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Aneuploidy triggers an immune response

ABSTRACT: Aneuploidy, a state of karyotype imbalance, is a hallmark of cancer. Changes in chromosome copy number have been proposed to drive disease by modulating the dosage of cancer driver genes and by promoting cancer genome evolution. Given the potential of cells with abnormal karyotypes to become cancerous, do pathways exist that limit the prevalence of such cells? By investigating the immediate consequences of aneuploidy on cell physiology, we identified mechanisms that eliminate aneuploid cells. We find that chromosome mis-segregation leads to replication stress, generating further genomic instability, increased karyotype complexity, and ultimately cell cycle arrest. Cells with complex karyotypes exhibit features of senescence and a pro-inflammatory response that promotes their clearance by the immune system. We propose that cells with abnormal karyotypes generate a signal for their own elimination that might well be a source of cancer cell immunosurveillance that must be overcome during malignant transformation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE83647 | GEO | 2017/06/20

SECONDARY ACCESSION(S): PRJNA326596

REPOSITORIES: GEO

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A transcriptional and metabolic signature of primary aneuploidy is present in chromosomally-unstable cancer cells and informs clinical prognosis

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