Inigo Martincorena

Group Leader

Inigo is a group leader at the Sanger Institute investigating somatic mutation in normal tissues, cancer and ageing.

In the past decade, 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 is 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., 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., 2018) and bladder (Lawson et al., 2020).

These findings revealed how little we know about how our cells mutate and compete during life and have raised questions about the role of these processes in cancer and ageing. Our research focuses on understanding the extent of somatic evolution in normal tissues, including developing new methods to study somatic mutagenesis at single-molecule resolution (Abascal et al., 2021), studies exploring the impact of somatic mutation in diseases unrelated to cancer and forays into somatic mutation in other species (Cagan, Baez-Ortega et al., 2022).

I also work on adapting evolutionary methods to study 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, an evolutionary method to study selection in cancer and somatic evolution.

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