title: Defective chromosome segregation and telomere dysfunction in aggressive Wilms' tumors.
abstract: OBJECTIVE
  In many childhood neoplasms, prognostic subgroups have been defined based on specific chromosome changes. In Wilms' tumor (WT), such subclassification has been hampered by the diverse and relatively unspecific pattern of chromosomal imbalances present in these tumors. Unspecific patterns of cytogenetic imbalances in tumors are often caused by mitotic segregation errors due to short dysfunctional telomeres. As an alternative to cytogenetic classification, we therefore have evaluated whether the rate of telomere-dependent chromosomal instability could influence the clinical course in WT patients.
  
  
  METHODS
  Telomere function and mitotic segregation errors were assessed in 12 cultured tumors and in tumor tissue sections from 41 WT patients.
  
  
  RESULTS
  Abnormal telomere shortening was found in cultured cells and in tissue sections from highly aggressive tumors. In vitro, dysfunctional telomeres were associated to specific cell division abnormalities, including anaphase bridges and multipolar mitoses. Assessment of mitotic figures in tissue sections revealed that anaphase bridges and multipolar mitoses were predominantly, but not exclusively, present in high-risk tumors and were predictors of poor event-free and overall survival.
  
  
  CONCLUSIONS
  Telomere-dependent mitotic instability is present in a subgroup of WT, predominantly consisting of high-risk tumors.
authors.affiliation: Department of Clinical Genetics, Lund University Hospital, Lund, Sweden. ylva.stewenius@med.lu.se
authors.forename: Ylva
authors.initials: Y
authors.lastname: Stewénius
authors.forename: Yuesheng
authors.initials: Y
authors.lastname: Jin
authors.forename: Ingrid
authors.initials: I
authors.lastname: Øra
authors.forename: Jan
authors.initials: J
authors.lastname: de Kraker
authors.forename: Johannes
authors.initials: J
authors.lastname: Bras
authors.forename: Attila
authors.initials: A
authors.lastname: Frigyesi
authors.forename: Jan
authors.initials: J
authors.lastname: Alumets
authors.forename: Bengt
authors.initials: B
authors.lastname: Sandstedt
authors.forename: Alan K
authors.initials: AK
authors.lastname: Meeker
authors.forename: David
authors.initials: D
authors.lastname: Gisselsson
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D020090:Chromosome Segregation; D005260:Female; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology*; D008297:Male; D008938:Mitosis; D011379:Prognosis; D016615:Telomere / Q000648:ultrastructure*; D009396:Wilms Tumor / Q000401:mortality / Q000473:pathology*