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Authors: Laura Urbanski, Nathan Leclair, Olga Anczuków*, image: Matt Wimsatt (The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06032)Alternative-splicing alterations in cancer. Human tumors exhibit recurrent mutations in, or changes in the levels of, splicing regulatory factors, the latter of which can occur due to copy number changes, or alterations in the transcriptional, post-transcriptional, or post-translational regulation of splicing factors in response to signaling changes (top panel). These changes in splicing-factor levels lead to alterations in the splicing of their downstream targets, promoting events that follow one of the following patterns: exon skipping (ES), alternative 5’ or 3’ splice site (SS) selection (A5’SS or A3’SS), inclusion of mutually exclusive exons (MXE), or intron retention (IR) (middle panel). Misregulated splicing of isoforms involved in key cellular pathways contributes to tumor initiation and progression. Examples of cancer hallmarks and associated tumor isoforms are indicated (bottom panel). The title of the review is “Alternative-splicing defects in cancer: splicing regulators and their downstream targets, guiding the way to novel cancer therapeutics” The journal is WIREs RNA. * Correspondence should be addressed to firstname.lastname@example.org