Fig. 1: BRD9 mis-splicing causes BRD9 loss and proliferative advantage in SF3B1-mutated cancers. | Nature

Fig. 1: BRD9 mis-splicing causes BRD9 loss and proliferative advantage in SF3B1-mutated cancers.

From: Spliceosomal disruption of the non-canonical BAF complex in cancer

Fig. 1

a, Unsupervised clustering of patient samples on the basis of events that are differentially spliced in UVM (MEL270) and myeloid leukaemia (K562) cells that express SF3B1K700E versus wild-type (WT) SF3B1. a3ss, alternative 3′ splice site; CLL, chronic lymphocytic leukaemia (data are from ref. 15); MDS, myelodysplastic syndromes (data are from ref. 27); mxe, mutually exclusive exons; PSI, percentage spliced in (fraction of mRNA that corresponds to the mutant SF3B1-promoted isoform), with per-event and per-cohort range normalization; ri, retained intron; se, skipped exon; TCGA, The Cancer Genome Atlas. Data for UVM are from ref. 10 (middle) or the TCGA (right). FAM192A, HRSP12, MTERFD3, NPIP and UQCC are also known as PSME3IP1, RIDA, MTERF2, NPIPA1 and UQCC1, respectively. b, Genes for which mutant SF3B1 promotes an isoform predicted to trigger NMD (alternative 3′ splice site and skipped exon events only) in one or more cohorts. c, CRISPR–Cas9-based positive-selection screen targeting genes for which mutant SF3B1 promotes an isoform predicted to trigger NMD. d, Per-gene scatter plot comparing CRISPR screen enrichment (y axis) to differential splicing in TCGA cohort of patients with UVM (x axis). Pten was used as a positive control. n = 6 biologically independent experiments. Per-gene significance computed with two-sided correlation-adjusted mean rank gene set (CAMERA) test. The false-discovery rate (FDR) was computed using the Benjamini–Hochberg method. e, BRD9 RNA sequencing (RNA-seq) read coverage in patient samples. n, number of patients. PE, BRD9 poison exon; 14 and 15, flanking constitutive exons. Repetitive elements from RepeatMasker28. f, Western blot for N-terminally haemagglutinin (HA)-tagged endogenous BRD9 in MEL270 cells transduced with empty vector (EV) or doxycycline-inducible Flag–SF3B1(WT) or Flag–SF3B1(K700E). Representative images from n = 3 biologically independent experiments.

Source data.

Back to article page