title: Biomarkers for genome instability in some genetic disorders: a pilot study.
abstract: BACKGROUND
  The study of genome integrity in some genetic disorders has diagnostic and prognostic importance because of the evident relationship between genome instability and both DNA repair deficiencies and cancer predisposition.
  
  
  OBJECTIVE
  The objective was to compare the chromosomal and DNA damage responses in lymphocytes from patients with Nijmegen breakage syndrome (NBS), Fanconi anemia (FA) and Williams-Beuren syndrome (WBS) to find additional biomarkers of genome instability.
  
  
  METHODS
  The cytogenetic approaches were combined with the alkaline Comet assay to estimate genome integrity in cultured or freshly isolated and H(2)O(2)-treated lymphocytes.
  
  
  RESULTS
  Basal frequencies of chromosome aberrations were significantly increased in NBS/FA probands and NBS heterozygous carriers. The NBS diagnosis was confirmed by detecting site-specific rearrangements, while the mitomycin C (MMC)-stress test was highly positive in a FA patient. Among patients with suspected WBS, 12 individuals had a 7q11.23 microdeletion. In the Comet assay, genome instability was revealed in all three disorders, impaired capacity to repair oxidative damage being observed in NBS and WBS in contrast to FA and controls.
  
  
  CONCLUSIONS
  The results indicate that the estimates of DNA damage response may be proposed as efficient biomarkers for detecting and characterizing genome instability in the genetic disorders under study.
authors.affiliation: Institute of Genetics and Cytolog, National Academy of Sciences of Belarus, Minsk, Republic of Belarus. n.savina@igc.bas-net.by
authors.forename: Nataliya V
authors.initials: NV
authors.lastname: Savina
authors.forename: Marharyta P
authors.initials: MP
authors.lastname: Smal
authors.forename: Tatyana D
authors.initials: TD
authors.lastname: Kuzhir
authors.forename: Tatyana M
authors.initials: TM
authors.lastname: Egorova
authors.forename: Olga M
authors.initials: OM
authors.lastname: Khurs
authors.forename: Anna D
authors.initials: AD
authors.lastname: Polityko
authors.forename: Roza I
authors.initials: RI
authors.lastname: Goncharova
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D016022:Case-Control Studies; D020552:Comet Assay; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D042822:Genomic Instability; D006801:Humans; D010865:Pilot Projects
chemical_list: D015415:Biomarkers