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Åke Borg

Åke Borg

Principal investigator

Åke Borg

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

Author

  • Helena Persson
  • Rolf Søkilde
  • Jari Häkkinen
  • Johan Vallon-Christersson
  • Felix Mitelman
  • Åke Borg
  • Mattias Höglund
  • Carlos Rovira

Summary, in English

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.

Department/s

  • LUCC: Lund University Cancer Centre
  • Functional Breast Cancer Genomics
  • Breastcancer-genetics
  • Cancer and non coding RNA
  • Division of Clinical Genetics
  • Familial Breast Cancer
  • Create Health

Publishing year

2020-06-15

Language

English

Pages

3343-3353

Publication/Series

International Journal of Cancer

Volume

146

Issue

12

Document type

Journal article

Publisher

John Wiley & Sons Inc.

Topic

  • Cancer and Oncology

Status

Published

Research group

  • Functional Breast Cancer Genomics
  • Cancer and non coding RNA
  • Familial Breast Cancer

ISBN/ISSN/Other

  • ISSN: 0020-7136