R4.5d: Immortality

Normal human cells have the ability to divide 60 – 70 times. During each division, the telomere at the end of each chromosome is shortened. The telomere prevents the cell from attempting to join the end of the chromosome with another. As the telomere becomes shorter, the cell may recognise the end of the chromosome as a ‘double strand break’ and attempt, through non-homologous end joining, to attach it to another end of a chromosome. This can lead to bizarre chromosome abnormalities, and if the cell attempts to divide may cause mitotic catastrophe.
Malignant cells avoid this fate by increasing expression of telomerase, an enzyme which builds on the telomeres. 85-90% of malignancies have increased levels of telomerase. The remaining 5-10% use alternative lengthening of telomeres, a form of DNA recombination.
It may be that as the early malignant cells develop shorter telomeres, the increased genomic instability may lead to further mutations including the increased expression of telomerase. This may explain the aneuploidy seen in many tumour cells.


1. Hanahan, D., & Weinberg, R. A. (2000). The hallmarks of cancer. Cell, 100(1), 57–70.
2. Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of Cancer: The Next Generation. Cell, 144(5), 646–674. doi:10.1016/j.cell.2011.02.013