The molecular landscape of well differentiated retroperitoneal liposarcoma

Robert Tyler, Mark P Dilworth, Jonathan James, Daniel Blakeway, Joanne D Stockton, Dion G Morton, Phillipe Taniere, David Gourevitch, Anant Desai, Andrew D Beggs

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Abstract

Well differentiated liposarcoma (WD-LPS) is a relatively rare tumour, with fewer than 50 cases occurring per year in the UK. These tumours are both chemotherapy- and radiotherapy-resistant and present a significant treatment challenge requiring radical surgery. Little is known of the molecular landscape of these tumours and no current targets for molecular therapy exist. We aimed to carry out a comprehensive molecular characterisation of WD-LPS via whole genome sequencing, RNA sequencing, and methylation array analysis. A recurrent mutation within exon 1 of FOXD4L3 was observed (chr9:70,918,189A>T; c.322A>T; p.Lys108Ter). Recurrent mutations were also observed in Wnt signalling, immunity, DNA repair, and hypoxia-associated genes. Recurrent amplification of HGMA2 was observed, although this was in fact part of a general amplification of the region around this gene. Recurrent gene fusions in HGMA2, SDHA, TSPAN31, and MDM2 were also observed as well as consistent rearrangements between chromosome 6 and chromosome 12. Our study has demonstrated a recurrent mutation within FOXD4L3, which shows evidence of interaction with the PAX pathway to promote tumourigenesis. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Original languageEnglish
Pages (from-to)132-140
Number of pages9
JournalJournal of Pathology
Volume255
Issue number2
Early online date22 Jun 2021
DOIs
Publication statusPublished - Oct 2021

Bibliographical note

Funding Information:
We thank Illumina UK (Miao He, Sean Humphray, Mahesh Vasipalli, Zoya Kingsbury, and David Bentley) for sequencing and bioinformatics support for this project. This work was partially funded by a pump priming grant from the Cancer Research UK Birmingham Experimental Cancer Medicine Centre. AB acknowledges funding from the Wellcome Trust (102732/Z/13/Z), Cancer Research UK (C31641/A23923), and the Medical Research Council (MR/M016587/1).

Publisher Copyright:
© 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Keywords

  • RNA sequencing
  • liposarcoma
  • methylation
  • whole genome sequencing

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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