Chromosomal rearrangements and duplications are often seen in the karyotype of cancer cells. Cells normally will stop in the cell cycle if DNA is damaged. Several proteins have been identified that act to halt the cell cycle until DNA damage is repaired. The p53 driven elimination of damaged cells represent the main component of defence against tumor development and obligatory during carcinogenesis. Shortening of telomere in cells direct senescence, but mutations of DNA maintenance pathway result in continued telomere addition and loss of telomere activity, inducing chromosomal instability.
Telomeres are repetitive DNA sequence flanking the end of linear chromosomes.
As cells undergo division telomeres are shortened by 50 to 200 bases because of the end-replication problem . Cells have strategies to stop this progressive telomere loss. But the most common in Eukaryote is an enzyme complex called Telomerase. It have been hypothesised that proliferation of tumour cells beyond the limits of cellular senescence must reactivate telomerase or mechanism in order to maintain telomeres. At this stage telomere function is impaired giving rise to chromosomal rearrangements leading to cancer genotype.