Consequences of somatic mutations affecting cis-acting pre-mRNA sequences. (A) A representative 3-exon pre-mRNA model is depicted with annotation of the location of common cis-acting sequences affected by somatic mutations. (B) Common splicing outcomes that are caused by somatic mutations in cis-acting sequences or splicing factors include exon inclusion, exon skipping, and intron retention. Other splicing outcomes include alternative 5′ or 3′ splice sites (mutually exclusive exons, coordinate cassette exons, and alternative first and last exons are not shown). The yellow color in exons 1 and 2 represents exonic sequence that is excluded when splicing into an alternative cryptic splice site occurs, as indicated by the dashed lines at the bottom of each cartoon. (C) The predominant type of pre-mRNA splicing alteration induced by mutations in various cis-acting sequences.