Ongoing chromosomal instability and karyotype evolution in human colorectal cancer organoids

Autor: Ana C.F. Bolhaqueiro, Nizar Hami, Devanjali Dutta, Nobuo Sasaki, Onno Kranenburg, Judith Vivié, Marc van de Wetering, Peter M. Lansdorp, Robert G.J. Vries, Alexander van Oudenaarden, Geert J. P. L. Kops, Hans Clevers, Diana C.J. Spierings, Hugo J. Snippert, Ingrid Verlaan-Klink, Bas Ponsioen, Emre Kucukkose, Richard H. van Jaarsveld, Bjorn Bakker, Sjoerd J Klaasen, Floris Foijer, Sylvia F. Boj
Přispěvatelé: Hubrecht Institute for Developmental Biology and Stem Cell Research, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Stem Cell Aging Leukemia and Lymphoma (SALL), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
HUMAN COLON
Colorectal cancer
TUMOR EVOLUTION
Aneuploidy
Imaging
0302 clinical medicine
Single-cell analysis
Chromosome instability
Chromosome Segregation
SEGREGATION ERRORS
Non-U.S. Gov't
0303 health sciences
Tumor
Research Support
Non-U.S. Gov't
Karyotype
3. Good health
Organoids
MIS-SEGREGATION
Mitosis/genetics
Microsatellite Instability
Single-Cell Analysis
Colorectal Neoplasms
DNA Copy Number Variations
Mitosis
Biology
Research Support
Cell Line
03 medical and health sciences
Imaging
Three-Dimensional
Cell Line
Tumor
Chromosomal Instability
Journal Article
Genetics
medicine
Humans
GENETIC INSTABILITY
030304 developmental biology
ANEUPLOIDY
Microsatellite instability
Cancer
IN-VITRO
medicine.disease
Colorectal Neoplasms/genetics
Organoids/pathology
DNA-DAMAGE
INTRATUMOR HETEROGENEITY
Karyotyping
Three-Dimensional
Mutation
CELLS
Cancer research
030217 neurology & neurosurgery
Zdroj: Nature Genetics, 51(5), 824-834. Nature Publishing Group
Nature Genetics, 51(5), 824. Nature Publishing Group
Nature Genetics
ISSN: 1061-4036
Popis: 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 karyo-types 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.
Databáze: OpenAIRE
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