title: Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma.
abstract: Cell-free circulating tumour DNA (ctDNA) in plasma has been shown to be informative of the genomic alterations present in tumours and has been used to monitor tumour progression and response to treatments. However, patients with brain tumours do not present with or present with low amounts of ctDNA in plasma precluding the genomic characterization of brain cancer through plasma ctDNA. Here we show that ctDNA derived from central nervous system tumours is more abundantly present in the cerebrospinal fluid (CSF) than in plasma. Massively parallel sequencing of CSF ctDNA more comprehensively characterizes the genomic alterations of brain tumours than plasma, allowing the identification of actionable brain tumour somatic mutations. We show that CSF ctDNA levels longitudinally fluctuate in time and follow the changes in brain tumour burden providing biomarkers to monitor brain malignancies. Moreover, CSF ctDNA is shown to facilitate and complement the diagnosis of leptomeningeal carcinomatosis.
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain.|Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.|Universitat Autònoma de Barcelona, 08193 Barcelona, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: De Mattos-Arruda
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Regina
authors.initials: R
authors.lastname: Mayor
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
authors.forename: Charlotte K Y
authors.initials: CKY
authors.lastname: Ng
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
authors.forename: Britta
authors.initials: B
authors.lastname: Weigelt
authors.affiliation: Universitat Autònoma de Barcelona, 08193 Barcelona, Spain.|Vall d'Hebron Institute of Research, Vall d'Hebron University Hospital, Ps Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Martínez-Ricarte
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Davis
authors.initials: D
authors.lastname: Torrejon
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Oliveira
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Arias
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Raventos
authors.affiliation: Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: Jiabin
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Guerini-Rocco
authors.affiliation: Vall d'Hebron Institute of Research, Vall d'Hebron University Hospital, Ps Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Martínez-Sáez
authors.affiliation: Vall d'Hebron Institute of Research, Vall d'Hebron University Hospital, Ps Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Lois
authors.affiliation: Vall d'Hebron Institute of Research, Vall d'Hebron University Hospital, Ps Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Marín
authors.affiliation: Vall d'Hebron Institute of Research, Vall d'Hebron University Hospital, Ps Vall d'Hebron 119-129, 08035 Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: de la Cruz
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
authors.forename: Salvatore
authors.identifier: 0000-0003-2686-2939
authors.initials: S
authors.lastname: Piscuoglio
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: Russel
authors.initials: R
authors.lastname: Towers
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Vivancos
authors.affiliation: Vall d'Hebron Institute of Research, Vall d'Hebron University Hospital, Ps Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Vicente
authors.identifier: 0000-0002-5203-6166
authors.initials: V
authors.lastname: Peg
authors.affiliation: Universitat Autònoma de Barcelona, 08193 Barcelona, Spain.|Vall d'Hebron Institute of Research, Vall d'Hebron University Hospital, Ps Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Ramon y Cajal
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Carles
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Rodon
authors.affiliation: Quirón Dexeus University Hospital, 08028 Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: González-Cao
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain.|Universitat Autònoma de Barcelona, 08193 Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain.|Universitat Autònoma de Barcelona, 08193 Barcelona, Spain.
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Felip
authors.affiliation: Universitat Autònoma de Barcelona, 08193 Barcelona, Spain.|Vall d'Hebron Institute of Research, Vall d'Hebron University Hospital, Ps Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Sahuquillo
authors.affiliation: Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.|Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Berger
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain.|Universitat Autònoma de Barcelona, 08193 Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Cortes
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain.|Universitat Autònoma de Barcelona, 08193 Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Seoane
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000556:secondary; D001943:Breast Neoplasms / Q000473:pathology; D004273:DNA, Neoplasm / Q000097:blood* / Q000134:cerebrospinal fluid*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D023281:Genomics; D005909:Glioblastoma / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D008527:Medulloblastoma / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics; D008577:Meningeal Neoplasms / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm