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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Vydáno v:	Oncogene Ročník 38; číslo 33; s. 6083 - 6094
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 15.08.2019 Nature Publishing Group Nature Publishing Group [1987-....]
Témata:	13/1 13/106 13/109 13/31 13/51 14/32 14/63 45/22 45/61 45/77 631/208/211 631/67/1798 631/67/2329 631/67/69 631/67/70 64/110 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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0950-9232 1476-5594 1476-5594
DOI:	10.1038/s41388-019-0859-6