Abstract
Aneuploidy, characterized by the gain or loss of chromosomes, plays a critical role in both cancer and congenital aneuploidy syndromes. For any aneuploidy, we can distinguish between its general effects and its chromosome-specific effects. General effects refer to the common cellular stresses induced by aneuploidy, such as impaired proliferation, proteotoxic stress, and altered metabolism, which occur regardless of the specific chromosome involved and profoundly impact cellular and organismal functions. These generalized stresses often hinder cell fitness but can also, under certain conditions, contribute to cancer progression. In contrast, chromosome-specific effects arise from the altered dosage of particular genes on the gained or lost chromosome. These effects vary depending on the chromosome involved and can provide specific fitness effects in cancer cells or distinct developmental phenotypes in congenital aneuploidies like Down syndrome. Understanding the interplay between these two levels of effects is crucial for deciphering the outcomes of aneuploidy. This review synthesizes current knowledge and discusses future directions for unraveling the hallmarks of aneuploidy.