Investigating the Consequences of Aneuploidy in Cancer and Normal Tissue

Aneuploidy is an unbalanced number of chromosomes arising from errors during cell division. Under normal conditions, cells use highly precise mechanisms to accurately segregate chromosomes during mitosis and meiosis. Errors in this process lead to chromosome missegregation and result in aneuploid daughter cells. Aneuploidy causes dosage imbalances of hundreds of different genes, disrupting homeostasis and causing adverse effects like genomic instability, metabolic and proteotoxic stress, cell cycle defects, and apoptosis (Hosea et al. 2024). Aneuploidy is the leading cause of miscarriage and congenital birth defects (Nagaoka et al. 2012). Somatic aneuploidy is found at low levels in neuronal cells and has also been observed post-mortem in brains with neurological pathologies such as Alzheimer's. Tetraploidy, octaploidy, and some aneuploidies are widely observed in hepatocytes, though their significance is not clearly understood (Simonetti et al. 2019). Additionally, aneuploidy is a hallmark of cancer, as 90% of solid tumors are aneuploid with whole chromosome or chromosome arm alterations (Taylor et al. 2018). This chapter will explore the causes and consequences of aneuploidy and its potential therapeutic implications.