Circulating tumour-derived DNA in metastatic soft tissue sarcoma

// Nicholas C. Eastley 1, 3 , Barbara Ottolini 4 , Rita Neumann 3 , Jin-Li Luo 4 , Robert K. Hastings 4 , Imran Khan 1 , David A. Moore 4 , Claire P. Esler 2 , Jacqueline A. Shaw 4 , Nicola J. Royle 3, * and Robert U. Ashford 1, 2, * 1 University Hospitals of Leicester NHS Trust, Trauma and Orthopaedics, Leicester, UK 2 Nottingham University Hospitals NHS Trust, Nottingham, UK 3 University of Leicester Department of Genetics, Leicester, UK 4 University of Leicester Department of Cancer Studies, Leicester, UK * Joint senior authors Correspondence to: Nicholas C. Eastley, email: nce8@le.ac.uk Keywords: soft tissue sarcoma; biomarker; circulating tumour DNA; cell free DNA; telomere Received: June 07, 2017 Accepted: January 09, 2018 Published: January 19, 2018 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.