LINE-1 hypomethylation in cell-free DNA of high-grade glioma patients correlates with tissue levels and is associated with reduced DNMT1 and H4K20me3 expression.
Angeliki-Ioanna Giannopoulou, Panagiotis Skouras, Panagiotis Sarantis, Alkinoos Armoundas, Kostas Palamaris, Antonios N Gargalionis, Athanasia Sepsa, Efstathios Boviatsis, Theodosis Kalamatianos, George Stranjalis, Penelope Korkolopoulou, Sarantis Chlamydas, Athanasios G Papavassiliou, Christina Piperi
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引用次数: 0
Abstract
Gliomas exhibit diverse genetic, molecular, and histological profiles with limited liquid biopsy biomarkers. Loss of Long Interspersed Nuclear Element-1 (LINE-1) methylation confers to genomic instability and tumorigenesis, primarily mediated by DNA methyltransferase 1 (DNMT1) through interaction with histone H4 lysine 20 trimethylation (H4K20me3) and histone H3 lysine 9 trimethylation (H3K9me3). The present study evaluates the utility of liquid biopsy in detecting LINE-1 methylation in gliomas and potential correlations with DNMT1, H4K20me3, H3K9me3 tissue levels, clinicopathological characteristics and patients' survival. LINE-1 methylation was measured in cell-free DNA (cfDNA) of glioma patients' plasma prior to surgery or any adjuvant therapy and age-matched controls as well as in glioma tissues along with DNMT1, H4K20me3 and H3K9me3 expression. LINE-1 methylation content in plasma cfDNA and tissue samples was decreased significantly in grade 4 gliomas compared to controls (p < 0.0001, respectively). Similarly, DNMT1, H4K20me3 and H3K9me3 expression was significantly reduced in grade 4 cases compared to grade 2 (p < 0.0001). cfLINE-1 methylation was positively correlated with tissue LINE-1 methylation levels (p = 0.036) as well as with DNMT1 and H4K20me3 tissue expression in grade 4 samples (p < 0.0001, respectively). Moreover, low LINE-1 methylation plasma levels and tissue expression of DNMT1, H4K20me3 and H3K9me3 were correlated with worse overall survival in the entire cohort (p = 0.041, p = 0.016, p < 0.0001, p = 0.001, respectively). The present study supports the utility of liquid biopsy for the detection of LINE-1 hypomethylation, as a complementary prognostic biomarker for grade 4 tumors.
期刊介绍：
Neurotherapeutics® is the journal of the American Society for Experimental Neurotherapeutics (ASENT). Each issue provides critical reviews of an important topic relating to the treatment of neurological disorders written by international authorities.
The Journal also publishes original research articles in translational neuroscience including descriptions of cutting edge therapies that cross disciplinary lines and represent important contributions to neurotherapeutics for medical practitioners and other researchers in the field.
Neurotherapeutics ® delivers a multidisciplinary perspective on the frontiers of translational neuroscience, provides perspectives on current research and practice, and covers social and ethical as well as scientific issues.
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