Commentary on Transcriptome sequencing to detect gene fusions in cancer: Maher CA, Kumar-Sinha C, Cao X, Kalyana-Sundaram S, Han B, Jing X, Sam L, Barrette T, Palanisamy N, Chinnaiyan AM, Michigan Center for Translational Pathology, Ann Arbor, MI

Recurrent gene fusions, typically associated with hematological malignancies and rare bone and soft-tissue tumors, have recently been described in common solid tumors. 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 chronic myelogenous leukemia cell line and the TMPRSS2-ERG gene fusion in a prostate cancer cell line and tissues. Additionally, we nominated, and experimentally validated, novel gene fusions resulting in chimaeras transcripts in cancer cell lines and tumors. 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.