Our cells accumulate somatic mutations during our lifetime due to multiple mutational processes. Each of these processes leave a specific mutational footprint that can be traced in the form of mutational signatures. Some chemotherapies, for instance, are mutagens and by analyzing whole-genomes from metastases of treated patients we can identify mutational signatures of cancer treatments.

Recent sequencing studies have uncovered abundant clonal expansions driven by somatic mutations in normal human tissues, suggesting that even strong cancer driver mutations are not sufficient for cancer formation. I will introduce the concept of promotion as the rate-limiting step in tumour development and I will explain how we are studying tumor promotion in normal tissues.

Somatic mutations can be used to track the developmental history of cells within an organism. I will explain how we are using somatic mutations for lineage tracing to understand pediatric cancer cases.

During my presentation I will talk about how we use somatic mutations to identify mutational signatures, time clonal expansions, study tumor promotion and perform lineage tracing.