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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 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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Proceedings of the National Academy of Sciences
volume
107
issue
47
pages
20489 - 20493
publisher
National Acad Sciences
external identifiers
  • wos:000284529000063
  • pmid:21059955
  • scopus:78650542319
ISSN
1091-6490
DOI
10.1073/pnas.1006829107
language
English
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yes
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51f483e4-504b-43cc-8888-b8534dd7aa5c (old id 1732181)
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http://www.ncbi.nlm.nih.gov/pubmed/21059955?dopt=Abstract
date added to LUP
2010-12-01 11:19:13
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2018-07-15 04:19:21
@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 Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Generation of trisomies in cancer cells by multipolar mitosis and incomplete cytokinesis.},
  url          = {http://dx.doi.org/10.1073/pnas.1006829107},
  volume       = {107},
  year         = {2010},
}