Definition
The failure of chromosomes to segregate properly during cell division, resulting in unequal distribution to daughter cells.
Related Claims
- Merotely causes chromosome missegregation in unstable cells
- Elevated merotely generates CIN in stable near-diploid cells
- Missegregation alone insufficient for aneuploid cell propagation
- CIN exists independently of classic mitotic defects in most cells
- CIN causality toward aneuploidy was previously unanswered
- Extra centrosomes promote chromosome missegregation during bipolar division
- Multipolar spindle intermediate allows merotelic attachment accumulation
- Array CGH replaces metaphase spreads with genomic clones on slide
Synthesis
Chromosome missegregation occurs when chromosomes fail to properly distribute to daughter cells during division, with merotelic kinetochore-microtubule attachments—where a single kinetochore binds microtubules from both spindle poles—emerging as a key mechanistic driver of this error, particularly in cells with extra centrosomes that pass through transient multipolar spindle states before clustering into bipolar configurations. The mechanistic chain linking centrosome amplification to chromosomal instability through merotelic attachment accumulation has been established, resolving earlier uncertainty about how supernumerary centrosomes promote segregation errors even during ultimately bipolar divisions. While elevated missegregation rates can induce chromosomal instability in previously stable near-diploid cells, a critical unresolved question concerns whether these elevated error rates alone can generate viable aneuploid populations, since missegregation appears to compromise proliferation capacity, suggesting that additional permissive phenotypic changes beyond the segregation defects themselves may be required for aneuploid cells to successfully propagate. This complexity reflects the broader puzzle that classic mitotic defects in spindle assembly and checkpoint function explain chromosomal instability in only a minority of aneuploid tumor cells, leaving the causative mechanisms in most chromosomally unstable cancers still undetermined.