Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Molecular Landscape of Well Differentiated Retroperitoneal Liposarcoma

Version 1 : Received: 31 December 2020 / Approved: 4 January 2021 / Online: 4 January 2021 (10:36:13 CET)

How to cite: Tyler, R.; Dilworth, M.; James, J.; Blakeway, D.; Stockton, J.; Morton, D.; Taniere, P.; Gourevitch, D.; Desai, A.; Beggs, A.D. The Molecular Landscape of Well Differentiated Retroperitoneal Liposarcoma. Preprints 2021, 2021010008 (doi: 10.20944/preprints202101.0008.v1). Tyler, R.; Dilworth, M.; James, J.; Blakeway, D.; Stockton, J.; Morton, D.; Taniere, P.; Gourevitch, D.; Desai, A.; Beggs, A.D. The Molecular Landscape of Well Differentiated Retroperitoneal Liposarcoma. Preprints 2021, 2021010008 (doi: 10.20944/preprints202101.0008.v1).

Abstract

Well differentiated liposarcoma (WD-LPS) is a relatively rare tumour, with less 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 exon1 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 tumorigenesis.

Keywords

Liposarcoma; WGS; RNAseq; Methylation

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