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

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Osteosarcoma: Novel prognostic biomarkers using circulating and cell-free tumour DNA. / Lyskjær, Iben; Kara, Neesha; De Noon, Solange et al.
In: European Journal of Cancer, Vol. 168, 06.2022, p. 1-11.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Harvard

Lyskjær, I, Kara, N, De Noon, S, Davies, C, Rocha, AM, Strobl, AC, Usher, I, Gerrand, C, Strauss, SJ, Schrimpf, D, von Deimling, A, Beck, S & Flanagan, AM 2022, 'Osteosarcoma: Novel prognostic biomarkers using circulating and cell-free tumour DNA', European Journal of Cancer, vol. 168, pp. 1-11. https://doi.org/10.1016/j.ejca.2022.03.002

APA

Lyskjær, I., Kara, N., De Noon, S., Davies, C., Rocha, A. M., Strobl, A. C., Usher, I., Gerrand, C., Strauss, S. J., Schrimpf, D., von Deimling, A., Beck, S., & Flanagan, A. M. (2022). Osteosarcoma: Novel prognostic biomarkers using circulating and cell-free tumour DNA. European Journal of Cancer, 168, 1-11. https://doi.org/10.1016/j.ejca.2022.03.002

CBE

Lyskjær I, Kara N, De Noon S, Davies C, Rocha AM, Strobl AC, Usher I, Gerrand C, Strauss SJ, Schrimpf D, et al. 2022. Osteosarcoma: Novel prognostic biomarkers using circulating and cell-free tumour DNA. European Journal of Cancer. 168:1-11. https://doi.org/10.1016/j.ejca.2022.03.002

MLA

Lyskjær, Iben et al. "Osteosarcoma: Novel prognostic biomarkers using circulating and cell-free tumour DNA". European Journal of Cancer. 2022, 168. 1-11. https://doi.org/10.1016/j.ejca.2022.03.002

Vancouver

Lyskjær I, Kara N, De Noon S, Davies C, Rocha AM, Strobl AC et al. Osteosarcoma: Novel prognostic biomarkers using circulating and cell-free tumour DNA. European Journal of Cancer. 2022 Jun;168:1-11. doi: 10.1016/j.ejca.2022.03.002

Author

Lyskjær, Iben ; Kara, Neesha ; De Noon, Solange et al. / Osteosarcoma : Novel prognostic biomarkers using circulating and cell-free tumour DNA. In: European Journal of Cancer. 2022 ; Vol. 168. pp. 1-11.

Bibtex

@article{6b732f6d1a92482a970e81a6debc8d20,
title = "Osteosarcoma: Novel prognostic biomarkers using circulating and cell-free tumour DNA",
abstract = "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.",
keywords = "Circulating tumour DNA, DNA methylation, Epigenetic biomarkers, Epigenetics, Liquid biopsy, Osteosarcoma, Prognosis",
author = "Iben Lyskj{\ae}r and Neesha Kara and {De Noon}, Solange and Christopher Davies and Rocha, {Ana Maia} and Strobl, {Anna Christina} and Inga Usher and Craig Gerrand and Strauss, {Sandra J.} and Daniel Schrimpf and {von Deimling}, Andreas and Stephan Beck and Flanagan, {Adrienne M.}",
note = "Publisher Copyright: {\textcopyright} 2022",
year = "2022",
month = jun,
doi = "10.1016/j.ejca.2022.03.002",
language = "English",
volume = "168",
pages = "1--11",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Pergamon",

}

RIS

TY - JOUR

T1 - Osteosarcoma

T2 - Novel prognostic biomarkers using circulating and cell-free tumour DNA

AU - Lyskjær, Iben

AU - Kara, Neesha

AU - De Noon, Solange

AU - Davies, Christopher

AU - Rocha, Ana Maia

AU - Strobl, Anna Christina

AU - Usher, Inga

AU - Gerrand, Craig

AU - Strauss, Sandra J.

AU - Schrimpf, Daniel

AU - von Deimling, Andreas

AU - Beck, Stephan

AU - Flanagan, Adrienne M.

N1 - Publisher Copyright: © 2022

PY - 2022/6

Y1 - 2022/6

N2 - 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.

AB - 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.

KW - Circulating tumour DNA

KW - DNA methylation

KW - Epigenetic biomarkers

KW - Epigenetics

KW - Liquid biopsy

KW - Osteosarcoma

KW - Prognosis

U2 - 10.1016/j.ejca.2022.03.002

DO - 10.1016/j.ejca.2022.03.002

M3 - Journal article

C2 - 35421838

AN - SCOPUS:85127771941

VL - 168

SP - 1

EP - 11

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

ER -