Ongoing chromosomal instability and karyotype evolution in human colorectal cancer organoids

Ana C F Bolhaqueiro; Bas Ponsioen; Bjorn Bakker; Sjoerd J Klaasen; Emre Kucukkose; Richard H van Jaarsveld; Judith Vivié; Ingrid Verlaan-Klink; Nizar Hami; Diana C J Spierings; Nobuo Sasaki; Devanjali Dutta; Sylvia F Boj; Robert G J Vries; Peter M Lansdorp; Marc van de Wetering; Alexander van Oudenaarden; Hans Clevers; Onno Kranenburg; Floris Foijer; Hugo J G Snippert; Geert J P L Kops

doi:10.1038/s41588-019-0399-6

Ongoing chromosomal instability and karyotype evolution in human colorectal cancer organoids

Ana C F Bolhaqueiro, Bas Ponsioen, Bjorn Bakker, Sjoerd J Klaasen, Emre Kucukkose, Richard H van Jaarsveld, Judith Vivié, Ingrid Verlaan-Klink, Nizar Hami, Diana C J Spierings, Nobuo Sasaki, Devanjali Dutta, Sylvia F Boj, Robert G J Vries, Peter M Lansdorp, Marc van de Wetering, Alexander van Oudenaarden, Hans Clevers, Onno Kranenburg, Floris FoijerHugo J G Snippert, Geert J P L Kops

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

150 Citaten (Scopus)

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Chromosome segregation errors cause aneuploidy and genomic heterogeneity, which are hallmarks of cancer in humans. A persistent high frequency of these errors (chromosomal instability (CIN)) is predicted to profoundly impact tumor evolution and therapy response. It is unknown, however, how prevalent CIN is in human tumors. Using three-dimensional live-cell imaging of patient-derived tumor organoids (tumor PDOs), we show that CIN is widespread in colorectal carcinomas regardless of background genetic alterations, including microsatellite instability. Cell-fate tracking showed that, although mitotic errors are frequently followed by cell death, some tumor PDOs are largely insensitive to mitotic errors. Single-cell karyotype sequencing confirmed heterogeneity of copy number alterations in tumor PDOs and showed that monoclonal lines evolved novel karyotypes over time in vitro. We conclude that ongoing CIN is common in colorectal cancer organoids, and propose that CIN levels and the tolerance for mitotic errors shape aneuploidy landscapes and karyotype heterogeneity.

Originele taal-2	Engels
Pagina's (van-tot)	824-834
Aantal pagina's	11
Tijdschrift	Nature Genetics
Volume	51
Nummer van het tijdschrift	5
DOI's	https://doi.org/10.1038/s41588-019-0399-6
Status	Gepubliceerd - mei 2019

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Bolhaqueiro, A. C. F., Ponsioen, B., Bakker, B., Klaasen, S. J., Kucukkose, E., van Jaarsveld, R. H., Vivié, J., Verlaan-Klink, I., Hami, N., Spierings, D. C. J., Sasaki, N., Dutta, D., Boj, S. F., Vries, R. G. J., Lansdorp, P. M., van de Wetering, M., van Oudenaarden, A., Clevers, H., Kranenburg, O., ... Kops, G. J. P. L. (2019). Ongoing chromosomal instability and karyotype evolution in human colorectal cancer organoids. Nature Genetics, 51(5), 824-834. https://doi.org/10.1038/s41588-019-0399-6

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title = "Ongoing chromosomal instability and karyotype evolution in human colorectal cancer organoids",

abstract = "Chromosome segregation errors cause aneuploidy and genomic heterogeneity, which are hallmarks of cancer in humans. A persistent high frequency of these errors (chromosomal instability (CIN)) is predicted to profoundly impact tumor evolution and therapy response. It is unknown, however, how prevalent CIN is in human tumors. Using three-dimensional live-cell imaging of patient-derived tumor organoids (tumor PDOs), we show that CIN is widespread in colorectal carcinomas regardless of background genetic alterations, including microsatellite instability. Cell-fate tracking showed that, although mitotic errors are frequently followed by cell death, some tumor PDOs are largely insensitive to mitotic errors. Single-cell karyotype sequencing confirmed heterogeneity of copy number alterations in tumor PDOs and showed that monoclonal lines evolved novel karyotypes over time in vitro. We conclude that ongoing CIN is common in colorectal cancer organoids, and propose that CIN levels and the tolerance for mitotic errors shape aneuploidy landscapes and karyotype heterogeneity.",

author = "Bolhaqueiro, {Ana C F} and Bas Ponsioen and Bjorn Bakker and Klaasen, {Sjoerd J} and Emre Kucukkose and {van Jaarsveld}, {Richard H} and Judith Vivi{\'e} and Ingrid Verlaan-Klink and Nizar Hami and Spierings, {Diana C J} and Nobuo Sasaki and Devanjali Dutta and Boj, {Sylvia F} and Vries, {Robert G J} and Lansdorp, {Peter M} and {van de Wetering}, Marc and {van Oudenaarden}, Alexander and Hans Clevers and Onno Kranenburg and Floris Foijer and Snippert, {Hugo J G} and Kops, {Geert J P L}",

year = "2019",

month = may,

doi = "10.1038/s41588-019-0399-6",

language = "English",

volume = "51",

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journal = "Nature Genetics",

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Bolhaqueiro, ACF, Ponsioen, B, Bakker, B, Klaasen, SJ, Kucukkose, E, van Jaarsveld, RH, Vivié, J, Verlaan-Klink, I, Hami, N, Spierings, DCJ, Sasaki, N, Dutta, D, Boj, SF, Vries, RGJ, Lansdorp, PM, van de Wetering, M, van Oudenaarden, A , Clevers, H, Kranenburg, O, Foijer, F, Snippert, HJG & Kops, GJPL 2019, 'Ongoing chromosomal instability and karyotype evolution in human colorectal cancer organoids', Nature Genetics, vol. 51, nr. 5, blz. 824-834. https://doi.org/10.1038/s41588-019-0399-6

TY - JOUR

T1 - Ongoing chromosomal instability and karyotype evolution in human colorectal cancer organoids

AU - Bolhaqueiro, Ana C F

AU - Ponsioen, Bas

AU - Bakker, Bjorn

AU - Klaasen, Sjoerd J

AU - Kucukkose, Emre

AU - van Jaarsveld, Richard H

AU - Vivié, Judith

AU - Verlaan-Klink, Ingrid

AU - Hami, Nizar

AU - Spierings, Diana C J

AU - Sasaki, Nobuo

AU - Dutta, Devanjali

AU - Boj, Sylvia F

AU - Vries, Robert G J

AU - Lansdorp, Peter M

AU - van de Wetering, Marc

AU - van Oudenaarden, Alexander

AU - Clevers, Hans

AU - Kranenburg, Onno

AU - Foijer, Floris

AU - Snippert, Hugo J G

AU - Kops, Geert J P L

PY - 2019/5

Y1 - 2019/5

N2 - Chromosome segregation errors cause aneuploidy and genomic heterogeneity, which are hallmarks of cancer in humans. A persistent high frequency of these errors (chromosomal instability (CIN)) is predicted to profoundly impact tumor evolution and therapy response. It is unknown, however, how prevalent CIN is in human tumors. Using three-dimensional live-cell imaging of patient-derived tumor organoids (tumor PDOs), we show that CIN is widespread in colorectal carcinomas regardless of background genetic alterations, including microsatellite instability. Cell-fate tracking showed that, although mitotic errors are frequently followed by cell death, some tumor PDOs are largely insensitive to mitotic errors. Single-cell karyotype sequencing confirmed heterogeneity of copy number alterations in tumor PDOs and showed that monoclonal lines evolved novel karyotypes over time in vitro. We conclude that ongoing CIN is common in colorectal cancer organoids, and propose that CIN levels and the tolerance for mitotic errors shape aneuploidy landscapes and karyotype heterogeneity.

AB - Chromosome segregation errors cause aneuploidy and genomic heterogeneity, which are hallmarks of cancer in humans. A persistent high frequency of these errors (chromosomal instability (CIN)) is predicted to profoundly impact tumor evolution and therapy response. It is unknown, however, how prevalent CIN is in human tumors. Using three-dimensional live-cell imaging of patient-derived tumor organoids (tumor PDOs), we show that CIN is widespread in colorectal carcinomas regardless of background genetic alterations, including microsatellite instability. Cell-fate tracking showed that, although mitotic errors are frequently followed by cell death, some tumor PDOs are largely insensitive to mitotic errors. Single-cell karyotype sequencing confirmed heterogeneity of copy number alterations in tumor PDOs and showed that monoclonal lines evolved novel karyotypes over time in vitro. We conclude that ongoing CIN is common in colorectal cancer organoids, and propose that CIN levels and the tolerance for mitotic errors shape aneuploidy landscapes and karyotype heterogeneity.

U2 - 10.1038/s41588-019-0399-6

DO - 10.1038/s41588-019-0399-6

M3 - Article

C2 - 31036964

SN - 1061-4036

VL - 51

SP - 824

EP - 834

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

Ongoing chromosomal instability and karyotype evolution in human colorectal cancer organoids

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