Clonal evolution through genetic bottlenecks and telomere attrition: Potential threats to in vitro data reproducibility

David Gisselsson, Daniel Lichtenzstejn, Polina Kachko, Jenny Karlsson, Esther Manor, Sabine Mai

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations

Abstract

Tissue cultures of immortalized human cells, also known as established cell lines, are broadly accessible and cost-efficient tools for biomedical research. We here review potential genetic sources of systematic error in cell line experiments due to clonal evolution in vitro. In particular, the authors highlight alterations in telomere function over prolonged culture and population bottlenecks, respectively, as two commonly overlooked phenomena that can result in significant alterations in cell line genotypes over just one or a few passages in vitro. These alterations may include changes in mutation status of oncogenes and large scale chromosomal imbalances. We introduce a simple list of factors to be avoided in order to reduce the risk of data misinterpretation due to clonal evolution, including unacknowledged in vitro selection pressures, prolonged culture per se, harsh population size reductions, experiments at early phases after establishment, and the employment of cell lines not sufficiently analyzed by high resolution genetic techniques.

Original languageEnglish
Pages (from-to)452-461
Number of pages10
JournalGenes Chromosomes and Cancer
Volume58
Issue number7
DOIs
StatePublished - 1 Jul 2019

Keywords

  • cancer
  • cell lines
  • clonal evolution
  • genetic bottleneck
  • telomeres

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