Abstract
The paucity of recurrent mutations has hampered efforts to understand the pathogenesis of neuroblastoma. Through analysis of RNA-sequenced neuroblastoma, we identified >900 primarily intrachromosomal fusion transcripts generated by genes in close proximity. Fusions were enriched in chromosomal regions gained or lost in neuroblastoma and included well-known neuroblastoma oncogenes. The majority of fusions contained canonical splicing sites and a subset exhibited increased sensitivity to spliceosome inhibition. As a proof-of-principle that a gene product with altered properties can be produced by these fusions, we characterized the ZNF451-BAG2 fusion which generates a truncated BAG2-protein capable of inhibiting retinoic acid-induced differentiation. Our findings elucidate a mechanism through which altered gene products, relevant for neuroblastoma pathogenesis and representing possible novel drug targets, can be generated.