Figure 3. Mutation accumulation doubling rates and mutational patterns.

(a) Somatic mutation accumulation doubling rate α_full versus cancer incidence rate doubling rate α_incidence for different cancer types. Cancers in men are denoted by circles, and cancers in women by diamonds according to the colour scheme on the right. A black spot is an average of rates over all cancers. Grey ovals are the contours of the 1σ and 2σ deviations from the average. Straight grey lines correspond to the human mortality doubling rate of 0.125 per year. Pinkish clouds correspond to cancers representing reproductive tissues (upper) and leukaemia (lower). The blue cloud represents cancer of the uvea. (b) Magnification of a showing cancers within the 1σ, 2σ areas. (c) Somatic mutation accumulation doubling rate α_full versus doubling rate α_silent for accumulation of silent mutations for different cancer types (gender-specific data combined). Points of the same colour correspond to the data sets representing the same cancer type, sequenced by different datacenters using different variant-calling pipelines. (d) Full average counts of somatic mutations per exome versus silent mutations for bladder urothelial carcinoma (BLCA) in men. Samples sequenced by Broad Institute, IlluminaGA pipeline. (e) The same for glioblastoma multiforme (GBM) in men. Samples sequenced by Broad Institute, IlluminaGA pipeline. (f) Identifying age-dependent mutational signatures for the breast invasive carcinoma (BRCA) data set. Samples sequenced by Washington University School of Medicine, IlluminaGA human-curated pipeline. Relative weights of different mutation types in the first mutational signature. The signature is dominated by CT and GA mutations (dark red rectangle), the contribution of simple indels is subdominant (violet rectangle). (g) Relative weights of the first six signatures, normalized to 1; the first signature dominates, corresponding to the pattern of somatic mutation accumulation associated with aging. (h) Behaviour of projections onto the first and second leading mutational signatures with age.