PT  - JOURNAL ARTICLE
AU  - Florent Mouliere
AU  - Anna M. Piskorz
AU  - Dineika Chandrananda
AU  - Elizabeth Moore
AU  - James Morris
AU  - Christopher G. Smith
AU  - Teodora Goranova
AU  - Katrin Heider
AU  - Richard Mair
AU  - Anna Supernat
AU  - Ioannis Gounaris
AU  - Susana Ros
AU  - Jonathan C. M. Wan
AU  - Mercedes Jimenez-Linan
AU  - Davina Gale
AU  - Kevin Brindle
AU  - Charles E. Massie
AU  - Christine A. Parkinson
AU  - James D. Brenton
AU  - Nitzan Rosenfeld
TI  - Selecting short DNA fragments in plasma improves detection of circulating tumour DNA
AID  - 10.1101/134437
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 134437
4099  - http://biorxiv.org/content/early/2017/05/05/134437.short
4100  - http://biorxiv.org/content/early/2017/05/05/134437.full
AB  - 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.