Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma
A partir d'échantillons de sang et de liquide cérébrospinal prélevés sur des patients atteints d'un glioblastome, d'un médulloblastome ou présentant des métastases cérébrales d'un cancer du poumon ou du sein, cette étude montre que l'analyse de l'ADN tumoral circulant dans le liquide cérébrospinal permet d'obtenir une meilleure image des anomalies génomiques tumorales que l'analyse de l'ADN circulant dans le plasma
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.
Nature Communications , article en libre accès, 2014