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Epigenetic methylation signature

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https://www.readbyqxmd.com/read/28074068/a-cpg-island-methylator-phenotype-in-acute-myeloid-leukemia-independent-of-idh-mutations-and-associated-with-a-favorable-outcome
#1
A D Kelly, H Kroeger, J Yamazaki, R Taby, F Neumann, S Yu, J T Lee, B Patel, Y Li, R He, S Liang, Y Lu, M Cesaroni, S A Pierce, S M Kornblau, C E Bueso-Ramos, F Ravandi, H M Kantarjian, J Jelinek, J-Pj Issa
Genetic changes are infrequent in acute myeloid leukemia (AML) compared to other malignancies and often involve epigenetic regulators, suggesting that an altered epigenome may underlie AML biology and outcomes. In 96 AML cases including 65 pilot samples selected for cured/not-cured, we found higher CpG island (CGI) promoter methylation in cured patients. Expanded genome-wide digital restriction enzyme analysis of methylation (DREAM) data revealed a CGI methylator phenotype independent of IDH1/2 mutations we term AML-CIMP (A-CIMP(+))...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28067321/methylome-wide-association-study-of-atrial-fibrillation-in-framingham-heart-study
#2
Honghuang Lin, Xiaoyan Yin, Zhijun Xie, Kathryn L Lunetta, Steven A Lubitz, Martin G Larson, Darae Ko, Jared W Magnani, Michael M Mendelson, Chunyu Liu, David D McManus, Daniel Levy, Patrick T Ellinor, Emelia J Benjamin
Atrial fibrillation (AF) is the most common cardiac arrhythmia, but little is known about the molecular mechanisms associated with AF arrhythmogenesis. DNA methylation is an important epigenetic mechanism that regulates gene expression and downstream biological processes. We hypothesize that DNA methylation might play an important role in the susceptibility to develop AF. A total of 2,639 participants from the Offspring Cohort of Framingham Heart Study were enrolled in the current study. These participants included 183 participants with prevalent AF and 220 with incident AF during up to 9 years follow up...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28052772/placental-mitochondrial-dna-and-cyp1a1-gene-methylation-as-molecular-signatures-for-tobacco-smoke-exposure-in-pregnant-women-and-the-relevance-for-birth-weight
#3
Bram G Janssen, Wilfried Gyselaers, Hyang-Min Byun, Harry A Roels, Ann Cuypers, Andrea A Baccarelli, Tim S Nawrot
BACKGROUND: Maternal smoking during pregnancy results in an increased risk of low birth weight through perturbations in the utero-placental exchange. Epigenetics and mitochondrial function in fetal tissues might be molecular signatures responsive to in utero tobacco smoke exposure. METHODS: In the framework of the ENVIRONAGE birth cohort, we investigated the effect of self-reported tobacco smoke exposure during pregnancy on birth weight and the relation with placental tissue markers such as, (1) relative mitochondrial DNA (mtDNA) content as determined by real-time quantitative PCR, (2) DNA methylation of specific loci of mtDNA (D-loop and MT-RNR1), and (3) DNA methylation of the biotransformation gene CYP1A1 (the last two determined by bisulfite-pyrosequencing)...
January 4, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28049580/epigenetic-regulation-on-the-gene-expression-signature-in-esophagus-adenocarcinoma
#4
Ting Xi, Guizhi Zhang
BACKGROUND: Understanding the molecular mechanisms represents an important step in the development of diagnostic and therapeutic measures of esophagus adenocarcinoma (NOS). The objective of this study is to identify the epigenetic regulation on gene expression in NOS, shedding light on the molecular mechanisms of NOS. METHODS: In this study, 78 patients with NOS were included and the data of mRNA, miRNA and DNA methylation of were downloaded from The Cancer Genome Atlas (TCGA)...
December 19, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28045128/epigenomics-alternations-and-dynamic-transcriptional-changes-in-responses-to-5-fluorouracil-stimulation-reveal-mechanisms-of-acquired-drug-resistance-of-colorectal-cancer-cells
#5
Y Shen, M Tong, Q Liang, Y Guo, H Q Sun, W Zheng, L Ao, Z Guo, F She
A drug-induced resistant cancer cell is different from its parent cell in transcriptional response to drug treatment. The distinct transcriptional response pattern of a drug-induced resistant cancer cell to drug treatment might be introduced by acquired DNA methylation aberration in the cell exposing to sustained drug stimulation. In this study, we performed both transcriptional and DNA methylation profiles of the HCT-8 wild-type cells (HCT-8/WT) for human colorectal cancer (CRC) and the 5-fluorouracil (5-FU)-induced resistant cells (HCT-8/5-FU) after treatment with 5-FU for 0, 24 and 48 h...
January 3, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28044062/opening-up-the-dna-methylome-of-dementia
#6
R Delgado-Morales, M Esteller
Dementia is a complex clinical condition characterized by several cognitive impairments that interfere with patient independence in executing everyday tasks. Various neurodegenerative disorders have dementia in common among their clinical manifestations. In addition, these diseases, such as Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies and frontotemporal dementia, share molecular alterations at the neuropathological level. In recent years, the field of neuroepigenetics has expanded massively and it is now clear that epigenetic processes, such as DNA methylation, are mechanisms involved in both normal and pathological brain function...
January 3, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28035374/activation-of-oncogenic-pathways-in-classical-hodgkin-lymphoma-by-decitabine-a-rationale-for-combination-with-small-molecular-weight-inhibitors
#7
Tatjana Maria Swerev, Thomas Wirth, Alexey Ushmorov
DNA methylation is an epigenetic control mechanism that contributes to the specific phenotype and to the oncogenic program of virtually all tumor entities. Although efficacy of demethylating agents in classical Hodgkin lymphoma (cHL) was not specifically tested, a case of regression of relapsed metastatic cHL was described as a fortunate side‑effect of the demethylating agent 5‑azacytidine in a patient with myelodysplastic syndrome. We investigated molecular mechanisms of decitabine (5‑Aza‑dC) antitumor activity in cHL using gene expression profiling followed by gene set enrichment analysis...
December 30, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/28035070/elucidation-of-the-genetic-and-epigenetic-landscape-alterations-in-rna-binding-proteins-in-glioblastoma
#8
Shruti Bhargava, Vikas Patil, Kulandaivelu Mahalingam, Kumaravel Somasundaram
RNA binding proteins (RBPs) have been implicated in cancer development. An integrated bioinformatics analysis of RBPs (n = 1756) in various datasets (n = 11) revealed several genetic and epigenetically altered events among RBPs in glioblastoma (GBM). We identified 13 mutated and 472 differentially regulated RBPs in GBM samples. Mutations in AHNAK predicted poor prognosis. Copy number variation (CNV), DNA methylation and miRNA targeting contributed to RBP differential regulation. Two sets of differentially regulated RBPs that may be implicated in initial astrocytic transformation and glioma progression were identified...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28011714/schizophrenia-associated-methylomic-variation-molecular-signatures-of-disease-and-polygenic-risk-burden-across-multiple-brain-regions
#9
Joana Viana, Eilis Hannon, Emma Dempster, Ruth Pidsley, Ruby Macdonald, Olivia Knox, Helen Spiers, Claire Troakes, Safa Al-Saraj, Gustavo Turecki, Leonard C Schalkwyk, Jonathan Mill
Genetic association studies provide evidence for a substantial polygenic component to schizophrenia, although the neurobiological mechanisms underlying the disorder remain largely undefined. Building on recent studies supporting a role for developmentally regulated epigenetic variation in the molecular etiology of schizophrenia, this study aimed to identify epigenetic variation associated with both a diagnosis of schizophrenia and elevated polygenic risk burden for the disease across multiple brain regions...
December 22, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28003999/synergistic-cytotoxic-effect-of-l-asparaginase-combined-with-decitabine-as-a-demethylating-agent-in-pediatric-t-all-with-specific-epigenetic-signature
#10
Salvatore Serravalle, Salvatore N Bertuccio, Annalisa Astolfi, Fraia Melchionda, Andrea Pession
T-Acute Lymphoblastic Leukemia (T-ALL) remains a subgroup of pediatric ALL, with a lower response to standard chemotherapy. Some recent studies established the fundamental role of epigenetic aberrations such as DNA hypermethylation, to influence patients' outcome and response to chemotherapy. Moreover, L-asparaginase is an important chemotherapeutic agent for treatment of ALL and resistance to this drug has been linked to ASNS expression, which can be silenced through methylation. Therefore, we tested whether the sensitivity of T-ALL cell lines towards L-asparaginase is correlated to the epigenetic status of ASNS gene and whether the sensitivity can be modified by concurrent demethylating treatment...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27993549/higher-naevus-count-exhibits-a-distinct-dna-methylation-signature-in-healthy-human-skin-implications-for-melanoma
#11
Leonie Roos, Johanna K Sandling, Christopher G Bell, Daniel Glass, Massimo Mangino, Tim D Spector, Panos Deloukas, Veronique Bataille, Jordana T Bell
High naevus count is the strongest risk factor for melanoma and although gene variants have been discovered for both traits, epigenetic variation is unexplored. We investigated 322 healthy human skin DNA methylomes associated with total body naevi count, incorporating genetic and transcriptomic variation. DNA methylation changes were identified at genes involved in melanocyte biology, such as RAF1 (p = 1.2 x 10(-6)) and CTC1 (region: p = 6.3 x 10(-4)), and other genes including ARRDC1 (p = 3.1 x 10(-7)). A subset exhibited coordinated methylation and transcription changes within the same biopsy...
December 16, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27982725/differential-analysis-of-genome-wide-methylation-and-gene-expression-in-mesenchymal-stem-cells-of-patients-with-fractures-and-osteoarthritis
#12
Alvaro Del Real, Flor M Pérez-Campo, Agustín F Fernández, Carolina Sañudo, Carmen G Ibarbia, María I Pérez-Núñez, Wim Van Criekinge, Maarten Braspenning, María A Alonso, Mario F Fraga, Jose A Riancho
Insufficient activity of the bone-forming osteoblasts leads to low bone mass and predisposes to fragility fractures. The functional capacity of mesenchymal stem cells (hMSCs), the precursors of osteoblasts, may be compromised in elderly individuals, in relation with the epigenetic changes associated with aging. However, the role of hMSCs in the pathogenesis of osteoporosis is still unclear. Therefore, we aimed to characterize the genome-wide methylation and gene expression signatures and the differentiation capacity of hMSCs from patients with hip fractures...
December 16, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27979589/in-vitro-hydroquinone-induced-instauration-of-histone-bivalent-mark-on-human-retroelements-line-1-in-hl60-cells
#13
Monica Mancini, Martina Mandruzzato, Alba C Garzia, Nora Sahnane, Elena Magnani, Filippo Macchi, Mustapha Oulad-Abdelghani, Pierre Oudet, Valentina Bollati, Silvia Fustinoni, Daniela Furlan, Ian M Bonapace
Benzene is extensively used in industry despite its leukemogenic activity, representing a significant occupational hazard. We investigated if long-term treatment with low-doses hydroquinone (HQ), a benzene metabolite, might be sufficient to alter in vitro the epigenetic signature underlining LINE-1 sequences, a poorly explored step in health risks associated with benzene exposure. In HL-60 cell line, exploring the epigenetic events occurring in chromatin, we found the transient instauration of the distinctive signature combining the repressive H3Lys27 tri-methylation mark and the activating H3Lys4 tri-methylation mark (H3K27me3/H3K4me3), indicating a tendency toward a poised chromatin conformation...
December 13, 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27965295/dna-methylation-derived-neutrophil-to-lymphocyte-ratio-an-epigenetic-tool-to-explore-cancer-inflammation-and-outcomes
#14
Devin C Koestler, Joseph L Usset, Brock C Christensen, Carmen J Marsit, Margaret R Karagas, Karl T Kelsey, John K Wiencke
BACKGROUND: The peripheral blood neutrophil-to-lymphocyte ratio (NLR) is a cytological marker of both inflammation and poor outcomes in cancer patients. DNA methylation is a key element of the epigenetic program defining different leukocyte subtypes and may provide an alternative to cytology in assessing leukocyte profiles. Our aim was to create a bioinformatic tool to estimate NLR using DNA methylation, and to assess its diagnostic and prognostic performance in human populations. METHODS: We developed a DNA methylation-derived NLR (mdNLR) index based on normal isolated leukocyte methylation libraries and established cell-mixture deconvolution algorithms...
December 13, 2016: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/27965059/epigenetics-of-psoriatic-disease-a-systematic-review-and-critical-appraisal
#15
Remy A Pollock, Fatima Abji, Dafna D Gladman
Psoriasis is an inflammatory disease of the skin that is sometimes accompanied by an auto-inflammatory arthritis called psoriatic arthritis (PsA). Psoriasis and PsA are multifactorial diseases that result from complex interactions of environmental and genetic risk factors. Epigenetic marks, which are labile chemical marks with diverse functions, form a layer of biological information that sits at the interface of genetics and the environment. Aberrant epigenetic regulation has been previously implicated in other rheumatological disorders...
December 10, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27955697/dna-methylation-signatures-of-chronic-low-grade-inflammation-are-associated-with-complex-diseases
#16
Symen Ligthart, Carola Marzi, Stella Aslibekyan, Michael M Mendelson, Karen N Conneely, Toshiko Tanaka, Elena Colicino, Lindsay L Waite, Roby Joehanes, Weihua Guan, Jennifer A Brody, Cathy Elks, Riccardo Marioni, Min A Jhun, Golareh Agha, Jan Bressler, Cavin K Ward-Caviness, Brian H Chen, Tianxiao Huan, Kelly Bakulski, Elias L Salfati, Giovanni Fiorito, Simone Wahl, Katharina Schramm, Jin Sha, Dena G Hernandez, Allan C Just, Jennifer A Smith, Nona Sotoodehnia, Luke C Pilling, James S Pankow, Phil S Tsao, Chunyu Liu, Wei Zhao, Simonetta Guarrera, Vasiliki J Michopoulos, Alicia K Smith, Marjolein J Peters, David Melzer, Pantel Vokonas, Myriam Fornage, Holger Prokisch, Joshua C Bis, Audrey Y Chu, Christian Herder, Harald Grallert, Chen Yao, Sonia Shah, Allan F McRae, Honghuang Lin, Steve Horvath, Daniele Fallin, Albert Hofman, Nicholas J Wareham, Kerri L Wiggins, Andrew P Feinberg, John M Starr, Peter M Visscher, Joanne M Murabito, Sharon L R Kardia, Devin M Absher, Elisabeth B Binder, Andrew B Singleton, Stefania Bandinelli, Annette Peters, Melanie Waldenberger, Giuseppe Matullo, Joel D Schwartz, Ellen W Demerath, André G Uitterlinden, Joyce B J van Meurs, Oscar H Franco, Yii-Der Ida Chen, Daniel Levy, Stephen T Turner, Ian J Deary, Kerry J Ressler, Josée Dupuis, Luigi Ferrucci, Ken K Ong, Themistocles L Assimes, Eric Boerwinkle, Wolfgang Koenig, Donna K Arnett, Andrea A Baccarelli, Emelia J Benjamin, Abbas Dehghan
BACKGROUND: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation. RESULTS: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111)...
December 12, 2016: Genome Biology
https://www.readbyqxmd.com/read/27942592/dna-methylation-in-lung-cells-is-associated-with-asthma-endotypes-and-genetic-risk
#17
Jessie Nicodemus-Johnson, Rachel A Myers, Noburu J Sakabe, Debora R Sobreira, Douglas K Hogarth, Edward T Naureckas, Anne I Sperling, Julian Solway, Steven R White, Marcelo A Nobrega, Dan L Nicolae, Yoav Gilad, Carole Ober
The epigenome provides a substrate through which environmental exposures can exert their effects on gene expression and disease risk, but the relative importance of epigenetic variation on human disease onset and progression is poorly characterized. Asthma is a heterogeneous disease of the airways, for which both onset and clinical course result from interactions between host genotype and environmental exposures, yet little is known about the molecular mechanisms for these interactions. We assessed genome-wide DNA methylation using the Infinium Human Methylation 450K Bead Chip and characterized the transcriptome by RNA sequencing in primary airway epithelial cells from 74 asthmatic and 41 nonasthmatic adults...
December 8, 2016: JCI Insight
https://www.readbyqxmd.com/read/27934915/the-defining-dna-methylation-signature-of-floating-harbor-syndrome
#18
Rebecca L Hood, Laila C Schenkel, Sarah M Nikkel, Peter J Ainsworth, Guillaume Pare, Kym M Boycott, Dennis E Bulman, Bekim Sadikovic
Floating-Harbor syndrome (FHS) is an autosomal dominant genetic condition characterized by short stature, delayed osseous maturation, expressive language impairment, and unique facial dysmorphology. We previously identified mutations in the chromatin remodeling protein SRCAP (SNF2-related CBP Activator Protein) as the cause of FHS. SRCAP has multiple roles in chromatin and transcriptional regulation; however, specific epigenetic consequences of SRCAP mutations remain to be described. Using high resolution genome-wide DNA methylation analysis, we identified a unique and highly specific DNA methylation "epi-signature" in the peripheral blood of individuals with FHS...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27932423/integrated-genomic-analysis-of-survival-outliers-in-glioblastoma
#19
Sen Peng, Harshil Dhurv, Brock Armstrong, Bodour Salhia, Christophe Legendre, Jeffrey Kiefer, Julianna Parks, Selene Virk, Andrew E Sloan, Quinn T Ostrom, Jill S Barnholtz-Sloan, Nhan L Tran, Michael E Berens
BACKGROUND: To elucidate molecular features associated with disproportionate survival of glioblastoma (GB) patients, we conducted deep genomic comparative analysis of a cohort of patients receiving standard therapy (surgery plus concurrent radiation and temozolomide); "GB outliers" were identified: long-term survivor of 33 months (LTS; n = 8) versus short-term survivor of 7 months (STS; n = 10). METHODS: We implemented exome, RNA, whole genome sequencing, and DNA methylation for collection of deep genomic data from STS and LTS GB patients...
December 8, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/27931182/exposure-of-bovine-oocytes-and-embryos-to-elevated-non-esterified-fatty-acid-concentrations-integration-of-epigenetic-and-transcriptomic-signatures-in-resultant-blastocysts
#20
K L J Desmet, V Van Hoeck, D Gagné, E Fournier, A Thakur, A M O'Doherty, C P Walsh, M A Sirard, P E J Bols, J L M R Leroy
BACKGROUND: Metabolic stress associated with negative energy balance in high producing dairy cattle and obesity in women is a risk factor for decreased fertility. Non-esterified fatty acids (NEFA) are involved in this pathogenesis as they jeopardize oocyte and embryo development. Growing evidence indicates that maternal metabolic disorders can disturb epigenetic programming, such as DNA methylation, in the offspring. Oocyte maturation and early embryo development coincide with methylation changes and both are sensitive to adverse environments...
December 8, 2016: BMC Genomics
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