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. Preprints2021, 2021010008. https://doi.org/10.20944/preprints202101.0008.v1
APA Style
Tyler, R., Dilworth, M., James, J., Blakeway, D., Stockton, J., Morton, D., Taniere, P., Gourevitch, D., Desai, A., & Beggs, A.D. (2021). The Molecular Landscape of Well Differentiated Retroperitoneal Liposarcoma. Preprints. https://doi.org/10.20944/preprints202101.0008.v1
Chicago/Turabian Style
Tyler, R., Anant Desai and Andrew D Beggs. 2021 "The Molecular Landscape of Well Differentiated Retroperitoneal Liposarcoma" Preprints. https://doi.org/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
Subject
Medicine and Pharmacology, Immunology and Allergy
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
