Fragmentation patterns and personalized sequencing of cellāfree DNA in urine and plasma of glioma patients
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Peer-reviewed
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Abstract: Gliomaāderived cellāfree DNA (cfDNA) is challenging to detect using liquid biopsy because quantities in body fluids are low. We determined the gliomaāderived 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 patientās tumor, we detected tumorāderived DNA in the majority of CSF (7/8), plasma (10/12), and urine samples (10/16), with a median tumor fraction of 6.4 Ć 10ā3, 3.1 Ć 10ā5, and 4.7 Ć 10ā5, respectively. We identified a shift in the size distribution of tumorāderived cfDNA fragments in these body fluids. We further analyzed cfDNA fragment sizes using wholeāgenome sequencing, in urine samples from 35 glioma patients, 27 individuals with nonāmalignant brain disorders, and 26 healthy individuals. cfDNA in urine of glioma patients was significantly more fragmented compared to urine from patients with nonāmalignant brain disorders (P = 1.7 Ć 10ā2) and healthy individuals (P = 5.2 Ć 10ā9). Machine learning models integrating fragment length could differentiate urine samples from glioma patients (AUC = 0.80ā0.91) suggesting possibilities for truly nonāinvasive cancer detection.
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Funder: FP7 Ideas: European Research Council (FP7 Ideas); Id: http://dx.doi.org/10.13039/100011199; Grant(s): 337905
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1757-4684
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KWF Kankerbestrijding (DCS) (12822)