Acta Neuropathologica

, Volume 119, Issue 3, pp 325–334 | Cite as

Heterozygous germ-line mutations in the NBN gene predispose to medulloblastoma in pediatric patients

  • Elżbieta Ciara
  • Dorota Piekutowska-Abramczuk
  • Ewa Popowska
  • Wiesława Grajkowska
  • Sławomir Barszcz
  • Danuta Perek
  • Bożenna Dembowska-Bagińska
  • Marta Perek-Polnik
  • Ewa Kowalewska
  • Aneta Czajńska
  • Małgorzata Syczewska
  • Kamila Czornak
  • Małgorzata Krajewska-Walasek
  • Marcin Roszkowski
  • Krystyna H. ChrzanowskaEmail author
Original Article


The NBN (NBS1) gene belongs to a group of double-strand break repair genes. Mutations in any of these genes cause genome instability syndromes and contribute to carcinogenesis. NBN gene mutations cause increased tumor risk in Nijmegen breakage syndrome (NBS) homozygotes as well as in NBN heterozygotes. NBS patients develop different types of malignancies; among solid tumors, medulloblastoma (MB), an embryonal tumor of the cerebellum, has been reported most frequently. The majority of medulloblastomas occur sporadically, some of them manifest within familial cancer syndromes. Several signaling pathways are known to be engaged in hereditary and sporadic MB. The aim of our study was to identify mutations in selected exons of the NBN gene and to determine the frequency of the most common NBN gene mutations in pediatric patients with different types of medulloblastoma. We screened a total of 104 patients with MB and identified 7 heterozygous carriers (6.7%) of two different germ-line mutations of NBN gene; all of them had classic MB. Our results indicate that heterozygous carriers of the germ-line NBN gene mutations (c.511A>G and c.657_661del5) may exhibit increased susceptibility to developing MB. The risk of medulloblastoma is estimated to be 3.0 (for c.511A>G) and 4.86 (for c.657_661del5) times higher than in the general Polish population (p < 0.05). These results suggest that heterozygous NBN germ-line mutations may contribute to the etiology of medulloblastoma.


NBN gene Germ-line mutations Medulloblastoma Cancer risk 



We are indebted to all of the patients and parents for their participation in this study. We would like to thank other collaborators from the Children’s Memorial Health Institute, Warsaw, i.e. the clinicians from the Department of Oncology: Agnieszka Brożyna, Iwona Daniluk, Monika Drogosiewicz, Iwona Filipek, Olga Rutynowska-Pronicka, Anna Wakulińska, and from the Department of Neurosurgery: Paweł Daszkiewicz, Krzysztof Drabik, Sławomir Przasnek, for collecting blood samples. We are also grateful to Mrs. Teresa Wojtasiak from the Department of Medical Genetics, CMHI, for excellent technical assistance. This study was supported by the Polish Committee for Scientific Research, Grant No. PBZ-KBN-090/P05/04-17 and the Children’s Memorial Health Institute, Grant No. S112/2009.

Conflict of interest statement

The authors declare no conflict of interest.


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Elżbieta Ciara
    • 1
  • Dorota Piekutowska-Abramczuk
    • 1
  • Ewa Popowska
    • 1
  • Wiesława Grajkowska
    • 2
  • Sławomir Barszcz
    • 3
  • Danuta Perek
    • 4
  • Bożenna Dembowska-Bagińska
    • 4
  • Marta Perek-Polnik
    • 4
  • Ewa Kowalewska
    • 4
  • Aneta Czajńska
    • 4
  • Małgorzata Syczewska
    • 5
  • Kamila Czornak
    • 1
  • Małgorzata Krajewska-Walasek
    • 1
  • Marcin Roszkowski
    • 3
  • Krystyna H. Chrzanowska
    • 1
    Email author
  1. 1.Department of Medical GeneticsThe Children’s Memorial Health InstituteWarsawPoland
  2. 2.Department of PathologyThe Children’s Memorial Health InstituteWarsawPoland
  3. 3.Department of NeurosurgeryThe Children’s Memorial Health InstituteWarsawPoland
  4. 4.Department of OncologyThe Children’s Memorial Health InstituteWarsawPoland
  5. 5.Department of Pediatric RehabilitationThe Children’s Memorial Health InstituteWarsawPoland

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