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Epigenetic methylation signature

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https://www.readbyqxmd.com/read/29774131/methylation-of-dna-and-chromatin-as-a-mechanism-of-oncogenesis-and-therapeutic-target-in-neuroblastoma
#1
REVIEW
Ram Mohan Ram Kumar, Nina Felice Schor
Neuroblastoma (NB), a developmental cancer, is often fatal, emphasizing the need to understand its pathogenesis and identify new therapeutic targets. The heterogeneous pathological and clinical phenotype of NB underscores the cryptic biological and genetic features of this tumor that result in outcomes ranging from rapid progression to spontaneous regression. Despite recent genome-wide mutation analyses, most primary NBs do not harbor driver mutations, implicating epigenetically-mediated gene regulatory mechanisms in the initiation and maintenance of NB...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29771158/global-methylation-profiles-in-buccal-cells-of-long-term-smokers-and-moist-snuff-consumers
#2
Walter J Jessen, Michael F Borgerding, G L Prasad
PURPOSE: Alternations in gene methylation and other epigenetic changes regulate normal development as well as drive disease progression. The aim of this study is to investigate global methylation changes in the buccal cells of smokers and smokeless tobacco users. MATERIALS AND METHODS: Generally healthy adult male subjects were recruited into Smoker (SMK), Moist Snuff Consumer (MSC) and Non-Tobacco Consumer (NTC) cohorts (40 subjects/cohort) (ClinicalTrials.gov Identifier: NCT01923402)...
May 17, 2018: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/29743404/-epigenetic-aberrations-in-adult-t-cell-leukemia-lymphoma-and-development-of-a-novel-ezh1-2-inhibitor
#3
Makoto Yamagishi
Histone H3 lysine 27 tri-methylation (H3K27me3) -dependent transcription regulation is a fundamental process of gene control. Although EZH2 mutation is observed in certain lymphoma types, many other cancers show global H3K27me3 accumulation irrespective of mutation. However, the underlying mechanisms of gene silencing and therapeutic efficacies of epigenetic drugs remain unclear. In this study, we showed that globally-accumulated H3K27me3 is induced by both cis-bound EZH1 and EZH2 in mature lymphocyte-derived malignancies...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29732534/epigenetic-loss-of-heparan-sulfate-3-o-sulfation-sensitizes-ovarian-carcinoma-to-oncogenic-signals-and-predicts-prognosis
#4
Rui-Lan Huang, Hsiang-Ju Chen, Lin-Yu Chen, Tai-Kuang Chao, Wei-Yu Lin, Phui-Ly Liew, Po-Hsuan Su, Yu-Chun Weng, Yu-Chi Wang, Chi-Chun Liao, Yaw-Wen Hsu, Hui- Chen Wang, Hung-Cheng Lai
Precision medicine requires markers for therapeutic guidance. The purpose of this study was to determine whether epithelial ovarian cancer (EOC) epigenetics can lead to the identification of biomarkers for precision medicine. Through integrative methylomics, we discovered and validated the epigenetic signature of NEFH and HS3ST2 as an independent prognostic factor for type II EOC in our dataset (n = 84), two independent methylomics datasets (total n = 467). Integrated transcriptomics dataset (n = 1147) and tissue microarrays (n = 54) of HS3ST2 also related to high-methylation statuses and the EOC prognosis...
May 7, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29732524/integrated-analysis-of-dynamic-fet-pet-ct-parameters-histology-and-methylation-profiling-of-44-gliomas
#5
Manuel Röhrich, Kristin Huang, Daniel Schrimpf, Nathalie L Albert, Thomas Hielscher, Andreas von Deimling, Ulrich Schüller, Antonia Dimitrakopoulou-Strauss, Uwe Haberkorn
PURPOSE: Dynamic 18 F-FET PET/CT is a powerful tool for the diagnosis of gliomas.18 F-FET PET time-activity curves (TAC) allow differentiation between histological low-grade gliomas (LGG) and high-grade gliomas (HGG). Molecular methods such as epigenetic profiling are of rising importance for glioma grading and subclassification. Here, we analysed dynamic 18 F-FET PET data, and the histological and epigenetic features of 44 gliomas. METHODS: Dynamic 18 F-FET PET was performed in 44 patients with newly diagnosed, untreated glioma: 10 WHO grade II glioma, 13 WHO grade III glioma and 21 glioblastoma (GBM)...
May 7, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29732401/posttranslational-modification-of-a-histone-like-protein-regulates-phenotypic-resistance-to-isoniazid-in-mycobacteria
#6
Alexandra Sakatos, Gregory H Babunovic, Michael R Chase, Alexander Dills, John Leszyk, Tracy Rosebrock, Bryan Bryson, Sarah M Fortune
There is increasing evidence that phenotypically drug-resistant bacteria may be important determinants of antibiotic treatment failure. Using high-throughput imaging, we defined distinct subpopulations of mycobacterial cells that exhibit heritable but semi-stable drug resistance. These subpopulations have distinct transcriptional signatures and growth characteristics at both bulk and single-cell levels, which are also heritable and semi-stable. We find that the mycobacterial histone-like protein HupB is required for the formation of these subpopulations...
May 2018: Science Advances
https://www.readbyqxmd.com/read/29731982/gene-specific-methylation-profiles-in-brca-mutation-positive-and-brca-mutation-negative-male-breast-cancers
#7
Piera Rizzolo, Valentina Silvestri, Virginia Valentini, Veronica Zelli, Ines Zanna, Giovanna Masala, Simonetta Bianchi, Domenico Palli, Laura Ottini
Male breast cancer (MBC) is a rare disease. Due to its rarity, MBC research and clinical approach are mostly based upon data derived from female breast cancer (FBC). Increasing evidence indicate that on molecular level MBC may be an heterogeneous disease different from FBC. In order to investigate whether epigenetic signatures could define molecular subgroups of MBCs, we performed promoter methylation analysis of genes involved in signal transduction and hormone signalling in BRCA1/2 mutation-positive and -negative MBCs...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29721079/dna-methylation-signatures-predicting-bevacizumab-efficacy-in-metastatic-breast-cancer
#8
Simon Peter Gampenrieder, Gabriel Rinnerthaler, Hubert Hackl, Walter Pulverer, Andreas Weinhaeusel, Suzana Ilic, Clemens Hufnagl, Cornelia Hauser-Kronberger, Alexander Egle, Angela Risch, Richard Greil
Background: Biomarkers predicting response to bevacizumab in breast cancer are still missing. Since epigenetic modifications can contribute to an aberrant regulation of angiogenesis and treatment resistance, we investigated the influence of DNA methylation patterns on bevacizumab efficacy. Methods: Genome-wide methylation profiling using the Illumina Infinium HumanMethylation450 BeadChip was performed in archival FFPE specimens of 36 patients with HER2-negative metastatic breast cancer treated with chemotherapy in combination with bevacizumab as first-line therapy ( learning set )...
2018: Theranostics
https://www.readbyqxmd.com/read/29717273/identification-of-an-episignature-of-human-colorectal-cancer-associated-with-obesity-by-genome-wide-dna-methylation-analysis
#9
Ana B Crujeiras, Sonsoles Morcillo, Angel Diaz-Lagares, Juan Sandoval, Daniel Castellano-Castillo, Esperanza Torres, David Hervas, Sebastian Moran, Manel Esteller, Manuel Macias-Gonzalez, Felipe F Casanueva, Francisco J Tinahones
BACKGROUND: Obesity was established as a relevant modifiable risk factor in the onset and progression of colorectal cancer (CRC). This relationship could be mediated by an epigenetic regulation. OBJECTIVES: The current work aimed to explore the effects of excess body weight on the DNA methylation profile of CRC using a genome-wide DNA methylation approach and to identify an epigenetic signature of obesity-related CRC. METHODS: Fifty-six CRC-diagnosed patients (50 years) were included in the study and categorized according to their body mass index (BMI) as non-obese (BMI ≤ 25 kg/m2 ) or overweight/obese (BMI > 25 kg/m2 )...
May 1, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29704316/genome-wide-and-digital-polymerase-chain-reaction-epigenetic-assessments-of-alcohol-consumption
#10
Robert Philibert, Meesha Dogan, Amanda Noel, Shelly Miller, Brianna Krukow, Emma Papworth, Joseph Cowley, April Knudsen, Steven R H Beach, Donald Black
The lack of readily employable biomarkers of alcohol consumption is a problem for clinicians and researchers. In 2014, we published a preliminary DNA methylation signature of heavy alcohol consumption that remits as a function of abstinence. Herein, we present new genome-wide methylation findings from a cohort of additional subjects and a meta-analysis of the data. Using DNA from 47 consecutive heavy drinkers admitted for alcohol detoxification in the context of alcohol treatment and 47 abstinent controls, we replicate the 2014 results and show that 21,221 CpG residues are differentially methylated in active heavy drinkers...
April 28, 2018: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/29691395/epigenetic-landscape-influences-the-liver-cancer-genome-architecture
#11
Natsuko Hama, Yasushi Totoki, Fumihito Miura, Kenji Tatsuno, Mihoko Saito-Adachi, Hiromi Nakamura, Yasuhito Arai, Fumie Hosoda, Tomoko Urushidate, Shoko Ohashi, Wakako Mukai, Nobuyoshi Hiraoka, Hiroyuki Aburatani, Takashi Ito, Tatsuhiro Shibata
The accumulations of different types of genetic alterations such as nucleotide substitutions, structural rearrangements and viral genome integrations and epigenetic alterations contribute to carcinogenesis. Here, we report correlation between the occurrence of epigenetic features and genetic aberrations by whole-genome bisulfite, whole-genome shotgun, long-read, and virus capture sequencing of 373 liver cancers. Somatic substitutions and rearrangement breakpoints are enriched in tumor-specific hypo-methylated regions with inactive chromatin marks and actively transcribed highly methylated regions in the cancer genome...
April 24, 2018: Nature Communications
https://www.readbyqxmd.com/read/29688621/an-epigenetic-signature-in-adipose-tissue-is-linked-to-nicotinamide-n-methyltransferase-gene-expression
#12
Ana B Crujeiras, Pavlos Pissios, Jose M Moreno-Navarrete, Angel Diaz-Lagares, Juan Sandoval, Antonio Gomez, Wilfredo Ricart, Manel Esteller, Felipe F Casanueva, Jose M Fernandez-Real
SCOPE: The enzyme nicotinamide N-methyltransferase (NNMT) is a major methyltransferase in adipose tissue. We hypothesized an epigenetic signature in association with NNMT gene expression in adipose tissue. METHODS AND RESULTS: The global human methylome was analyzed in visceral adipose tissue (VAT) from morbidly obese patients using the Infinium HumanMethylation450 BeadChip array (discovery cohort: n  =  11). The findings were confirmed in two additional independent cohorts (Cohort 1: n  =  60; BMI 20-60 kg/m2 and cohort 2: n  =  40; BMI >40 kg/m2 ) and validated after weight loss (using microarray data)...
April 24, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29682088/-gli2-promoter-hypermethylation-in-saliva-of-children-with-a-respiratory-allergy
#13
Sabine A S Langie, Matthieu Moisse, Katarzyna Szarc Vel Szic, Ellen Van Der Plas, Gudrun Koppen, Sofie De Prins, Tijs Louwies, Vera Nelen, Guy Van Camp, Diether Lambrechts, Greet Schoeters, Wim Vanden Berghe, Patrick De Boever
Background: The prevalence of respiratory allergy in children is increasing. Epigenetic DNA methylation changes are plausible underlying molecular mechanisms. Results: Saliva samples collected in substudies of two longitudinal birth cohorts in Belgium (FLEHS1 & FLEHS2) were used to discover and confirm DNA methylation signatures that can differentiate individuals with respiratory allergy from healthy subjects. Genome-wide analysis with Illumina Methylation 450K BeadChips revealed 23 differentially methylated gene regions (DMRs) in saliva from 11y old allergic children (N=26) vs...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29670286/pluripotency-factors-functionally-premark-cell-type-restricted-enhancers-in-es-cells
#14
Hong Sook Kim, Yuliang Tan, Wubin Ma, Daria Merkurjev, Eugin Destici, Qi Ma, Tom Suter, Kenneth Ohgi, Meyer Friedman, Dorota Skowronska-Krawczyk, Michael G Rosenfeld
Enhancers for embryonic stem (ES) cell-expressed genes and lineage-determining factors are characterized by conventional marks of enhancer activation in ES cells1-3 , but it remains unclear whether enhancers destined to regulate cell-type-restricted transcription units might also have distinct signatures in ES cells. Here we show that cell-type-restricted enhancers are 'premarked' and activated as transcription units by the binding of one or two ES cell transcription factors, although they do not exhibit traditional enhancer epigenetic marks in ES cells, thus uncovering the initial temporal origins of cell-type-restricted enhancers...
April 18, 2018: Nature
https://www.readbyqxmd.com/read/29669575/effects-of-senolytic-drugs-on-human-mesenchymal-stromal-cells
#15
Clara Grezella, Eduardo Fernandez-Rebollo, Julia Franzen, Mónica Sofia Ventura Ferreira, Fabian Beier, Wolfgang Wagner
BACKGROUND: Senolytic drugs are thought to target senescent cells and might thereby rejuvenate tissues. In fact, such compounds were suggested to increase health and lifespan in various murine aging models. So far, effects of senolytic drugs have not been analysed during replicative senescence of human mesenchymal stromal cells (MSCs). METHODS: In this study, we tested four potentially senolytic drugs: ABT-263 (navitoclax), quercetin, nicotinamide riboside, and danazol...
April 18, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29668342/sequencing-the-next-generation-of-glioblastomas
#16
Ivana Jovčevska
The most aggressive brain malignancy, glioblastoma, accounts for 60-70% of all gliomas and is uniformly fatal. According to the molecular signature, glioblastoma is divided into four subtypes (proneural, neural, classical, and mesenchymal), each with its own genetic background. The Cancer Genome Atlas project provides information about the most common genetic changes in glioblastoma. They involve mutations in TP53, TERT, and PTEN, and amplifications in EFGR, PDGFRA, CDK4, CDK6, MDM2, and MDM4. Recently, epigenetics was used to demonstrate the oncogenic roles of miR-124, miR-137, and miR-128...
April 18, 2018: Critical Reviews in Clinical Laboratory Sciences
https://www.readbyqxmd.com/read/29667349/asb1-differential-methylation-in-ischaemic-cardiomyopathy-relationship-with-left-ventricular-performance-in-end-stage-heart-failure-patients
#17
Ana Ortega, Estefanía Tarazón, Carolina Gil-Cayuela, Luis Martínez-Dolz, Francisca Lago, José Ramón González-Juanatey, Juan Sandoval, Manuel Portolés, Esther Roselló-Lletí, Miguel Rivera
AIMS: Ischaemic cardiomyopathy (ICM) leads to impaired contraction and ventricular dysfunction, causing high rates of morbidity and mortality. Epigenomics allows the identification of epigenetic signatures in human diseases. We analyse the differential epigenetic patterns of the ASB gene family in ICM patients and relate these alterations to their haemodynamic and functional status. METHODS AND RESULTS: Epigenomic analysis was carried out using 16 left ventricular (LV) tissue samples, eight from ICM patients undergoing heart transplantation and eight from control (CNT) subjects without cardiac disease...
April 17, 2018: ESC Heart Failure
https://www.readbyqxmd.com/read/29643477/accurate-estimation-of-5-methylcytosine-in-mammalian-mitochondrial-dna
#18
Shigeru Matsuda, Takehiro Yasukawa, Yuriko Sakaguchi, Kenji Ichiyanagi, Motoko Unoki, Kazuhito Gotoh, Kei Fukuda, Hiroyuki Sasaki, Tsutomu Suzuki, Dongchon Kang
Whilst 5-methylcytosine (5mC) is a major epigenetic mark in the nuclear DNA in mammals, whether or not mitochondrial DNA (mtDNA) receives 5mC modification remains controversial. Herein, we exhaustively analysed mouse mtDNA using three methods that are based upon different principles for detecting 5mC. Next-generation bisulfite sequencing did not give any significant signatures of methylation in mtDNAs of liver, brain and embryonic stem cells (ESCs). Also, treatment with methylated cytosine-sensitive endonuclease McrBC resulted in no substantial decrease of mtDNA band intensities in Southern hybridisation...
April 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29622466/comparative-molecular-analysis-of-gastrointestinal-adenocarcinomas
#19
Yang Liu, Nilay S Sethi, Toshinori Hinoue, Barbara G Schneider, Andrew D Cherniack, Francisco Sanchez-Vega, Jose A Seoane, Farshad Farshidfar, Reanne Bowlby, Mirazul Islam, Jaegil Kim, Walid Chatila, Rehan Akbani, Rupa S Kanchi, Charles S Rabkin, Joseph E Willis, Kenneth K Wang, Shannon J McCall, Lopa Mishra, Akinyemi I Ojesina, Susan Bullman, Chandra Sekhar Pedamallu, Alexander J Lazar, Ryo Sakai, Vésteinn Thorsson, Adam J Bass, Peter W Laird
We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing of MLH1 in the context of CpG island methylator phenotype, plus tumors with elevated single-nucleotide variants associated with mutations in POLE...
April 2, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29607455/epigenetic-signatures-in-cardiac-fibrosis-special-emphasis-on-dna-methylation-and-histone-modification
#20
REVIEW
Hui Tao, Zheng-Yu Song, Xuan-Sheng Ding, Jing-Jing Yang, Kai-Hu Shi, Jun Li
Cardiac fibrosis is defined as excess deposition of extracellular matrix (ECM), resulting in tissue scarring and organ dysfunction. In recent years, despite the underlying mechanisms of cardiac fibrosis are still unknown, numerous studies suggest that epigenetic regulation of cardiac fibrosis. Cardiac fibrosis is regulated by a myriad of factors that converge on the transcription of genes encoding extracellular matrix protein, a process the epigenetic machinery plays a pivotal role. Epigenetic modifications contain three main processes: DNA methylation, histone modifications, and noncoding RNAs...
April 2, 2018: Heart Failure Reviews
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