Definition
An elevated per-division rate of chromosome missegregation resulting in ongoing changes to chromosome number in 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
- CENP-E reduction generates aneuploidy and chromosomal instability
- Aneuploidy increases spontaneous tumor formation in aged animals
- Increased aneuploidy inhibits chemically and genetically induced tumorigenesis
- Aneuploidy exhibits dual roles as oncogenic and tumor-suppressive
- Multipolar divisions are rare and typically produce inviable progeny
- Extra centrosomes correlate with chromosomal instability in tumors
- Aneuploid tumors inactivate Stat1 signaling with increased Myc activity
- Chromosomal instability promotes immune cell infiltration into tumors
- Stat1 loss combined with Myc activation alleviates CIN-induced immune infiltration
- Stat1 inactivation mechanism is conserved between mouse and human aneuploid cancers
- Array CGH detects segmental deletions smaller than 34 Mb
- Gene expression scales proportionally to whole chromosome copy number in chromosomally unstable CSCs
- Gene expression levels can computationally infer large-scale copy number variations in chromosomally unstable cells
- Single-cell sequencing reveals karyotype heterogeneity in lymphomas
- Mps1 truncation-induced CIN generates convergent recurrent chromosome gains
Synthesis
Chromosomal instability is established across sources as an elevated rate of chromosome missegregation during cell division that generates ongoing changes in chromosome number, producing aneuploidy and cellular heterogeneity through mechanisms such as merotely, improper microtubule-kinetochore attachments that occur even in the absence of classic mitotic defects like spindle assembly checkpoint failure. A key mechanistic relationship links chromosomal instability to immune surveillance, where the genomic chaos generates immunogenic signals that recruit immune cell infiltration into tumors, representing a significant fitness cost that unstable cells must overcome through active immune evasion strategies, particularly via Stat1 signaling inactivation combined with Myc activation. The most contested aspect of chromosomal instability concerns its dual role in cancer, where it demonstrates paradoxical tumor-suppressive and oncogenic effects depending on context: elevated aneuploidy promotes spontaneous tumor formation in aged animals but simultaneously inhibits chemically or genetically induced tumorigenesis, revealing that the same genomic instability phenotype can either drive or prevent malignant transformation based on the cellular environment and initiating events.