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Analysis of fusion transcripts indicates widespread deregulation of snoRNAs and their host genes in breast cancer

Persson, Helena LU orcid ; Søkilde, Rolf LU orcid ; Häkkinen, Jari LU orcid ; Vallon-Christersson, Johan LU orcid ; Mitelman, Felix LU orcid ; Borg, Åke LU ; Höglund, Mattias LU and Rovira, Carlos LU (2020) In International Journal of Cancer 146(12). p.3343-3353
Abstract

Genomic rearrangements in cancer can join the sequences of two separate genes. Studies of such gene fusion events have mainly focused on identification of fusion proteins from the chimeric transcripts. We have previously investigated how fusions instead can affect the expression of intronic microRNA (miRNA) genes that are encoded within fusion gene partners. Here, we extend our analysis to small nucleolar RNAs (snoRNAs) that also are embedded within protein-coding or non-coding host genes. We found that snoRNA hosts are selectively enriched in fusion transcripts, like miRNA host genes, and that this enrichment is associated with all snoRNA classes. These structural changes may have functional consequences for the cell; proteins involved... (More)

Genomic rearrangements in cancer can join the sequences of two separate genes. Studies of such gene fusion events have mainly focused on identification of fusion proteins from the chimeric transcripts. We have previously investigated how fusions instead can affect the expression of intronic microRNA (miRNA) genes that are encoded within fusion gene partners. Here, we extend our analysis to small nucleolar RNAs (snoRNAs) that also are embedded within protein-coding or non-coding host genes. We found that snoRNA hosts are selectively enriched in fusion transcripts, like miRNA host genes, and that this enrichment is associated with all snoRNA classes. These structural changes may have functional consequences for the cell; proteins involved in the protein translation machinery are overrepresented among snoRNA host genes, a gene architecture assumed to be needed for closely coordinated expression of snoRNAs and host proteins. Our data indicate that this structure is frequently disrupted in cancer. We furthermore observed that snoRNA genes involved in fusions tend to associate with stronger promoters than the natural host, suggesting a mechanism that selects for snoRNA overexpression. In summary, we highlight a previously unexplored frequent structural change in cancer that affects important components of cellular physiology. This article is protected by copyright. All rights reserved.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International Journal of Cancer
volume
146
issue
12
pages
11 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85081261626
  • pmid:32067223
ISSN
0020-7136
DOI
10.1002/ijc.32927
language
English
LU publication?
yes
additional info
This article is protected by copyright. All rights reserved.
id
3a8fb80a-4a03-4701-b3d8-731e07bb8ff5
date added to LUP
2020-02-20 08:38:09
date last changed
2024-04-17 04:52:51
@article{3a8fb80a-4a03-4701-b3d8-731e07bb8ff5,
  abstract     = {{<p>Genomic rearrangements in cancer can join the sequences of two separate genes. Studies of such gene fusion events have mainly focused on identification of fusion proteins from the chimeric transcripts. We have previously investigated how fusions instead can affect the expression of intronic microRNA (miRNA) genes that are encoded within fusion gene partners. Here, we extend our analysis to small nucleolar RNAs (snoRNAs) that also are embedded within protein-coding or non-coding host genes. We found that snoRNA hosts are selectively enriched in fusion transcripts, like miRNA host genes, and that this enrichment is associated with all snoRNA classes. These structural changes may have functional consequences for the cell; proteins involved in the protein translation machinery are overrepresented among snoRNA host genes, a gene architecture assumed to be needed for closely coordinated expression of snoRNAs and host proteins. Our data indicate that this structure is frequently disrupted in cancer. We furthermore observed that snoRNA genes involved in fusions tend to associate with stronger promoters than the natural host, suggesting a mechanism that selects for snoRNA overexpression. In summary, we highlight a previously unexplored frequent structural change in cancer that affects important components of cellular physiology. This article is protected by copyright. All rights reserved.</p>}},
  author       = {{Persson, Helena and Søkilde, Rolf and Häkkinen, Jari and Vallon-Christersson, Johan and Mitelman, Felix and Borg, Åke and Höglund, Mattias and Rovira, Carlos}},
  issn         = {{0020-7136}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{12}},
  pages        = {{3343--3353}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{International Journal of Cancer}},
  title        = {{Analysis of fusion transcripts indicates widespread deregulation of snoRNAs and their host genes in breast cancer}},
  url          = {{http://dx.doi.org/10.1002/ijc.32927}},
  doi          = {{10.1002/ijc.32927}},
  volume       = {{146}},
  year         = {{2020}},
}