The impact of monosomies, trisomies and segmental aneuploidies on chromosomal stability

PLoS One. 2022 Jul 1;17(7):e0268579. doi: 10.1371/journal.pone.0268579. eCollection 2022.

Abstract

Aneuploidy and chromosomal instability are both commonly found in cancer. Chromosomal instability leads to karyotype heterogeneity in tumors and is associated with therapy resistance, metastasis and poor prognosis. It has been hypothesized that aneuploidy per se is sufficient to drive CIN, however due to limited models and heterogenous results, it has remained controversial which aspects of aneuploidy can drive CIN. In this study we systematically tested the impact of different types of aneuploidies on the induction of CIN. We generated a plethora of isogenic aneuploid clones harboring whole chromosome or segmental aneuploidies in human p53-deficient RPE-1 cells. We observed increased segregation errors in cells harboring trisomies that strongly correlated to the number of gained genes. Strikingly, we found that clones harboring only monosomies do not induce a CIN phenotype. Finally, we found that an initial chromosome breakage event and subsequent fusion can instigate breakage-fusion-bridge cycles. By investigating the impact of monosomies, trisomies and segmental aneuploidies on chromosomal instability we further deciphered the complex relationship between aneuploidy and CIN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy*
  • Chromosomal Instability
  • Genetic Testing
  • Humans
  • Monosomy
  • Trisomy* / genetics

Grants and funding

Marie Curie Initial Training Network Project PLOIDYNET: Mar Soto, Rene H. Medema FP7-PEOPLE-2013; KWF Kankerbestrijding (DCS): Jonne A. Raaijmakers KWF- Young Investigator Grant- 12233. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.