2020
DOI: 10.1101/2020.09.25.314229
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Abstract: Aneuploidy is a ubiquitous feature of human tumors, but the acquisition of aneuploidy is typically detrimental to cellular fitness. To investigate how aneuploidy could contribute to tumor growth, we triggered periods of chromosomal instability (CIN) in human cells and then exposed them to a variety of different culture environments. While chromosomal instability was universally detrimental under normal growth conditions, we discovered that transient CIN reproducibly accelerated the ability of cells to adapt an… Show more

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Cited by 8 publications
(50 citation statements)
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References 45 publications
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“…In a mouse model, low-to-moderate levels of CIN were found to promote tumorigenesis, while high levels of CIN suppressed tumor progression [ 163 ]. As a result of these observations, it has been proposed that exacerbating CIN beyond a tolerable level may be a viable therapeutic strategy [ 190 ], but such an approach should be considered with caution [ 191 , 192 ].…”
Section: Aneuploidy and Polyploidy Can Both Promote And Buffer Karyotypic Heterogeneitymentioning
confidence: 99%
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“…In a mouse model, low-to-moderate levels of CIN were found to promote tumorigenesis, while high levels of CIN suppressed tumor progression [ 163 ]. As a result of these observations, it has been proposed that exacerbating CIN beyond a tolerable level may be a viable therapeutic strategy [ 190 ], but such an approach should be considered with caution [ 191 , 192 ].…”
Section: Aneuploidy and Polyploidy Can Both Promote And Buffer Karyotypic Heterogeneitymentioning
confidence: 99%
“…Direct gain of 4q may not have been favorable in this context because it harbors numerous tumor suppressor genes, indicating that genetic interactions between specific aneuploidies and other chromosomes influence karyotype evolution (as reported in yeast [ 301 ]). In a similar study, recurrent aneuploidies were also detected in various cell lines following Mps1 disruption and drug pressure; however, the observed karyotypic changes were unique for each cell line used even when challenged with the same drug [ 191 ]. Although the mechanisms underlying resistance were not identified in this study, the unique karyotypic routes to drug resistance across cell types demonstrate there are multiple genomic paths to a given phenotype (drug resistance) and the cell’s genomic and/or epigenetic background is an important factor for the observed effects of chromosomal alterations.…”
Section: The Role Of Aneuploidy and Polyploidy In Tumor Niche Constructionmentioning
confidence: 99%
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“…Importantly, CIN potentiates tumorigenesis (Foijer et al, 2017;Levine et al, 2017;Silk et al, 2013) and associates with therapeutic resistance (Ippolito et al, 2020;Lee et al, 2011;Lukow et al, 2020;Pavelka et al, 2010), metastasis (Bakhoum et al, 2018) and poor survival outcomes (Bakhoum et al, 2011;Denu et al, 2016;Jamal-Hanjani et al, 2017). Thus, CIN is an important characteristic of cancer biology.…”
Section: Introductionmentioning
confidence: 99%
“…These observations highlight the confounding role of karyotype selection in measuring CIN in human tumors. Indeed, karyotype selection reduces karyotype variance in cancer cell populations, even after exhibiting mitotic errors (Gerstung et al, 2020;Ippolito et al, 2020;Lukow et al, 2020). It may be possible to overcome this limitation by modeling chromosomal instability and explicitly considering the evolutionary selection of aneuploid cells.…”
Section: Introductionmentioning
confidence: 99%