Driver mutation

Aberrations of the DNA that give a tumor clone the decisive growth advantage over normal cells.

The DNA of tumor cells is characterized by a combination of mutations: translocations, base pair exchanges and different sets of chromosomes.

Of crucial importance is the question which mutations are of growth-determining importance for carcinogenesis.

The majority of detectable changes in the DNA code are so-called "passenger mutations". They arise in the course of the many cell divisions of a clone, but are not crucial for the survival and uninhibited proliferation of the cells.

Crucial for this are the so-called "driver mutations" also known as drivers. These aberrations of the DNA give the tumour clone the decisive growth advantage over normal cells. So far, > 500 mutated key genes (oncogenes) have been discovered for individual tumours, which is about 2.5% of all protein-coding genes.

An example of a driver mutation is the ABL kinase, which is constitutively expressed in the frequent 9:22 translocation in chronic myeloid leukaemia. Its inhibitor is imatinib. For malignant melanoma a mutation of the B-RAF gene is of growth determining importance. Trastuzumab is an effective antibody in breast cancer therapy, which is directed against the permanent presence of the epidermal growth factor receptor HER2/neu; Her2-positive patients have a rather poor prognosis.

It is now known that most malignancies (e.g. breast, ovarian, pancreatic carcinoma) have between 1,000 and 10,000 somatic mutations. Tumour types in which damaging environmental influences have a co-triggering cause (e.g. bronchial carcinoma - smoking, malignant melanoma - UV rays) have far above-average (>100,000) mutations in their genome.