Chromosomal instability and aneuploidy: a conundrum in cancer evolution

Abstract

Chromosomal instability (CIN), defined as an increased rate of gain or loss of whole chromosomes, leads to aneuploid cells, which are cells that display an abnormal number of chromosomes. Both CIN and aneuploidy are hallmarks of cancer, yet the underlying mechanisms of CIN and aneuploidy and their impact on tumourigenesis have remained poorly defined. Although multiple mechanisms have been proposed to explain the role of CIN and aneuploidy in tumourigenesis, this review focuses on three principal pathways leading to CIN: spindle assembly checkpoint defects, merotelic attachments, and cohesion defects. Here, we provide a brief overview of the current understanding of the roles of these mechanisms in CIN and aneuploidy. We also present emerging evidence that contradicts the importance of certain mechanisms in cancer evolution. A clearer understanding of these fundamental pathways could prove to be helpful in developing effective cancer therapies.