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

  title={Short- and long-term effects of chromosome mis-segregation and aneuploidy},
  author={Stefano Santaguida and Angelika Amon},
  journal={Nature Reviews Molecular Cell Biology},
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… 
The Dynamic Instability of the Aneuploid Genome
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?
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
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
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.
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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.
A System to Study Aneuploidy In Vivo.
  • S. Pfau, A. Amon
  • Biology, Medicine
    Cold Spring Harbor symposia on quantitative biology
  • 2015
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
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
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
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.


Examining the link between chromosomal instability and aneuploidy in human cells
It is shown that improper microtubule–chromosome attachment (merotely) is a cause of chromosome missegregation in unstable cells and that increasing chromosome misSEgregation rates by elevating merotely during consecutive mitoses generates CIN in otherwise stable, near-diploid cells.
Causes and consequences of aneuploidy in cancer
Recent progress in understanding the roles of whole-chromosome aneuploidy in cancer is reviewed, including the mechanistic causes of aneuPLoidy, the cellular responses to chromosome gains or losses and how cells might adapt to tolerate these usually detrimental alterations.
Aneuploid proliferation defects in yeast are not driven by copy number changes of a few dosage-sensitive genes.
It is concluded that phenotypic thresholds can be crossed by mass action of copy number changes that, on their own, are benign.
Transcriptional consequences of aneuploidy
It is demonstrated that aneuploidies of different chromosomes and in different organisms impact similar cellular pathways and cause a stereotypical antiproliferative response that must be overcome before transformation.
Aneuploidy Affects Proliferation and Spontaneous Immortalization in Mammalian Cells
The data indicate that aneuploidy decreases not only organismal but also cellular fitness and elicits traits that are shared between different aneuPLoid cells.
Effects of Aneuploidy on Cellular Physiology and Cell Division in Haploid Yeast
It is concluded that aneuploidy causes not only a proliferative disadvantage but also a set of phenotypes that is independent of the identity of the individual extra chromosomes.
Aneuploidy Drives Genomic Instability in Yeast
Aneuploidy-induced genomic instability could facilitate the development of genetic alterations that drive malignant growth in cancer.
Generating chromosome instability through the simultaneous deletion of Mad2 and p53.
It is concluded that the mitotic checkpoint is not essential for viability per se and that a CIN phenotype can be established in culture through the inactivation of both the Mad2- and p53-dependent checkpoint pathways.
Chromosome instability induced by Mps1 and p53 mutation generates aggressive lymphomas exhibiting aneuploidy-induced stress
It is found that CIN dramatically accelerates cancer in a genetically predisposed background and that the resulting aneuploid cancers are metabolically deranged, a vulnerability that may open new avenues to treating aneuPLoid cancers.