Authors
Florent Mouliere, Dineika Chandrananda, Anna M Piskorz, Elizabeth K Moore, James Morris, Lise Barlebo Ahlborn, Richard Mair, Teodora Goranova, Francesco Marass, Katrin Heider, Jonathan CM Wan, Anna Supernat, Irena Hudecova, Ioannis Gounaris, Susana Ros, Mercedes Jimenez-Linan, Javier Garcia-Corbacho, Keval Patel, Olga Østrup, Suzanne Murphy, Matthew D Eldridge, Davina Gale, Grant D Stewart, Johanna Burge, Wendy N Cooper, Michiel S van der Heijden, Charles E Massie, Colin Watts, Pippa Corrie, Simon Pacey, Kevin M Brindle, Richard D Baird, Morten Mau-Sørensen, Christine A Parkinson, Christopher G Smith, James D Brenton, Nitzan Rosenfeld
Publication date
2018/11/7
Journal
Science translational medicine
Volume
10
Issue
466
Pages
eaat4921
Publisher
American Association for the Advancement of Science
Description
Existing methods to improve detection of circulating tumor DNA (ctDNA) have focused on genomic alterations but have rarely considered the biological properties of plasma cell-free DNA (cfDNA). We hypothesized that differences in fragment lengths of circulating DNA could be exploited to enhance sensitivity for detecting the presence of ctDNA and for noninvasive genomic analysis of cancer. We surveyed ctDNA fragment sizes in 344 plasma samples from 200 patients with cancer using low-pass whole-genome sequencing (0.4×). To establish the size distribution of mutant ctDNA, tumor-guided personalized deep sequencing was performed in 19 patients. We detected enrichment of ctDNA in fragment sizes between 90 and 150 bp and developed methods for in vitro and in silico size selection of these fragments. Selecting fragments between 90 and 150 bp improved detection of tumor DNA, with more than twofold …
Scholar articles
F Mouliere, D Chandrananda, AM Piskorz, EK Moore… - Science translational medicine, 2018