Fig. 1.

Mutational signatures generated experimentally and extracted from human tumours by whole genome sequencing. Each signature has 96 components, comprised of six possible base pair substitutions, each of which has four possible 5′ neighbouring bases and four possible 3′ neighbouring bases. The experimental signatures, shown on the left, were produced from induced human pluripotent stem cells exposure to mutagens [31]. The human tumour signatures, on the right, are from the COSMIC database (http://cancer.sanger.ac.uk/cosmic/signatures). The figure shows that propagation of cells in culture without treatment generates a signature similar to the COSMIC signature 18; simulated sunlight produces a signature similar to COSMIC signature 7; aristolochic acid produces a signature similar to COSMIC signature 22; benzo[a]pyrene produces a signature similar to COSMIC signature 4 (the “smoking” signature); temozolomide produces a signature that is distinctly different from COSMIC signature 11.