Chromosomal instability and cancer: a complex relationship with therapeutic potential

J Clin Invest. 2012 Apr;122(4):1138-43. doi: 10.1172/JCI59954. Epub 2012 Apr 2.


Chromosomal instability (CIN) is a hallmark of human neoplasms. Despite its widespread prevalence, knowledge of the mechanisms and contributions of CIN in cancer has been elusive. It is now evident that the role of CIN in tumor initiation and growth is more complex than previously thought. Furthermore, distinguishing CIN, which consists of elevated rates of chromosome missegregation, from aneuploidy, which is a state of abnormal chromosome number, is crucial to understanding their respective contributions in cancer. Collectively, experimental evidence suggests that CIN enables tumor adaptation by allowing tumors to constantly sample the aneuploid fitness landscape. This complex relationship, together with the potential to pharmacologically influence chromosome missegregation frequencies in cancer cells, offers previously unrecognized means to limit tumor growth and its response to therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aneuploidy
  • Animals
  • Antineoplastic Agents / therapeutic use
  • Aurora Kinases
  • Chromosomal Instability*
  • Chromosome Breakage
  • Chromosome Deletion
  • Chromosome Segregation / drug effects
  • Chromosome Segregation / physiology
  • Humans
  • Mice
  • Molecular Targeted Therapy
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / pathology
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Selection, Genetic
  • Sequence Deletion
  • Spindle Apparatus / drug effects
  • Spindle Apparatus / physiology


  • Antineoplastic Agents
  • Neoplasm Proteins
  • Protein Kinase Inhibitors
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases