Abstract for presentation at 11th International Congress of Human Genetics

Molecular variants of the NBS1 gene in primary pediatric brain tumors

  • Krystyna Chrzanowska, Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland
  • Dr Elzbieta Ciara, Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland
  • Dr Ewa Popowska, Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland
  • Dr Dorota Piekutowska-Abramczuk, Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland
  • MD, PhD Wieslawa Grajkowska, Department of Medical Genetics, The Children’s Memorial Health Institute, Warsaw, Poland
  • MD, PhD Malgorzata Krajewska-Walasek, Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland
  • MD, PhD Danuta Perek, Department of Medical Genetics, The Children’s Memorial Health Institute, Warsaw, Poland
  • MD, PhD Marcin Roszkowski, Department of Medical Genetics, The Children’s Memorial Health Institute, Warsaw, Poland

    • Nijmegen breakage syndrome (NBS) is a human autosomal recessive cancer-predisposing disease with defects in DNA repair. Approximately 40-50% of patients with NBS develop malignancy under the age of 15 years, of which 5-10% is solid tumor. Among the latter a few cases of medulloblastoma, the most frequent and most aggressive childhood brain tumor, have been reported. In addition, several studies suggest strongly that NBS1 heterozygosity may be associated with elevated risk of some cancers.
    To investigate the potential role of the NBS1 gene in the pathogenesis of primary pediatric brain tumors, the panel of tumor DNA samples from 97 different sporadic cancers (including 45 cases of medulloblastoma) were screened for two the most common mutations, c.657del5 (p.fsX234) and c.643C>T (p.R215W), in NBS1 exon 6. In patients with medulloblastoma further six exons (3, 5, 7, 8, 10 and 13) of the NBS1 gene were analyzed. Molecular studies consisted of PCR, SSCP and sequencing analyses.
    In the group of 45 medulloblastoma cases two different mutations, c.511A>G (p.I171V) and c.657del5 (p.fsX234), on one allele of the NBS1 gene were identified. Besides, five different polymorphic substitutions, three localized in the coding sequence and two in the intronic sequence, were detected. The frequency of NBS1 coding region polymorphisms in medulloblastoma patients is different from that observed in general population. Among the remaining 52 patients with other tumors one mutation, c.643C>T (p.R215W), in heterozygous state was observed
    Further studies are needed to evaluate the impact of the NBS1 gene heterozygosity in susceptibility to pediatric brain tumors.
    This study was supported by grant No PBZ-KBN-090/P05/04-17.

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