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Epigenetic methylation signature

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https://www.readbyqxmd.com/read/29351917/a-novel-method-for-rapid-molecular-subgrouping-of-medulloblastoma
#1
Soledad Gómez, Alícia Garrido-Garcia, Laura Garcia-Gerique, Isadora Lemos, Mariona Suñol, Carmen de Torres, Marta Kulis, Sara Perez-Jaume, Angel M Carcaboso, Betty Luu, Mark W Kieran, Nada Jabado, Alexey Kozlenkov, Stella Dracheva, Vijay Ramaswamy, Volker Hovestadt, Pascal Johann, David T W Jones, Stefan M Pfister, Andrés Morales La Madrid, Ofelia Cruz, Michael D Taylor, Jose I Martín-Subero, Jaume Mora, Cinzia Lavarino
PURPOSE: The classification of medulloblastoma into WNT, SHH, Group 3 and Group 4 subgroups has become of critical importance for patient risk-stratification and subgroup-tailored clinical trials. Here, we aimed to develop a simplified, clinically applicable classification approach that can be implemented in the majority of centers treating patients with medulloblastoma. EXPERIMENTAL DESIGN: We analyzed 1,577 samples comprising previously published DNA methylation microarray data (913 medulloblastomas, 457 non-medulloblastoma tumors, 85 normal tissues), and 122 frozen and formalin-fixed paraffin-embedded medulloblastoma samples...
January 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29350455/a-novel-prognostic-six-cpg-signature-in-glioblastomas
#2
An-An Yin, Nan Lu, Amandine Etcheverry, Marc Aubry, Jill Barnholtz-Sloan, Lu-Hua Zhang, Jean Mosser, Wei Zhang, Xiang Zhang, Yu-He Liu, Ya-Long He
AIMS: We aimed to identify a clinically useful biomarker using DNA methylation-based information to optimize individual treatment of patients with glioblastoma (GBM). METHODS: A six-CpG panel was identified by incorporating genome-wide DNA methylation data and clinical information of three distinct discovery sets and was combined using a risk-score model. Different validation sets of GBMs and lower-grade gliomas and different statistical methods were implemented for prognostic evaluation...
January 19, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29344313/dna-methylation-as-a-predictor-of-fetal-alcohol-spectrum-disorder
#3
Alexandre A Lussier, Alexander M Morin, Julia L MacIsaac, Jenny Salmon, Joanne Weinberg, James N Reynolds, Paul Pavlidis, Albert E Chudley, Michael S Kobor
Background: Fetal alcohol spectrum disorder (FASD) is a developmental disorder that manifests through a range of cognitive, adaptive, physiological, and neurobiological deficits resulting from prenatal alcohol exposure. Although the North American prevalence is currently estimated at 2-5%, FASD has proven difficult to identify in the absence of the overt physical features characteristic of fetal alcohol syndrome. As interventions may have the greatest impact at an early age, accurate biomarkers are needed to identify children at risk for FASD...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29339543/genes-predisposed-to-dna-hypermethylation-during-acquired-resistance-to-chemotherapy-are-identified-in-ovarian-tumors-by-bivalent-chromatin-domains-at-initial-diagnosis
#4
Edward Curry, Constanze Zeller, Nahal Masrour, Darren Patten, John Gallon, Charlotte S Wilhelm-Benartzi, Sadaf Ghaem-Maghami, David D L Bowtell, Robert Brown
Bivalent chromatin domains containing both active H3K4me3 and repressive H3K27me3 histone marks define gene sets poised for expression or silencing in differentiating embryonic stem (ES) cells. In cancer cells aberrantly poised genes may facilitate changes in transcriptional states after exposure to anti-cancer drugs. In this study, we used ChIP-seq to characterize genome-wide positioning of H3K4me3 and H3K27me3-associated chromatin in primary high-grade serous ovarian carcinomas and in normal ovarian surface and fallopian tube tissue...
January 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29337038/back-to-the-future-epigenetic-clock-plasticity-towards-healthy-aging
#5
REVIEW
Ken Declerck, Wim Vanden Berghe
Aging is the most important risk factor for major human lifestyle diseases, including cancer, neurological and cardiometabolic disorders. Due to the complex interplay between genetics, lifestyle and environmental factors, some individuals seem to age faster than others, whereas centenarians seem to have a slower aging process. Therefore, a biochemical biomarker reflecting the relative biological age would be helpful to predict an individual's health status and aging disease risk. Although it is already known for years that cumulative epigenetic changes occur upon aging, DNA methylation patterns were only recently used to construct an epigenetic clock predictor for biological age, which is a measure of how well your body functions compared to your chronological age...
January 11, 2018: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/29330145/mbd2-ablation-impairs-lymphopoiesis-and-impedes-progression-and-maintenance-of-t-all
#6
Mi Zhou, Kuangguo Zhou, Ling Cheng, Xing Chen, Jue Wang, Xiao-Min Wang, Yingchi Zhang, Qilin Yu, Shu Zhang, Di Wang, Liang Huang, Mei Huang, Ding Ma, Tao Cheng, Cong-Yi Wang, Weiping Yuan, Jianfeng Zhou
Aberrant DNA methylation patterns in leukemia might be exploited for therapeutic targeting. In this study, we employed a genetically deficient mouse model to explore the role of the methylated DNA binding protein MBD2 in normal and malignant hematopoiesis. MBD2 ablation led to diminished lymphocytes. Functional defects of the lymphoid compartment were also observed after in vivo reconstitution of MBD2-deficient hematopoietic stem cells (HSC). In an established model of Notch1-driven T cell acute lymphoblastic leukemia (T-ALL), MBD2 ablation impeded malignant progression and maintenance by attenuating the Wnt signaling pathway...
January 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29304373/genomic-dna-methylation-signatures-enable-concurrent-diagnosis-and-clinical-genetic-variant-classification-in-neurodevelopmental-syndromes
#7
Erfan Aref-Eshghi, David I Rodenhiser, Laila C Schenkel, Hanxin Lin, Cindy Skinner, Peter Ainsworth, Guillaume Paré, Rebecca L Hood, Dennis E Bulman, Kristin D Kernohan, Kym M Boycott, Philippe M Campeau, Charles Schwartz, Bekim Sadikovic
Pediatric developmental syndromes present with systemic, complex, and often overlapping clinical features that are not infrequently a consequence of Mendelian inheritance of mutations in genes involved in DNA methylation, establishment of histone modifications, and chromatin remodeling (the "epigenetic machinery"). The mechanistic cross-talk between histone modification and DNA methylation suggests that these syndromes might be expected to display specific DNA methylation signatures that are a reflection of those primary errors associated with chromatin dysregulation...
January 4, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29287311/hypomethylation-of-cyp2e1-and-dusp22-promoters-associated-with-disease-activity-and-erosive-disease-among-rheumatoid-arthritis-patients
#8
Amanda Mok, Brooke Rhead, Calliope Holingue, Xiaorong Shao, Hong L Quach, Diana Quach, Elizabeth Sinclair, Jonathan Graf, John Imboden, Thomas Link, Ruby Harrison, Vladimir Chernitskiy, Lisa F Barcellos, Lindsey A Criswell
OBJECTIVE: Epigenetic modifications have previously been associated with rheumatoid arthritis (RA). This study aimed to determine whether differential DNA methylation in peripheral blood cell subpopulations is associated with four clinical outcomes among RA patients. METHODS: Peripheral blood samples were taken from 63 patients in the University of California, San Francisco RA cohort (all satisfied ACR classification criteria; 57 were seropositive). Cells were FACS-sorted into four immune cell subpopulations (CD14+ monocytes, CD19+ B cells, CD4+ naïve T cells, and CD4+ memory T cells) per individual, and 229 epigenome-wide DNA methylation profiles were generated using Illumina HumanMethylation450 BeadChips...
December 29, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29277749/cancer-progenitor-cells-the-result-of-an-epigenetic-event
#9
REVIEW
Karolina Lapinska, Gabriela Faria, Sandra McGonagle, Kate Morgan Macumber, Sarah Heerboth, Sibaji Sarkar
The concept of cancer stem cells was proposed in the late 1990s. Although initially the idea seemed controversial, the existence of cancer stem cells is now well established. However, the process leading to the formation of cancer stem cells is still not clear and thus requires further research. This article discusses epigenetic events that possibly produce cancer progenitor cells from predisposed cells by the influence of their environment. Every somatic cell possesses an epigenetic signature in terms of histone modifications and DNA methylation, which are obtained during lineage-specific differentiation of pluripotent stem cells, which is specific to that particular tissue...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29229600/genomic-and-epigenomic-signatures-in-ovarian-cancer-associated-with-re-sensitization-to-platinum-drugs
#10
Fang Fang, Horacio Cardenas, Hao Huang, Guanglong Jiang, Susan M Perkins, Chi Zhang, Harold N Keer, Yunlong Liu, Kenneth P Nephew, Daniela Matei
DNA methylation aberrations have been implicated in acquired resistance to platinum drugs in ovarian cancer (OC). In this study, we elucidated an epigenetic signature associated with platinum drug re-sensitization that may offer utility in predicting the outcomes of patients who are co-administered a DNA methyltransferase inhibitror. The OC specimens we analyzed were derived from a recent clinical trial that compared the responses of patients with recurrent platinum-resistant OC who received carboplatin plus the DNA methyltransferase inhibitor guadecitabine or a standard of care chemotherapy regimen selected by the treating physician...
December 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/29228692/epigenetic-landscape-change-analysis-during-human-emt-sheds-light-on-a-key-emt-mediator-trim29
#11
Sung Kyung Choi, Kurinji Pandiyan, Jung Woo Eun, Xiaojing Yang, Seong Hwi Hong, Suk Woo Nam, Peter A Jones, Gangning Liang, Jueng Soo You
Epithelial to mesenchymal transition (EMT) is a key trans-differentiation process, which plays a critical role in physiology and pathology. Although gene expression changes in EMT have been scrutinized, study of epigenome is in its infancy. To understand epigenetic changes during TWIST-driven EMT, we used the AcceSssIble assay to study DNA methylation and chromatin accessibility in human mammary epithelial cells (HMECs). The DNA methylation changes were found to have functional significance in EMT - i.e. methylated genes were enriched for E-box motifs that can be recognized by TWIST, at the promoters suggesting a potential targeting phenomenon, whereas the demethylated regions were enriched for pro-metastatic genes, supporting the role of EMT in metastasis...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29227468/metagenomic-binning-and-association-of-plasmids-with-bacterial-host-genomes-using-dna-methylation
#12
John Beaulaurier, Shijia Zhu, Gintaras Deikus, Ilaria Mogno, Xue-Song Zhang, Austin Davis-Richardson, Ronald Canepa, Eric W Triplett, Jeremiah J Faith, Robert Sebra, Eric E Schadt, Gang Fang
Shotgun metagenomics methods enable characterization of microbial communities in human microbiome and environmental samples. Assembly of metagenome sequences does not output whole genomes, so computational binning methods have been developed to cluster sequences into genome 'bins'. These methods exploit sequence composition, species abundance, or chromosome organization but cannot fully distinguish closely related species and strains. We present a binning method that incorporates bacterial DNA methylation signatures, which are detected using single-molecule real-time sequencing...
December 11, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/29221210/the-molecular-classification-of-astrocytic-tumors
#13
Chen-Xue Mao, Ji-Ye Yin, Ying Zhang, Zhi-Bin Wang, Zhi-Quan Yang, Zheng-Wen He, Xiang-Min Li, Xiao-Yuan Mao, Ru-Tao Cui, Xue-Jun Li, Xi Li, Wei Zhang, Hong-Hao Zhou, Zhao-Qian Liu
Aim: This study will explore the genetic and epigenetic alterations in astrocytomas, and identify the critical molecular signatures and signaling pathways for prognosis assessment by multiplatform comprehensive analysis. Method: We performed integration analyses of incorporating DNA methylation, mRNA expression, microRNA expression, and long non-coding RNA (lncRNA) expression in 33 astrocytic tumor tissues and 9 non-tumor brain tissues. Result: We observed that 11,795 DNA methylation sites, 3,627 genes, 136 microRNAs, and 3,334 lncRNAs were significantly differential between tumors and non-tumor brain tissues, and the filtered signatures through comprehensive analysis were significantly enriched in calcium signaling pathway...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29213343/exome-sequencing-characterizes-the-somatic-mutation-spectrum-of-early-serrated-lesions-in-a-patient-with-serrated-polyposis-syndrome-sps
#14
Sukanya Horpaopan, Jutta Kirfel, Sophia Peters, Michael Kloth, Robert Hüneburg, Janine Altmüller, Dmitriy Drichel, Margarete Odenthal, Glen Kristiansen, Christian Strassburg, Jacob Nattermann, Per Hoffmann, Peter Nürnberg, Reinhard Büttner, Holger Thiele, Philip Kahl, Isabel Spier, Stefan Aretz
Background: Serrated or Hyperplastic Polyposis Syndrome (SPS, HPS) is a yet poorly defined colorectal cancer (CRC) predisposition characterised by the occurrence of multiple and/or large serrated polyps throughout the colon. A serrated polyp-CRC sequence (serrated pathway) of CRC formation has been postulated, however, to date only few molecular signatures of serrated neoplasia (BRAF, KRAS, RNF43 mutations, CpG Island Methylation, MSI) have been described in a subset of SPS patients and neither the etiology of the syndrome nor the distinct genetic alterations during tumorigenesis have been identified...
2017: Hereditary Cancer in Clinical Practice
https://www.readbyqxmd.com/read/29207054/use-of-methylation-profiling-to-identify-significant-differentially-methylated-genes-in-bone-marrow-mesenchymal-stromal-cells-from-acute-myeloid-leukemia
#15
Jing Huang, Zhi Liu, Yufan Sun, Qi Zhong, Li Xu, Ruimin Ou, Cheng Li, Rui Chen, Mengdong Yao, Qing Zhang, Shuang Liu
The present study aimed to characterize the epigenetic architecture by studying the DNA methylation signature in bone marrow mesenchymal stem cells (BM‑MSCs) from patients with acute myeloid leukemia (AML). Microarray dataset GSE79695 was downloaded from the Gene Expression Omnibus database. Differentially methylated sites and differentially methylated CpG islands were identified in BM‑MSC samples from patients with AML compared with controls. MicroRNAs (miRs) encoding genes covering differentially methylated sites were found and the regulation network was constructed...
November 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29204143/local-chromatin-features-including-pu-1-and-ikaros-binding-and-h3k4-methylation-shape-the-repertoire-of-immunoglobulin-kappa-genes-chosen-for-v-d-j-recombination
#16
Louise S Matheson, Daniel J Bolland, Peter Chovanec, Felix Krueger, Simon Andrews, Hashem Koohy, Anne E Corcoran
V(D)J recombination is essential for the generation of diverse antigen receptor (AgR) repertoires. In B cells, immunoglobulin kappa (Igκ) light chain recombination follows immunoglobulin heavy chain (Igh) recombination. We recently developed the DNA-based VDJ-seq assay for the unbiased quantitation of Igh VH and DH repertoires. Integration of VDJ-seq data with genome-wide datasets revealed that two chromatin states at the recombination signal sequence (RSS) of VH genes are highly predictive of recombination in mouse pro-B cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29196255/hypermethylation-of-pgcp-gene-is-associated-with-human-bronchial-epithelial-cells-immortalization
#17
Chen Gao, Xiumei Xing, Zhini He, Shen Chen, Shan Wang, Qingye Li, Ping Guo, Haiyan Zhang, Huiyao Li, Liping Chen, Qing Wang, Jian Zhao, Yongmei Xiao, Wen Chen, Daochuan Li
Cell immortalization is the initial step for cancer development. To identify the differentially expressed genes regulated by DNA methylation over the course of human primary bronchial epithelial cell (HPBECs) immortalization, an immortalized HBE cell line (HBETT) was generated via introduction of an SV40 LT and a catalytic subunit of human telomerase reverse transcriptase (hTERT) into the HPBECs. Microarrays of mRNA and DNA methylation were performed to compare the transcriptomes and DNA methylomes between these two types of cells...
November 28, 2017: Gene
https://www.readbyqxmd.com/read/29194108/epigenetics-of-inflammatory-arthritis
#18
Deepa Hammaker, Gary S Firestein
PURPOSE OF REVIEW: Aberrant epigenetic changes in DNA methylation, histone marks, and noncoding RNA expression regulate the pathogenesis of many rheumatic diseases. The present article will review the recent advances in the epigenetic profile of inflammatory arthritis and discuss diagnostic biomarkers and potential therapeutic targets. RECENT FINDINGS: Methylation signatures of fibroblast-like synoviocytes not only distinguish rheumatoid arthritis (RA) and osteoarthritis (OA), but also early RAs from late RAs or juvenile idiopathic arthritis...
November 30, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/29193426/low-osteogenic-yield-in-human-pluripotent-stem-cells-associates-with-differential-neural-crest-promoter-methylation
#19
Nicole Renee Lee Sparks, Ivann Kenneth Carvajal Martinez, Cristina Helen Soto, Nicole Isolde Zur Nieden
Human pluripotent stem cell-derived osteoblasts possess great potential for utilization in bone disorder elucidation and repair; yet, while the general ability of human pluripotent stem cells to differentiate into osteoblasts and lay down bone-specific matrix has been shown, previous studies lack the complete characterization of the process whereby such osteoblasts are derived as well as a comparison between the osteogenic efficiency of multiple cell lines. Here, we compared the osteogenic potential of two human induced pluripotent stem cell lines (RIV9 and RIV4) to human H9 embryonic stem cells...
November 29, 2017: Stem Cells
https://www.readbyqxmd.com/read/29175436/3d-chromatin-architecture-of-large-plant-genomes-determined-by-local-a-b-compartments
#20
Pengfei Dong, Xiaoyu Tu, Po-Yu Chu, Peitao Lü, Ning Zhu, Donald Grierson, Baijuan Du, Pinghua Li, Silin Zhong
The spatial organization of the genome plays an important role in the regulation of gene expression. However, the core structural features of animal genomes, such as topologically associated domains (TADs) and chromatin loops, are not prominent in the extremely compact Arabidopsis genome. In this study, we have examined the chromatin architecture, as well as their DNA methylation, histone modifications, accessible chromatin and gene expression, of maize, tomato, sorghum, foxtail millet and rice with genome sizes ranging from 0...
November 21, 2017: Molecular Plant
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