Fusion-mediated chromosomal instability promotes aneuploidy patterns that resemble human tumors

Oncogenesis is considered to result from chromosomal instability, in addition to oncogene and tumor-suppressor alterations. Intermediate to aneuploidy and chromosomal instability, genome doubling is a frequent event in tumor development but the mechanisms driving tetraploidization and its impact rem...

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Veröffentlicht in:Oncogene Jg. 38; H. 33; S. 6083 - 6094
Hauptverfasser: Delespaul, Lucile, Merle, Candice, Lesluyes, Tom, Lagarde, Pauline, Le Guellec, Sophie, Pérot, Gaëlle, Baud, Jessica, Carlotti, Martina, Danet, Coralie, Fèvre, Murielle, Rousseau, Benoit, Durrieu, Stéphanie, Teichmann, Martin, Coindre, Jean-Michel, Lartigue, Lydia, Chibon, Frédéric
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 15.08.2019
Nature Publishing Group
Nature Publishing Group [1987-....]
Schlagworte:
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Aneuploidy
Animals
Apoptosis
Cancer
Carcinogenesis
Care and treatment
Cell Biology
Cell differentiation
Cell Fusion
Cell Transformation, Neoplastic - genetics
Cells, Cultured
Chromosomal Instability - physiology
Development and progression
Genetic aspects
Genomes
Genomic Instability
Health aspects
Human Genetics
Humans
Hybrid Cells - cytology
Hybrid Cells - metabolism
Internal Medicine
Latency
Life Sciences
Medicine
Medicine & Public Health
Membrane fusion
Mesenchyme
Mice
Mice, Inbred NOD
Mice, Transgenic
Neoplasms - genetics
Neoplasms - pathology
Oncology
Risk factors
Structure
Tetraploidy
Tumorigenesis
Tumors
France
ISSN:0950-9232, 1476-5594, 1476-5594
Online-Zugang:Volltext
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Zusammenfassung:Oncogenesis is considered to result from chromosomal instability, in addition to oncogene and tumor-suppressor alterations. Intermediate to aneuploidy and chromosomal instability, genome doubling is a frequent event in tumor development but the mechanisms driving tetraploidization and its impact remain unexplored. Cell fusion, one of the pathways to tetraploidy, is a physiological process involved in mesenchymal cell differentiation. Besides simple genome doubling, cell fusion results in the merging of two different genomes that can be destabilized upon proliferation. By testing whether cell fusion is involved in mesenchymal oncogenesis, we provide evidence that it induces genomic instability and mediates tumor initiation. After a latency period, the tumor emerges with the cells most suited for its development. Furthermore, hybrid tumor genomes were stabilized after this selection process and were very close to those of human pleomorphic mesenchymal tumors. Thus genome restructuring triggered by cell fusion may account for the chromosomal instability involved in oncogenesis.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0950-9232
1476-5594
1476-5594
DOI:10.1038/s41388-019-0859-6