Affordable Access

Publisher Website

Recurrent FOSL1 rearrangements in desmoplastic fibroblastoma.

Authors
  • De Noon, Solange1, 2
  • Piggott, Robert3
  • Trotman, Jamie3
  • Tadross, John A3, 4, 5
  • Fittall, Matthew6, 7
  • Hughes, Debbie8
  • Ye, Hongtao2
  • Munasinghe, Emani2
  • Murray, Matthew9, 10
  • Tirabosco, Roberto2
  • Amary, Fernanda2
  • Coleman, Nicholas10
  • Watkins, James3, 4
  • Hubank, Michael11, 12
  • Tarpey, Patrick3
  • Behjati, Sam9, 13, 14
  • Flanagan, Adrienne M1, 2
  • 1 Research Department of Pathology, University College London Cancer Institute, London, UK.
  • 2 Department of Histopathology, Royal National Orthopaedic Hospital, Stanmore, UK.
  • 3 Cambridge Genomics Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
  • 4 Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
  • 5 MRC Metabolic Diseases Unit, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
  • 6 Department of Oncology, University College London Hospitals NHS Foundation Trust, London, UK.
  • 7 Division of Oncology, University College London Cancer Institute, London, UK.
  • 8 Paediatric Tumour Biology, Division of Clinical Studies, The Institute of Cancer Research, London, UK.
  • 9 Department of Paediatric Haematology and Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
  • 10 Department of Pathology, University of Cambridge, Cambridge, UK.
  • 11 Clinical Genomics, The Royal Marsden NHS Foundation Trust, London, UK.
  • 12 Molecular Pathology, The Institute of Cancer Research, London, UK.
  • 13 Cellular Genetics, Wellcome Sanger Institute, Hinxton, UK.
  • 14 Department of Paediatrics, University of Cambridge, Cambridge, UK.
Type
Published Article
Journal
The Journal of Pathology
Publisher
Wiley (John Wiley & Sons)
Publication Date
Feb 01, 2023
Volume
259
Issue
2
Pages
119–124
Identifiers
DOI: 10.1002/path.6038
PMID: 36426824
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The FOS gene family has been implicated in tumourigenesis across several tumour types, particularly mesenchymal tumours. The rare fibrous tumour desmoplastic fibroblastoma is characterised by overexpression of FOSL1. However, previous studies using cytogenetic and molecular techniques did not identify an underlying somatic change involving the FOSL1 gene to explain this finding. Prompted by an unusual index case, we report the discovery of a novel FOSL1 rearrangement in desmoplastic fibroblastoma using whole-genome and targeted RNA sequencing. We investigated 15 desmoplastic fibroblastomas and 15 fibromas of tendon sheath using immunohistochemistry, in situ hybridisation and targeted RNA sequencing. Rearrangements in FOSL1 and FOS were identified in 10/15 and 2/15 desmoplastic fibroblastomas respectively, which mirrors the pattern of FOS rearrangements observed in benign bone and vascular tumours. Fibroma of tendon sheath, which shares histological features with desmoplastic fibroblastoma, harboured USP6 rearrangements in 9/15 cases and did not demonstrate rearrangements in any of the four FOS genes. The overall concordance between FOSL1 immunohistochemistry and RNA sequencing results was 90%. These findings illustrate that FOSL1 and FOS rearrangements are a recurrent event in desmoplastic fibroblastoma, establishing this finding as a useful diagnostic adjunct and expanding the spectrum of tumours driven by FOS gene family alterations. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. This record was last updated on 04/28/2023 and may not reflect the most current and accurate biomedical/scientific data available from NLM. The corresponding record at NLM can be accessed at https://www.ncbi.nlm.nih.gov/pubmed/36426824
Report this publication

Statistics

Seen <100 times