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

Research output: Contribution to journalReview article


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.


External organisations
  • University of Manitoba
  • Ben Gurion University of the Negev
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology


  • cancer, cell lines, clonal evolution, genetic bottleneck, telomeres
Original languageEnglish
Pages (from-to)452-461
JournalGenes Chromosomes and Cancer
Issue number7
Early online date2018 Sep
Publication statusPublished - 2019
Publication categoryResearch