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Review
. 2019 May 14:12:17.
doi: 10.1186/s13039-019-0429-1. eCollection 2019.

The emerging links between chromosomal instability (CIN), metastasis, inflammation and tumour immunity

Andréa E Tijhuis  1 , Sarah C Johnson  1 , Sarah E McClelland  1
Affiliations
Review

The emerging links between chromosomal instability (CIN), metastasis, inflammation and tumour immunity

Andréa E Tijhuis et al. Mol Cytogenet. .

Abstract

Many cancers possess an incorrect number of chromosomes, a state described as aneuploidy. Aneuploidy is often caused by Chromosomal Instability (CIN), a process of continuous chromosome mis-segregation. CIN is believed to endow tumours with enhanced evolutionary capabilities due to increased intratumour heterogeneity, and facilitating adaptive resistance to therapies. Recently, however, additional consequences and associations with CIN have been revealed, prompting the need to understand this universal hallmark of cancer in a multifaceted context. This review is focused on the investigation of possible links between CIN, metastasis and the host immune system in cancer development and treatment. We specifically focus on these links since most cancer deaths are due to the consequences of metastasis, and immunotherapy is a rapidly expanding novel avenue of cancer therapy.

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Conflict of interest statement

Not applicable.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
A karyogram from a high grade serous ovarian carcinoma cell (Kuramochi) showing extensive numerical (e.g. chromosome 3, green) and structural (e.g. chromosome 1 (red) translocation to chromosome 5 (turquoise) aneuploidy
Fig. 2
Fig. 2
Mitotic and chromosome replicative defects that can lead to CIN. Common defects in mitosis leading to CIN include cohesion defects, spindle assembly checkpoint dysfunction, supernumerary centrosomes and cytokinesis failure. Problems upstream of mitosis, during DNA replication and repair can include telomere dysfunction, leading to breakage-fusion-bridge (BFB) cycles, and replication stress
Fig. 3
Fig. 3
Schematic indicating the pathway from Micronucleus formation to activation of the cGAS-STING pathway, and canonical and non-canonical routes to Type I interferon response
Fig. 4
Fig. 4
Diagram depicting the relationships between CIN, ITH, inflammation and metastasis discussed in this review
See this image and copyright information in PMC

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