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Genetic instability in the RAD51 and BRCA1 regions in breast cancer

Cellular & Molecular Biology Letters volume 12, pages 192–205 (2007)Cite this article

Abstract

Breast cancer is the most prevalent cancer type in women. Accumulating evidence indicates that the fidelity of double-strand break repair in response to DNA damage is an important step in mammary neoplasias. The RAD51 and BRCA1 proteins are involved in the repair of double-strand DNA breaks by homologous recombination. In this study, we evaluated loss of heterozygosity (LOH) in the RAD51 and BRCA1 regions, and their association with breast cancer. The polymorphic markers D15S118, D15S214 and D15S1006 were the focus for RAD51, and D17S855 and D17S1323 for BRCA1. Genomic deletion detected by allelic loss varied according to the regions tested, and ranged from 29 to 46% of informative cases for the RAD51 region and from 38 to 42% of informative cases for the BRCA1 region. 25% of breast cancer cases displayed LOH for at least one studied marker in the RAD51 region exclusively. On the other hand, 31% of breast cancer cases manifested LOH for at least one microsatellite marker concomitantly in the RAD51 and BRCA1 regions. LOH in the RAD51 region, similarly as in the BRCA1 region, appeared to correlate with steroid receptor status. The obtained results indicate that alteration in the RAD51 region may contribute to the disturbances of DNA repair involving RAD51 and BRCA1 and thus enhance the risk of breast cancer development.

Abbreviations

AML:

acute myeloid leukemia

BACH1:

helicase

BRCA1 :

interacting protein C-terminal helicase 1 [Homo sapiens]

BRCA1 :

breast cancer susceptibility gene 1

BRCT:

BRCA C-terminus

LOH:

loss of heterozygosity

RecA:

RecA protein (Recombinase A)

MRE11:

meiotic recombination 11 homologue A

NBS1:

Nijmegen breakage syndrome 1 (nibrin, NBN)

p53:

tumor protein 53

RAD50 :

RAD50 homologue (Saccharomyces cerevisiae) [Homo sapiens]

RAD51 :

RAD51 homologue (RecA homologue, Escherichia coli) (Saccharomyces cerevisiae) [Homo sapiens]

RAD52 :

RAD52 homologue (Saccharomyces cerevisiae) [Homo sapiens]

t-AML:

therapy related AML

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Authors and Affiliations

  1. Department of Cytobiochemistry, University of Łódź, Banacha 12/16, 90-237, Łódź, Poland

    Maria Nowacka-Zawisza, Magdalena Bryś & Wanda M. Krajewska

  2. Department of Clinical Pathomorphology, Polish Mother’s Memorial Hospital, Research Institute, Rzgowska 281/289, 93-338 Łódź, Poland

    Hanna Romanowicz-Makowska & Andrzej Kulig

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  1. Maria Nowacka-Zawisza
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Nowacka-Zawisza, M., Bryś, M., Romanowicz-Makowska, H. et al. Genetic instability in the RAD51 and BRCA1 regions in breast cancer. Cell Mol Biol Lett 12, 192–205 (2007). https://doi.org/10.2478/s11658-006-0063-x

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Key words

  • RAD51
  • BRCA1
  • Loss of heterozygosity (LOH)
  • Breast cancer

Cellular & Molecular Biology Letters

ISSN: 1689-1392

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