Mutational signatures are the imprints of DNA damage and DNA repair processes that have been operative during tumorigenesis. They are biologically informative, reporting on the processes that have contributed to the developmental history of each patient's cancer. In this lecture, on behalf of my team and my collaborators, I shall provide an update on the field, focusing on validation of these abstract mathematical concepts, untangling the mechanisms underpinning mutation patterns in human somatic cells, and describing the new insights that we have gained through combinations of computational analysis and experiments in cell-based systems. We showcase how mutational-signature-based clinical algorithms have been developed, describe the path taken in translating these towards medical utility and for balance, highlight some of the hurdles that need to be navigated in this type of translational research.

Citation Format: Serena Nik-Zainal. Harnessing the value of mutational signatures in whole cancer genomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr PL02-02.