Fig. 5

Misregulation of alternative polyadenylation in primary tumors. (A) Comparison of ψ values in matched patient tumor and control samples for genes whose ψ value was significantly different between these samples (FDR < 0.05). The number of genes with significant Δψ values in each comparison is indicated by the bar graph. (B) As in A, ψ values for all genes were calculated in matched patient tumor and normal tissue samples, and genes with significantly different ψ values across samples within a cancer type were identified (FDR < 0.05). The fraction of significant tandem UTR and ALE genes with positive Δψ values were plotted on the x and y axes, respectively. Each dot represents one patient sample pair. (C) Genes with significantly different ψ values across samples within a cancer type (FDR < 0.05) are colored according to their Δψ value (tumor - control). Columns represent matched patient samples while rows represent genes. Black ticks (right) represent whether or not the gene displayed a significantly different ψ value (FDR < 0.05) between biochemically defined cytosolic and membrane-associated fractions in HepG2 and K562 cells (Fig. 2D). Genes were further separated into classes of those with increased ψ values in KIRC and THCA tumor samples (red ticks, right) and those with decreased ψ values in BRCA, LUAD and LUSC tumor samples (blue ticks, right). (D-E) Survival analysis for APA misregulation in head and neck squamous cell carcinoma and kidney renal clear cell carcinoma, respectively. Patients were grouped into extreme quartiles by ranked median ψ values for misregulated genes as defined in Fig. 5A for the respective tumors. In Fig. 5A, HNSC tumors were associated with decreased ψ values. Here, lower ψ values are associated with poor prognosis. Conversely, in Fig. 5A KIRC tumors were associated with increased ψ values, and here, increased ψ values are associated with poor prognosis