Fig. 2: Transcript variants in TP53 splice mutated colorectal cancers.

a Estimated relative expression levels of TP53 transcript variants in 16 splice mutated samples. Samples are ordered according to the relative expression level of the canonical splicing variant. Canonical splicing, cryptic splice sites and exon skipping events were quantified in the Sashimi plots, while intron retention values are the median depth of the relevant intronic region as measured by IRFinder. b Sashimi plots from two tumor samples with point mutation in the canonical splice acceptor site of intron 7 (marked with a dashed line) compared with a normal sample. Reads spanning exon junctions are represented by arcs, and each arc is labeled with the number of supporting reads. The arc representing an aberrant splicing event is colored in orange. Heights of bars reflect the read depth at each genomic position (reading frame right to left). Schematic visualization of the canonical TP53 transcript variant is shown in the top panel, and the two aberrant variants caused by the splice site mutation below, with coding sequences in light gray and noncoding sequences in black. In sample 8, 20 junction reads span transcripts using a cryptic acceptor site located 24 basepairs into exon 8, while 106 reads retain intron 7 (median depth of intron 7 as measured by IRFinder). Contrastingly, in both sample 16 and the normal sample all junction reads between exon 7 and exon 8 span the canonical splice sites. The transcript variant retaining intron 7 is predicted to generate a premature stop codon. The usage of an alternative splice acceptor site will lead to loss of nine amino acids in the 5′ part of exon 8 followed by disturbed reading frame but no generation of a premature stop codon. c Sashimi plot visualizing aberrant splicing variants in a sample with a TP53 mutation in the splice acceptor site of intron 6 compared with a nonmatched normal colonic mucosa sample. The transcript variant using a cryptic splice acceptor site located 49 basepairs upstream of the canonical splice site is identical with the p53ψ isoform, which is truncated due to the introduction of a premature stop codon. The aberrant transcript due to intron retention contains a premature stop codon in intron 6. Sashimi plots for the remaining samples with TP53 splice mutations are shown in Supplementary Fig. 1