Targeted Next-Generation Sequencing of Plasma DNA from Cancer Patients: Factors Influencing Consistency with Tumour DNA and Prospective Investigation of Its Utility for Diagnosis.
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.
The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.|National Institute for Health Research Oxford Biomedical Research Centre (NIHR Oxford BRC), Oxford, United Kingdom.
Pamela J
PJ
Kaisaki
Biomedical Research Centre/National Health Service Translational Molecular Diagnostics Centre, Oxford University Hospitals, John Radcliffe Hospital, Oxford, United Kingdom.
Anthony
A
Cutts
The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.|National Institute for Health Research Oxford Biomedical Research Centre (NIHR Oxford BRC), Oxford, United Kingdom.
Niko
N
Popitsch
The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.|National Institute for Health Research Oxford Biomedical Research Centre (NIHR Oxford BRC), Oxford, United Kingdom.
Carme
C
Camps
The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.|National Institute for Health Research Oxford Biomedical Research Centre (NIHR Oxford BRC), Oxford, United Kingdom.
Melissa M
MM
Pentony
The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.|National Institute for Health Research Oxford Biomedical Research Centre (NIHR Oxford BRC), Oxford, United Kingdom.
Gareth
G
Wilson
Biomedical Research Centre/National Health Service Translational Molecular Diagnostics Centre, Oxford University Hospitals, John Radcliffe Hospital, Oxford, United Kingdom.
Suzanne
S
Page
The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.|National Institute for Health Research Oxford Biomedical Research Centre (NIHR Oxford BRC), Oxford, United Kingdom.
Kulvinder
K
Kaur
The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.|National Institute for Health Research Oxford Biomedical Research Centre (NIHR Oxford BRC), Oxford, United Kingdom.|Biomedical Research Centre/National Health Service Translational Molecular Diagnostics Centre, Oxford University Hospitals, John Radcliffe Hospital, Oxford, United Kingdom.
Dimitris
D
Vavoulis
Biomedical Research Centre/National Health Service Translational Molecular Diagnostics Centre, Oxford University Hospitals, John Radcliffe Hospital, Oxford, United Kingdom.
Shirley
S
Henderson
National Institute for Health Research Oxford Biomedical Research Centre (NIHR Oxford BRC), Oxford, United Kingdom.|Department of Oncology, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
Avinash
A
Gupta
National Institute for Health Research Oxford Biomedical Research Centre (NIHR Oxford BRC), Oxford, United Kingdom.|Department of Oncology, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
Mark R
MR
Middleton
National Institute for Health Research Oxford Biomedical Research Centre (NIHR Oxford BRC), Oxford, United Kingdom.|Department of Oncology, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
Ioannis
I
Karydis
Department of Oncology, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
Denis C
DC
Talbot
Biomedical Research Centre/National Health Service Translational Molecular Diagnostics Centre, Oxford University Hospitals, John Radcliffe Hospital, Oxford, United Kingdom.
Anna
A
Schuh
The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.|National Institute for Health Research Oxford Biomedical Research Centre (NIHR Oxford BRC), Oxford, United Kingdom.
Jenny C
JC
Taylor
D001706:Biopsy; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008545:Melanoma / Q000175:diagnosis / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction
D004273:DNA, Neoplasm