Frequent miRNA-convergent fusion gene events in breast cancer

Helena Persson, Rolf Søkilde, Jari Häkkinen, Anna Chiara Pirona, Johan Vallon-Christersson, Anders Kvist, Fredrik Mertens, Åke Borg, Felix Mitelman, Mattias Höglund and Carlos Rovira ()
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Helena Persson: Lund University Cancer Center, Lund University
Rolf Søkilde: Lund University Cancer Center, Lund University
Jari Häkkinen: Lund University Cancer Center, Lund University
Anna Chiara Pirona: Lund University Cancer Center, Lund University
Johan Vallon-Christersson: Lund University Cancer Center, Lund University
Anders Kvist: Lund University Cancer Center, Lund University
Fredrik Mertens: Lund University
Åke Borg: Lund University Cancer Center, Lund University
Felix Mitelman: Lund University
Mattias Höglund: Lund University Cancer Center, Lund University
Carlos Rovira: Lund University Cancer Center, Lund University

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract Studies of fusion genes have mainly focused on the formation of fusions that result in the production of hybrid proteins or, alternatively, on promoter-switching events that put a gene under the control of aberrant signals. However, gene fusions may also disrupt the transcriptional control of genes that are encoded in introns downstream of the breakpoint. By ignoring structural constraints of the transcribed fusions, we highlight the importance of a largely unexplored function of fusion genes. Here, we show, using breast cancer as an example, that miRNA host genes are specifically enriched in fusion genes and that many different, low-frequency, 5ʹ partners may deregulate the same miRNA irrespective of the coding potential of the fusion transcript. These results indicate that the concept of recurrence, defined by the rate of functionally important aberrations, needs to be revised to encompass convergent fusions that affect a miRNA independently of transcript structure and protein-coding potential.

Date: 2017
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DOI: 10.1038/s41467-017-01176-1

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