Mutations in the acceptor splice site of BAP1 exon 11 lead to exon skipping and loss of function
(A) Patient TCGA-BP-4798 has a somatic mutation in the acceptor splice site of exon 11 (c.IVS932-2A>G) as depicted by whole-genome sequencing (WES) and RNA-Seq of the tumor (T) but not normal kidney (N) WES. Exon 11 skipping for patient TCGA-BP-4798 is evidenced by RNA-Seq reads spanning from exon 10 to exon 12 and highlighted in red. The red arrow indicates the splice-site mutation.
(B) Patient TCGA-CZ-5985 has a somatic mutation in the acceptor splice site of exon 11 (c.IVS932-1G>T) as depicted by whole-genome sequencing (WES) and RNA-Seq of the tumor (T) but not normal kidney (N). Exon 11 skipping for patient TCGA-CZ-5985 is indicated by RNA-Seq reads spanning from exon 10 to exon 12 and highlighted in red. The red arrow indicates the splice-site mutation.
(C–F) Log2-transformed RNA-Seq RSEM normalized gene expression for BAP1 (C), RPPA for BAP1 (D), total ribosomal protein S6 expression (E) and S6 phosphorylation at S235/S236 (F) from KIRC-TCGA for patients TCGA-BP-4798 (in cyan) and TCGA-CZ-5985 (in orange).
(G) Diagram illustrating the summary of this study, where a synonymous mutation near the acceptor splice site of exon 11 of BAP1 leads to exon skipping, frameshift and premature stop codon, inducing its mRNA and protein degradation and loss of function.