The impact of monosomies, trisomies and segmental aneuploidies on chromosomal stability.
Aneuploidy and chromosomal instability are both commonly found in cancer. Chromosomal instability leads to karyotype heterogeneity in tumors and is associated with therapy resistance, metastasis and poor prognosis. It has been hypothesized that aneuploidy per se is sufficient to drive CIN, however d...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0268579 |
| _version_ | 1818096412000256000 |
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| author | Dorine C Hintzen Mar Soto Michael Schubert Bjorn Bakker Diana C J Spierings Karoly Szuhai Peter M Lansdorp Roel J C Kluin Floris Foijer René H Medema Jonne A Raaijmakers |
| author_facet | Dorine C Hintzen Mar Soto Michael Schubert Bjorn Bakker Diana C J Spierings Karoly Szuhai Peter M Lansdorp Roel J C Kluin Floris Foijer René H Medema Jonne A Raaijmakers |
| author_sort | Dorine C Hintzen |
| collection | DOAJ |
| description | Aneuploidy and chromosomal instability are both commonly found in cancer. Chromosomal instability leads to karyotype heterogeneity in tumors and is associated with therapy resistance, metastasis and poor prognosis. It has been hypothesized that aneuploidy per se is sufficient to drive CIN, however due to limited models and heterogenous results, it has remained controversial which aspects of aneuploidy can drive CIN. In this study we systematically tested the impact of different types of aneuploidies on the induction of CIN. We generated a plethora of isogenic aneuploid clones harboring whole chromosome or segmental aneuploidies in human p53-deficient RPE-1 cells. We observed increased segregation errors in cells harboring trisomies that strongly correlated to the number of gained genes. Strikingly, we found that clones harboring only monosomies do not induce a CIN phenotype. Finally, we found that an initial chromosome breakage event and subsequent fusion can instigate breakage-fusion-bridge cycles. By investigating the impact of monosomies, trisomies and segmental aneuploidies on chromosomal instability we further deciphered the complex relationship between aneuploidy and CIN. |
| first_indexed | 2024-12-10T23:04:12Z |
| format | Article |
| id | doaj.art-f584554feac24a5684cb7d0cfee58281 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T23:04:12Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f584554feac24a5684cb7d0cfee582812022-12-22T01:30:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01177e026857910.1371/journal.pone.0268579The impact of monosomies, trisomies and segmental aneuploidies on chromosomal stability.Dorine C HintzenMar SotoMichael SchubertBjorn BakkerDiana C J SpieringsKaroly SzuhaiPeter M LansdorpRoel J C KluinFloris FoijerRené H MedemaJonne A RaaijmakersAneuploidy and chromosomal instability are both commonly found in cancer. Chromosomal instability leads to karyotype heterogeneity in tumors and is associated with therapy resistance, metastasis and poor prognosis. It has been hypothesized that aneuploidy per se is sufficient to drive CIN, however due to limited models and heterogenous results, it has remained controversial which aspects of aneuploidy can drive CIN. In this study we systematically tested the impact of different types of aneuploidies on the induction of CIN. We generated a plethora of isogenic aneuploid clones harboring whole chromosome or segmental aneuploidies in human p53-deficient RPE-1 cells. We observed increased segregation errors in cells harboring trisomies that strongly correlated to the number of gained genes. Strikingly, we found that clones harboring only monosomies do not induce a CIN phenotype. Finally, we found that an initial chromosome breakage event and subsequent fusion can instigate breakage-fusion-bridge cycles. By investigating the impact of monosomies, trisomies and segmental aneuploidies on chromosomal instability we further deciphered the complex relationship between aneuploidy and CIN.https://doi.org/10.1371/journal.pone.0268579 |
| spellingShingle | Dorine C Hintzen Mar Soto Michael Schubert Bjorn Bakker Diana C J Spierings Karoly Szuhai Peter M Lansdorp Roel J C Kluin Floris Foijer René H Medema Jonne A Raaijmakers The impact of monosomies, trisomies and segmental aneuploidies on chromosomal stability. PLoS ONE |
| title | The impact of monosomies, trisomies and segmental aneuploidies on chromosomal stability. |
| title_full | The impact of monosomies, trisomies and segmental aneuploidies on chromosomal stability. |
| title_fullStr | The impact of monosomies, trisomies and segmental aneuploidies on chromosomal stability. |
| title_full_unstemmed | The impact of monosomies, trisomies and segmental aneuploidies on chromosomal stability. |
| title_short | The impact of monosomies, trisomies and segmental aneuploidies on chromosomal stability. |
| title_sort | impact of monosomies trisomies and segmental aneuploidies on chromosomal stability |
| url | https://doi.org/10.1371/journal.pone.0268579 |
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