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 J.; Osorio, Ana; Broeks, Annegien; Huusko, Pia; Spurr, Nigel K.; Borg, Åke; Cleton‐Jansen, Anne‐Marie; Veer, Laura van’t; Benı́tez, Javier; Casey, Graham; Peterlin, Borut; Olàh, Edith; Varley, Jenny; Bignon, Yves‐Jean; Scherneck, Siegfried; Sigurðardóttir, Valgerður; Lidereau, Rosette; Eyfjörd, Jórunn E.; Beckmann, Matthias W.; Winqvist, Robert; Skovlund, Eva; Børresen‐Dale, Anne‐Lise

doi:10.1002/(sici)1098-2264(199907)25:3<212::aid-gcc3>3.3.co;2-7

Cited by 9 publications

(13 citation statements)

References 18 publications

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“…It may involve subtle effects on genes neighbouring the translocation. Both 22q11 and 11q23 have been suspected of harbouring breast cancer genes, since they sometimes display LOH in tumors (Devilee et al 1991;Laake et al 1999;Larsson et al 1990;Lindblom et al 1993). Further work needs to be done in the area of gene identification in the t(11;22) translocation flanking regions of the breakpoint on both 22q11 and 11q23.…”

Section: Discussionmentioning

confidence: 99%

“…Carriers of the constitutional translocation t(11;22)(q23;q11) have been reported as having a predisposition to breast cancer (Lindblom et al 1994). It is interesting to note that 11q23 and 22q often show loss of heterozygosity (LOH) in sporadic and familial breast cancers (Devilee et al 1991;Laake et al 1999;Larsson et al 1990;Lindblom et al 1993); this suggests the existence of a gene(s) predisposing to breast cancer in these regions. Analysis of the gene content in these areas may shed light on the pathogenesis of breast cancer.…”

Section: Introductionmentioning

confidence: 99%

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Fine mapping of the constitutional translocation t(11;22)(q23;q11)

Tapia-Páez

OʼBrien²,

Kost‐Alimova

et al. 2000

Hum Genet

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Translocation t(11;22)(q23;q11) is the most common constitutional reciprocal translocation in man. Balanced carriers are phenotypically normal, except for decreased fertility, an increased spontaneous abortion rate and a possible predisposition to breast cancer in some families. Here, we report the high resolution mapping of the t(11;22)(q23;q11) breakpoint. We have localised the breakpoint, by using fluorescence in situ hybidisation (FISH) walking, to a region between D11S1340 and WI-8564 on chromosome 11, and D22S134 and D22S264 on chromosome 22. We report the isolation of a bacterial artificial chromosome (BAC) clone spanning the breakpoint in 11q23. We have narrowed down the breakpoint to an 80-kb sequenced region on chromosome 11 and FISH analysis has revealed a variation of the breakpoint position between patients. In 22q11, we have sequenced two BACs (BAC2280L11 and BAC41C4) apparently mapping to the region; these contain low copy repeats (LCRs). Southern blot analysis with probes from BAC2280L11 has revealed different patterns between normal controls and translocation carriers, indicating that sequences similar/identical to these probes flank the translocation breakpoint. The occurrence of LCRs has previously been associated with genomic instability and "unclonable" regions. Hence, the presence of such repeats renders standard translocation breakpoint cloning techniques ineffective. Thus, we have used high resolution fiber-FISH to study this region in normal and translocation cases by using probes from 22q11, LCRs and 11q23. We demonstrate that the LCR containing the gap in 22q11 is probably substantially larger than the previous estimates of 100 kb. Using fiber-FISH, we have localised the breakpoint in 22q11 to approximately 20-40 kb from the centromeric border of the LCR (i.e. the telomeric end of AC006547) and have confirmed the breakpoint position on 11q23.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fine mapping of the constitutional translocation t(11;22)(q23;q11)

Tapia-Páez

OʼBrien²,

Kost‐Alimova

et al. 2000

Hum Genet

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“…The ataxia telangiectasia-mutated (ATM) gene located on chromosome 11q23, the region which is frequently involved in chromosomal losses in breast cancer, is composed of 66 exons and codes for a 13-kb mRNA and plays an important role in double-stranded DNA break signaling and cell-cycle checkpoints [2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Importance of ATM gene as a susceptible trait: predisposition role of D1853N polymorphism in breast cancer

et al. 2010

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The involvement of ATM gene and specifically, the important role of D1853N polymorphism, as a three-hit hypothesis has been previously reported in an Iranian proband affected with brain tumor and this polymorphism could be screened in her relatives as well. The aim of present study was to investigate the involvement of D1853N polymorphism as a predisposition factor in 129 Iranian patients affected with primary breast cancer and 248 sex- and age-matched healthy controls. Mutant allele-specific PCR amplification (MASA) assay was performed to analyze the D1853N polymorphism in the ATM gene. The frequency of D1853N polymorphism in cases, internal and external controls was 31.0% (40/129), 26.9% (28/104) and 12.5% (18/144), respectively. The frequency of D1853N in total control groups, including normal external control and pedigree internal control, was 18.6% (46/248). The odds ratio was calculated with the logistic regression test, with an estimated relative risk of 2.579 (P=0.005). The significant difference was observed between the patient-carriers of this alteration and external controls (P=0.001). The number of controls harboring D1853N polymorphism was higher in internal control compared to external controls, and the difference was statistically significant (P=0.004). The significant difference was observed between the patient-carriers and external controls and could be considered as a predisposing and diagnostic marker in the population and specifically in the cancer-prone pedigrees.

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“…This is particu- larly true in breast tumors, whereas patterns of deletion are often very complex. 14,18,19 The deletions observed in this series of IBC involved the entire chromosome arms in most cases, notably at 6p, 8p and 11q. No authentic TSG has yet been detected on 8p or 6p.…”

Section: Discussionmentioning

confidence: 71%

“…It has rarely been linked to clinical or histologic features of breast cancer and no somatic mutation of the remaining allele has been found. 19 However, heterozygous ATM carriers may be at a higher risk of developing breast cancer. 22 Moreover, the role of ATM in doublestrand DNA break repair and genomic instability makes it a good candidate for breast tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Evidence of chromosome regions and gene involvement in inflammatory breast cancer

Lerebours¹,

Bertheau²,

Bièche³

et al. 2002

Intl Journal of Cancer

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Inflammatory breast cancer (IBC) is a rare but particularly aggressive form of primary breast cancer. In contrast to noninflammatory breast cancer (non IBC), the molecular alterations underlying IBC are poorly known. We postulated that the kind and frequency of these alterations might differ between IBC and non IBC and account for its particular aggressiveness. We investigated allelic losses associated with primary breast cancer (on chromosome arms 1p, 3p, 6p, 6q, 7q, 8p, 9p, 11p, 11q, 16q, 17p and 17q) by analyzing 71 microsatellite markers in 66 cases of IBC. Loss of heterozygosity (LOH) was frequent, with a mean fractional allelic loss (FAL) index of 52%. Relative to published data on non IBC, allelic loss was particularly frequent at 3p21-p14, 6p, 8p22, 11q, 13q14 and 17q21, suggesting the presence of genes that are markedly altered in IBC. In contrast, the DNA amplification levels of ERBB2, MYC and CCND1, as measured by real-time quantitative PCR, did not differ between IBC and non IBC. Key words: inflammatory breast cancer; LOH; tumor suppressor genesInflammatory breast cancer (IBC), which accounts for less than 5% of all diagnosed breast cancers, is a unique clinical diagnosis. It requires the presence of rapidly progressing signs such as localized or generalized induration, redness and edema of the breast. Its extremely high metastastic potential makes IBC the most severe form of primary breast tumor. 1 Very little is known of the biologic mechanisms underlying IBC, for several reasons. First, IBC is rare. Second, tumor samples are difficult to obtain, as IBC does not qualify for initial surgery. Third, because of its similar outcome and treatment, IBC is rarely studied separately from other forms of locally advanced breast cancer (LABC), despite differences in incidence, clinical presentation and histology. IBC is more frequently estrogen receptor (ER) negative and may have higher proliferation rates than non IBC, including other forms of LABC. 2 Some authors have described more amplification and/or overexpression of the ERBB2 and EGFR oncogenes and more p53 protein overexpression in IBC than in noninflammatory breast cancer (non IBC). 3-5 Other oncogenes and tumor suppressor genes (TSGs) are likely to be involved in IBC. 6 Recurrent loss of heterozygosity (LOH) at specific loci is frequent in breast cancer and might point to TSGs with roles in breast carcinogenesis. LOH has not previously been studied in IBC.We postulated that distinct genetic features might explain some of the clinical, histologic and prognostic disparities between IBC and non IBC. We screened a series of 66 IBC for LOH/allelic imbalance (AI) on some of the most frequently deleted chromosome arms in breast tumors (1p, 3p, 6p, 6q, 7q, 8p, 9p, 11p, 11q, 13q, 16q, 17p and 17q), by using multiplex PCR (MPCR) and 71 polymorphic markers. Frequencies of LOH in IBC were compared with median frequencies at the same loci in non IBC, as deduced from published data. Because of their highest frequencies of amplification in primary breast tumors,...

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Loss of heterozygosity at 11q23.1 and survival in breast cancer: Results of a large European study

Cited by 9 publications

References 18 publications

Fine mapping of the constitutional translocation t(11;22)(q23;q11)

Fine mapping of the constitutional translocation t(11;22)(q23;q11)

Importance of ATM gene as a susceptible trait: predisposition role of D1853N polymorphism in breast cancer

Evidence of chromosome regions and gene involvement in inflammatory breast cancer

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