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

Experimental Cell Research
David GisselssonHerman Yeger

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 pot...Continue Reading

References

Apr 10, 1997·Nature·C LengauerB Vogelstein
May 11, 2000·Proceedings of the National Academy of Sciences of the United States of America·D GisselssonN Mandahl
Sep 25, 2003·International Journal of Cancer. Journal International Du Cancer·Jennifer AlamiHerman Yeger
Feb 6, 2004·Breast Cancer Research and Treatment·Marc Lacroix, Guy Leclercq
Apr 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Ylva StewéniusDavid Gisselsson
Jun 6, 2008·Chromosoma·David Gisselsson
Nov 21, 2009·Genes, Chromosomes & Cancer·Turid KnutsenThomas Ried

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