Chromosome instability

Chromosomal instability (CIN) is a type of genomic instability in which chromosomes are unstable, such that either whole chromosomes or parts of chromosomes are duplicated or deleted. The unequal distribution of DNA to daughter cells upon mitosis results in a failure to maintain euploidy (the correct number of chromosomes) leading to aneuploidy (incorrect number of chromosomes). In other words, the daughter cells do not have the same number of chromosomes as the cell they originated from.

These changes have been studied in solid tumors, which may or may not be cancerous. CIN is a common occurrence in solid and haematological cancers, especially colorectal cancer. Although many tumours show chromosomal abnormalities, CIN is characterised by an increased rate of these errors.

Numerical CIN is a high rate of either gain or loss of whole chromosomes; causing aneuploidy. Normal cells make errors in chromosome segregation in 1% of cell divisions, whereas cells with CIN make these errors approximately 20% of cell divisions. Because aneuploidy is a common feature in tumour cells, the presence of aneuploidy in cells does not necessarily mean CIN is present; a high rate of errors is definitive of CIN. One way of differentiating aneuploidy without CIN and CIN-induced aneuploidy is that CIN causes widely variable (heterogeneous) chromosomal aberrations; whereas when CIN is not the causal factor, chromosomal alterations are often more clonal.

Structural CIN is different in that rather than whole chromosomes, fragments of chromosomes may be duplicated or deleted. The rearrangement of parts of chromosomes (translocations) and amplifications or deletions within a chromosome may also occur in structural CIN.

CIN often results in aneuploidy. There are three ways that aneuploidy can occur. It can occur due to loss of a whole chromosome, gain of a whole chromosome or rearrangement of partial chromosomes known as gross chromosomal rearrangements (GCR). All of these are hallmarks of some cancers. Segmental aneuploidy can occur due to deletions, amplifications or translocations, which arise from breaks in DNA, while loss and gain of whole chromosomes is often due to errors during mitosis.

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