title: Mutations in the Nijmegen breakage syndrome gene in medulloblastomas.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  We provide evidence of medulloblastomas characterized by NBS1 mutations typically associated with mutational inactivation of the TP53 gene.
authors.affiliation: IARC, Lyon, France.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Michael A
authors.initials: MA
authors.lastname: Grotzer
authors.forename: Takuya
authors.initials: T
authors.lastname: Watanabe
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Hewer
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.forename: Stefan
authors.initials: S
authors.lastname: Rutkowski
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ohgaki
mesh_terms: D000293:Adolescent; D017398:Alternative Splicing; D018797:Cell Cycle Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D016158:Genes, p53; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000235:genetics*; D009154:Mutation; D049932:Nijmegen Breakage Syndrome / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins