Extended Data Fig. 3: TRIM28-dependent developmental heterogeneity primes cancer outcomes.

Endpoint data shaded. a) Proportion of Trim28^+/D9-heavy and -light males with malignant aggressive or endpoint tumors, as percentage of tumor-bearing animals per group. Actual numbers in fractions. Two-sided two-sample test for equality of proportions without continuity correction, significance for p<0.05: aggressive tumors, p=0.01466, χ²=5.9571, df=1; endpoint tumors, p=0.04153, χ²=4.1544, df=1. N=23 male mice (15 -heavy, 8 -light). b) Tissues with malignant endpoint tumors across genotypes. Top: mouse anatomy plots; non-targeted tissues in light-grey and targeted tissues colored by genotype: WT (black), Trim28^+/D9 (orange), Tp53^R270H/+ (green), Tp53^R270H/+;Trim28^+/D9 (purple). Bottom: organs with tumors in each morph. N=15 male mice (12 -heavy, 3 -light). c) Prevalence of endpoint tumor types in Trim28^+/D9-heavy and -light male animals, as percentage of total endpoint tumors per group. Actual numbers in fractions. N=28 endpoint tumors (malignant and benign, 22 in -heavy and 6 in -light). d) Distribution of malignant endpoint tumor types in Trim28^+/D9-heavy and -light male mice, as percentages of total malignant endpoint tumor-bearing animals in each group. Tumor categories are color-coded on the right: age-related carcinoma (red); carcinoma (gold); leukemia (light-green); sarcoma (pink); germ-cell tumors (dark-green); other (teal). N=15 male mice (12 -heavy, 3 -light) e) Fraction of Trim28^+/D9-heavy and -light males with 0 or multiple malignant endpoint tumors. Actual numbers in fractions. N=15 male mice (12 -heavy, 3 -light). f) Top: boxplots of nuclear TRIM28 mean fluorescence intensity (MFI) across genotypes and tissues. Two-sided Kruskal-Wallis test. Bottom: MFI in Trim28^+/D9-heavy and -light animals across tissues. Two-sided Wilcoxon test. The lower and upper hinges of the boxplots correspond to the first and third quartiles. Boxplot hinges represent the first and third quartiles. Whiskers extend to 1.5 times the interquartile range. 22,964,279 nuclei analyzed from 38 male mice (intestine: 4 WT, 3 Trim28^+/D9-light, 5 -heavy, 3 Tp53^R270H/+, and 4 Tp53^R270H/+;Trim28^+/D9; lungs: 3 WT, 5 Trim28^+/D9-light, 5 -heavy, 4 Tp53^R270H/+, and 3 Tp53^R270H/+;Trim28^+/D9; pancreas: 4 WT, 4 Trim28^+/D9-light, 5 -heavy, 4 Tp53^R270H/+, and 4 Tp53^R270H/+;Trim28^+/D9; prostate: 3 WT, 3 Trim28^+/D9-light, 4 -heavy, 3 Tp53^R270H/+, and 3 Tp53^R270H/+;Trim28^+/D9; seminal vesicles: 3 WT, 5 Trim28^+/D9-light, 4 -heavy, 4 Tp53^R270H/+, and 3 Tp53^R270H/+;Trim28^+/D9). Panel b, top created with BioRender.com.

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