R4.5i: Genomic Instability

This is not a hallmark as such, but rather an 'enabling feature'

The ability of malignant cells to develop a wide array of mutations in multiple oncogenes and tumour suppressor genes suggests a much higher rate of mutation than is seen in normal cells. Malignant cells have been shown to downregulate the normal cellular mechanisms that detect and prevent mutation, allowing them to accelerate the rate of mutation acquisition.

This helps to explain the ability of tumours to adapt to therapies such as chemotherapy or radiotherapy through a process of natural selection - the cells with the ability to mutate (or with mutations that have already been acquired) their genome to avoid destruction are those which survive and reproliferate the tumour.

Patients with congential mutations in tumour suppressor genes (e.g. TP53) have much higher rates of malignancy. Once the other, normal gene is mutated, cells are able to acquire mutations much more rapidly.