Chromosome mis-segregation and cytokinesis failure in trisomic human cells
- Virginia Tech, United States
- Universidade do Porto, Portugal
- University of California, San Francisco, United States
- National Institutes of Health, United States
- Institut D'Investigacions Biomèdiques August Pi i Sunyer, Spain
Abstract
Cancer cells display aneuploid karyotypes and typically mis-segregate chromosomes at high rates, a phenotype referred to as chromosomal instability (CIN). To test the effects of aneuploidy on chromosome segregation and other mitotic phenotypes we used the colorectal cancer cell line DLD1 (2n=46) and two variants with trisomy 7 or 13 (DLD1+7 and DLD1+13), as well as euploid and trisomy 13 amniocytes (AF and AF+13). We found that trisomic cells displayed higher rates of chromosome mis-segregation compared to their euploid counterparts. Furthermore, cells with trisomy 13 displayed a distinctive cytokinesis failure phenotype. We showed that up-regulation of SPG20 expression, brought about by trisomy 13 in DLD1+13 and AF+13 cells, is both required and sufficient for the cytokinesis failure phenotype. Overall, our study shows that aneuploidy can induce chromosome mis-segregation. Moreover, we identified a trisomy 13-specific mitotic phenotype that is driven by up-regulation of a gene encoded on the aneuploid chromosome.
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Ethics
Human subjects: The study acknowledged the ethics guidelines under national rules and accordingly to the principles of the Declaration of Helsinki, and was approved by the Ethics Committee of Hospital de S. Jo�o-Porto (dispatch 14 Nov 2012) (approval number 237/2012). Informed consent forms with detailed information were provided to all patients. The study did not imply collection of extra material from the healthy donor females (only surplus cells/tissues were used); the study didn't bring any direct benefits to the volunteers; there were no risks or costs for the volunteers; there was no access to patient clinical data (samples were obtained in anonymous form from the Hospital Genetics Department); participation was volunteer and free to be interrupted at any moment; there are no ethical impacts predicted; there will be no commercial interests.
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This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Chromosome mis-segregation and cytokinesis failure in trisomic human cells
eLife 4:e05068.
https://doi.org/10.7554/eLife.05068
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