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01.03.2010 | Original Article

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

verfasst von: 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. Chrzanowska

Erschienen in: Acta Neuropathologica | Ausgabe 3/2010

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Abstract

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.

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Titel: Heterozygous germ-line mutations in the NBN gene predispose to medulloblastoma in pediatric patients
verfasst von: 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. Chrzanowska
Publikationsdatum: 01.03.2010
Verlag: Springer-Verlag
Erschienen in: Acta Neuropathologica / Ausgabe 3/2010
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-009-0608-y

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