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Mechanisms of Whole Chromosome Gains in Tumors - Many Answers to a Simple Question.

Gisselsson Nord, David LU (2011) In Cytogenetic and Genome Research 133. p.190-201
Abstract
Whole chromosome gain is the most common type of gross genomic abnormality observed in human tumors. It is particularly frequent in lympho-haematopoietic and embryonic neoplasms, where trisomies and tetrasomies are typically present together with few or no other cytogenetic imbalances, resulting in hyperdiploid chromosome numbers. Despite the high prevalence of whole chromosome gains in neoplastic cells, their mechanism of origin remains disputed. Here, 4 potential models for the generation of whole chromosome gains are reviewed: (1) loss of chromosomes from the tetraploid level, (2) sequential sister chromatid non-disjunction, (3) multipolar mitosis coupled to sister chromatid non-disjunction, and (4) multipolar mitosis coupled to... (More)
Whole chromosome gain is the most common type of gross genomic abnormality observed in human tumors. It is particularly frequent in lympho-haematopoietic and embryonic neoplasms, where trisomies and tetrasomies are typically present together with few or no other cytogenetic imbalances, resulting in hyperdiploid chromosome numbers. Despite the high prevalence of whole chromosome gains in neoplastic cells, their mechanism of origin remains disputed. Here, 4 potential models for the generation of whole chromosome gains are reviewed: (1) loss of chromosomes from the tetraploid level, (2) sequential sister chromatid non-disjunction, (3) multipolar mitosis coupled to sister chromatid non-disjunction, and (4) multipolar mitosis coupled to incomplete cytokinesis. Each of these mechanisms may in theory result in the generation of hyperdiploid neoplastic clones, but none of them were single-handedly able to reproduce the scenario of chromosome copy number alterations in tumors when cell populations resulting from these models were simulated in silico and compared to published cytogenetic data. To develop models for the generation of whole chromosome gains further, it is critical to improve our knowledge of the principles of clonal selection in tumors and of the baseline rate of chromosome segregation errors in human cells. To illustrate this, a model combining multipolar mitosis coupled to incomplete cytokinesis with a low rate of baseline sister chromatid non-disjunction was shown readily to reproduce copy number distributions in hyperdiploid karyotypes from human tumors. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cytogenetic and Genome Research
volume
133
pages
190 - 201
publisher
Karger
external identifiers
  • wos:000289679800013
  • pmid:21124017
  • scopus:79954578030
ISSN
1424-859X
DOI
10.1159/000322480
language
English
LU publication?
yes
id
900db4f2-2ceb-4d5e-a3a0-5d6b97fd9e01 (old id 1756825)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21124017?dopt=Abstract
date added to LUP
2011-01-03 12:09:33
date last changed
2017-01-01 07:41:36
@article{900db4f2-2ceb-4d5e-a3a0-5d6b97fd9e01,
  abstract     = {Whole chromosome gain is the most common type of gross genomic abnormality observed in human tumors. It is particularly frequent in lympho-haematopoietic and embryonic neoplasms, where trisomies and tetrasomies are typically present together with few or no other cytogenetic imbalances, resulting in hyperdiploid chromosome numbers. Despite the high prevalence of whole chromosome gains in neoplastic cells, their mechanism of origin remains disputed. Here, 4 potential models for the generation of whole chromosome gains are reviewed: (1) loss of chromosomes from the tetraploid level, (2) sequential sister chromatid non-disjunction, (3) multipolar mitosis coupled to sister chromatid non-disjunction, and (4) multipolar mitosis coupled to incomplete cytokinesis. Each of these mechanisms may in theory result in the generation of hyperdiploid neoplastic clones, but none of them were single-handedly able to reproduce the scenario of chromosome copy number alterations in tumors when cell populations resulting from these models were simulated in silico and compared to published cytogenetic data. To develop models for the generation of whole chromosome gains further, it is critical to improve our knowledge of the principles of clonal selection in tumors and of the baseline rate of chromosome segregation errors in human cells. To illustrate this, a model combining multipolar mitosis coupled to incomplete cytokinesis with a low rate of baseline sister chromatid non-disjunction was shown readily to reproduce copy number distributions in hyperdiploid karyotypes from human tumors.},
  author       = {Gisselsson Nord, David},
  issn         = {1424-859X},
  language     = {eng},
  pages        = {190--201},
  publisher    = {Karger},
  series       = {Cytogenetic and Genome Research},
  title        = {Mechanisms of Whole Chromosome Gains in Tumors - Many Answers to a Simple Question.},
  url          = {http://dx.doi.org/10.1159/000322480},
  volume       = {133},
  year         = {2011},
}