A little CIN may cost a lot: revisiting aneuploidy and cancer

Chandhok, Namrata S; Pellman, David

doi:10.1016/j.gde.2008.12.004

Cited by 56 publications

(41 citation statements)

References 61 publications

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“…It is clear that, although genetic change and tumor progression require CIN (which results in miss-segregation of chromosomes and aneuploidy), limitless accumulation of CIN ultimately interferes with a cells capacity to divide (Cahill et al, 1999;Duesberg et al, 2006;Weaver and Cleveland, 2007;Chandhok and Pellman, 2009). In a recent paper (Vitale et al, 2010), a decrease in aneuploidy through unstable transient tetraploidy to para-diploidy was reported for the first time.…”

Section: Reversible Polyploidy and Reversible Aneuploidy Of Tumor Cellsmentioning

confidence: 99%

MOS, aneuploidy and the ploidy cycle of cancer cells

Ērenpreisa

Cragg

2010

Oncogene

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After DNA or spindle damage, p53-defective tumor cells undergo a complex cycle of reversible polyploidy. How this process occurs and more importantly, why, has recently become the focus of several research groups, prompting this review in which we discuss two related phenomena that accompany the reversible polyploidy of tumor cells: the induction of meiosis genes such as MOS and the decrease in genomic instability observed during the reversion from polyploidy to para-diploidy. The reversible polyploidy likely provides the means through which the balance between increased chromosome instability (CIN), driving genetic variation and decreased CIN, necessary for perpetuating these malignant clones, is maintained. These concepts are integrated with recent findings that many meiotic and self-renewal genes become activated during reversible polyploidy and lead us to the hypothesis that tumor cell immortality may be achieved through germline-like transmission.

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Section: Reversible Polyploidy and Reversible Aneuploidy Of Tumor Cellsmentioning

confidence: 99%

MOS, aneuploidy and the ploidy cycle of cancer cells

Ērenpreisa

Cragg

2010

Oncogene

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“…Although aneuploidy generally has adverse consequences (Torres et al 2007(Torres et al , 2008Williams et al 2008;Oromendia et al 2012), it may provide selective advantage under various stresses (Pavelka et al 2010;Sheltzer and Amon 2011). The selective advantage of aneuploidy cells has medical implications as shown for tumors (Weaver et al 2007;Chandhok and Pellman 2009) and drug resistance in pathogenic fungi (Selmecki et al 2006(Selmecki et al , 2009Semighini et al 2011). Moreover, advantageous aneuploidy can be a common step in evolution.…”

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confidence: 99%

The Sister Chromatid Cohesion Pathway Suppresses Multiple Chromosome Gain and Chromosome Amplification

et al. 2014

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Gain or loss of chromosomes resulting in aneuploidy can be important factors in cancer and adaptive evolution. Although chromosome gain is a frequent event in eukaryotes, there is limited information on its genetic control. Here we measured the rates of chromosome gain in wild-type yeast and sister chromatid cohesion (SCC) compromised strains. SCC tethers the newly replicated chromatids until anaphase via the cohesin complex. Chromosome gain was measured by selecting and characterizing copper-resistant colonies that emerged due to increased copies of the metallothionein gene CUP1. Although all defective SCC diploid strains exhibited increased rates of chromosome gain, there were 15-fold differences between them. Of all mutants examined, a hypomorphic mutation at the cohesin complex caused the highest rate of chromosome gain while disruption of WPL1, an important regulator of SCC and chromosome condensation, resulted in the smallest increase in chromosome gain. In addition to defects in SCC, yeast cell type contributed significantly to chromosome gain, with the greatest rates observed for homozygous mating-type diploids, followed by heterozygous mating type, and smallest in haploids. In fact, wpl1-deficient haploids did not show any difference in chromosome gain rates compared to wild-type haploids. Genomic analysis of copper-resistant colonies revealed that the "driver" chromosome for which selection was applied could be amplified to over five copies per diploid cell. In addition, an increase in the expected driver chromosome was often accompanied by a gain of a small number of other chromosomes. We suggest that while chromosome gain due to SCC malfunction can have negative effects through gene imbalance, it could also facilitate opportunities for adaptive changes. In multicellular organisms, both factors could lead to somatic diseases including cancer.

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“…Symmetrical distribution of chromosomes during mitosis is critical for genomic stability and cell survival (8,9). During metaphase, chromosomes congression from spindle poles to the metaphase midplate is driven by the plus end-directed kinesin centromere protein E (CENP-E) (10).…”

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confidence: 99%

Evolutionarily conserved protein ERH controls CENP-E mRNA splicing and is required for the survival of KRAS mutant cancer cells

Weng

Lee

Shu

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Cancers with Ras mutations represent a major therapeutic problem. Recent RNAi screens have uncovered multiple nononcogene addiction pathways that are necessary for the survival of Ras mutant cells. Here, we identify the evolutionarily conserved gene enhancer of rudimentary homolog (ERH), in which depletion causes greater toxicity in cancer cells with mutations in the small GTPase KRAS compared with KRAS WT cells. ERH interacts with the spliceosome protein SNRPD3 and is required for the mRNA splicing of the mitotic motor protein CENP-E. Loss of ERH leads to loss of CENP-E and consequently, chromosome congression defects. Gene expression profiling indicates that ERH is required for the expression of multiple cell cycle genes, and the gene expression signature resulting from ERH down-regulation inversely correlates with KRAS signatures. Clinically, tumor ERH expression is inversely associated with survival of colorectal cancer patients whose tumors harbor KRAS mutations. Together, these findings identify a role of ERH in mRNA splicing and mitosis, and they provide evidence that KRAS mutant cancer cells are dependent on ERH for their survival.synthetic lethality | spliceosome

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A little CIN may cost a lot: revisiting aneuploidy and cancer

Cited by 56 publications

References 61 publications

MOS, aneuploidy and the ploidy cycle of cancer cells

MOS, aneuploidy and the ploidy cycle of cancer cells

The Sister Chromatid Cohesion Pathway Suppresses Multiple Chromosome Gain and Chromosome Amplification

Evolutionarily conserved protein ERH controls CENP-E mRNA splicing and is required for the survival of KRAS mutant cancer cells

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