1. The molecular landscape of well differentiated retroperitoneal liposarcoma.
- Author
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Tyler, Robert, Dilworth, Mark P, James, Jonathan, Blakeway, Daniel, Stockton, Joanne D, Morton, Dion G, Taniere, Phillipe, Gourevitch, David, Desai, Anant, and Beggs, Andrew D
- Subjects
LIPOSARCOMA ,GENE fusion ,RNA sequencing ,WNT signal transduction ,DNA repair ,CHROMOSOMAL rearrangement - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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