Recurrent gene fusions, typically associated with haematological malignancies and rare bone and soft-tissue tumours1, have recently been described in common solid tumours2–9. Here we use an integrative analysis of high-throughput long- and short-read transcriptome sequencing of cancer cells to discover novel gene fusions. As a proof of concept, we successfully used integrative transcriptome

sequencing to ‘re-discover’ the BCR–ABL1 (ref. 10) gene fusion in a chronicmyelogenous leukaemia cell line and theTMPRSS2–ERG2,3 gene fusion in a prostate cancer cell line and tissues.Additionally,we

nominated, and experimentally validated, novel gene fusions resulting in chimaeric transcripts in cancer cell lines and tumours. Taken together, this study establishes a robust pipeline for the discovery of

novel gene chimaeras using high-throughput sequencing, opening up an important class of cancer-related mutations for comprehensive characterization.