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PLoS One. 2016 Sep 14;11(9):e0162809. doi: 10.1371/journal.pone.0162809. eCollection 2016.

Targeted Next-Generation Sequencing of Plasma DNA from Cancer Patients: Factors Influencing Consistency with Tumour DNA and Prospective Investigation of Its Utility for Diagnosis.

Author information

1
The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
2
National Institute for Health Research Oxford Biomedical Research Centre (NIHR Oxford BRC), Oxford, United Kingdom.
3
Biomedical Research Centre/National Health Service Translational Molecular Diagnostics Centre, Oxford University Hospitals, John Radcliffe Hospital, Oxford, United Kingdom.
4
Department of Oncology, University of Oxford, Churchill Hospital, Oxford, United Kingdom.

Abstract

Use of circulating tumour DNA (ctDNA) as a liquid biopsy has been proposed for potential identification and monitoring of solid tumours. We investigate a next-generation sequencing approach for mutation detection in ctDNA in two related studies using a targeted panel. The first study was retrospective, using blood samples taken from melanoma patients at diverse timepoints before or after treatment, aiming to evaluate correlation between mutations identified in biopsy and ctDNA, and to acquire a first impression of influencing factors. We found good concordance between ctDNA and tumour mutations of melanoma patients when blood samples were collected within one year of biopsy or before treatment. In contrast, when ctDNA was sequenced after targeted treatment in melanoma, mutations were no longer found in 9 out of 10 patients, suggesting the method might be useful for detecting treatment response. Building on these findings, we focused the second study on ctDNA obtained before biopsy in lung patients, i.e. when a tentative diagnosis of lung cancer had been made, but no treatment had started. The main objective of this prospective study was to evaluate use of ctDNA in diagnosis, investigating the concordance of biopsy and ctDNA-derived mutation detection. Here we also found positive correlation between diagnostic lung biopsy results and pre-biopsy ctDNA sequencing, providing support for using ctDNA as a cost-effective, non-invasive solution when the tumour is inaccessible or when biopsy poses significant risk to the patient.

PMID:
27626278
PMCID:
PMC5023174
DOI:
10.1371/journal.pone.0162809
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: PJK has received royalties in the past two years from a license agreement with Correlagen, related to early-onset non-insulin-dependent diabetes mellitus. AG has received fees from Bristol Myers Squibb for leading webinar based teaching sessions organised by them for other doctors. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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