lastname: Casey
authors.forename: B
authors.initials: B
authors.lastname: Peterlin
authors.forename: E
authors.initials: E
authors.lastname: Olah
authors.forename: A L
authors.initials: AL
authors.lastname: Børresen-Dale
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008875:Middle Aged; D015996:Survival Rate; D014178:Translocation, Genetic
chemical_list: D005819:Genetic Markers