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.
Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma / L. De Mattos-Arruda, R. Mayor, C.K.Y. Ng, B. Weigelt, F. Martínez-Ricarte, D. Torrejon, M. Oliveira, A. Arias, C. Raventos, J. Tang, E. Guerini-Rocco, E. Martínez-Saéz, S. Lois, O. Marín, X. De La Cruz, S. Piscuoglio, R. Towers, A. Vivancos, V. Peg, S.R.Y. Cajal, J. Carles, J. Rodon, M. González-Cao, J. Tabernero, E. Felip, J. Sahuquillo, M.F. Berger, J. Cortes, J.S. Reis-Filho, J. Seoane. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 6(2015 Nov), pp. 8839.1-8839.6.
|Titolo:||Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma|
|Parole Chiave:||Brain Neoplasms; Breast Neoplasms; DNA, Neoplasm; Female; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Lung Neoplasms; Medulloblastoma; Meningeal Neoplasms; Genomics; Chemistry (all); Biochemistry, Genetics and Molecular Biology (all); Physics and Astronomy (all)|
|Settore Scientifico Disciplinare:||Settore MED/08 - Anatomia Patologica|
Settore MED/06 - Oncologia Medica
|Data di pubblicazione:||nov-2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/ncomms9839|
|Appare nelle tipologie:||01 - Articolo su periodico|