An increased rate of aneuploidaneuploidy drives an elevated level of spontaneous lymphomas and lung tumors in aged animals. This demonstrates that elevated chromosomal instability is associated with spontaneous tumor development, supporting Boveri’s century-old hypothesis that aneuploidy causes tumorigenesis. [@weaver_aneuploidy_2007]
Definitions
Synthesis
Studies establish that aneuploidy can promote spontaneous tumor formation in aged animals, demonstrating an oncogenic capacity for chromosomal instability in certain contexts. This tumor-promoting effect appears mechanistically linked to the ability of aneuploid cells to inactivate Stat1 signaling while simultaneously increasing Myc activity, thereby suppressing immune infiltration and enabling evasion of immune surveillance despite the cellular stress imposed by chromosomal instability. However, this oncogenic role of aneuploidy exists in tension with findings showing that increased aneuploidy actually inhibits chemically and genetically induced tumorigenesis, revealing a context-dependent duality where the same genomic instability phenotype can be either tumor-suppressive or tumor-promoting. The resolution of when aneuploidy acts as an oncogenic driver versus a tumor suppressor remains contested, though evidence suggests that spontaneous age-related tumor formation may represent a distinct biological context from experimentally induced carcinogenesis.
Related
- Stat1 inactivation mechanism is conserved between mouse and human aneuploid cancers
- Mps1 truncation-induced CIN generates convergent recurrent chromosome gains
- Multipolar divisions are rare and typically produce inviable progeny
- Increased aneuploidy inhibits chemically and genetically induced tumorigenesis
- Aneuploid tumors inactivate Stat1 signaling with increased Myc activity
- Extra centrosomes correlate with chromosomal instability in tumors
- Stat1 loss combined with Myc activation alleviates CIN-induced immune infiltration
- CIN exists independently of classic mitotic defects in most cells
- Single-cell sequencing reveals karyotype heterogeneity in lymphomas
- Aneuploidy exhibits dual roles as oncogenic and tumor-suppressive
- CIN causality toward aneuploidy was previously unanswered
- CENP-E reduction generates aneuploidy and chromosomal instability
- Missegregation alone insufficient for aneuploid cell propagation