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Detection of cell-free DNA fragmentation and copy number alterations in cerebrospinal fluid from glioma patients.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Mair, Richard 
Chandrananda, Dineika  ORCID logo  https://orcid.org/0000-0002-8834-9500
Marass, Francesco 
Smith, Christopher G 

Abstract

Glioma is difficult to detect or characterize using current liquid biopsy approaches. Detection of cell-free tumor DNA (cftDNA) in cerebrospinal fluid (CSF) has been proposed as an alternative to detection in plasma. We used shallow whole-genome sequencing (sWGS, at a coverage of < 0.4×) of cell-free DNA from the CSF of 13 patients with primary glioma to determine somatic copy number alterations and DNA fragmentation patterns. This allowed us to determine the presence of cftDNA in CSF without any prior knowledge of point mutations present in the tumor. We also showed that the fragmentation pattern of cell-free DNA in CSF is different from that in plasma. This low-cost screening method provides information on the tumor genome and can be used to target those patients with high levels of cftDNA for further larger-scale sequencing, such as by whole-exome and whole-genome sequencing.

Description

Keywords

cell‐free DNA, cerebrospinal fluid, fragmentation, glioma, shallow WGS, Cerebrospinal Fluid, Circulating Tumor DNA, DNA Fragmentation, Glioma, Humans, Whole Genome Sequencing

Journal Title

EMBO Mol Med

Conference Name

Journal ISSN

1757-4676
1757-4684

Volume Title

10

Publisher

Springer Science and Business Media LLC
Sponsorship
Cancer Research UK (CB4100)
Addenbrooke's Charitable Trust (ACT) (unknown)
Cancer Research UK (C14303/A17197)
Cancer Research Uk (None)
Cancer Research UK (C48525/A18345)
European Research Council (337905)
Cancer Research UK (17242)
Cancer Research UK (20240)