Methylation patterns of cell-free plasma DNA in relapsing–remitting multiple sclerosis

Liggett, Thomas; Melnikov, Anatoliy A.; Tilwalli, Shilpa; Yi, Qilong; Chen, Haiyan; Replogle, Charles; Feng, Xuan; Reder, Anthony T.; Stefoski, Dusan; Balabanov, Roumen; Levenson, Victor

doi:10.1016/j.jns.2009.12.018

Cited by 88 publications

(54 citation statements)

References 41 publications

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“…Second, the inclusion of a multiplexed, pre-amplification step increases the dynamic range of detectability of the target gene and enables quantitation of a panel of markers in the amount of DNA normally used to evaluate one gene. The use of external standards has a further advantage in that it avoids the pitfalls inherent to endogenous reference DNAs, where total DNA may fluctuate up to 15-fold under healthy conditions independent of tumor burden, such as occurs in exercise overtraining (17, 18), trauma (19), surgery (20), sepsis (21), chronic inflammatory diseases (22–24), and pregnancy (25, 26). …”

Section: Discussionmentioning

confidence: 99%

Novel Methylated Biomarkers and a Robust Assay to Detect Circulating Tumor DNA in Metastatic Breast Cancer

et al. 2014

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The ability to consistently detect cell-free tumor-specific DNA in peripheral blood of patients with metastatic breast cancer provides the opportunity to detect changes in tumor burden and to monitor response to treatment. We developed cMethDNA, a quantitative multiplexed methylation-specific PCR assay for a panel of ten genes, consisting of novel and known breast cancer hypermethylated markers identified by mining our previously reported study of DNA methylation patterns in breast tissue (103 cancer, 21 normal on the Illumina HumanMethylation27 Beadchip) and then validating the 10-gene panel in a TCGA breast cancer methylome database. For cMethDNA, a fixed physiological level (50 copies) of artificially constructed, standard non-human reference DNA specific for each gene is introduced into in a constant volume of serum (300 μl) prior to purification of the DNA, facilitating a sensitive, specific, robust and quantitative assay of tumor DNA, with broad dynamic range. Cancer-specific methylated DNA was detected in Training (28 normal, 24 cancer) and Test (27 normal, 33 cancer) sets of recurrent Stage 4 patient sera with a sensitivity of 91% and a specificity of 96% in the test set. In a pilot study, cMethDNA assay faithfully reflected patient response to chemotherapy (N = 29). A core methylation signature present in the primary breast cancer was retained in serum and metastatic tissues collected at autopsy 2–11 years after diagnosis of the disease. Together, our data suggest that the cMethDNA assay can detect advanced breast cancer, and monitor tumor burden and treatment response in women with metastatic breast cancer.

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Section: Discussionmentioning

confidence: 99%

Novel Methylated Biomarkers and a Robust Assay to Detect Circulating Tumor DNA in Metastatic Breast Cancer

et al. 2014

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“…According to our results, pretreatment with 5-Aza can prevent the onset of such diseases (for example, EAE). On the other hand, it was demonstrated that gene promoter hypermethylation was more prominent in cell-free DNA isolated from relapsing remitting MS patients than from healthy individuals (39). This result suggests that MS might be an epigenetic disease, and reversing epigenetic repression of the Foxp3 methylated promoter by demethylating agents may have therapeutic potential for the treatment of this autoimmune disease.…”

Section: Discussionmentioning

confidence: 99%

Low-Dose 5-Aza-2′-deoxycytidine Pretreatment Inhibits Experimental Autoimmune Encephalomyelitis by Induction of Regulatory T Cells

Chan

Chang

Tung

et al. 2014

Mol Med

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Forkhead box P3 (Foxp3) is the major transcription factor controlling the development and function of regulatory T (Treg) cells. Previous studies have indicated epigenetic regulation of Foxp3 expression. Here, we investigated whether the deoxyribonucleic acid (DNA) methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-Aza) applied peripherally could modulate central nervous system (CNS) inflammation, by using a mouse experimental autoimmune encephalomyelitis (EAE) model. We found that disease activity was inhibited in a myelin oligodendrocyte glycoprotein (MOG) peptide-induced EAE mouse briefly pretreated with low-dose (0.15 mg/kg) 5-Aza, ameliorating significant CNS inflammatory responses, as indicated by greatly decreased proinflammatory cytokines. On the contrary, control EAE mice expressed high levels of IFN-γ and interleukin (IL)-17. In addition, 5-Aza treatment in vitro increased GFP expression in CD4 + GFP -T cells isolated from GFP knock-in Foxp3 transgenic mice. Importantly, 5-Aza treatment increased Treg cell numbers, in EAE mice, at both disease onset and peak. However, Treg inhibition assays showed 5-Aza treatment did not enhance per-cell Treg inhibitory function, but did maintain a lower activation threshold for effector cells in EAE mice. In conclusion, 5-Aza treatment prevented EAE development and suppressed CNS inflammation, by increasing the number of Treg cells and inhibiting effector cells in the periphery.

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“…Esta desmetilación del gen FOXP3 puede inhibir la diferenciación a células Th1 y Th2 y al mismo tiempo puede promover las células T reguladoras (Treg) y Th17. El equilibrio Th1/Th2 y Treg/Th17 influye en el estado de la enfermedad de manera que alteraciones en el mismo pueden conducir a la aparición de una nueva lesión o a su reparación, y es precisamente la metilación del ADN uno de los factores que regulan este equilibrio 40,41 .…”

Section: Inflamación Y Metilación Del Adnunclassified

Modificaciones epigenéticas en neurología: alteraciones en la metilación del ADN en la esclerosis múltiple

et al. 2017

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Methylation patterns of cell-free plasma DNA in relapsing–remitting multiple sclerosis

Cited by 88 publications

References 41 publications

Novel Methylated Biomarkers and a Robust Assay to Detect Circulating Tumor DNA in Metastatic Breast Cancer

Novel Methylated Biomarkers and a Robust Assay to Detect Circulating Tumor DNA in Metastatic Breast Cancer

Low-Dose 5-Aza-2′-deoxycytidine Pretreatment Inhibits Experimental Autoimmune Encephalomyelitis by Induction of Regulatory T Cells

Modificaciones epigenéticas en neurología: alteraciones en la metilación del ADN en la esclerosis múltiple

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