Adam Eyre-Walker Project
The pattern of somatic mutation in cancer genomes
Most cancer is caused by the somatic mutation of one or more or genes, which leads to uncontrolled cell division, the destruction of adjacent tissue, and if metastases form, the invasion into other parts of the body. Which mutations ultimately cause cancer principally depends on three factors; the penetrance or effect of the mutation, the mutation rate, and if the effects are recessive, whether the mutation is segregating within the population. Mutations with large and highly penetrant effects are more likely to be the cause of cancer, but if we have several mutations with similar levels of effect, the ones that are most likely to be the cause of cancer are those with the highest mutation rate. The relative roles of effect size and mutation rate in determining which mutations and genes are responsible for cancer has not been determined. Furthermore, it is unknown whether the pattern of somatic mutation varies between individuals and how this might affect the probability of developing cancer; an individual might have a higher probability of developing cancer if he or she has a higher mutation rate in a region that has an oncogene or tumour suppressing gene.
The aim of this project is to:
1. Characterise the scale at which the mutation rate varies across the genomes from cancer and other somatic tissues.
2. Investigate whether the pattern of somatic mutation rate variation differs between individuals and between tissues.
3. Evaluate the relative roles of mutation rate variation and penetrance in determining the probability that a gene will be involved in cancer.
The project will involve bioinformatic and statistical analyses of next generation sequencing data from cancer genomes, and will build on the supervisors work on mutation rate variation in both somatic and germ-line cells (see Hodgkinson et al. 2011; Hodgkinson and Eyre-Walker 2011).
Hodgkinson, A. and Eyre-Walker, A. (2011) Variation in the mutation rate across the mammalian genome. Nat. Rev. Genet. 12, 756-766
Hodgkinson, A., Chen, Y. and Eyre-Walker, A. (2011) The large scale distribution of somatic mutations in cancer. Human Mutation (published online)
For further project details contact Prof Adam Eyre-Walker (A.C.Eyre-Walker@sussex.ac.uk)