Monosomies, trisomies and segmental aneuploidies differentially affect chromosomal stability
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
Abstract 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 in segmental aneuploidies. This suggests that monosomies, trisomies and segmental aneuploidies have fundamentally different effects on chromosomal instability and these results help us to decipher the complex relationship between aneuploidy and CIN.
Authors 10
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The Netherlands Cancer Institute · Oncode Institute
Affiliation as printed
Oncode Institute, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
Oncode Institute, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 2, 066 CX, Amsterdam, The Netherlands
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The Netherlands Cancer Institute · Oncode Institute
Affiliation as printed
Oncode Institute, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
Oncode Institute, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 2, 066 CX, Amsterdam, The Netherlands
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The Netherlands Cancer Institute · Oncode Institute
Affiliation as printed
Oncode Institute, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
Oncode Institute, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 2, 066 CX, Amsterdam, The Netherlands
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Affiliation as printed
The Francis Crick Institute, 1 Midland Road, London NW1 1AT, United Kingdom
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University Medical Center Groningen · University of Groningen
Affiliation as printed
European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, A. Deusinglaan 1, Groningen 9713 AV, The Netherlands
European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, A. Deusinglaan 1, Groningen 971 AV, The Netherlands
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Károly Szuhai Aachen
Leiden University Medical Center
Affiliation as printed
. Leids Universitair Medisch Centrum, Einthovenweg 20, 2333 ZC Leiden, The Netherlands
Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
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Affiliation as printed
The Francis Crick Institute, 1 Midland Road, London NW1 1AT, United Kingdom
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University Medical Center Groningen · University of Groningen
Affiliation as printed
European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, A. Deusinglaan 1, Groningen 9713 AV, The Netherlands
European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, A. Deusinglaan 1, Groningen 971 AV, The Netherlands
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René H. Medema corresponding
The Netherlands Cancer Institute · Oncode Institute
Affiliation as printed
Oncode Institute, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
Oncode Institute, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 2, 066 CX, Amsterdam, The Netherlands
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Jonne A. Raaijmakers corresponding
The Netherlands Cancer Institute · Oncode Institute
Affiliation as printed
Oncode Institute, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
Oncode Institute, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 2, 066 CX, Amsterdam, The Netherlands
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