Noncanonical secondary structures arising from non-B DNA motifs are determinants of mutagenesis

Non-B motifs contribute to locally elevated mutation rates resulting in recurrent mutations in the human genome. (A) Distribution of the number of recurrent events for 3,476,890 somatic mutations from 560 breast cancers (Nik-Zainal et al. 2016). The values do not fit a truncated Poisson distribution (χ² test, P < 1 × 10⁻¹⁶) as there are more recurrent mutations than predicted by the null model. (B) Enrichment of nonrecurrent mutations overlapping non-B DNA motifs for indels (I) and substitutions (S). (C) Enrichment of recurrent mutations overlapping non-B DNA motifs for indels (I) and substitutions (S). Mann-Whitney U test for substitutions: P-value < 0.001 for all non-B DNA motifs. Mann-Whitney U test for indels: P-value < 0.001 for STR, H-DNA, Z-DNA, and MR, and P-value < 0.05 for DR and G4.