Extended Data Fig. 7: Mutational landscape of normal esophageal epithelium at 10 days post-DEN treatment.
From: Mutant clones in normal epithelium outcompete and eliminate emerging tumours
(a) Protocol: wild-type mice were treated for two months with DEN. 10 days after DEN withdrawal, normal epithelial samples matching the size of the tumors (Extended Data Fig. 4b) were collected and sequenced with a targeted approach (192 gene panel). (b) Number of mutations per sample, including essential splice, frameshift, missense, nonsense and silent mutations (n = 81 samples from 2 mice). (c) Percentage of mutation types identified in normal epithelium and tumors collected 10 days post-DEN treatment. (d) Mutational spectrum of 10-day post-DEN tumors and normal epithelium. The bar plots illustrate the number of mutations in each of the 96 possible trinucleotides. (e) Dots show the value of the mutation with maximum VAF identified in each sample (n = 81 samples). Lines are mean ± s.e.m. (f) dN/dS ratios for missense and truncating (nonsense + essential splice site) mutations of positively selected genes (dN/dS >1) (only significant genes are shown, q < 0.05 calculated with R package dNdScv26). (g) Number and type of mutations in the positively selected genes identified by dN/dS. (h) Estimated percentage of 10 days post-DEN normal epithelium carrying non-synonymous mutations in the positively selected genes. Range indicates upper and lower bound estimates.
