Chromosome Instability; Implications in Cancer Development, Progression, and Clinical Outcomes
1
Research Institute in Oncology & Hematology, CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada
2
Department of Biochemistry & Medical Genetics, University of Manitoba, Winnipeg, MB R3E 0J9, Canada
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(4), 824; https://doi.org/10.3390/cancers12040824
Received: 10 March 2020
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Revised: 27 March 2020
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Accepted: 28 March 2020
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Published: 29 March 2020
(This article belongs to the Special Issue Chromosome Instability – Implications in Disease Pathogenesis, Health Outcomes and Therapeutic Targeting)
Chromosome instability (CIN) refers to an ongoing rate of chromosomal changes and is a driver of genetic, cell-to-cell heterogeneity. It is an aberrant phenotype that is intimately associated with cancer development and progression. The presence, extent, and level of CIN has tremendous implications for the clinical management and outcomes of those living with cancer. Despite its relevance in cancer, there is still extensive misuse of the term CIN, and this has adversely impacted our ability to identify and characterize the molecular determinants of CIN. Though several decades of genetic research have provided insight into CIN, the molecular determinants remain largely unknown, which severely limits its clinical potential. In this review, we provide a definition of CIN, describe the two main types, and discuss how it differs from aneuploidy. We subsequently detail its impact on cancer development and progression, and describe how it influences metastatic potential with reference to cancer prognosis and outcomes. Finally, we end with a discussion of how CIN induces genetic heterogeneity to influence the use and efficacy of several precision medicine strategies, including patient and risk stratification, as well as its impact on the acquisition of drug resistance and disease recurrence.
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Keywords:
chromosome instability; genome instability; aneuploidy; cancer; tumor heterogeneity; prognosis; metastasis; clinical outcome; therapeutic targeting; chemoresistance
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
MDPI and ACS Style
Vishwakarma, R.; McManus, K.J. Chromosome Instability; Implications in Cancer Development, Progression, and Clinical Outcomes. Cancers 2020, 12, 824. https://doi.org/10.3390/cancers12040824
AMA Style
Vishwakarma R, McManus KJ. Chromosome Instability; Implications in Cancer Development, Progression, and Clinical Outcomes. Cancers. 2020; 12(4):824. https://doi.org/10.3390/cancers12040824
Chicago/Turabian StyleVishwakarma, Raghvendra, and Kirk J. McManus. 2020. "Chromosome Instability; Implications in Cancer Development, Progression, and Clinical Outcomes" Cancers 12, no. 4: 824. https://doi.org/10.3390/cancers12040824
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