Reanalysis of RNA-sequencing data reveals several additional fusion genes with multiple isoforms

PLoS One. 2012;7(10):e48745. doi: 10.1371/journal.pone.0048745. Epub 2012 Oct 31.


RNA-sequencing and tailored bioinformatic methodologies have paved the way for identification of expressed fusion genes from the chaotic genomes of solid tumors. We have recently successfully exploited RNA-sequencing for the discovery of 24 novel fusion genes in breast cancer. Here, we demonstrate the importance of continuous optimization of the bioinformatic methodology for this purpose, and report the discovery and experimental validation of 13 additional fusion genes from the same samples. Integration of copy number profiling with the RNA-sequencing results revealed that the majority of the gene fusions were promoter-donating events that occurred at copy number transition points or involved high-level DNA-amplifications. Sequencing of genomic fusion break points confirmed that DNA-level rearrangements underlie selected fusion transcripts. Furthermore, a significant portion (>60%) of the fusion genes were alternatively spliced. This illustrates the importance of reanalyzing sequencing data as gene definitions change and bioinformatic methods improve, and highlights the previously unforeseen isoform diversity among fusion transcripts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Comparative Genomic Hybridization
  • DNA Copy Number Variations*
  • Female
  • Gene Expression Profiling / methods*
  • Gene Fusion*
  • Gene Rearrangement / genetics
  • Genetic Predisposition to Disease / genetics
  • Humans
  • MCF-7 Cells
  • Models, Genetic
  • Molecular Sequence Data
  • Promoter Regions, Genetic / genetics
  • Protein Isoforms / genetics
  • RNA Splicing
  • Sequence Analysis, RNA / methods*


  • Protein Isoforms

Grant support

This work was supported by an Academy of Finland Post-Doctoral Researcher Grant (SK)(, the Academy of Finland Center of Excellence Grant in Translational Genome-Scale Biology (, the Sigrid Juselius Foundation ( and the Cancer Society of Finland ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.