aneuploidAneuploidy reduces fitness at both the organismal level and the individual cell level, demonstrating that chromosomal imbalance creates a broad cellular stress. This fitness reduction manifests through impaired cell proliferationproliferation, altered metabolism, and reduced immortalization capacity across different aneuploid cell types. [@williams_aneuploidy_2008]

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It is well established across multiple model systems that aneuploidy—the presence of an abnormal chromosome number—consistently reduces fitness at both the organismal and cellular levels, regardless of which specific chromosome is gained or lost. This general fitness cost operates through pleiotropic cellular stress mechanisms that manifest as impaired proliferation, altered metabolic properties, and reduced immortalization capacity in trisomic mammalian cells, as well as proliferative disadvantages in aneuploid yeast strains carrying different extra chromosomes. The mechanistic basis for this fitness reduction involves chromosomal imbalance creating fundamental physiological constraints, though the precise molecular pathways remain incompletely resolved. What is particularly notable is that aneuploid cancer cells must evolve specific compensatory mechanisms—such as inactivating Stat1 signaling to evade immune surveillance—to overcome these inherent fitness costs, suggesting that aneuploidy-induced stress and the cellular responses to it represent contested selective pressures during tumor evolution.

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