Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/26081
Title: Cerebrospinal fluid liquid biopsy for detecting somatic mosaicism in brain.
Austin Authors: Ye, Zimeng;Chatterton, Zac;Pflueger, Jahnvi;Damiano, John A;McQuillan, Lara ;Harvey, Anthony Simon;Malone, Stephen;Do, Hongdo;Maixner, Wirginia;Schneider, Amy L ;Nolan, Bernadette;Wood, Martin;Lee, Wei Shern;Gillies, Greta;Pope, Kate;Wilson, Michael;Lockhart, Paul J;Dobrovic, Alexander ;Scheffer, Ingrid E ;Bahlo, Melanie;Leventer, Richard J;Lister, Ryan;Berkovic, Samuel F ;Hildebrand, Michael S 
Affiliation: Department of Anatomical Pathology, St. Vincent's Hospital, Melbourne, Victoria 3065, Australia
Neurosurgical Department, Queensland Children's Hospital, Brisbane, Queensland 4101, Australia
Department of Neurosciences, Queensland Children's Hospital, Brisbane, Queensland 4101, Australia
Department of Neurosurgery, Royal Children's Hospital, Melbourne, Victoria 3052, Australia
Medicine (University of Melbourne)
Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney, New South Wales 2050, Australia
School of Cancer Medicine, La Trobe University, Melbourne, Victoria 3086, Australia
Department of Clinical Pathology, University of Melbourne, Melbourne, Victoria 3010, Australia
Olivia Newton-John Cancer Research Institute
Murdoch Children's Research Institute, Melbourne, Victoria 3052, Australia
Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Victoria 3052, Australia
Department of Neurology, Royal Children's Hospital, Melbourne, Victoria 3052, Australia
Australian Research Council Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Perth, Western Australia 6009, Australia
Harry Perkins Institute of Medical Research, Perth, Western Australia 6150, Australia
Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia
Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3010, Australia
Issue Date: 21-Jan-2021
metadata.dc.date: 2021-01-21
Publication information: Brain Communications 2021; 3(1): fcaa235
Abstract: Brain somatic mutations are an increasingly recognized cause of epilepsy, brain malformations and autism spectrum disorders and may be a hidden cause of other neurodevelopmental and neurodegenerative disorders. At present, brain mosaicism can be detected only in the rare situations of autopsy or brain biopsy. Liquid biopsy using cell-free DNA derived from cerebrospinal fluid has detected somatic mutations in malignant brain tumours. Here, we asked if cerebrospinal fluid liquid biopsy can be used to detect somatic mosaicism in non-malignant brain diseases. First, we reliably quantified cerebrospinal fluid cell-free DNA in 28 patients with focal epilepsy and 28 controls using droplet digital PCR. Then, in three patients we identified somatic mutations in cerebrospinal fluid: in one patient with subcortical band heterotopia the LIS1 p. Lys64* variant at 9.4% frequency; in a second patient with focal cortical dysplasia the TSC1 p. Phe581His*6 variant at 7.8% frequency; and in a third patient with ganglioglioma the BRAF p. Val600Glu variant at 3.2% frequency. To determine if cerebrospinal fluid cell-free DNA was brain-derived, whole-genome bisulphite sequencing was performed and brain-specific DNA methylation patterns were found to be significantly enriched (Pā€‰=ā€‰0.03). Our proof of principle study shows that cerebrospinal fluid liquid biopsy is valuable in investigating mosaic neurological disorders where brain tissue is unavailable.
URI: https://ahro.austin.org.au/austinjspui/handle/1/26081
DOI: 10.1093/braincomms/fcaa235
ORCID: 0000-0001-5132-0774
Journal: Brain Communications
PubMed URL: 33738444
Type: Journal Article
Subjects: cell-free DNA
cerebrospinal fluid
focal epilepsy
liquid biopsy
somatic mutations
Appears in Collections:Journal articles

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