Despite carrying different extra chromosomes, distinct aneuploid cell lines exhibit shared phenotypephenotypesphenotypic traits related to reduced cellular fitness. This indicates that aneuploidaneuploidy produces common cellular consequences regardless of which specific chromosome is duplicated, suggesting a general mechanism of chromosomal imbalance stress. [@williams_aneuploidy_2008]
Definitions
- aneuploidaneuploidy
- aneuploid cells
- phenotypephenotypesphenotypic traits
- cellular fitness
- chromosomal imbalance
- euploid cells
- aneuploid
Synthesis
Studies across multiple model systems establish that aneuploid cells exhibit shared fitness defects regardless of which specific chromosomes are gained or lost, including impaired proliferation, altered metabolism, cell cycle progression defects, and reduced immortalization capacity in both yeast and mammalian cells. These common phenotypes arise mechanistically from the imbalanced protein composition that results when extra chromosome genes are expressed, creating a pleiotropic cellular stress that fundamentally constrains cellular physiology. However, the relationship between aneuploidy and fitness remains contested in cancer contexts, where aneuploid cells can overcome these inherent costs through specific adaptations such as inactivating Stat1 signaling while activating Myc, which suppresses immune surveillance and allows chromosomally unstable tumors to persist and even exhibit oncogenic properties despite the baseline fitness penalty. What remains unresolved is how selection pressures drive convergent karyotypic states in unstable populations and whether the fitness costs observed in experimental models fully explain the complex dual role of aneuploidy as both tumor-suppressive in some contexts and tumor-promoting in others.
Related
- Mps1 truncation-induced CIN generates convergent recurrent chromosome gains
- Aneuploid cancers inactivate Stat1 to circumvent immune surveillance
- Aneuploidy impairs cell cycle progression in haploid yeast
- Whole genome amplification enables single-cell array CGH analysis
- Extra chromosome genes drive aneuploid phenotypes through imbalanced protein composition
- Aneuploidy impairs cell proliferation in trisomic lines
- Aneuploid tumors inactivate Stat1 signaling with increased Myc activity
- Stat1 loss combined with Myc activation alleviates CIN-induced immune infiltration
- Aneuploidy exhibits dual roles as oncogenic and tumor-suppressive
- Aneuploidy decreases both organismal and cellular fitness