Mutations in the Nijmegen breakage syndrome gene in medulloblastomas.

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Version: Final published version
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Serval ID
serval:BIB_4AD5082F1092
Type
Article: article from journal or magazin.
Collection
Publications
Title
Mutations in the Nijmegen breakage syndrome gene in medulloblastomas.
Journal
Clinical cancer research
Author(s)
Huang J., Grotzer M.A., Watanabe T., Hewer E., Pietsch T., Rutkowski S., Ohgaki H.
ISSN
1078-0432 (Print)
ISSN-L
1078-0432
Publication state
Published
Issued date
01/07/2008
Peer-reviewed
Oui
Volume
14
Number
13
Pages
4053-4058
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Cerebellar medulloblastoma is a highly malignant, invasive embryonal tumor with preferential manifestation in children. Nijmegen breakage syndrome (NBS) with NBS1 germ-line mutations is a rare autosomal recessive disease with clinical features that include microcephaly, mental and growth retardation, immunodeficiency, increased radiosensitivity, and predisposition to cancer. There may be functional interactions between NBS1 and the TP53 pathways. The objective of the present study is to assess whether NBS1 mutations play a role in the pathogenesis of sporadic medulloblastomas.
Forty-two cases of medulloblastomas were screened for mutations in the NBS1 gene (all 16 exons) and the TP53 gene (exons 5-8) by single-stranded conformational polymorphism followed by direct DNA sequencing.
Seven of 42 (17%) medulloblastomas carried a total of 15 NBS1 mutations. Of these, 10 were missense point mutations and 5 were intronic splicing mutations. None of these were reported previously as germ-line mutations in NBS patients. No NBS1 mutations were detected in peritumoral brain tissues available in two patients. Of 5 medulloblastomas with TP53 mutations, 4 (80%) contained NBS1 mutations, and there was a significant association between TP53 mutations and NBS1 mutations (P = 0.001).
We provide evidence of medulloblastomas characterized by NBS1 mutations typically associated with mutational inactivation of the TP53 gene.
Keywords
Adolescent, Alternative Splicing, Cell Cycle Proteins/genetics, Child, Child, Preschool, DNA Mutational Analysis, Female, Genes, p53, Humans, Infant, Male, Medulloblastoma/genetics, Mutation, Nijmegen Breakage Syndrome/genetics, Nuclear Proteins/genetics, Sequence Analysis, DNA
Pubmed
Web of science
Open Access
Yes
Create date
31/08/2020 12:02
Last modification date
10/11/2020 6:26
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