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Selecting short DNA fragments in plasma improves detection of circulating tumour DNA

View ORCID ProfileFlorent Mouliere, Anna M. Piskorz, Dineika Chandrananda, Elizabeth Moore, James Morris, Christopher G. Smith, Teodora Goranova, Katrin Heider, Richard Mair, Anna Supernat, Ioannis Gounaris, Susana Ros, Jonathan C. M. Wan, Mercedes Jimenez-Linan, Davina Gale, Kevin Brindle, Charles E. Massie, Christine A. Parkinson, James D. Brenton, Nitzan Rosenfeld
doi: https://doi.org/10.1101/134437
Florent Mouliere
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
2Cancer Research UK Major Centre – Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK
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  • ORCID record for Florent Mouliere
Anna M. Piskorz
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
2Cancer Research UK Major Centre – Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK
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Dineika Chandrananda
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
2Cancer Research UK Major Centre – Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK
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Elizabeth Moore
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
2Cancer Research UK Major Centre – Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK
3Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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James Morris
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
2Cancer Research UK Major Centre – Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK
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Christopher G. Smith
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
2Cancer Research UK Major Centre – Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK
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Teodora Goranova
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
2Cancer Research UK Major Centre – Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK
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Katrin Heider
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
2Cancer Research UK Major Centre – Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK
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Richard Mair
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
2Cancer Research UK Major Centre – Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK
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Anna Supernat
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
2Cancer Research UK Major Centre – Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK
4Medical University of Gdansk, Gdansk, Poland
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Ioannis Gounaris
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
2Cancer Research UK Major Centre – Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK
3Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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Susana Ros
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
2Cancer Research UK Major Centre – Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK
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Jonathan C. M. Wan
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
2Cancer Research UK Major Centre – Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK
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Mercedes Jimenez-Linan
2Cancer Research UK Major Centre – Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK
3Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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Davina Gale
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
2Cancer Research UK Major Centre – Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK
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Kevin Brindle
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
2Cancer Research UK Major Centre – Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK
5Department of Biochemistry, University of Cambridge, Cambridge, UK
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Charles E. Massie
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
2Cancer Research UK Major Centre – Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK
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Christine A. Parkinson
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
2Cancer Research UK Major Centre – Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK
3Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
6Department of Oncology, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK
7NIHR Cambridge Biomedical Research Centre, Cambridge, UK
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James D. Brenton
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
2Cancer Research UK Major Centre – Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK
3Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
6Department of Oncology, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK
7NIHR Cambridge Biomedical Research Centre, Cambridge, UK
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  • For correspondence: james.brenton@cruk.cam.ac.uk nitzan.rosenfeld@cruk.cam.ac.uk
Nitzan Rosenfeld
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
2Cancer Research UK Major Centre – Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK
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  • For correspondence: james.brenton@cruk.cam.ac.uk nitzan.rosenfeld@cruk.cam.ac.uk
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Introductory paragraph

Non-invasive analysis of cancer genomes using cell-free circulating tumour DNA (ctDNA) is being widely implemented for clinical indications. The sensitivity for detecting the presence of ctDNA and genomic changes in ctDNA is limited by its low concentration compared to cell-free DNA of non-tumour origin. We studied the feasibility for enrichment of ctDNA by size selection, in plasma samples collected before and during chemotherapy treatment in 13 patients with recurrent high-grade serous ovarian cancer. We evaluated the effects using targeted and whole genome sequencing. Selecting DNA fragments between 90-150 bp before analysis yielded enrichment of mutated DNA fraction of up to 11-fold. This allowed identification of adverse copy number alterations, including MYC amplification, otherwise not observed. Size selection allows detection of tumour alterations masked by non-tumour DNA in plasma and could help overcome sensitivity limitations of liquid biopsy for applications in early diagnosis, detection of minimal residual disease, and genomic profiling.

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Posted May 05, 2017.
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Selecting short DNA fragments in plasma improves detection of circulating tumour DNA
Florent Mouliere, Anna M. Piskorz, Dineika Chandrananda, Elizabeth Moore, James Morris, Christopher G. Smith, Teodora Goranova, Katrin Heider, Richard Mair, Anna Supernat, Ioannis Gounaris, Susana Ros, Jonathan C. M. Wan, Mercedes Jimenez-Linan, Davina Gale, Kevin Brindle, Charles E. Massie, Christine A. Parkinson, James D. Brenton, Nitzan Rosenfeld
bioRxiv 134437; doi: https://doi.org/10.1101/134437
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Selecting short DNA fragments in plasma improves detection of circulating tumour DNA
Florent Mouliere, Anna M. Piskorz, Dineika Chandrananda, Elizabeth Moore, James Morris, Christopher G. Smith, Teodora Goranova, Katrin Heider, Richard Mair, Anna Supernat, Ioannis Gounaris, Susana Ros, Jonathan C. M. Wan, Mercedes Jimenez-Linan, Davina Gale, Kevin Brindle, Charles E. Massie, Christine A. Parkinson, James D. Brenton, Nitzan Rosenfeld
bioRxiv 134437; doi: https://doi.org/10.1101/134437

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