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

Research output: Contribution to journalArticleAcademic

Abstract

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.
Original languageEnglish
JournalBiorxiv
Publication statusPublished - 2017

Cite this

Mouliere, F., Piskorz, A. M., Chandrananda, D., Moore, E., Morris, J., Smith, C. G., ... Rosenfeld, N. (2017). Selecting Short DNA Fragments In Plasma Improves Detection Of Circulating Tumour DNA. Biorxiv.