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Defective chromosome segregation and telomere dysfunction in aggressive Wilms' tumors

Stewénius, Ylva LU ; Jin, Yuesheng LU ; Øra, Ingrid LU ; de Kraker, Jan; Bras, Johannes; Frigyesi, Attila LU ; Alumets, Jan LU ; Sandstedt, Bengt; Meeker, Alan K. and Gisselsson Nord, David LU (2007) In Clinical Cancer Research 13(22). p.6593-6602
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 inWT patients. Experimental Design: Telomere function and mitotic segregation errors were assessed in 12 cultured tumors and in tumor tissue sections from... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical Cancer Research
volume
13
issue
22
pages
6593 - 6602
publisher
American Association for Cancer Research
external identifiers
  • wos:000251207100008
  • scopus:36749050382
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-07-1081
language
English
LU publication?
yes
id
a0a83936-7f34-4267-a633-5f5557022dfe (old id 968920)
date added to LUP
2008-01-30 09:01:03
date last changed
2017-02-12 03:35:43
@article{a0a83936-7f34-4267-a633-5f5557022dfe,
  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 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.},
  author       = {Stewénius, Ylva and Jin, Yuesheng and Øra, Ingrid and de Kraker, Jan and Bras, Johannes and Frigyesi, Attila and Alumets, Jan and Sandstedt, Bengt and Meeker, Alan K. and Gisselsson Nord, David},
  issn         = {1078-0432},
  language     = {eng},
  number       = {22},
  pages        = {6593--6602},
  publisher    = {American Association for Cancer Research},
  series       = {Clinical Cancer Research},
  title        = {Defective chromosome segregation and telomere dysfunction in aggressive Wilms' tumors},
  url          = {http://dx.doi.org/10.1158/1078-0432.CCR-07-1081},
  volume       = {13},
  year         = {2007},
}