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Defective chromosome segregation and telomere dysfunction in aggressive Wilms' tumors

In English

Författare

Summary, in English

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 inWT 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.

Publiceringsår

2007

Språk

Engelska

Sidor

6593-6602

Publikation/Tidskrift/Serie

Clinical Cancer Research

Volym

13

Issue

22

Dokumenttyp

Artikel i tidskrift

Förlag

American Association for Cancer Research

Ämne

  • Cancer and Oncology

Status

Published

Forskningsgrupp

  • Pathways of cancer cell evolution

ISBN/ISSN/Övrigt

  • ISSN: 1078-0432