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Iben Lyskjær Heimann

Osteosarcoma: Novel prognostic biomarkers using circulating and cell-free tumour DNA

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Iben Lyskjær
  • Neesha Kara, University College London
  • ,
  • Solange De Noon, University College London, Royal National Orthopaedic Hospital NHS Trust
  • ,
  • Christopher Davies, University College London, Royal National Orthopaedic Hospital NHS Trust
  • ,
  • Ana Maia Rocha, University College London, Royal National Orthopaedic Hospital NHS Trust
  • ,
  • Anna Christina Strobl, Royal National Orthopaedic Hospital NHS Trust
  • ,
  • Inga Usher, University College London
  • ,
  • Craig Gerrand, Royal National Orthopaedic Hospital NHS Trust
  • ,
  • Sandra J. Strauss, University College London
  • ,
  • Daniel Schrimpf, Heidelberg University 
  • ,
  • Andreas von Deimling, Heidelberg University 
  • ,
  • Stephan Beck, University College London
  • ,
  • Adrienne M. Flanagan, University College London, Royal National Orthopaedic Hospital NHS Trust

Aim: Osteosarcoma (OS) is the most common primary bone tumour in children and adolescents. Circulating free (cfDNA) and circulating tumour DNA (ctDNA) are promising biomarkers for disease surveillance and prognostication in several cancer types; however, few such studies are reported for OS. The purpose of this study was to discover and validate methylation-based biomarkers to detect plasma ctDNA in patients with OS and explore their utility as prognostic markers. Methods: Candidate CpG markers were selected through analysis of methylation array data for OS, non-OS tumours and germline samples. Candidates were validated in two independent OS datasets (n = 162, n = 107) and the four top-performing markers were selected. Methylation-specific digital droplet PCR (ddPCR) assays were designed and experimentally validated in OS tumour samples (n = 20) and control plasma samples. Finally, ddPCR assays were applied to pre-operative plasma and where available post-operative plasma from 72 patients with OS, and findings correlated with outcome. Results: Custom ddPCR assays detected ctDNA in 69% and 40% of pre-operative plasma samples (n = 72), based on thresholds of one or two positive markers respectively. ctDNA was detected in 5/17 (29%) post-operative plasma samples from patients, which in four cases were associated with or preceded disease relapse. Both pre-operative cfDNA levels and ctDNA detection independently correlated with overall survival (p = 0.0015 and p = 0.0096, respectively). Conclusion: Our findings illustrate the potential of mutation-independent methylation-based ctDNA assays for OS. This study lays the foundation for multi-institutional collaborative studies to explore the utility of plasma-derived biomarkers in the management of OS.

Original languageEnglish
JournalEuropean Journal of Cancer
Pages (from-to)1-11
Number of pages11
Publication statusPublished - Jun 2022

Bibliographical note

Publisher Copyright:
© 2022

    Research areas

  • Circulating tumour DNA, DNA methylation, Epigenetic biomarkers, Epigenetics, Liquid biopsy, Osteosarcoma, Prognosis

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