Abstract
Following treatment 40% of soft tissue sarcoma (STS) patients suffer disease recurrence. In certain cancers circulating cell free DNA (cfDNA) and circulating tumour-derived DNA (ctDNA) characteristics correlate closely with disease burden, making them exciting potential sources of biomarkers. Despite this, the circulating nucleic acid characteristics of only 2 STS patients have been reported to date.To address this we used an Ion AmpliSeq™ panel custom specifically designed for STS patients to conduct a genetic characterisation of plasma cfDNA, buffy coat (germline) DNA and where available Formalin-Fixed Paraffin-Embedded (FFPE) primary STS tissue DNA in a cohort of 11 metastatic STS patients. We found that total cfDNA levels were significantly elevated in the STS patients analysed, and weakly correlated with disease burden. Using our Ion AmpliSeq™ panel we also successfully detected ctDNA in 4/11 (36%) patients analysed with a wide variety of STS subtypes and disease burdens. This evidence included the presence of cancer associated TP53 / PIK3CA mutations in 2 patients’ plasma and matched primary STS tumour tissue, and in the plasma alone for 2 patients. We also identified 2 potential examples of allelic loss of heterozygosity in an additional patient's STS DNA and cfDNA.This is the largest study performed characterising STS patient cfDNA/ctDNA and confirms that the field remains an attractive potential source of novel STS biomarkers. Further work is required to investigate the circulating nucleic acid characteristics of individual STS subtypes, and the potential prognostic or therapeutic roles that cfDNA/ctDNA may hold for patients with these complex tumours.
Highlights
Soft tissue sarcomas (STSs) are a heterogeneous group of malignant solid tumors derived from mesenchymal origin
The high turnover rate and necrosis of malignant cells compared with healthy cells means that in cancer patients a high proportion of cell free DNA (cfDNA) is released from tumour cells within primary and/or metastatic lesions [5]
soft tissue sarcoma (STS) are a complex group of tumours with a relatively poor prognosis compared with many other solid cancers
Summary
Soft tissue sarcomas (STSs) are a heterogeneous group of malignant solid tumors derived from mesenchymal origin. The curative treatment of STSs revolves around surgical resection and peri-operative radiotherapy [1] Following this treatment the aggressive biological behaviour of many STS subtypes means that 17%-24% of tumors will either recur locally [2] or with metastatic disease [3]. As a consequence very little is known about the circulating nucleic acid characteristics of STS patients, including what proportion of STSs shed DNA into the circulation To address this paucity of knowledge we aimed to characterise the cfDNA levels of a cohort of 11 STS patients with metastatic disease, and using targeted generation sequencing (tNGS) investigate the same patients’ ctDNA characteristics
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