Aneuploidy is defined as an abnormal karyotype that is not a multiple of the haploid complement.
Chromosome mis-segregation causes DNA damage.
Micronuclei form during chromosome mis-segregation. Chromosomes within micronuclei are under-replicated and undergo chromothripsis.
Chromosome mis-segregation leads to p53 activation.
The complex phenotypes caused by aneuploidy are produced by changes in the dosage of specific genes and a generic aneuploidy-associated stress response.
Aneuploidy causes proteotoxic stress and impairs proliferation.
Aneuploidy is a hallmark of cancer but the relationship between aneuploidy and cancer is complex. Depending on the context, aneuploidy can promote or antagonize malignant transformation.
Dividing cells that experience chromosome mis-segregation generate aneuploid daughter cells, which contain an incorrect number of chromosomes. Although aneuploidy interferes with the proliferation of untransformed cells, it is also, paradoxically, a hallmark of cancer, a disease defined by increased proliferative potential. These contradictory effects are also observed in mouse models of chromosome instability (CIN). CIN can inhibit and promote tumorigenesis. Recent work has provided insights into the cellular consequences of CIN and aneuploidy. Chromosome mis-segregation per se can alter the genome in many more ways than just causing the gain or loss of chromosomes. The short- and long-term effects of aneuploidy are caused by gene-specific effects and a stereotypic aneuploidy stress response. Importantly, these recent findings provide insights into the role of aneuploidy in tumorigenesis.
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The authors apologize to our colleagues whose work we were not able to cite owing to space limitations. Work in the Amon laboratory is supported by grants from the US National Institutes of Health (GM56800), the Howard Hughes Medical Institute and the Kathy and Curt Marble Cancer Research Fund. S.S. was supported by the American Italian Cancer Foundation and by a Fellowship in Cancer Research from Marie Curie Actions and the Italian Association for Cancer Research.
The authors declare no competing financial interests.
- Spectral karyotyping
(SKY). A cytogenetic technique used to simultaneously visualize all chromosomes in a cell by using different fluorescently labelled probes for each chromosome.
A process in which entire chromosomes become fragmented and then are repaired in a seemingly random manner, leading to dozens (sometimes even hundreds) of rearrangements within a single chromosome.
- Dosage compensation
Alteration of mRNA or protein expression to compensate for variation in DNA copy number.
- Chromosomal instability
(CIN). A condition in which the rate of chromosome mis-segregation is elevated.
- Proteotoxic stress
A cellular stress elicited by unfolded and/or misfolded proteins.
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Santaguida, S., Amon, A. Short- and long-term effects of chromosome mis-segregation and aneuploidy. Nat Rev Mol Cell Biol 16, 473–485 (2015). https://doi.org/10.1038/nrm4025
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