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Frequent miRNA-convergent fusion gene events in breast cancer

Persson, Helena LU ; Søkilde, Rolf LU ; Häkkinen, Jari LU ; Pirona, Anna Chiara ; Vallon-Christersson, Johan LU ; Kvist, Anders LU ; Mertens, Fredrik LU ; Borg, Åke LU ; Mitelman, Felix LU and Höglund, Mattias LU , et al. (2017) In Nature Communications 8(1).
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, 5 partners may deregulate the same miRNA irrespective of the coding potential of the fusion... (More)

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.

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Nature Communications
volume
8
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85030675333
  • wos:000412362400003
ISSN
2041-1723
DOI
10.1038/s41467-017-01176-1
language
English
LU publication?
yes
id
7eaedc22-0a3b-4e9f-aeb0-aea4894d2c35
date added to LUP
2017-10-16 08:15:23
date last changed
2018-08-12 04:40:04
@article{7eaedc22-0a3b-4e9f-aeb0-aea4894d2c35,
  abstract     = {<p>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.</p>},
  articleno    = {788},
  author       = {Persson, Helena and Søkilde, Rolf and Häkkinen, Jari and Pirona, Anna Chiara  and Vallon-Christersson, Johan and Kvist, Anders and Mertens, Fredrik and Borg, Åke and Mitelman, Felix and Höglund, Mattias and Rovira, Carlos},
  issn         = {2041-1723},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Frequent miRNA-convergent fusion gene events in breast cancer},
  url          = {http://dx.doi.org/10.1038/s41467-017-01176-1},
  volume       = {8},
  year         = {2017},
}