Fig. 5: Congruence of autosomal copy number and chromosome X derived relationships suggests selection of AR alterations in established clones. | Nature Communications

Fig. 5: Congruence of autosomal copy number and chromosome X derived relationships suggests selection of AR alterations in established clones.

From: Copy number architectures define treatment-mediated selection of lethal prostate cancer clones

Fig. 5: Congruence of autosomal copy number and chromosome X derived relationships suggests selection of AR alterations in established clones.The alt text for this image may have been generated using AI.

Tanglegrams for CA63 (a) and PEA172 (b) with autosomal SCRATCH relationship network of metastases on the left and chromosome X-based SCRATCH relationship network on the right. Gray lines between relational networks are connecting the same metastatic cores between two SCRATCH determined metastatic relationships. c AR scores plotted as a function of AR expression (‘voom’ normalized, x-axis) for CA63, CA76, CA83 and PEA172 (Supplementary Data 9). Linear regression lines are drawn for each patient with the p-values of the correlation test in legend. d Boxplots showing the expression of AR and two of it’s regulated genes KLK3 and TMPRSS2 detected by ddPCR, on a logarithmic scale (y-axis), against the AR copy number status (gain or wild type) for patients CA63 (ngain,cluster1,3 = 4 samples, nwt,cluster2 = 4 samples) and PEA172 (ngain,cluster1 = 3 samples, ngain,cluster2 = 4 samples). In each box central line represents the mean and the whiskers represent mean ± IQR * 1.5 and p-values generated from the two-tailed Mann-Whitney U test are shown on the top for each comparing pair. Cluster numbers are shown below the x-axis. e, f Cartoons of postulated metastatic evolutionary relationships of dominant clones for CA63 (e, three clusters, denoted as Cl1, Cl2 and Cl3) and PEA172 (f, two clusters, denoted as Cl1 and Cl2) are shown with bidirectional trajectories as reverse migration of metastatic clone(s) cannot be ruled out. Bar charts show common or cluster-specific shared copy number transition points for respective patients. g Normalized expression of AR gene and distribution of AR-V12 mimics in the two different SCRATCH-defined autosomal clusters (depicted with purple and red circles at the base) are shown as circles for patient PEA172 (N = 20 samples). One-sided Fisher’s exact test (alternative = “less”) showed a significant difference (p = 0.0047) in the distribution of AR-V12 mimics between clusters.

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