Clonal evolution through genetic bottlenecks and telomere attrition: Potential threats to in vitro data reproducibility. Issue 7 (29th November 2018)

• Record Type: Journal Article
• Authors: Gisselsson, David; Lichtenzstejn, Daniel; Kachko, Polina; Karlsson, Jenny; Manor, Esther; Mai, Sabine
• Other Names: Mai Sabine guestEditor.
• Is Part Of: Genes, chromosomes & cancer. Volume 58:Issue 7(2019)
• Page Start: 452
• Page End: 461
• Publication Date: 2018-11-29
• Subjects: cancer -- cell lines -- clonal evolution -- genetic bottleneck -- telomeres; Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22685
• Languages: English
• ISSNs: 1045-2257

Abstract

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.