Impact of Chromosomal Instability and Aneuploidy in Cancer Development

Somatic human cells contain a diploid genome consisting of 23 pairs of chromosomes. The maintenance of this diploid state is essential across all layers of biological organization, ranging from the physiology of individual cells to the proper regulation of tissue homeostasis and organismal development. Most cancer cells, however, harbor an aneuploid genome with an abnormal number of chromosomes, including whole and/or partial chromosome gains and losses. These alterations arise as a consequence of mitotic chromosome segregation errors and/or ongoing chromosomal instability (CIN). While aneuploidy usually imposes a fitness cost to nontransformed cells, certain recurrent aneuploidies confer adaptive advantages that are subjected to positive selection throughout tumorigenesis. In this review, we discuss how aneuploidy impacts cellular physiology, fitness, and adaptability in the context of cancer development. We also examine how the aneuploid state and CIN can create vulnerabilities that may be exploited for therapeutic intervention.