How Many Mutations for Cancer?

During our lifetime our somatic cells (non-reproductive cells) constantly accumulate mutations – in some cases these mutations lead to uncontrolled proliferation and allow the cells to invade other tissues and spread to other organs – i.e. become cancerous. Most of the mutations in cancerous cells are unimportant – it is only a few that are ‘drivers’ of cancer and dictate the way the cell behaves. However, we do not know how many mutations are actually required to cause cancer, or whether this number varies across cancer types.

Researchers working for the Wellcome Trust looked at over 7,500 tumours of 29 cancer types using methods adapted from molecular evolution to see which mutations were more common in cancerous than in non-cancerous cells.[1] They found that, on average, cancerous cells have around four coding substitutions (where a DNA nucleobase is exchanged for another, such as switching from adenine to guanine) that are ‘driver mutations’. This ranged from around one mutation per tumour in thyroid and testicular cancer, four in breast and liver cancer, to more than ten in endometrial and colorectal cancer. Of these ‘driver mutations’ around half occur in cancer genes that have yet to be discovered.

In the long-term these findings could help advance the development of precision cancer treatment, allowing drugs to be specifically targeted at the appropriate mutation(s).

— Peter Chilton, Research Fellow

Reference:

  1. Matrincorena I, Raine KM, Gerstung M, Dawson KJ, Haase K, Van Loo P, Davies H, Stratton MR, Campbell PJ. Universal Patterns of Selection in Cancer and Somatic Tissues. Cell. 2017.
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