Fig. 6: PBRM1 loss prohibits PBAF assembly and blocks the synovial sarcoma phenotype. | Nature Communications

Fig. 6: PBRM1 loss prohibits PBAF assembly and blocks the synovial sarcoma phenotype.

From: Synovial sarcoma reprograms transcription by GBAF activation of polycomb targets and loss of CBAF enhancers

Fig. 6: PBRM1 loss prohibits PBAF assembly and blocks the synovial sarcoma phenotype.The alternative text for this image may have been generated using AI.

a Growth trajectories of mean tumor size (sample sizes indicated are biological replicates: individual tumors developing in individual mice; shading indicates ± standard deviations; p-values from two-tailed, heteroscedastic t tests, with individual p-values listed in Source Data file.) in hSS2 mice injected with TATCre at day 8 of life comparing littermates with varied Pbrm1-fl genotypes. b Pie charts indicating the histomorphology of hSS2;Pbrm1-fl/fl versus hSS2;Pbrm1-wt/wt tumors (n = 15, n = 10, biological replicates of individual tumors). c Example photomicrographs of the modest nuclear atypia noted in hSS2;Pbrm1-fl/fl (An H&E stained section of each of the tumors produced was reviewed at the same sample size as in (b) but representative photomicrographs were procured secondarily; each magnification bar is 10 µm). d Differential expression (by bulk tumor RNA-seq) of SAT pattern genes and e MAT pattern genes of hSS2 tumors with wildtype versus homozygous floxed Pbrm1. f Expression heatmap of BAF component genes in hSS2 tumors with or without Pbrm1 disruption. g Western blots for BAF components after glycerol gradients of nuclear fractions of a hSS2;Pbrm1-fl/fl tumor (This experiment was repeated on two biological replicates, presenting the aggregate clearest blots for one sample). h Graphical histograms indicating the relative contribution of GBAF, CBAF, and PBAF to SMARCC1 distributions in an hSS2, Pbrm1-disrupted tumor. i DPF2 versus PBRM1 ChIP-seq enrichment across merged peaks between the two. j Growth trajectories of mean tumor size in hSS1 mice littermates with varied Pbrm1-fl genotypes (sample sizes indicated are biological replicates: individual tumors developing in individual mice; shading indicates ± standard deviations; p-values from two-tailed, heteroscedastic t tests, with individual p-values listed in Source Data file.) k Photomicrograph examples demonstrating retained SyS phenotypes without nuclear atypia in the hSS1;Pbrm1-fl/fl tumors which develop more slowly than tumors in hSS2;Pbrm1-fl/fl mice (An H&E stained section of each of the tumors produced was reviewed at the same sample size as the tumorigenesis experiments in (j) but representative photomicrographs were procured secondarily; each magnification bar is 10 µm). l PCA plot in two dimensions from bulk RNA-seq of whole tumor transcriptomes in hSS1;Pbrm1-fl/fl, and hSS2;Pbrm1-fl/fl, mice. Source data are provided as a Source Data file.

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