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The Circulating Nucleic Acid Characteristics of Non-Metastatic Soft Tissue Sarcoma Patients

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posted on 2021-04-29, 11:04 authored by Nicholas Eastley, Aurore Sommer, Barbara Ottolini, Rita Neumann, Jin-Li Luo, Robert K Hastings, Thomas McCulloch, Claire P Esler, Jacqueline A Shaw, Robert U Ashford, Nicola J Royle
Soft tissue sarcomas (STS) are rare, malignant tumours with a generally poor prognosis. Our aim was to explore the potential of cell free DNA (cfDNA) and circulating tumour DNA (ctDNA) analysis to track non-metastatic STS patients undergoing attempted curative treatment. The analysed cohort (n = 29) contained multiple STS subtypes including myxofibrosarcomas, undifferentiated pleomorphic sarcomas, leiomyosarcomas, and dedifferentiated liposarcomas amongst others. Perioperative cfDNA levels trended towards being elevated in patients (p = 0.07), although did not correlate with tumour size, grade, recurrence or subtype, suggesting a limited diagnostic or prognostic role. To characterise ctDNA, an amplicon panel covering three genes commonly mutated in STSswas first trialled on serial plasma collected fromnine patients throughout follow-up. This approach only identified ctDNA in 2.5% (one in 40) of the analysed samples. Next custom-designed droplet digital PCR assays and Ion AmpliSeq™ panels were developed to track single nucleotide variants identified in patients’ STSs by whole exome sequencing (1-6 per patient). These approaches identified ctDNA in 17% of patients. Although ctDNA was identified before radiologically detectable recurrence in two cases, the absence of demonstrable ctDNA in 83% of cases highlights the need for much work before circulating nucleic acids can become a useful means to track STS patients.

Funding

: This work was supported by The Royal College of Surgeons (Eng) (One year Research fellowship), the Medical Research Council (MR/N02107X/1), the Rosetrees trust (A1076), the University of Leicester NHS Trust Orthopaedic department (Foxtrot charity) and the Leicestershire charity HOPE against cancer

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Citation

Eastley, N.; Sommer, A.; Ottolini, B.; Neumann, R.; Luo, J.-L.; Hastings, R.K.; McCulloch, T.; Esler, C.P.; Shaw, J.A.; Ashford, R.U.; Royle, N.J. The Circulating Nucleic Acid Characteristics of Non-Metastatic Soft Tissue Sarcoma Patients. Int. J. Mol. Sci. 2020, 21, 4483. https://doi.org/10.3390/ijms21124483

Version

  • VoR (Version of Record)

Published in

International Journal of Molecular Sciences

Volume

21

Issue

12

Pagination

4483

Publisher

MDPI

issn

1661-6596

eissn

1422-0067

Acceptance date

2020-06-19

Copyright date

2020

Available date

2021-04-29

Spatial coverage

Switzerland

Language

English

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