Fig. 1: Brca1−/−;Trp53−/− lesion formation is accompanied by fields of morphologically normal ducts carrying mutant cells.
From: Mechanisms that clear mutations drive field cancerization in mammary tissue
a, Schematic of the Brcafl/fl;Trp53fl/fl;R26R-Confetti mouse model used in this study. Recombination was induced by an intraductal injection method with TAT-Cre recombinant protein, leading to sporadic deletion of the Brca1;Trp53 alleles and at the same time stochastic recombination of the Confetti construct resulting in the expression of one of the four fluorophores. b, Timeline of lineage tracing experiments performed in the adult mammary gland. c,d, Brca1;Trp53 confetti lesions with a transformed ductal morphology (c) and partially transformed ductal morphology and local invasion (d). e, Transformed luminal (L, orange) and basal (B, red) clones as a percentage of the total number of luminal and basal clones, respectively. Each dot indicates an individual mouse; boxplots mark the 25th and 75th percentile, the line indicates the median and the whiskers mark the minimum and maximum values. f, Representative whole-mount confocal images of non-transformed Brca1−/−;Trp53−/− confetti clones showing extensive field cancerization within the existing ductal structure. c,d,f, Images show 3D rendering of Z-stacks, with the confetti-labelled cells in their respective colours and the mammary ducts labelled with an antibody against SMA (white). Representative examples of n = 6 mice. g, Charts representing the fraction of non-transformed luminal and basal clones (grey), the transformed luminal clones (orange) and the transformed basal clones (red) at different time points after recombination for all analysed glands combined. The total number of quantified Brca1−/−;Trp53−/− confetti clones is indicated below the charts and the number of transformed clones is indicated within the charts. See Supplementary Information 1 for sample sizes and descriptive statistics for e and g. Scale bars, 100 μm.
