The Role of Aneuploidy in Cancer Evolution

Sansregret, Laurent; Swanton, Charles

doi:10.1101/cshperspect.a028373

Cited by 223 publications

(171 citation statements)

References 142 publications

(174 reference statements)

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“…Telomere shortening induces a high level of chromosomal instability, thereby leading to liver tumor initiation . Detrimental chromosome instability adversely affects tumor cell viability . We hypothesized that telomere maintenance through H 2 O 2 ‐mediated AKT activity and telomerase activity is essential in the progression toward advanced HCC (Fig.…”

Section: Discussionmentioning

confidence: 99%

Telomere length and reactive oxygen species levels are positively associated with a high risk of mortality and recurrence in hepatocellular carcinoma

Seo

Jung

2018

Hepatology

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Section: Discussionmentioning

confidence: 99%

Telomere length and reactive oxygen species levels are positively associated with a high risk of mortality and recurrence in hepatocellular carcinoma

Seo

Jung

2018

Hepatology

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“…Because chromosome segregation errors can be observed during mitosis, much work has focussed on elucidating mitotic defects that contribute to chromosomal instability (CIN) in cancer. A brief summary of these defects is given below as this subject has been extensively covered elsewhere (Funk et al 2016, Naylor & van Deursen 2016, Sansregret & Swanton 2017. Proper control of the dynamics of microtubules is essential for the correct attachment of chromosomes to the mitotic spindle.…”

Section: Mechanisms Driving Chromosomal Instabilitymentioning

confidence: 99%

Role of chromosomal instability in cancer progression

McClelland

2017

Endocrine-Related Cancer

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Cancer cells often display chromosomal instability (CIN), a defect that involves loss or rearrangement of the cell's genetic material -chromosomes -during cell division. This process results in the generation of aneuploidy, a deviation from the haploid number of chromosomes, and structural alterations of chromosomes in over 90% of solid tumours and many haematological cancers. This trait is unique to cancer cells as normal cells in the body generally strictly maintain the correct number and structure of chromosomes. This key difference between cancer and normal cells has led to two important hypotheses: (i) cancer cells have had to overcome inherent barriers to changes in chromosomes that are not tolerated in non-cancer cells and (ii) CIN represents a cancer-specific target to allow the specific elimination of cancer cells from the body. To exploit these hypotheses and design novel approaches to treat cancer, a full understanding of the mechanisms driving CIN and how CIN contributes to cancer progression is required. Here, we will discuss 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 instability.

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“…Although mechanisms of DNA reduction are not well understood, aneuploidy to increase genetic diversity and resistance to chronic liver injury occurs frequently in human (30-90%) and mice (60%) 60,78 . Whereas aneuploidy can sometimes be maladaptive leading to oncogenesis or cell death, polyploidy generally allows for preservation of normal cellular function 79,80 . Tetraploidy can arise from "mitotic catastrophe" when a proliferating cell fails to undergo cytokinesis following DNA replication, but in general this primarily leads to cell cycle arrest 81 .…”

Section: Discussionmentioning

confidence: 99%

Cardiac interstitial tetraploid cells that escape replicative senescence are found in rodents but not large mammals

Broughton

Khieu

Nguyen

et al. 2019

Preprint

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Ploidy for cardiomyocytes is well described but remains obscure in cardiac interstitial cells (CICs). Ploidy of c-kit+CICs (cCICs) were assessed using a combination of confocal, karyotypic, and flow cytometric assessments coupled with molecular and bioinformatic analyses. Fundamental differences were found between cultured rodent (rat, mouse) cCICs possessing mononuclear tetraploid (4n) content versus large mammal (human, swine) with mononuclear diploid (2n) content. In-situ analysis, confirmed with fresh isolates, revealed diploid content in cCICs from human and a mixture of diploid and tetraploid nuclei in mouse. Molecular assessment of the p53 signaling pathway provides a plausible explanation for escape from replicative senescence in rodent but not human cCICs. Single cell transcriptional profiling reveals distinctions between diploid versus tetraploid populations in mouse cCICs, alluding to functional divergences. Collectively, these data reveal fundamental species-specific biological differences in cCICs that could account for challenges in extrapolation of myocardial preclinical studies from rodent to large animal models.

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The Role of Aneuploidy in Cancer Evolution

Cited by 223 publications

References 142 publications

Telomere length and reactive oxygen species levels are positively associated with a high risk of mortality and recurrence in hepatocellular carcinoma

Telomere length and reactive oxygen species levels are positively associated with a high risk of mortality and recurrence in hepatocellular carcinoma

Role of chromosomal instability in cancer progression

Cardiac interstitial tetraploid cells that escape replicative senescence are found in rodents but not large mammals

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