Fig. 3: Trp53, together with WGD, results in therapy resistance associated with increased CIN and cell-to-cell variability. | Nature Communications

Fig. 3: Trp53, together with WGD, results in therapy resistance associated with increased CIN and cell-to-cell variability.

From: Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling

Fig. 3

a Dot plot of mean cancer cell fraction per tumor of early losses in naïve (E, n = 23; EP n = 20) and resistant E (n = 9 yellow) and EP (n = 10 green) tumors. b Frequency of copy-number gains (positive y-axis) and losses (negative y-axis) in treatment naïve (yellow) vs resistant (green) tumors with either E (upper panel) or EP (lower panel) genotypes. c Ploidy-relative copy-number gains (red colors) are reported across all mouse tumors, separating treatment naïve vs resistant and E vs EP (ploidy represented in gray colors) for 18 genes whose amplification is known to have an impact on TKI resistance. d For every group (triangle shape) of single cells obtained from the same FACS ploidy peak (red colors) from either naïve E (top row), naïve EP (second row), resistant E (third row), or resistant EP (bottom row) mouse tumors, the fraction of the genome affected by different SCNAs (yellow-to-blue colors) was computed between every pair of cells (square within a triangle) as a proxy to measure cell-to-cell diversity. e Dot plot of average Shannon evenness index measured per tumor from naïve (n = 21) and resistant (n = 7) E (yellow) vs naïve (n = 19) and resistant (n = 710) EP (green) mouse tumors (naïve p = 0.0066, resistant p = 0.0004, two-sided Mann–Whitney U-tests). Bar charts showing WGD frequencies in lesions from patients with E and EP tumors from f Tx421 (using WES data, ns, two-sided chi-squared test) and g OncoSG cohort (using WES data, p = 0.0080, two-sided chi-squared test). Dot plot showing weighted Genome Instability Index (wGII) of tumors with or without WGD in patients with E or EP lesions from the h Tx421 (non-WGD: E n = 3, EP n = 1. WGD: E n = 9, EP n = 11 p = 0.0310, two-sided Mann–Whitney U-test) and i OncoSG cohorts (non-WGD: E n = 26, EP n = 10, p = 0.8758. WGD: n = 9 E, n = 11 EP, p = 0.0392, two-sided Mann–Whitney U-test). Source data are provided as a Source Data file.

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