Chromosomal instability and its effect on cell lines

Abstract

Background: Cancer cell lines are invaluable model systems for biomedical research because they provide an almost unlimited supply of biological materials. However, there is considerable skepticism regarding the reproducibility of data derived from these in vitro models.

Recent findings: Chromosomal instability (CIN) is one of the primary issues associated with cell lines, which can cause genetic heterogeneity and unstable cell properties within a cell population. Many of these problems can be avoided with some precautions. Here we review the underlying causes of CIN, including merotelic attachment, telomere dysfunction, DNA damage response defects, mitotic checkpoint defects and cell cycle disturbances.

Conclusion: In this review we summarize studies highlighting the consequences of CIN in various cell lines and provide suggestions on monitoring and controlling CIN during cell culture.

Keywords: cell culture; cell lines; chromosome instability; mitotic checkpoint; telomere.

FIGURE 1

Three major forms of mitotic errors. Lagging centric chromosomes are whole chromosomes lagging in the spindle midzone. Lagging acentric fragments are partial chromosomes that lack centromeric signals. Anaphase bridges may lead to chromosomal breakage and structurally abnormal chromosomes.

FIGURE 2

Abnormal kinetochore‐microtubule attachments. (A) Types of kinetochore‐microtubule attachment. (i) Bipolar attachment. (ii) Monotelic attachment. (iii) Syntelic attachment. (iv) Merotelic attachment. (B) Consequences of merotelic attachment. (i) Whole‐chromosome aneuploidy. (ii) Formation of micronuclei.

FIGURE 3

Telomere dysfunction leading to breakage‐fusion‐bridge cycles.