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Genetic bottlenecks and the hazardous game of population reduction in cell line based research.

Gisselsson Nord, David LU ; Lindgren, David LU ; Holmquist Mengelbier, Linda LU ; Øra, Ingrid LU and Yeger, Herman (2010) In Experimental Cell Research 316. p.3379-3386
Abstract
Established tumour cell lines are ubiquitous tools in research, but their representativity is often debated. One possible caveat is that many cell lines are derived from cells with genomic instability, potentially leading to genotype changes in vitro. We applied SNP-array analysis to an established tumour cell line (WiT49). Even though WiT49 exhibited chromosome segregation errors in 30% of cell divisions, only a single chromosome segment exhibited a shift in copy number after 20 population doublings in culture. In contrast, sub-populations derived from single cells expanded for an equal number of population doublings showed on average 5.8 and 8.9 altered segments compared to the original culture and to each other, respectively. Most copy... (More)
Established tumour cell lines are ubiquitous tools in research, but their representativity is often debated. One possible caveat is that many cell lines are derived from cells with genomic instability, potentially leading to genotype changes in vitro. We applied SNP-array analysis to an established tumour cell line (WiT49). Even though WiT49 exhibited chromosome segregation errors in 30% of cell divisions, only a single chromosome segment exhibited a shift in copy number after 20 population doublings in culture. In contrast, sub-populations derived from single cells expanded for an equal number of population doublings showed on average 5.8 and 8.9 altered segments compared to the original culture and to each other, respectively. Most copy number variants differentiating these single cell clones corresponded to pre-existing variations in the original culture. Furthermore, no sub-clonal variation was detected in any of the populations derived from single cells. This indicates that genetic bottlenecks resulting from population reduction poses a higher threat to genetic representativity than prolonged culture per se, even in cell lines with a high rate of genomic instability. Genetic bottlenecks should therefore be considered a potential caveat in all studies involving sub-cloning, transfection and other conditions leading to a temporary reduction in cell number. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Experimental Cell Research
volume
316
pages
3379 - 3386
publisher
Academic Press
external identifiers
  • wos:000284523600006
  • pmid:20643124
  • scopus:78149406442
ISSN
1090-2422
DOI
10.1016/j.yexcr.2010.07.010
language
English
LU publication?
yes
id
7e1103ff-de16-4af7-9991-78f643fe06ec (old id 1644784)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20643124?dopt=Abstract
date added to LUP
2010-08-05 09:29:09
date last changed
2018-05-29 11:49:40
@article{7e1103ff-de16-4af7-9991-78f643fe06ec,
  abstract     = {Established tumour cell lines are ubiquitous tools in research, but their representativity is often debated. One possible caveat is that many cell lines are derived from cells with genomic instability, potentially leading to genotype changes in vitro. We applied SNP-array analysis to an established tumour cell line (WiT49). Even though WiT49 exhibited chromosome segregation errors in 30% of cell divisions, only a single chromosome segment exhibited a shift in copy number after 20 population doublings in culture. In contrast, sub-populations derived from single cells expanded for an equal number of population doublings showed on average 5.8 and 8.9 altered segments compared to the original culture and to each other, respectively. Most copy number variants differentiating these single cell clones corresponded to pre-existing variations in the original culture. Furthermore, no sub-clonal variation was detected in any of the populations derived from single cells. This indicates that genetic bottlenecks resulting from population reduction poses a higher threat to genetic representativity than prolonged culture per se, even in cell lines with a high rate of genomic instability. Genetic bottlenecks should therefore be considered a potential caveat in all studies involving sub-cloning, transfection and other conditions leading to a temporary reduction in cell number.},
  author       = {Gisselsson Nord, David and Lindgren, David and Holmquist Mengelbier, Linda and Øra, Ingrid and Yeger, Herman},
  issn         = {1090-2422},
  language     = {eng},
  pages        = {3379--3386},
  publisher    = {Academic Press},
  series       = {Experimental Cell Research},
  title        = {Genetic bottlenecks and the hazardous game of population reduction in cell line based research.},
  url          = {http://dx.doi.org/10.1016/j.yexcr.2010.07.010},
  volume       = {316},
  year         = {2010},
}