Fig. 2. Timing of mutational processes and candidate drivers shows UV damage and DNA repair dysfunction dominate in chronologically distinct phases.

A Mutational signatures in early and late disease. Shown signatures, represented by COSMIC identifiers, were identified in at least 2 patients. Vertical lines indicate the normalised inferred weight per patient with the indicated signature in early (upper) and late (lower) disease. B Recurrently mutated melanoma or COSMIC cancer genes in early or late disease. Shown genes were mutated in at least 2 patients and are presented in decreasing number of patients. Dotted mutations indicate predicted deleterious or COSMIC mutations. C Distribution of hotspot mutations²⁷ across the cohort. Mutations surrounded by black indicate those occurring in late disease.