Figure 1.

Differential aberrant splicing events across SF3B1 mutant cancers. A, Location and frequency of SF3B1 hotspot mutations from the pan-cancer dataset on the HEAT repeat domains (green hexagons) of SF3B1. The numbers in the center/on the edge of each circle denote the sample size of each mutation across all/specific to each cohort (see Supplementary tables for abbreviations). B, Hierarchical clustering and heatmap analysis of differential 3’ splice sites (3’ss) between SF3B1 mutant and wild-type (WT) samples. Rows and columns represent cryptic 3’ss events and samples, respectively. 1,401 cryptic 3’ss identified from the Pan-cancer dataset are shown. Z-score in the matrix represents normalized Percent-Spliced-In (PSI). C, Density plot of distance in base pairs from associated canonical 3’ss to cryptic 3’ss. D, Volcano plot representation of differentially spliced changes between SF3B1^K700E mutations (CLL, BRCA and MDS) and SF3B1^R625 mutations (UVM and SKCM) showing the magnitude (difference of PSI; x-axis) and significance (-log₁₀(q-value); y-axis). E, Representative gene sets significantly enriched in gene set enrichment analysis (GSEA) comparing all SF3B1 mutant and WT samples, as well as the results from comparisons done within each cancer type.