Fig. 4.

Potentiating SF3B1 mutation through 16p13 germline variation. A) Increase in SF3B1 somatic mutation rate with the rs8051518 minor allele at 16p13. B) Manhattan plot of germline association with SF3B1 mutation rate across this locus, which encodes the single gene RBFOX1. C) Current model by which RBFOX1 functionally interacts with SF3B1 to regulate RNA splicing. D) RBFOX1 increases in mRNA expression in the presence of the rs8051518 minor allele. Analysis is across all TCGA tissues, normalizing for mean expression within each tissue type. E) The number of differentially spliced exon-exon junctions was compared between individuals homozygous for the rs8051518 major allele and those harboring one or more copies of the minor allele. The number of differentially spliced junctions in each group was determined by comparing tumors with WT SF3B1 to tumors with mutant SF3B1. For correct comparison, individuals with the major allele are subsampled so that this cohort is the same size as that of the minor allele (43 individuals, error bar shows ±2σ).