Journal article
Fragmentation patterns and personalized sequencing of cell-free DNA in urine and plasma of glioma patients
F Mouliere, CG Smith, K Heider, J Su, Y van der Pol, M Thompson, J Morris, JCM Wan, D Chandrananda, J Hadfield, M Grzelak, I Hudecova, DL Couturier, W Cooper, H Zhao, D Gale, M Eldridge, C Watts, K Brindle, N Rosenfeld Show all
EMBO Molecular Medicine | Published : 2021
Open access
Abstract
Glioma-derived cell-free DNA (cfDNA) is challenging to detect using liquid biopsy because quantities in body fluids are low. We determined the glioma-derived DNA fraction in cerebrospinal fluid (CSF), plasma, and urine samples from patients using sequencing of personalized capture panels guided by analysis of matched tumor biopsies. By sequencing cfDNA across thousands of mutations, identified individually in each patient’s tumor, we detected tumor-derived DNA in the majority of CSF (7/8), plasma (10/12), and urine samples (10/16), with a median tumor fraction of 6.4 × 10−3, 3.1 × 10−5, and 4.7 × 10−5, respectively. We identified a shift in the size distribution of tumor-derived cfDNA fragme..
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Awarded by Mark Foundation For Cancer Research
Funding Acknowledgements
We wish to thank for their help and support the Cancer Research UK Cambridge Institute core facilities, in particular bio-repository, bioinformatics, and genomics. cfDNA isolation was performed by the Cancer Molecular Diagnostics Laboratory, which is supported by Cambridge NIHR Biomedical Research Centre, Cambridge Cancer Centre, and the Mark Foundation of Cancer Research. We would also like to acknowledge the support of The University of Cambridge, Cancer Research UK (grant numbers A20240, A29580, A17197, and A16465). The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement n. 337905. Florent Mouliere is supported by a Dutch Cancer Fund (KWF-12822).