Frequent miRNA-convergent fusion gene events in breast cancer

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T1 - Frequent miRNA-convergent fusion gene events in breast cancer

AU - Persson, Helena

AU - Søkilde, Rolf

AU - Häkkinen, Jari

AU - Pirona, Anna Chiara

AU - Vallon-Christersson, Johan

AU - Kvist, Anders

AU - Mertens, Fredrik

AU - Borg, Åke

AU - Mitelman, Felix

AU - Höglund, Mattias

AU - Rovira, Carlos

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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, 5 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.

AB - 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, 5 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.

U2 - 10.1038/s41467-017-01176-1

DO - 10.1038/s41467-017-01176-1

M3 - Article

VL - 8

JO - Nature Communications

T2 - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 788

ER -