Advertisement

Breast Cancer Research and Treatment

, Volume 133, Issue 2, pp 809–811 | Cite as

Germline mutations 657del5 and 643C>T (R215W) in NBN are not likely to be associated with increased risk of breast cancer in Czech women

  • Martin Mateju
  • Petra Kleiblova
  • Zdenek Kleibl
  • Marketa Janatova
  • Jana Soukupova
  • Ivana Ticha
  • Jan Novotny
  • Petr PohlreichEmail author
Letter to the Editor

To the Editor,

The NBN (formerly NBS1) gene (OMIM*602667) is located on chromosome 8q21 and encodes a 754-amino acid protein known as nibrin. Nibrin is a component of the MRE11/RAD50/NBN (MRN) complex and is involved in the DNA double-strand break repair, telomere maintenance, and cell-cycle checkpoint control. Individuals homozygous for deleterious mutations in NBN develop an autosomal recessive disorder, Nijmegen breakage syndrome (NBS; #251260), characterized by microcephaly, growth retardation, immunodeficiency, hypersensitivity to X-irradiation, and increased risk of lymphoid malignancies [1]. About 90 % of NBS patients carry the homozygous mutation 657del5 (c.657_661delACAAA) affecting exon 6 of the NBN gene that has been predominantly identified in Slavic populations [2, 3]. Another potentially deleterious NBNalteration, the missense substitution c.643C>T (p.R215W), is also located in exon 6 and has been described in two severely affected NBS siblings who were compound...

Keywords

Breast Cancer Breast Cancer Patient High Resolution Melting Male Breast Cancer Nijmegen Breakage Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We would like to thank Stanislav Kormunda for the statistical analyses and Marie Epsteinova for her excellent technical assistance. The project was supported by the Internal Grant Agency of the Ministry of Health of the Czech Republic, Grant No. NS 10304-3/2009.

Conflict of interest

None.

References

  1. 1.
    Varon R, Vissinga C, Platzer M, Cerosaletti KM, Chrzanowska KH, Saar K, Beckmann G, Seemanová E, Cooper PR, Nowak NJ, Stumm M, Weemaes CM, Gatti RA, Wilson RK, Digweed M, Rosenthal A, Sperling K, Concannon P, Reis A (1998) Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell 93:467–476PubMedCrossRefGoogle Scholar
  2. 2.
    Varon R, Seemanova E, Chrzanowska K, Hnateyko O, Piekutowska-Abramczuk D, Krajewska-Walasek M, Sykut-Cegielska J, Sperling K, Reis A (2000) Clinical ascertainment of Nijmegen breakage syndrome (NBS) and prevalence of the major mutation, 657del5, in three Slav populations. Eur J Hum Genet 8:900–902PubMedCrossRefGoogle Scholar
  3. 3.
    Maurer MH, Hoffmann K, Sperling K, Varon R (2010) High prevalence of the NBN gene mutation c.657–661del5 in Southeast Germany. J Appl Genet 51:211–214PubMedCrossRefGoogle Scholar
  4. 4.
    di Masi A, Antoccia A (2008) NBS1 heterozygosity and cancer risk. Curr Genomics 9:275–281PubMedCrossRefGoogle Scholar
  5. 5.
    Gorski B, Debniak T, Masojc B, Mierzejewski M, Medrek K, Cybulski C, Jakubowska A, Kurzawski G, Chosia M, Scott R, Lubinski J (2003) Germline 657del5 mutation in the NBS1 gene in breast cancer patients. Int J Cancer 106:379–381PubMedCrossRefGoogle Scholar
  6. 6.
    Steffen J, Nowakowska D, Niwinska A, Czapczak D, Kluska A, Piatkowska M, Wisniewska A, Paszko Z (2006) Germline mutations 657del5 of the NBS1 gene contribute significantly to the incidence of breast cancer in Central Poland. Int J Cancer 119:47–472Google Scholar
  7. 7.
    Bogdanova N, Feshchenko S, Schurmann P, Waltes R, Wieland B, Hillemanns P, Rogov YI, Dammann O, Bremer M, Karstens JH, Sohn C, Varon R, Dörk T (2008) Nijmegen breakage syndrome mutations and risk of breast cancer. Int J Cancer 122:802–806PubMedCrossRefGoogle Scholar
  8. 8.
    Carlomagno F, Chang-Claude J, Dunning AM, Ponder BA (1999) Determination of the frequency of the common 657del5 Nijmegen breakage syndrome mutation in the German population: no association with risk of breast cancer. Genes Chromosomes Cancer 25:393–395PubMedCrossRefGoogle Scholar
  9. 9.
    He M, Di GH, Cao AY, Hu Z, Jin W, Shen ZZ, Shao ZM (2011) RAD50 and NBS1 are not likely to be susceptibility genes in Chinese non-BRCA1/2 hereditary breast cancer. Breast Cancer Res Treat. doi: 10.1007/s10549-011-1700-2 Google Scholar
  10. 10.
    Pohlreich P, Zikan M, Stribrna J, Kleibl Z, Janatova M, Kotlas J, Zidovska J, Novotny J, Petruzelka L, Szabo C, Matous B (2005) High proportion of recurrent germline mutations in the BRCA1 gene in breast and ovarian cancer patients from the Prague area. Breast Cancer Res 7:R728–R736PubMedCrossRefGoogle Scholar
  11. 11.
    Kleibl Z, Havranek O, Novotny J, Kleiblova P, Soucek P, Pohlreich P (2008) Analysis of CHEK2 FHA domain in Czech patients with sporadic breast cancer revealed distinct rare genetic alterations. Breast Cancer Res Treat 112:159–164PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Martin Mateju
    • 1
  • Petra Kleiblova
    • 2
  • Zdenek Kleibl
    • 2
  • Marketa Janatova
    • 2
  • Jana Soukupova
    • 2
  • Ivana Ticha
    • 2
    • 3
  • Jan Novotny
    • 1
  • Petr Pohlreich
    • 2
    Email author
  1. 1.Department of OncologyFirst Faculty of Medicine, Charles University in Prague and General University Hospital in PraguePragueCzech Republic
  2. 2.Institute of Biochemistry and Experimental Oncology, First Faculty of MedicineCharles University in PraguePrague 2Czech Republic
  3. 3.Division of Clinical Sciences, Department of Clinical and Experimental Medicine, Faculty of Health SciencesLinköping UniversityLinköpingSweden

Personalised recommendations