Issues

Deregulated control of alternative splicing has been implicated in many cancers. To map the genetic regulation of splicing in neuroblastoma, Chen and colleagues integrated genome and transcriptome data from a mouse model of neuroblastoma. Characterization of splicing quantitative trait loci (sQTL) highlighted genes that regulate alternative splicing and strain-specific splicing of genes that correlated with patient survival. In addition, the authors identified unique intronic splicing motifs in genes that were recurrently mutated in human neuroblastoma and glioblastoma. Mutation of these motifs resulted in functional changes in alternative splicing, and altered expression of the corresponding genes correlated with patient outcome in neuroblastoma. These results identify splicing factors and intronic splicing motifs that modulate alternative splicing across cancers and highlight candidate genes potentially involved in neuroblastoma. For details, please see the article by Chen and colleagues on page 380.