In the past two decades, genome sequencing of tumours has revolutionised our understanding of the genetics of cancer. This has revealed that most cancers carry thousands of mutations in their genomes, accumulated through the lifetime of their cells. However, owing to technical limitations, little was known about the earliest steps of cancer and how normal cells in our tissues accumulate mutations during ageing and in different diseases.
In 2015 we published the first comprehensive description of somatic mutation and selection in a healthy solid tissue, revealing that human skin is a patchwork of thousands of competing clones carrying cancer-driver mutations (Martincorena et al., Science, 2015). At that time, it was unclear whether sun-exposed skin was an exceptional tissue, owing to a lifetime of sun damage. In subsequent studies we described similar patterns in normal oesophagus (Martincorena et al., Science, 2018) and bladder (Lawson et al., Science, 2020). These discoveries revealed a rich and previously unseen landscape of mutation and selection in our cells as we age, raising questions about the role of these processes in cancer, ageing and other diseases.
Our current research focuses on understanding the extent and impact of somatic evolution in normal and disease tissues. This includes developing new methods to detect somatic mutations down to single-molecule sensitivity -NanoSeq- (Abascal et al., Nature, 2021; Lawson et al., Nature 2025), studies exploring the impact of somatic mutation in diseases unrelated to cancer and forays into somatic mutation in other species (Cagan et al., Nature, 2022). A significant amount of our work at the moment is focused on understanding the role of somatic mutations in autoimmune disease (Nicola et al, Nature, 2026).
I also work on adapting evolutionary methods to quantify selection in somatic evolution and on the development of computational methods for discovering new cancer genes and non-coding driver mutations. This includes the development of dNdScv (Martincorena et al, Cell, 2017), an evolutionary method to study selection in cancer and somatic evolution, which has enabled our studies across tissues and diseases.