Transcriptome sequencing to detect gene fusions in cancer

Nature. 2009 Mar 5;458(7234):97-101. doi: 10.1038/nature07638. Epub 2009 Jan 11.


Recurrent gene fusions, typically associated with haematological malignancies and rare bone and soft-tissue tumours, have recently been described in common solid tumours. 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 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • Fusion Proteins, bcr-abl / analysis
  • Fusion Proteins, bcr-abl / genetics
  • Gene Expression Profiling / methods*
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Male
  • Molecular Sequence Data
  • Neoplasms / genetics*
  • Oncogene Proteins, Fusion / analysis*
  • Oncogene Proteins, Fusion / genetics*
  • Prostatic Neoplasms / genetics
  • Sequence Analysis, DNA / instrumentation
  • Sequence Analysis, DNA / methods*


  • MIPOL1-DGKB fusion protein, human
  • Oncogene Proteins, Fusion
  • SLC45A3-ELK4 fusion protein, human
  • TMPRSS2-ERG fusion protein, human
  • Fusion Proteins, bcr-abl

Associated data

  • GENBANK/FJ423742
  • GENBANK/FJ423743
  • GENBANK/FJ423744
  • GENBANK/FJ423745
  • GENBANK/FJ423746
  • GENBANK/FJ423747
  • GENBANK/FJ423748
  • GENBANK/FJ423749
  • GENBANK/FJ423750
  • GENBANK/FJ423751
  • GENBANK/FJ423752
  • GENBANK/FJ423753
  • GENBANK/FJ423754
  • GENBANK/FJ423755