Identification of fusion genes in breast cancer by paired-end RNA-sequencing

Henrik Edgren, Astrid Murumaegi, Sara Kangaspeska, Daniel Nicorici, Vesa Hongisto, Kristine Kleivi, Inga H. Rye, Sandra Nyberg, Maija Wolf, Anne-Lise Børresen-Dale, Olli Kallioniemi (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

196 Citations (Scopus)

Abstract

Background
Until recently, chromosomal translocations and fusion genes have been an underappreciated class of mutations in solid tumors. Next-generation sequencing technologies provide an opportunity for systematic characterization of cancer cell transcriptomes, including the discovery of expressed fusion genes resulting from underlying genomic rearrangements.

Results
We applied paired-end RNA-seq to identify 24 novel and 3 previously known fusion genes in breast cancer cells. Supported by an improved bioinformatic approach, we had a 95% success rate of validating gene fusions initially detected by RNA-seq. Fusion partner genes were found to contribute promoters (5' UTR), coding sequences and 3' UTRs. Most fusion genes were associated with copy number transitions and were particularly common in high-level DNA amplifications. This suggests that fusion events may contribute to the selective advantage provided by DNA amplifications and deletions. Some of the fusion partner genes, such as GSDMB in the TATDN1-GSDMB fusion and IKZF3 in the VAPB-IKZF3 fusion, were only detected as a fusion transcript, indicating activation of a dormant gene by the fusion event. A number of fusion gene partners have either been previously observed in oncogenic gene fusions, mostly in leukemias, or otherwise reported to be oncogenic. RNA interference-mediated knock-down of the VAPB-IKZF3 fusion gene indicated that it may be necessary for cancer cell growth and survival.

Conclusions
In summary, using RNA-sequencing and improved bioinformatic stratification, we have discovered a number of novel fusion genes in breast cancer, and identified VAPB-IKZF3 as a potential fusion gene with importance for the growth and survival of breast cancer cells.
Original languageEnglish
Article numberR6
JournalGenome Biology
Volume12
Issue number1
DOIs
Publication statusPublished - 2011
MoE publication typeA1 Journal article-refereed

    Fingerprint

Keywords

  • breast cancer
  • cancer

Cite this

Edgren, H., Murumaegi, A., Kangaspeska, S., Nicorici, D., Hongisto, V., Kleivi, K., Rye, I. H., Nyberg, S., Wolf, M., Børresen-Dale, A-L., & Kallioniemi, O. (2011). Identification of fusion genes in breast cancer by paired-end RNA-sequencing. Genome Biology, 12(1), [R6]. https://doi.org/10.1186/gb-2011-12-1-r6