Skip to main content

Genetic instability in the RAD51 and BRCA1 regions in breast cancer

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

References

  1. Nathanson, K.L. and Weber, B.L. "Other" breast cancer susceptibility genes: searching for more holy grail. Hum. Mol. Genet. 10 (2001) 715–720.

    Article  CAS  PubMed  Google Scholar 

  2. Welcsh, P.L. and King, M.C. BRCA1 and BRCA2 and the genetics of breast and ovarian cancer. Hum. Mol. Genet. 10 (2001) 705–713.

    Article  CAS  PubMed  Google Scholar 

  3. Auranen, A., Song, H., Waterfall, C., Dicioccio, R.A., Kuschel, B., Kjaer, S.K., Hogdall, E., Hogdall, C., Stratton, J., Whittemore, A.S., Easton, D.F., Ponder, B.A., Novik, K.L., Dunning, A.M., Gayther, S. and Pharoah, P.D. Polymorphisms in DNA repair genes and epithelial ovarian cancer risk. Int. J. Cancer 117 (2005) 611–618.

    Article  CAS  PubMed  Google Scholar 

  4. Cousineau, I., Abaji C. and Belmaaza, A. BRCA1 regulates RAD51 function in response to DNA damage and suppresses spontaneous sister chromatid replication slippage: implications for sister chromatid cohesion, genome stability, and carcinogenesis. Cancer Res. 65 (2005) 11384–11391.

    Article  CAS  PubMed  Google Scholar 

  5. Schmutte, C., Tombline, G., Rhiem, K., Sadoff, M.M., Schmutzler, R., von Deimling, A. and Fishel, R. Characterization of the human Rad51 genomic locus and examination of tumors with 15q14-15 loss of heterozygosity (LOH). Cancer Res. 59 (1999) 4564–4569.

    CAS  PubMed  Google Scholar 

  6. Shinohara, A., Ogawa, H., Matsuda, Y., Ushio, N., Ikoe, K. and Ogawa, T. Cloning of human, mouse and fission yeast recombination genes homologous to RAD51 and recA. Nature Genet. 4 (1993) 239–243.

    Article  CAS  PubMed  Google Scholar 

  7. Takahashi, E., Matsuda, Y., Hori, T., Yasuda, N., Tsuji, S., Mori, M., Yoshimura, Y., Yamamoto, A., Morita, T. and Matsushiro, A. Chromosome mapping of the human (RECA) and mouse (Reca) homologs of the yeast RAD51 and Escherichia coli recA genes to human (15q15.1) and mouse (2F1) chromosomes by direct R-banding fluorescence in situ hybridization. Genomics 19 (1994) 376–378.

    Article  CAS  PubMed  Google Scholar 

  8. Benson, F.E., Stasiak, A. and West S.C. Purification and characterization of the human Rad51 protein, an analogue of E. coli RecA. EMBO J. 13 (1994) 5764–5771.

    CAS  PubMed  Google Scholar 

  9. Baumann, P., Benson, F.E. and West, S.C. Human Rad51 protein promotes ATP-dependent homologous pairing and strand transfer reactions in vitro. Cell 87 (1996) 757–766.

    Article  CAS  PubMed  Google Scholar 

  10. Gupta, R., Bazemore, L.R., Golub, E.I. and Radding, C.M. Activities of human recombination protein Rad51. Proc Natl. Acad. Sci. USA 94 (1997) 463–468.

    Google Scholar 

  11. Yamamoto, A., Taki, T., Yagi, H., Habu, T., Yoshida, K., Yoshimura, Y., Yamamoto, K., Matsushiro, A., Nishimune, Y. and Morita, T. Cell cycledependent expression of the mouse Rad51 gene in proliferating cells. Mol. Gen. Genet. 251 (1996) 1–12.

    CAS  PubMed  Google Scholar 

  12. Chen, F., Nastasi, A., Shen, Z., Brenneman, M., Crissman, H. and Chen, D.J. Cell cycle-dependent protein expression of mammalian homologs of yeast DNA double-strand break repair genes Rad51 and Rad52. Mutat. Res. 384 (1997) 205–211.

    CAS  PubMed  Google Scholar 

  13. Xia, S.J., Shammas, M.A. and Shmookler Reis, R.J. Elevated recombination in immortal human cells is mediated by HsRAD51 recombinase. Mol. Cell. Biol. 17 (1997) 7151–7158.

    CAS  PubMed  Google Scholar 

  14. Shen, Z., Cloud, K.G., Chen, D.J. and Park, M.S. Specific interactions between the human RAD51 and RAD52 proteins. J. Biol. Chem. 271 (1996) 148–152.

    Article  CAS  PubMed  Google Scholar 

  15. Sturzbecher, H.W., Donzelmann, B., Henning, W., Knippschild, U. and Buchhop, S. p53 is linked directly to homologous recombination processes via RAD51/RecA protein interaction. EMBO J. 15 (1996) 1992–2002.

    CAS  PubMed  Google Scholar 

  16. Buchhop, S., Gibson, M.K., Wang, X.W., Wagner, P., Sturzbecher, H.W. and Harris, C.C. Interaction of p53 with the human Rad51 protein. Nucleic Acids Res. 25 (1997) 3868–3874.

    Article  CAS  PubMed  Google Scholar 

  17. Wong, A.K., Pero, R., Ormonde, P.A., Tavtigian, S.V. and Bartel, P.L. RAD51 interacts with the evolutionarily conserved BRC motifs in the human breast cancer susceptibility gene brca2. J. Biol. Chem. 272 (1997) 31941–31944.

    Article  CAS  PubMed  Google Scholar 

  18. Marmorstein, L.Y., Ouchi, T. and Aaronson, S.A. The BRCA2 gene product functionally interacts with p53 and RAD51. Proc. Natl. Acad. Sci. USA. 95 (1998) 13869–13874.

    Article  CAS  PubMed  Google Scholar 

  19. Scully, R. Chen, J., Plug, A., Xiao, Y., Weaver, D., Feunteun, J., Ashley, T. and Livingston, D.M. Association of BRCA1 with Rad51 in mitotic and meiotic cells. Cell 188 (1997) 265–275.

    Article  Google Scholar 

  20. Zhong, Q., Chen, C.F., Li, S., Chen, Y., Wang, C.C., Xiao, J., Chen, P.L., Sharp, Z.D. and Lee, W.H. Association of BRCA1 with the hRad50--hMre11-p95 complex and the DNA damage response. Science 285 (1999) 747–750.

    Article  CAS  PubMed  Google Scholar 

  21. Hall, J.M., Lee, M.K., Newman, B., Morrow, J.E., Anderson, L.A., Huey, B. and King, M.C. Linkage of early-onset familial breast cancer to chromosome 17q21. Science 250 (1990) 1684–1689.

    Article  CAS  PubMed  Google Scholar 

  22. Miki, Y., Swensen, J., Shattuck-Eidens, D., Futreal, P.A., Harshman, K., Tavtigian, S., Liu, Q., Cochran, C., Bennett, L.M., Ding, W. Bell, R., Rosenthal, J., Hussey, C., Tran, T., McClure, M., Frye, C., Hattier, T., Phelps, R., Haugen-Strano, A., Katcher, H., Yakumo, K., Gholami, Z., Shaffer, D., Stone, S., Bayer, S., Wray, C., Bogden, R., Dayananth, P., Ward, J., Tonin, P., Narod, S., Bristow, P.K., Norris, F.H. Helvering, L., Morrison, P., Rosteck, P., Lai, M., Barrett, J.C., Lewis, C., Neuhausen, S., Cannon-Albright, L., Goldgar, D., Wiseman, R., Kamb, A., Skolnick, M.H. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266 (1994) 66–71.

    Article  CAS  PubMed  Google Scholar 

  23. Monteiro, A.N., August, A. and Hanafusa, H. Evidence for a trans-criptional activation function of BRCA1 C-terminal region. Proc. Natl. Acad. Sci. USA 93 (1996) 13595–13599.

    Article  CAS  PubMed  Google Scholar 

  24. Huyton, T., Bates, P.A., Zhang, X., Sternberg, M.J. and Freemont, P.S. The BRCA1 C-terminal domain: structure and function. Mutat. Res. 460 (2000) 319–332.

    CAS  PubMed  Google Scholar 

  25. Koonin, E.V., Altschul, S.F. and Bork, P. BRCA1 protein products … Functional motifs…. Nat. Genet. 13 (1996) 266–268.

    Article  CAS  PubMed  Google Scholar 

  26. Bork, P., Hofmann, K., Bucher, P., Neuwald, A.F., Altschul, S.F.and Koonin, E.V. A superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint proteins. FASEB J. 11 (1997) 68–76.

    CAS  PubMed  Google Scholar 

  27. Larson, J.S., Tonkinson, J.L. and Lai, M.T. A BRCA1 mutant alters G2-M cell cycle control in human mammary epithelial cells. Cancer Res. 57 (1997) 3351–3355.

    CAS  PubMed  Google Scholar 

  28. Moynahan, M.E., Chiu, J.W., Koller, B.H. and Jasin, M. Brca1 controls homology-directed DNA repair. Mol. Cell 4 (1999) 511–518.

    Article  CAS  PubMed  Google Scholar 

  29. Scully, R. and Livingston, D.M. In search of the tumour-suppressor functions of BRCA1 and BRCA2. Nature 408 (2000) 429–432.

    Article  CAS  PubMed  Google Scholar 

  30. Wang, Y., Cortez, D., Yazdi, P., Neff, N., Elledge, S.J. and Qin, J. BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Genes Dev. 14 (2000) 927–939.

    CAS  PubMed  Google Scholar 

  31. Cantor, S.B., Bell, D.W., Ganesan, S., Kass, E.M., Drapkin, R., Grossman, S., Wahrer, D.C., Sgroi, D.C., Lane, W.S., Haber, D.A. and Livingston, D.M. BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function. Cell 105 (2001) 149–160.

    Article  CAS  PubMed  Google Scholar 

  32. Garcia-Higuera, I., Taniguchi, T., Ganesan, S., Meyn, M.S., Timmers, C., Hejna, J., Grompe, M. and D’Andrea, A.D. Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway. Mol. Cell 7 (2001) 249–262.

    Article  CAS  PubMed  Google Scholar 

  33. Franchitto, A. and Pichierri, P. Bloom’s syndrome protein is required for correct relocalization of RAD50/MRE11/NBS1 complex after replication fork arrest. J. Cell Biol. 157 (2002) 19–30.

    Article  CAS  PubMed  Google Scholar 

  34. Liu, Y. and West, S.C. Distinct functions of BRCA1 and BRCA2 in doublestrand break repair. Breast Cancer Res. 4 (2002) 9–13.

    Article  CAS  PubMed  Google Scholar 

  35. Manke, I.A., Lowery, D.M., Nguyen, A. and Yaffe, M.B. BRCT repeats as phosphopeptide-binding modules involved in protein targeting. Science 302 (2003) 636–639.

    Article  CAS  PubMed  Google Scholar 

  36. Yu, X., Chini, C.C., He, M., Mer, G. and Chen, J. The BRCT domain is a phospho-protein binding domain. Science 302 (2003) 639–642.

    Article  CAS  PubMed  Google Scholar 

  37. Beckmann, M.W., Schnurch, H.G., Bodden-Heidrich, R., Mosny, D.S., Crombach, G., Nitz, U., Achnoula, M. and Bender, H.G. Early cancer detection programmes for women at high risk for breast and ovarian cancer: a proposal of practical guidelines. Eur. J. Cancer Prev. 5 (1996) 468–475.

    CAS  PubMed  Google Scholar 

  38. Hanby, A.M., Kelsell, D.P., Potts, H.W., Gillett, C.E., Bishop, D.T., Spurr, N.K. and Barnes, D.M. Association between loss of heterozygosity of BRCA1 and BRCA2 and morphological attributes of sporadic breast cancer. Int. J. Cancer 88 (2000) 204–208.

    Article  CAS  PubMed  Google Scholar 

  39. Wright, D.K. and Manson, M.M. Sample preparation from paraffinembedded tissues. in: PCR Protocols: A Guide to Methods and Application, (Innis, M.A., Ed.), Academic Press, Inc., 1990, 153–156.

  40. Rolfs, A., Schuller, I., Finckh, U. and Weber-Rolfs, J. PCR: clinical diagnostic and research. Springer Lab., 1992, 81–84.

  41. Cawkwell, L., Bell, S.M., Lewis, F.A., Dixon, M.F., Taylor, G.R. and Quirke, P. Rapid detection of allele loss in colorectal tumours using microsatellites and fluorescent DNA technology. Br. J. Cancer 67 (1993) 1262–1267.

    CAS  PubMed  Google Scholar 

  42. Simpson, A.J. The natural somatic mutation frequency and human carcinogenesis. Adv. Cancer Res. 71 (1997) 209–240.

    CAS  PubMed  Article  Google Scholar 

  43. Thiagalingam, S., Foy, R.L., Cheng, K., Lee, H.J., Thiagalingam, A. and Ponte, J.F. Loss of heterozygosity as a predictor to map tumor suppressor genes in cancer: molecular basis of its occurrence. Curr. Opin. Oncol. 14 (2002) 65–72.

    Article  CAS  PubMed  Google Scholar 

  44. Chen, J.J., Silver, D., Cantor, S., Livingston, D.M. and Scully, R. BRCA1, BRCA2, and Rad51 operate in a common DNA damage response pathway. Cancer Res. 59 (1999) 1752s–1756s.

    CAS  PubMed  Google Scholar 

  45. Dasika, G.K., Lin, S.C., Zhao, S,, Sung, P., Tomkinson, A. and Lee, E,Y. DNA damage-induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis. Oncogene 18 (1999) 7883–7899.

    Article  CAS  PubMed  Google Scholar 

  46. Wang, W.W., Spurdle, A.B., Kolachana, P., Bove, B., Modan, B., Ebbers, S.M., Suthers, G., Tucker, M.A., Kaufman, D.J., Doody, M.M., Tarone, R.E., Daly, M., Levavi, H., Pierce, H., Chetrit, A., Yechezkel, G.H., Chenevix-Trench, G., Offit, K., Godwin, A.K. and Struewing, J.P. A single nucleotide polymorphism in the 5′ untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers. Cancer Epidemiol. Biomarkers Prev. 10 (2001) 955–960.

    CAS  PubMed  Google Scholar 

  47. Levy-Lahad E, Lahad, A., Eisenberg, S., Dagan, E., Paperna, T., Kasinetz, L., Catane, R., Kaufman, B., Beller, U., Renbaum, P. and Gershoni-Baruch, R. A single nucleotide polymorphism in the RAD51 gene modifies cancer risk in BRCA2 but not BRCA1 carriers. Proc. Natl. Acad. Sci. USA. 98 (2001) 3232–3236.

    Article  CAS  PubMed  Google Scholar 

  48. Goode, E.L., Dunning, A.M., Kuschel, B., Healey, C.S., Day, N.E., Ponder, B.A., Easton, D.F. and Pharoah, P.P. Effect of germ-line genetic variation on breast cancer survival in a population-based study. Cancer Res. 62 (2002) 3052–3057.

    CAS  PubMed  Google Scholar 

  49. Błasiak, J., Przybyłowska, K., Czechowska, A., Zadrożzny, M., Pertyński, T., Rykała, J., Kołacińska, A., Morawiec, Z. and Drzewoski, J. Analysis of the G/C polymorphism in the 5′-untranslated region of the RAD51 gene in breast cancer. Acta Biochim. Pol. 50 (2003) 249–253.

    PubMed  Google Scholar 

  50. Romanowicz-Makowska, H., Smolarz, B. and Kulig, A. Germline BRCA1 mutations and G/C polymorphism in the 5′-untranslated region of the RAD51 gene in Polish women with breast cancer. Pol. J. Pathol. 56 (2005) 161–165.

    PubMed  Google Scholar 

  51. Jakubowska, A., Narod, S.A., Goldgar, D.E., Mierzejewski, M., Masojc, B., Nej, K., Huzarska, J., Byrski, T., Górski, B. and Lubiński, J. Breast cancer risk reduction associated with the RAD51 polymorphism among carriers of the BRCA1 5382insC mutation in Poland. Cancer Epidemiol. Biomarkers Prev. 12 (2003) 457–459.

    CAS  PubMed  Google Scholar 

  52. Seedhouse, C., Faulkner, R., Ashraf, N., Das-Gupta, E. and Russell, N. Polymorphisms in genes involved in homologous recombination repair interact to increase the risk of developing acute myeloid leukemia. Clin. Cancer Res. 10 (2004) 2675–2680.

    Article  CAS  PubMed  Google Scholar 

  53. Carling, T., Imanishi, Y., Gaz, R.D. and Arnold, A. RAD51 as a candidate parathyroid tumour suppressor gene on chromosome 15q: absence of somatic mutations. Clin. Endocrinol. (Oxf) 51 (1999) 403–407.

    Article  CAS  Google Scholar 

  54. Kato, M., Yano, K., Matsuo, F., Saito, H., Katagiri, T., Kurumizaka, H., Yoshimoto, M., Kasumi, F., Akiyama, F., Sakamoto, G., Nagawa, H., Nakamura, Y. and Miki, Y. Identification of Rad51 alteration in patients with bilateral breast cancer. J. Hum. Genet. 45 (2000) 133–137.

    Article  CAS  PubMed  Google Scholar 

  55. Wick, W., Petersen, I., Schmutzler, R.K., Wolfarth, B., Lenartz, D., Bierhoff, E., Hummerich, J., Muller, D.J., Stangl, A.P., Schramm, J., Wiestler, O.D. and von Deimling, A. Evidence for a novel tumor suppressor gene on chromosome 15 associated with progression to a metastatic stage in breast cancer. Oncogene 12 (1996) 973–978.

    CAS  PubMed  Google Scholar 

  56. Gonzalez, R., Silva, J.M., Dominguez, G., Garcia, J.M., Martinez, G., Vargas, J., Provencio, M., Espana, P. and Bonilla, F. Detection of loss of heterozygosity at RAD51, RAD52, RAD54 and BRCA1 and BRCA2 loci in breast cancer: pathological correlations. Br. J. Cancer 81 (1999) 503–509.

    Article  CAS  PubMed  Google Scholar 

  57. Shen, C.Y., Yu, J.C., Lo, Y.L., Kuo, C.H., Yue, C.T., Jou, Y.S., Huang, C.S., Lung, J.C. and Wu, C.W. Genome-wide search for loss of heterozygosity using laser capture microdissected tissue of breast carcinoma: an implication for mutator phenotype and breast cancer pathogenesis. Cancer Res. 60 (2000) 3884–3892.

    CAS  PubMed  Google Scholar 

  58. Balsara, B.R., Bell, D.W., Sonoda, G., De Rienzo, A., du Manoir, S., Jhanwar, S.C. and Testa, J.R. Comparative genomic hybridization and loss of heterozygosity analyses identify a common region of deletion at 15q11.1–15 in human malignant mesothelioma. Cancer Res. 59 (1999) 450–454.

    CAS  PubMed  Google Scholar 

  59. De Rienzo, A., Balsara, B.R., Apostolou, S., Jhanwar, S.C. and Testa, J.R. Loss of heterozygosity analysis defines a 3-cM region of 15q commonly deleted in human malignant mesothelioma. Oncogene 20 (2001) 6245–6249.

    Article  PubMed  CAS  Google Scholar 

  60. Natrajan, R., Louhelainen, J., Williams, S., Laye, J. and Knowles, M.A. High-resolution deletion mapping of 15q13.2-q21.1 in transitional cell carcinoma of the bladder. Cancer Res. 63 (2003) 7657–7662.

    CAS  PubMed  Google Scholar 

  61. Hanby, A.M., Kelsell, D.P., Potts, H.W., Gillett, C.E., Bishop, D.T., Spurr, N.K. and Barnes, D.M. Association between loss of heterozygosity of BRCA1 and BRCA2 and morphological attributes of sporadic breast cancer. Int. J. Cancer 88 (2000) 204–208.

    Article  CAS  PubMed  Google Scholar 

  62. Johnson, S.M., Shaw, J.A. and Walker, R.A. Sporadic breast cancer in young women: prevalence of loss of heterozygosity at p53, BRCA1 and BRCA2. Int. J. Cancer 98 (2002) 205–209.

    Article  CAS  PubMed  Google Scholar 

  63. Smith, S.A., Easton, D.F., Evans, D.G. and Ponder, B.A. Allele losses in the region 17q12-21 in familial breast and ovarian cancer involve the wild-type chromosome. Nat. Genet. 2 (1992) 128–131.

    Article  CAS  PubMed  Google Scholar 

  64. Garcia, J.M., Rodriguez, R., Dominguez, G., Silva, J.M., Provencio, M., Silva, J., Colmenarejo, A., Millan, I., Munoz, C., Salas, C., Coca, S., Espana, P. and Bonilla, F. Prognostic significance of the allelic loss of the BRCA1 gene in colorectal cancer. Gut 52 (2003) 1756–1763.

    Article  CAS  PubMed  Google Scholar 

  65. Silva, J.M., Gonzalez, R., Provencio, M., Dominguez, G., Garcia, J.M., Gallego, I., Palacios, J., Espana, P. and Bonilla, F. Loss of heterozygosity in BRCA1 and BRCA2 markers and high-grade malignancy in breast cancer. Breast Cancer Res. Treat. 53 (1999) 9–17.

    Article  CAS  PubMed  Google Scholar 

  66. Rio, P.G., Maurizis, J.C., Peffault de Latour, M., Bignon, Y.J. and Bernard-Gallon, D.J. Quantification of BRCA1 protein in sporadic breast carcinoma with or without loss of heterozygosity of the BRCA1 gene. Int. J. Cancer 80 (1999) 823–826.

    Article  CAS  PubMed  Google Scholar 

  67. Santos, S.C., Cavalli, L.R., Cavalli, I.J., Lima, R.S., Haddad, B.R. and Ribeiro, E.M. Loss of heterozygosity of the BRCA1 and FHIT genes in patients with sporadic breast cancer from Southern Brazil. J. Clin. Pathol. 57 (2004) 374–377.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wanda M. Krajewska.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2478/s11658-006-0063-x

Key words

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