Short- and long-term effects of chromosome mis-segregation and aneuploidy

@article{Santaguida2015ShortAL,
  title={Short- and long-term effects of chromosome mis-segregation and aneuploidy},
  author={Stefano Santaguida and Angelika Amon},
  journal={Nature Reviews Molecular Cell Biology},
  year={2015},
  volume={16},
  pages={473-485}
}
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… 
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190 Citations
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190 Citations

The Dynamic Instability of the Aneuploid Genome
TLDR
The main consequences of chromosome segregation errors on genome stability are reviewed, with a special focus on the bidirectional relationship between aneuploidy and DNA damage.
Consequences of Chromosome Loss: Why Do Cells Need Each Chromosome Twice?
TLDR
This work summarizes the current models of chromosome loss and the understanding of its consequences, particularly in comparison to chromosome gains, and investigates the consequences of aneuploidy.
Cancer tolerance to chromosomal instability is driven by Stat1 inactivation in vivo
TLDR
A genome-wide mutagenesis screen in mice finds that specifically aneuploid tumors inactivate Stat1 signaling in combination with increased Myc activity, finding that this mechanism is preserved in human aneuPLoid cancers.
Chromosome instability and aneuploidy as context-dependent activators or inhibitors of antitumor immunity
TLDR
Understanding this interplay is essential for the success of immunotherapy in tumors exhibiting CIN/aneuploidy, regardless of whether the efficacy of Immunotherapy is increased by combination with strategies to promote CIN or by designing immunotherapies to target CIN /aneu ploidy directly.
Role of chromosomal instability in cancer progression.
TLDR
The possible mechanisms driving chromosomal instability, how CIN may contribute to the progression at multiple stages of tumour evolution and possible future therapeutic directions based on targeting cancer chromosomal Stability are discussed.
Gene copy-number changes and chromosomal instability induced by aneuploidy confer resistance to chemotherapy.
A System to Study Aneuploidy In Vivo.
  • S. Pfau, A. Amon
  • Biology, Medicine
    Cold Spring Harbor symposia on quantitative biology
  • 2015
TLDR
It is hoped that further characterization of aneuploid cells in vivo will provide insight both into the origins of hematopoietic phenotypes observed in DS individuals as well as the role of different types ofAneuploids cells in the genesis of cancers of the blood.
The emerging links between chromosomal instability (CIN), metastasis, inflammation and tumour immunity
TLDR
This review is focused on the investigation of possible links between CIN, metastasis and the host immune system in cancer development and treatment, since most cancer deaths are due to the consequences of metastasis, and immunotherapy is a rapidly expanding novel avenue of cancer therapy.
Selective vulnerability of aneuploid human cancer cells to inhibition of the spindle assembly checkpoint
TLDR
A novel synthetic lethal interaction between aneuploidy and the SAC, which may have direct therapeutic relevance for the clinical application of SAC inhibitors is revealed and its cellular and molecular underpinnings are explored.
Karyotypic Aberrations in Oncogenesis and Cancer
TLDR
The impact of abnormal karyotypes on oncogenesis, tumor progression, and response to treatment is discussed, focusing on the biochemical and metabolic liabilities of non-diploid cells that can be harnessed for the development of novel chemo (immuno)therapeutic regimens against cancer.
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