1. Michigan Center for Translational Pathology,
2. Howard Hughes Medical Institute,
3. Department of Pathology,
4. Department of Urology,
5. Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
6. These authors contributed equally to this work.

Correspondence to: Arul M. Chinnaiyan^1,2,3,4,5 Correspondence and requests for materials should be addressed to A.M.C. (Email: arul@umich.edu).

Abstract

Recurrent gene fusions, typically associated with haematological malignancies and rare bone and soft-tissue tumours¹, have recently been described in common solid tumours^{2, 3, 4, 5, 6, 7, 8, 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 chronic myelogenous leukaemia cell line and the TMPRSS2–ERG^{2, 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.

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