Fig. 1: Tissue priming determines tumour multiplicity in response to ENU mutagenesis.
From: Decay of driver mutations shapes the landscape of intestinal transformation
a, The experimental protocol for priming (TE) experiments. Tam, tamoxifen. b, Cumulative tumour burden by intestinal region in control (ENU only) mice. Proximal and distal SI are defined as the first 20 cm from the pyloric sphincter and the remaining length, respectively. c, Intestinal tumour burden and survival after ENU treatment in control mice. Inset: cause of death. HEP, humane end point; HEP(L), presence of lymphoma/leukaemia at the humane end point. d, Kaplan–Meier plot of control and primed cohorts (KrasG12D, Trp53null, Fbxw7null) with and without ENU treatment. Mdn, median. e, The mean ± s.d. tumour counts per mouse for each priming event in relation to the median survival after ENU treatment. f, Maximum-likelihood estimates from the dN/dS ratio analysis of tumour nonsense and missense mutations identified by hybridization capture. Genes under positive selection with a q value for all substitutions of <0.25 are labelled. g, Oncoprint for genes under positive selection in the control and primed groups. Synonymous mutations are excluded. SI10, SI20, SI30, SI40 and SI50 refer to tissue samples taken at 0–10, 10–20, 20–30, 30–40 and 40–50 cm distance from the pyloric sphincter. h, The proportions of tumours in each cohort containing detected Apc or Ctnnb1 mutations. i, The proportions of monoclonal (presence of one or two Apc-truncating mutations or a single Ctnnb1 exon-3 mutation) and polyclonal tumours across cohorts for Apc- and Ctnnb1-driven tumours. j,k, The fold change in Apc-driven (j) or Ctnnb1-driven (k) tumours relative to the control. P values were calculated using log-rank tests (d), a two-sample test of equality of Apc proportions with continuity correction (d.f. = 1; two sided) (h) and two-sided Fisher’s exact tests (i).
