Personalized sequencing for the noninvasive diagnosis of gliomas
2021
Cancer Centre Amsterdam, Amsterdam, Netherlands(1)
Cancer Research UK Cambridge Institute, Cambridge, United Kingdom(2)
University of Cambridge, Cambridge, United Kingdom(3)
Cancer Research UK Cambridge Institute, Cambridge, United Kingdom(2)
University of Cambridge, Cambridge, United Kingdom(3)
Glioma-derived cell-free DNA (cfDNA) is challenging to detect using liquid biopsy because quantities in body fluids are low. Here, the glioma-derived DNA fraction in cerebrospinal fluid (CSF), plasma, and urine samples from patients was determined, 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, tumor-derived DNA in the majority of CSF, plasma, and urine samples was detected. Further, cfDNA fragment sizes were analysed using whole-genome sequencing, in urine samples from 35 glioma patients, 27 individuals with non-malignant brain disorders, and 26 healthy individuals. cfDNA in the urine of glioma patients was significantly more fragmented compared to urine from patients with non-malignant brain disorders and healthy individuals. Machine learning models integrating fragment length could differentiate urine samples from glioma patients, suggesting possibilities for truly non-invasive cancer detection.
Fragmentation patterns and personalized sequencing of cell-free DNA in urine and plasma of glioma patients
Florent Mouliere(1), Richard Mair(2), Nitzan Rosenfeld(2), Kevin Brindle(3)
Added on: 10-04-2021
[1] https://www.embopress.org/doi/full/10.15252/emmm.202012881?emci=9ab55efe-6dfc-eb11-b563-501ac57b8fa7&emdi=31ff5b9c-7bfc-eb11-b563-501ac57b8fa7&ceid=2015591
