Defective chromosome segregation and telomere dysfunction in aggressive Wilms' tumors

Ylva Stewénius, Yuesheng Jin, Ingrid Øra, Jan De Kraker, Johannes Bras, Attila Frigyesi, Jan Alumets, Bengt Sandstedt, Alan K. Meeker, David Gisselsson

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: 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. Experimental Design: 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, predominately consisting of high-risk tumors.

Original languageEnglish (US)
Pages (from-to)6593-6602
Number of pages10
JournalClinical Cancer Research
Volume13
Issue number22
DOIs
StatePublished - Nov 15 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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