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Generation of trisomies in cancer cells by multipolar mitosis and incomplete cytokinesis.

Gisselsson Nord, David LU ; Jin, Yuesheng LU ; Lindgren, David LU ; Persson, Johan ; Gisselsson, Lennart LU ; Hanks, Sandra ; Sehic, Daniel LU ; Holmquist Mengelbier, Linda LU ; Øra, Ingrid LU orcid and Rahman, Nazneen , et al. (2010) In Proceedings of the National Academy of Sciences 107(47). p.20489-20493
Abstract
One extra chromosome copy (i.e., trisomy) is the most common type of chromosome aberration in cancer cells. The mechanisms behind the generation of trisomies in tumor cells are largely unknown, although it has been suggested that dysfunction of the spindle assembly checkpoint (SAC) leads to an accumulation of trisomies through failure to correctly segregate sister chromatids in successive cell divisions. By using Wilms tumor as a model for cancers with trisomies, we now show that trisomic cells can form even in the presence of a functional SAC through tripolar cell divisions in which sister chromatid separation proceeds in a regular fashion, but cytokinesis failure nevertheless leads to an asymmetrical segregation of chromosomes into two... (More)
One extra chromosome copy (i.e., trisomy) is the most common type of chromosome aberration in cancer cells. The mechanisms behind the generation of trisomies in tumor cells are largely unknown, although it has been suggested that dysfunction of the spindle assembly checkpoint (SAC) leads to an accumulation of trisomies through failure to correctly segregate sister chromatids in successive cell divisions. By using Wilms tumor as a model for cancers with trisomies, we now show that trisomic cells can form even in the presence of a functional SAC through tripolar cell divisions in which sister chromatid separation proceeds in a regular fashion, but cytokinesis failure nevertheless leads to an asymmetrical segregation of chromosomes into two daughter cells. A model for the generation of trisomies by such asymmetrical cell division accurately predicted several features of clones having extra chromosomes in vivo, including the ratio between trisomies and tetrasomies and the observation that different trisomies found in the same tumor occupy identical proportions of cells and colocalize in tumor tissue. Our findings provide an experimentally validated model explaining how multiple trisomies can occur in tumor cells that still maintain accurate sister chromatid separation at metaphase-anaphase transition and thereby physiologically satisfy the SAC. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Proceedings of the National Academy of Sciences
volume
107
issue
47
pages
20489 - 20493
publisher
National Academy of Sciences
external identifiers
  • wos:000284529000063
  • pmid:21059955
  • scopus:78650542319
  • pmid:21059955
ISSN
1091-6490
DOI
10.1073/pnas.1006829107
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Paediatrics (Lund) (013002000), Division of Clinical Genetics (013022003), Laboratory for Experimental Brain Research (013041000), Molecular Tumour Biology (013017540) Department affilation moved from v1000583 (Molecular Tumour Biology) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:41:48.
id
51f483e4-504b-43cc-8888-b8534dd7aa5c (old id 1732181)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21059955?dopt=Abstract
date added to LUP
2016-04-04 08:30:32
date last changed
2024-10-12 17:41:10
@article{51f483e4-504b-43cc-8888-b8534dd7aa5c,
  abstract     = {{One extra chromosome copy (i.e., trisomy) is the most common type of chromosome aberration in cancer cells. The mechanisms behind the generation of trisomies in tumor cells are largely unknown, although it has been suggested that dysfunction of the spindle assembly checkpoint (SAC) leads to an accumulation of trisomies through failure to correctly segregate sister chromatids in successive cell divisions. By using Wilms tumor as a model for cancers with trisomies, we now show that trisomic cells can form even in the presence of a functional SAC through tripolar cell divisions in which sister chromatid separation proceeds in a regular fashion, but cytokinesis failure nevertheless leads to an asymmetrical segregation of chromosomes into two daughter cells. A model for the generation of trisomies by such asymmetrical cell division accurately predicted several features of clones having extra chromosomes in vivo, including the ratio between trisomies and tetrasomies and the observation that different trisomies found in the same tumor occupy identical proportions of cells and colocalize in tumor tissue. Our findings provide an experimentally validated model explaining how multiple trisomies can occur in tumor cells that still maintain accurate sister chromatid separation at metaphase-anaphase transition and thereby physiologically satisfy the SAC.}},
  author       = {{Gisselsson Nord, David and Jin, Yuesheng and Lindgren, David and Persson, Johan and Gisselsson, Lennart and Hanks, Sandra and Sehic, Daniel and Holmquist Mengelbier, Linda and Øra, Ingrid and Rahman, Nazneen and Mertens, Fredrik and Mitelman, Felix and Mandahl, Nils}},
  issn         = {{1091-6490}},
  language     = {{eng}},
  number       = {{47}},
  pages        = {{20489--20493}},
  publisher    = {{National Academy of Sciences}},
  series       = {{Proceedings of the National Academy of Sciences}},
  title        = {{Generation of trisomies in cancer cells by multipolar mitosis and incomplete cytokinesis.}},
  url          = {{https://lup.lub.lu.se/search/files/5181779/1748587.pdf}},
  doi          = {{10.1073/pnas.1006829107}},
  volume       = {{107}},
  year         = {{2010}},
}