Oxidative stress accelerates intestinal tumorigenesis by enhancing 8-oxoguanine-mediated mutagenesis in MUTYH-deficient mice

Mutation pattern of KBrO₃-induced tumor in Mutyh^−/− mice. The mutation pattern is displayed based on the 96-base substitution classification defined by the substitution class and sequence context immediately 3′ and 5′ to the mutated base. The y-axis indicates the contribution of each mutation to the total mutation number. The x-axis indicates 96 trinucleotide types. (A) Somatic mutations in the tumor samples of KBrO₃-treated Mutyh^−/− mice detected using WES. (B) Somatic mutations were detected in the normal intestinal tissues (pre-tumor-initiation stage) of KBrO₃-treated Mutyh^−/− mice using the rpsL assay. (C) Mutation pattern of de novo germline mutations detected in TOY mice (Ohno et al. 2014). (D) Mutation pattern of tumor samples from human patients with MAP (see Methods). (E) Signature 18 in COSMIC mouse ver.2. (F) SBS 36 in COSMIC mouse ver.3. (G) SBS 45 in COSMIC mouse ver.3.