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cancer chromosomal instability

Wednesday 19 November 2003

chromosome instability, CIN; cancer chromosomal instability; chromosomal instability in cancer

Definition: Cancer chromosomal instability (CIN) results in an increased rate of change of chromosome number and structure and generates intratumour heterogeneity. CIN is observed in most solid tumours and is associated with both poor prognosis and drug resistance.

Genomic instability can be divided into 2 categories:
- chromosomal instability (CIN)
- microsatellite instability (MSI).

CIN has been linked to aneuploidy and chromosomal aberrations, and high-level loss of heterozygosity (LOH-H) has been suggested to be an indicator of CIN.

High-level MSI (MSI-H), which results from nonfunctional mismatch repair, has previously been suggested to be mutually exclusive with CIN.

For example, the most common form of genomic instability observed in colorectal cancer is chromosomal instability (CIN), whose molecular bases remain to be determined.

Cancer cells frequently exhibit gross chromosomal alterations such as translocations, deletions, or gene amplifications an important source of chromosomal instability in malignant cells.

Chromosomal instabilities are related to abnormalities of DNA metabolism, DNA repair, cell-cycle governance, or control of apoptosis.

Anaphase bridges-chromosomes

One of the better-documented mechanism of chromosomal instability is the formation of anaphase bridges-chromosomes pulled in opposite directions by the spindle apparatus. Anaphase bridges are associated with DNA double strand breaks (DSBs).

While the majority of DSBs are repaired correctly, to restore the original chromosome structure, incorrect fusion events also occur leading to bridging.

Chromosomal instability syndromes

- ataxia telangiectasia
- Fanconi anaemia
- Bloom syndrome
- Nijmegen breakage syndrome
- ataxia telangiectasia-like disorder

Chromosomal segregation

Inactivation in human cells of several components of the Pes1-Bop1 complex (BOP1, GRWD1, PES1, ORC6L, and RPL3), involved in ribosome biogenesis, altered chromosome segregation. (16804918)


Chromosome instability, which is equated to mitotic defects and consequential chromosome segregation errors, provides a formidable basis for the acquisition of further malignant phenotypes during tumour progression.

Centrosomes have a crucial role in the formation of bipolar mitotic spindles, which are essential for accurate chromosome segregation.

Mutations of certain oncogenic and tumour-suppressor proteins directly induce chromosome instability by disrupting the normal function and numeral integrity of centrosomes.

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