Fig. 2: Loss of PRC1-mediated transcriptional repression in high-risk UM. | Nature Communications

Fig. 2: Loss of PRC1-mediated transcriptional repression in high-risk UM.

From: Loss of polycomb repressive complex 1 activity and chromosomal instability drive uveal melanoma progression

Fig. 2

a Unbiased hierarchical clustering of UM cell lines, 92.1 and MP38, in biological triplicates, based on normalized FPKM values of the GEP 12-discriminant geneset19. b Western blot of BAP1 and PRC1 core ligases RING1 and RNF2 relative to actin in 92.1 and MP38 cells. Data representative of biological triplicates. c Immunofluorescence of ubiquitinated H2A (green) and DAPI (blue) in MSK-UM03 (greatest proportion of GEP1 tumor cells in the cohort) and MSK-UM01 (greatest proportion of GEP2 tumor cells in the cohort). Representative images from six biological specimens. d Heatmaps representing CUT&RUN intensities of H2AK119Ub normalized to IgG in 92.1 and MP38. Data representative of biological duplicates. e Expression of H2AK119Ub target genes for individual tumor cells ranked by average imputed expression of the GEP2 gene signature (gene signatures annotated in Supplementary Data File 1) in ascending order from left to right. For each gene, imputed expression was z-normalized across all cells and smoothed using a 20-cell moving average window. Top, filled area plot showing average expression of GEP2 signature genes across ranked tumor cells. f Expression of H2AK119Ub target genes across the 4 molecular TCGA subtypes. Statistical significance tested using one-way ANOVA; p = 7.3 × 10−6; n = 80. Bars, mean of average expression; error bars, standard error of the mean. g Overall survival of (n = 80) TCGA-UM patients with primary tumors stratified by high (top 50th percentile, n = 40) and low (bottom 50th percentile, n = 40) expression of the ‘H2AK119Ub targets’ geneset. Statistical significance tested using two-sided log-rank test.

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