Multi-omics of soft tissue sarcomas with complex karyotypes: Investigating genomic and transcriptomic differences between cell lines of the same subtype

BackgroundSoft tissue sarcomas with complex karyotypes (STSCK) is a difficult to treat group of tumours, with its genetic heterogeneity posing a challenge to therapy. Next-generation sequencing is already aiding in the characterisation of STS subtypes and shows potential to lead us towards a personalised medicine approach in STSCK treatment. We are currently analysing multi-omics data from STSCK cell lines – undifferentiated pleomorphic sarcoma (UPS), leiomyosarcoma, myxofibrosarcoma and dedifferentiated liposarcoma. We aim to identify differential molecular biomarkers for STSCK with the potential that these be used in building a profile predictive of treatment outcome.MethodsEstablished patient-derived STSCK cell lines underwent low-pass whole genome/whole-exome/RNA sequencing. Data were assessed for copy number variation, structural variants, as well as differential gene expression (DGE) between same subtype cell lines. Presently, we are characterising transcriptomic data for enriched pathways/signalling networks.Resultsindicate that our STSCK cell lines possess defined omic profiles. DGE between UPS cell lines showed differential expression of oncogenic genes, such as TP53 and YAP1, and distinct mutational signatures were also seen in signalling pathways – UPS1 showed specific mutations in genes of the Wnt pathway whereas mutations in UPS2 cell line affected the Hippo pathway.ConclusionsThe observed differential molecular profiles reinforce the hypothesis that, even within same subtype STS, there are key gene expression differences which have the potential to be further explored to guide targeted drug testing and subsequent treatment decisions. To validate the obtained signatures, future work includes comparing our omic profiles with drug sensitivities obtained for these cell lines against a panel of more than 40 novel and approved drugs.Legal entity responsible for the studyUniversity of Sheffield.FundingSarcoma UK.DisclosureAll authors have declared no conflicts of interest.