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Review
. 2017 Dec 28;10(1):4.
doi: 10.3390/cancers10010004.

The Role of Chromosomal Instability in Cancer and Therapeutic Responses

Natalia Vargas-Rondón  1 , Victoria E Villegas  2 , Milena Rondón-Lagos  3
Affiliations
Review

The Role of Chromosomal Instability in Cancer and Therapeutic Responses

Natalia Vargas-Rondón et al. Cancers (Basel). .

Abstract

Cancer is one of the leading causes of death, and despite increased research in recent years, control of advanced-stage disease and optimal therapeutic responses remain elusive. Recent technological improvements have increased our understanding of human cancer as a heterogeneous disease. For instance, four hallmarks of cancer have recently been included, which in addition to being involved in cancer development, could be involved in therapeutic responses and resistance. One of these hallmarks is chromosome instability (CIN), a source of genetic variation in either altered chromosome number or structure. CIN has become a hot topic in recent years, not only for its implications in cancer diagnostics and prognostics, but also for its role in therapeutic responses. Chromosomal alterations are mainly used to determine genetic heterogeneity in tumors, but CIN could also reveal treatment efficacy, as many therapies are based on increasing CIN, which causes aberrant cells to undergo apoptosis. However, it should be noted that contradictory findings on the implications of CIN for the therapeutic response have been reported, with some studies associating high CIN with a better therapeutic response and others associating it with therapeutic resistance. Considering these observations, it is necessary to increase our understanding of the role CIN plays not only in tumor development, but also in therapeutic responses. This review focuses on recent studies that suggest possible mechanisms and consequences of CIN in different disease types, with a primary focus on cancer outcomes and therapeutic responses.

Keywords: cancer outcomes; cancer prognosis; chromosomal instability; predictive markers; therapeutic resistance.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Chromosomal instability (CIN) Characteristics. CIN is characterized by aberrant distribution of chromosomes to the daughter cells deviating from the modal number (numerical CIN—aneuploidy and euploidy) or an elevated frequency of structural chromosome aberrations such as gain or loss of partial chromosomes (structural CIN).
Figure 2
Figure 2
Numerical and structural CIN arise during mitotic chromosome segregation errors. Dysfunctional chromosome duplication or segregation during mitosis can conduce to whole chromosome gains and losses (numerical CIN) and/or alterations in the structure of chromosomes (structural CIN) including translocations, deletions, and derivative chromosome, among other. Both numerical and structural alterations predispose chromosomes to subsequent chromosomal alterations, thereby increasing CIN.
Figure 3
Figure 3
Chromosomal alterations most frequently observed in several types of cancer.
Figure 4
Figure 4
CIN Positive or Negative Response to Treatment. (A) The administration of chemotherapy or radiotherapy to tumor cells (B) can lead to the induction of new numerical and structural chromosomal alterations; This condition could generate two cellular responses; (C) one of them related to the induction of apoptosis (probably due to the excess of genotoxicity), improving the prognosis for the patient by tumor regression, and the other (D) related to the fixation of numerical and structural alterations; (E) consequently leading to clonal expansion of new oncogenic alterations and thus (F) to an overall increase in heterogeneity and development of resistance to therapy.
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