scholarly journals Reliable tumor detection by whole-genome methylation sequencing of cell-free DNA in cerebrospinal fluid of pediatric medulloblastoma

2020 ◽  
Vol 6 (42) ◽  
pp. eabb5427
Author(s):  
Jia Li ◽  
Sibo Zhao ◽  
Minjung Lee ◽  
Yue Yin ◽  
Jin Li ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cerebrospinal Fluid ◽  
Low Frequency ◽  
Pediatric Medulloblastoma ◽  
Oncogenic Mutations ◽  
Genome Methylation ◽  
Epigenetic Analysis ◽  
Public Datasets ◽  
Pediatric Brain ◽  
Normal Cerebellum

Medulloblastoma (MB), the most common form of pediatric brain malignancy, has a low frequency of oncogenic mutations but pronouncedly abnormal DNA methylation changes. Epigenetic analysis of circulating cell-free tumor DNA (ctDNA) by liquid biopsy offers an approach for real-time monitoring of tumor status without tumor dissection. In this study, we identified 6598 differentially methylated CpGs in both MB tumors and the ctDNA isolated from matched cerebrospinal fluid (CSF) compared with normal cerebellum, which could be used to detect MB tumor occurrence and determine its subtype. Furthermore, DNA methylation changes in serial CSF samples could be used to monitor the treatment response and tumor recurrence. Integrating our data with large public datasets, we identified reliable MB DNA methylation signatures in ctDNA that have potential diagnostic and prognostic values. Our study sets the stage for exploiting epigenetic markers in CSF to improve the clinical management of patients with MB.

TMOD-23. MODELING PEDIATRIC BRAIN CANCER WITH HUMAN ORGANOIDS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi220-vi220
Author(s):  
Luca Tiberi
Keyword(s):  
Dna Methylation ◽  
Brain Cancer ◽  
Cancer Biology ◽  
Genetic Alterations ◽  
Cancer Model ◽  
The Past ◽  
Pediatric Medulloblastoma ◽  
Infant Brain ◽  
Human Ipsc ◽  
Pediatric Brain

Abstract Among children/infant brain tumors, Medulloblastoma (MB) is the most common and stands as a cause for a high percentage of morbidity and mortality among patients During the past few years, studies on human MB have uncovered the existence of four major MB groups: WNT, SHH, Group3 and Group4. Patients with Group3 MB currently have the worst outcome among the four groups, and nearly 50% are metastatic at the time of diagnosis. In the last 3 years in our laboratory, we have developed a novel pediatric Medulloblastoma organoid model. We generated human iPSC-derived cancer organoids upon c-MYC/OTX2 and C-MYC/Gfi1 overexpression, mimicking human MB genetic alterations. Furthermore, the use of DNA methylation signature in combination with MB-specific markers analysis indicates that our organoid-based cancer model recapitulates several features of human MB. Now, we are taking advantage of this technology to produce novel brain cancer organoids that we are using to address cancer biology questions.

Genome-scale sequence data processing and epigenetic analysis of DNA methylation

2013 ◽  
Vol 35 (6) ◽  
pp. 685-694
Author(s):  
Ting-Zhang WANG ◽  
Gao SHAN ◽  
Jian-Hong XU ◽  
Qing-Zhong XUE
Keyword(s):  
Dna Methylation ◽  
Data Processing ◽  
Sequence Data ◽  
Epigenetic Analysis ◽  
Genome Scale ◽  
Scale Sequence

scholarly journals Slithering CSF: Cerebrospinal Fluid Dynamics in the Stationary and Moving Viper Boa, Candoia aspera

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 672
Author(s):  
Bruce A. Young ◽  
Skye Greer ◽  
Michael Cramberg
Keyword(s):  
Cerebrospinal Fluid ◽  
Cardiac Cycle ◽  
Low Frequency ◽  
Mean Amplitude ◽  
The Body ◽  
Body Waves ◽  
Lower Amplitude ◽  
Lateral Undulation ◽  
Recovery From Anesthesia ◽  
The Relationship

In the viper boa (Candoia aspera), the cerebrospinal fluid (CSF) shows two stable overlapping patterns of pulsations: low-frequency (0.08 Hz) pulses with a mean amplitude of 4.1 mmHg that correspond to the ventilatory cycle, and higher-frequency (0.66 Hz) pulses with a mean amplitude of 1.2 mmHg that correspond to the cardiac cycle. Manual oscillations of anesthetized C. aspera induced propagating sinusoidal body waves. These waves resulted in a different pattern of CSF pulsations with frequencies corresponding to the displacement frequency of the body and with amplitudes greater than those of the cardiac or ventilatory cycles. After recovery from anesthesia, the snakes moved independently using lateral undulation and concertina locomotion. The episodes of lateral undulation produced similar influences on the CSF pressure as were observed during the manual oscillations, though the induced CSF pulsations were of lower amplitude during lateral undulation. No impact on the CSF was found while C. aspera was performing concertina locomotion. The relationship between the propagation of the body and the CSF pulsations suggests that the body movements produce an impulse on the spinal CSF.

scholarly journals Gene set enrichment analysis for genome-wide DNA methylation data

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jovana Maksimovic ◽  
Alicia Oshlack ◽  
Belinda Phipson
Keyword(s):  
Dna Methylation ◽  
Enrichment Analysis ◽  
R Package ◽  
Gene Set Enrichment Analysis ◽  
Methylation Array ◽  
Gene Set ◽  
Genome Wide ◽  
Genome Methylation ◽  
Unbiased Gene ◽  
Gene Set Testing

AbstractDNA methylation is one of the most commonly studied epigenetic marks, due to its role in disease and development. Illumina methylation arrays have been extensively used to measure methylation across the human genome. Methylation array analysis has primarily focused on preprocessing, normalization, and identification of differentially methylated CpGs and regions. GOmeth and GOregion are new methods for performing unbiased gene set testing following differential methylation analysis. Benchmarking analyses demonstrate GOmeth outperforms other approaches, and GOregion is the first method for gene set testing of differentially methylated regions. Both methods are publicly available in the missMethyl Bioconductor R package.

Low Frequency of Adenylate Kinase Release into Cerebrospinal Fluid during Balanced, Normotensive Anaesthesia and a Non-Orthognathic Surgical Procedure

1997 ◽  
Vol 25 (2) ◽  
pp. 92-97 ◽  
Author(s):  
M Enlund ◽  
O Mentell ◽  
L Edmark ◽  
G Ronquist
Keyword(s):  
Cerebrospinal Fluid ◽  
Adenylate Kinase ◽  
Orthognathic Surgery ◽  
Cell Injury ◽  
Low Frequency ◽  
Brain Cell ◽  
Contributing Factors ◽  
Oscillating Saw ◽  
The Difference ◽  
Increased Activity

Activity of strictly intracellular enzymes in the cerebrospinal fluid (CSF) may indicate leakage from dysfunctional brain cells. Increased activity of adenylate kinase (AK) in the CSF is indicative of brain cell injury arising from several sources, among them orthognathic surgery. The mechanism in the latter case is obscure, but the use of an oscillating saw which generates vibrations, and the site of surgery close to the brain may be contributing factors. Anaesthesia may also play a role. In the present study, CSF-AK activity was measured after hysterectomy and was compared with activity after orthognathic surgery in two other studies. Four of 19 patients (21%) in the present study expressed pathological activity, compared with 34 of 47 (72%) orthognathic patients in the two other studies. No firm conclusion may be drawn from historical comparisons, and the difference in activity seen between the two types of surgery might not necessarily be the result of surgical factors. Until this is investigated further, however, we conclude that there may be a difference in postoperative CSF-AK activity between orthognathic and lower abdominal surgery.

scholarly journals Importance of Genetic Factors in Male Fertility Disorders, Clinical Relevance of Epigenetic Markers in Male Infertility

2019 ◽  
Vol 70 (7) ◽  
pp. 2566-2570
Author(s):  
Dragos Botezatu ◽  
Cristina Popescu ◽  
Andrei-Dan Korodi ◽  
Cristian Furau ◽  
Gheorghe Furau ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Male Infertility ◽  
Male Fertility ◽  
Complex Problem ◽  
The Body ◽  
Control Group ◽  
Global Methylation ◽  
Methylation Of Dna ◽  
Genome Methylation ◽  
Methylation Patterns

Male infertility is a common and complex problem affecting 1 out of 20 men. Despite extensive research in this area, in many cases, the underlying causes are unknown. Epigenetic changes control a series of processes within the body, including male fertility. Classification of infertile men using a more detailed analysis of DNA methylation patterns could reveal a new level of low rates of fertilization, implantation, or pregnancy. In this context, it seemed to us to use the techniques available to evaluate the degree of global methylation of DNA in infertile patients who have modified sperm counts, but also those who apparently do not have a clear cause of infertility. For this we used the Quest 5mC-Zymoresaerch-ELISA kit that can detect within about 5 hours the global level of genome methylation. Claims on which common illnesses have an epigenetic base are still open to speculation, but if true, it can imprint a new direction in medicine. Our data, although from a pilot study, are consistent with those in the literature. A recent study has shown that DNA methylation levels were significantly higher in oligoasthenoteratozoospermia patients than in the control group and the increase in global DNA methylation and histone retention in men with oligoasthenoteratozoospermia.

scholarly journals Honeybee (Apis mellifera) Maternal Effect Causes Alternation of DNA Methylation Regulating Queen Development

Sociobiology ◽  
2021 ◽  
Vol 68 (1) ◽  
pp. 5935
Author(s):  
Xu Jiang He ◽  
Hao Wei ◽  
Wu Jun Jiang ◽  
Yi Bo Liu ◽  
Xiao Bo Wu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Apis Mellifera ◽  
Signaling Pathways ◽  
Maternal Effect ◽  
Caste Differentiation ◽  
Hippo Signaling ◽  
Thorax Length ◽  
Queen Cell ◽  
Epigenetic Analysis ◽  
Worker Caste

Queen-worker caste dimorphism is a typical trait for honeybees (Apis mellifera). We previously showed a maternal effect on caste differentiation and queen development, where queens emerged from queen-cell eggs (QE) had higher quality than queens developed from worker cell eggs (WE). In this study, newly-emerged queens were reared from QE, WE, and 2-day worker larvae (2L). The thorax size and DNA methylation levels of queens were measured. We found that queens emerging from QE had significantly larger thorax length and width than WE and 2L. Epigenetic analysis showed that QE/2L comparison had the most different methylated genes (DMGs, 612) followed by WE/2L (473), and QE/WE (371). Interestingly, a great number of DMGs (42) were in genes belonging to mTOR, MAPK, Wnt, Notch, Hedgehog, FoxO, and Hippo signaling pathways that are involved in regulating caste differentiation, reproduction and longevity. This study proved that honeybee maternal effect causes epigenetic alteration regulating caste differentiation and queen development.

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