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It is well known that environmental mutagens are associated with increased cancer risk. However, why cancers of different tissues tend to have their own specific collections of mutations remains unanswered. In a paper published in Nature Communications, Temko et al. from Benjamin Schuster-Böckler’s group have found that whilst mutational processes influence the spectrum of mutations in a cancer, the subsequent selection of certain mutations that give the cancer cell an advantage is also required to give the observed signatures.