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Clinical Epigenetics

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https://www.readbyqxmd.com/read/28439316/epigenetic-assays-for-chemical-biology-and-drug-discovery
#1
REVIEW
Sheraz Gul
The implication of epigenetic abnormalities in many diseases and the approval of a number of compounds that modulate specific epigenetic targets in a therapeutically relevant manner in cancer specifically confirms that some of these targets are druggable by small molecules. Furthermore, a number of compounds are currently in clinical trials for other diseases including cardiovascular, neurological and metabolic disorders. Despite these advances, the approved treatments for cancer only extend progression-free survival for a relatively short time and being associated with significant side effects...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28439315/36%C3%A2-h-fasting-of-young-men-influences-adipose-tissue-dna-methylation-of-lep-and-adipoq-in-a-birth-weight-dependent-manner
#2
Line Hjort, Sine W Jørgensen, Linn Gillberg, Elin Hall, Charlotte Brøns, Jan Frystyk, Allan A Vaag, Charlotte Ling
BACKGROUND: Subjects born with low birth weight (LBW) display a more energy-conserving response to fasting compared with normal birth weight (NBW) subjects. However, the molecular mechanisms explaining these metabolic differences remain unknown. Environmental influences may dynamically affect epigenetic marks, also in postnatal life. Here, we aimed to study the effects of short-term fasting on leptin (LEP) and adiponectin (ADIPOQ) DNA methylation and gene expression in subcutaneous adipose tissue (SAT) from subjects with LBW and NBW...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28428831/cord-blood-hematopoietic-cells-from-preterm-infants-display-altered-dna-methylation-patterns
#3
Olivia M de Goede, Pascal M Lavoie, Wendy P Robinson
BACKGROUND: Premature infants are highly vulnerable to infection. This is partly attributable to the preterm immune system, which differs from that of the term neonate in cell composition and function. Multiple studies have found differential DNA methylation (DNAm) between preterm and term infants' cord blood; however, interpretation of these studies is limited by the confounding factor of blood cell composition. This study evaluates the epigenetic impact of preterm birth in isolated hematopoietic cell populations, reducing the concern of cell composition differences...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28416970/dna-methylation-profiling-in-peripheral-lung-tissues-of-smokers-and-patients-with-copd
#4
Isaac K Sundar, Qiangzong Yin, Brian S Baier, Li Yan, Witold Mazur, Dongmei Li, Martha Susiarjo, Irfan Rahman
BACKGROUND: Epigenetics changes have been shown to be affected by cigarette smoking. Cigarette smoke (CS)-mediated DNA methylation can potentially affect several cellular and pathophysiological processes, acute exacerbations, and comorbidity in the lungs of patients with chronic obstructive pulmonary disease (COPD). We sought to determine whether genome-wide lung DNA methylation profiles of smokers and patients with COPD were significantly different from non-smokers. We isolated DNA from parenchymal lung tissues of patients including eight lifelong non-smokers, eight current smokers, and eight patients with COPD and analyzed the samples using Illumina's Infinium HumanMethylation450 BeadChip...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28413567/differential-adipokine-dna-methylation-and-gene-expression-in-subcutaneous-adipose-tissue-from-adult-offspring-of-women-with-diabetes-in-pregnancy
#5
Azadeh Houshmand-Oeregaard, Ninna S Hansen, Line Hjort, Louise Kelstrup, Christa Broholm, Elisabeth R Mathiesen, Tine D Clausen, Peter Damm, Allan Vaag
BACKGROUND: Offspring of women with diabetes in pregnancy are at increased risk of type 2 diabetes mellitus (T2DM), potentially mediated by epigenetic mechanisms. The adipokines leptin, adiponectin, and resistin (genes: LEP, ADIPOQ, RETN) play key roles in the pathophysiology of T2DM. We hypothesized that offspring exposed to maternal diabetes exhibit alterations in epigenetic regulation of subcutaneous adipose tissue (SAT) adipokine transcription. We studied adipokine plasma levels, SAT gene expression, and DNA methylation of LEP, ADIPOQ, and RETN in adult offspring of women with gestational diabetes (O-GDM, N = 82) or type 1 diabetes (O-T1DM, N = 67) in pregnancy, compared to offspring of women from the background population (O-BP, N = 57)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28405244/clusterization-in-head-and-neck-squamous-carcinomas-based-on-lncrna-expression-molecular-and-clinical-correlates
#6
Pelayo G de Lena, Abel Paz-Gallardo, Jesús M Paramio, Ramón García-Escudero
BACKGROUND: Long non-coding RNAs (lncRNAs) have emerged as key players in a remarkably variety of biological processes and pathologic conditions, including cancer. Next-generation sequencing technologies and bioinformatics procedures predict the existence of tens of thousands of lncRNAs, from which we know the functions of only a handful of them, and very little is known in cancer types such as head and neck squamous cell carcinomas (HNSCCs). RESULTS: Here, we use RNAseq expression data from The Cancer Genome Atlas (TCGA) and various statistic and software tools in order to get insight about the lncRNome in HNSCC...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28396702/interaction-between-prenatal-pesticide-exposure-and-a-common-polymorphism-in-the-pon1-gene-on-dna-methylation-in-genes-associated-with-cardio-metabolic-disease-risk-an-exploratory%C3%A2-study
#7
Ken Declerck, Sylvie Remy, Christine Wohlfahrt-Veje, Katharina M Main, Guy Van Camp, Greet Schoeters, Wim Vanden Berghe, Helle R Andersen
BACKGROUND: Prenatal environmental conditions may influence disease risk in later life. We previously found a gene-environment interaction between the paraoxonase 1 (PON1) Q192R genotype and prenatal pesticide exposure leading to an adverse cardio-metabolic risk profile at school age. However, the molecular mechanisms involved have not yet been resolved. It was hypothesized that epigenetics might be involved. The aim of the present study was therefore to investigate whether DNA methylation patterns in blood cells were related to prenatal pesticide exposure level, PON1 Q192R genotype, and associated metabolic effects observed in the children...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28396701/aberrant-dna-methylation-in-melanoma-biomarker-and-therapeutic-opportunities
#8
REVIEW
Goran Micevic, Nicholas Theodosakis, Marcus Bosenberg
Aberrant DNA methylation is an epigenetic hallmark of melanoma, known to play important roles in melanoma formation and progression. Recent advances in genome-wide methylation methods have provided the means to identify differentially methylated genes, methylation signatures, and potential biomarkers. However, despite considerable effort and advances in cataloging methylation changes in melanoma, many questions remain unanswered. The aim of this review is to summarize recent developments, emerging trends, and important unresolved questions in the field of aberrant DNA methylation in melanoma...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28392843/validation-of-the-methylationepic-beadchip-for-fresh-frozen-and-formalin-fixed-paraffin-embedded-tumours
#9
Teresia Kling, Anna Wenger, Stephan Beck, Helena Carén
DNA methylation is the most studied epigenetic modification due to its role in regulating gene expression, and its involvement in the pathogenesis of cancer and several diseases upon aberrations in methylation. The method of choice to evaluate genome-wide methylation has been the Illumina HumanMethylation450 BeadChip (450K), but it was recently replaced with the MethylationEPIC BeadChip (EPIC). We therefore sought to validate the EPIC array in comparison to the 450K array for both fresh-frozen (FF) and formalin-fixed paraffin-embedded (FFPE) tumours...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28392842/dna-methylation-signatures-for-2016-who-classification-subtypes-of-diffuse-gliomas
#10
Yashna Paul, Baisakhi Mondal, Vikas Patil, Kumaravel Somasundaram
BACKGROUND: Glioma is the most common of all primary brain tumors with poor prognosis and high mortality. The 2016 World Health Organization classification of the tumors of central nervous system uses molecular parameters in addition to histology to redefine many tumor entities. The new classification scheme divides diffuse gliomas into low-grade glioma (LGG) and glioblastoma (GBM) as per histology. LGGs are further divided into isocitrate dehydrogenase (IDH) wild type or mutant, which is further classified into either oligodendroglioma that harbors 1p/19q codeletion or diffuse astrocytoma that has an intact 1p/19q loci but enriched for ATRX loss and TP53 mutation...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28392841/assessing-alternative-base-substitutions-at-primer-cpg-sites-to-optimise-unbiased-pcr-amplification-of-methylated-sequences
#11
Ida L M Candiloro, Thomas Mikeska, Alexander Dobrovic
BACKGROUND: Determining the role of DNA methylation in various biological processes is dependent on the accurate representation of often highly complex patterns. Accurate representation is dependent on unbiased PCR amplification post bisulfite modification, regardless of methylation status of any given epiallele. This is highly dependent on primer design. Particular difficulties are raised by the analysis of CpG-rich regions, which are the usual regions of interest. Here, it is often difficult or impossible to avoid placing primers in CpG-free regions, particularly if one wants to target a specific part of a CpG-rich region...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28360947/a-novel-method-for-isolation-of-histones-from-serum-and-its-implications-in-therapeutics-and-prognosis-of-solid-tumours
#12
Divya Reddy, Bharat Khade, Riddhi Pandya, Sanjay Gupta
BACKGROUND: Dysregulation in post-translational modifications of histones and their modifiers are now well-recognized as a hallmark of cancer and can be used as biomarkers and potential therapeutic targets for disease progression and prognosis. In most solid tumours, a biopsy is challenging, costly, painful or potentially risky for the patient. Therefore, non-invasive methods like 'liquid biopsy' for analysis of histone modifications and their modifiers if possible will be helpful in the better clinical management of cancer patients...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28360946/associations-of-lep-crh-icam-1-and-line-1-methylation-measured-in-saliva-with-waist-circumference-body-mass-index-and-percent-body-fat-in-mid-childhood
#13
Jocelyn Dunstan, Joseph P Bressler, Timothy H Moran, Jonathan S Pollak, Annemarie G Hirsch, Lisa Bailey-Davis, Thomas A Glass, Brian S Schwartz
BACKGROUND: Genetics explains a small proportion of variance in body mass index at the population level. Epigenetics, commonly measured by gene methylation, holds promise for understanding obesity risk factors and mechanisms. METHODS: Participants were 431 adolescents aged 10-15 years. BMI z-score, waist circumference z-score, and percent body fat were measured. Saliva samples were collected and methylation of promoter regions of four candidate genes or sequences (LEP, ICAM-1, CRH, and LINE-1) were measured in 3-4 CpG sites each...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28360945/epigenetic-signatures-of-gestational-diabetes-mellitus-on-cord-blood-methylation
#14
Larissa Haertle, Nady El Hajj, Marcus Dittrich, Tobias Müller, Indrajit Nanda, Harald Lehnen, Thomas Haaf
BACKGROUND: Intrauterine exposure to gestational diabetes mellitus (GDM) confers a lifelong increased risk for metabolic and other complex disorders to the offspring. GDM-induced epigenetic modifications modulating gene regulation and persisting into later life are generally assumed to mediate these elevated disease susceptibilities. To identify candidate genes for fetal programming, we compared genome-wide methylation patterns of fetal cord bloods (FCBs) from GDM and control pregnancies...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28331555/erratum-to-monoallelic-germline-methylation-and-sequence-variant-in-the-promoter-of-the-rb1-gene-a-possible-constitutive-epimutation-in-hereditary-retinoblastoma
#15
Guadalupe Quiñonez-Silva, Mercedes Dávalos-Salas, Félix Recillas-Targa, Patricia Ostrosky-Wegman, Diego Arenas Aranda, Luis Benítez-Bribiesca
[This corrects the article DOI: 10.1186/s13148-015-0167-0.].
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28293327/the-dynamic-dna-methylation-landscape-of-the-mutl-homolog-1-shore-is-altered-by-mlh1-93g-a-polymorphism-in-normal-tissues-and-colorectal-cancer
#16
Andrea J Savio, Miralem Mrkonjic, Mathieu Lemire, Steven Gallinger, Julia A Knight, Bharat Bapat
BACKGROUND: Colorectal cancers (CRCs) undergo distinct genetic and epigenetic alterations. Expression of mutL homolog 1 (MLH1), a mismatch repair gene that corrects DNA replication errors, is lost in up to 15% of sporadic tumours due to mutation or, more commonly, due to DNA methylation of its promoter CpG island. A single nucleotide polymorphism (SNP) in the CpG island of MLH1 (MLH1-93G>A or rs1800734) is associated with CpG island hypermethylation and decreased MLH1 expression in CRC tumours...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28293326/line-1-is-preferentially-hypomethylated-within-adenomatous-polyps-in-the-presence-of-synchronous-colorectal-cancer
#17
Alice Chu Jiang, Lela Buckingham, William Barbanera, Amoah Yeboah Korang, Faraz Bishesari, Joshua Melson
BACKGROUND: Conventional tubular adenomas are frequently detected in patients undergoing average risk screening colonoscopy and are over-represented in patients who will develop colorectal cancer (CRC). Whether features of adenomas could serve as predictors of synchronous CRC is not known. Here, we investigate whether global methylation markers, including LINE-1, differ within adenomas in patients with and without synchronous CRC. METHODS: Colorectal tubular/tubulovillous adenomatous polyps in the absence (P group, n = 45) and in the presence of synchronous CRC (PC group, n = 32) were identified...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28289479/colorectal-adenoma-and-carcinoma-specific-mirna-profiles-in-biopsy-and-their-expression-in-plasma-specimens
#18
Zsófia Brigitta Nagy, Barnabás Wichmann, Alexandra Kalmár, Orsolya Galamb, Barbara Kinga Barták, Sándor Spisák, Zsolt Tulassay, Béla Molnár
BACKGROUND: MiRNA expression markers are well characterized in colorectal cancer (CRC), but less is known about miRNA expression profiles in colorectal adenomas. Genome-wide miRNA and mRNA expression analyses were conducted through the colorectal adenoma dysplasia sequence. Furthermore, analysis of the expression levels of miRNAs in matched plasma samples was performed, focusing on biomarker candidates; miRNA and mRNA expression analyses were performed on colorectal biopsies and plasma samples (20 normals; 11 tubular and 9 tubulovillous adenomas; 20 colorectal carcinomas) by miRNA 3...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28289478/cerebral-white-matter-hyperintensities-on-mri-and-acceleration-of-epigenetic-aging-the-atherosclerosis-risk-in-communities-study
#19
Abhay Raina, Xiaoping Zhao, Megan L Grove, Jan Bressler, Rebecca F Gottesman, Weihua Guan, James S Pankow, Eric Boerwinkle, Thomas H Mosley, Myriam Fornage
BACKGROUND: Cerebral white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) are part of the spectrum of brain vascular injury accompanying aging and are associated with a substantial risk of stroke and dementia. We investigated the association of cerebral WMH burden on MRI with a DNA methylation-based biomarker of aging, termed DNA methylation age acceleration, which represents the deviation of the DNA methylation-predicted age from the chronologic age. RESULTS: In this cross-sectional observational study of 713 African-American participants of the Atherosclerosis Risk in Communities study, aged 51-73 years, estimates of predicted age were obtained based on two algorithms (Hannum et al...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28289477/obesity-accelerates-epigenetic-aging-in-middle-aged-but-not-in-elderly-individuals
#20
Tapio Nevalainen, Laura Kananen, Saara Marttila, Juulia Jylhävä, Nina Mononen, Mika Kähönen, Olli T Raitakari, Antti Hervonen, Marja Jylhä, Terho Lehtimäki, Mikko Hurme
BACKGROUND: Human aging is associated with profound changes in one of the major epigenetic mechanisms, DNA methylation. Some of these changes occur in a clock-like fashion, i.e., correlating with the calendar age of an individual, thus providing a new aging biomarker. Some reports have identified factors associated with the acceleration of the epigenetic age. However, it is also important to analyze the temporal changes in the epigenetic age, i.e., the duration of the observed acceleration, and the effects of the possible therapeutic and lifestyle modifications...
2017: Clinical Epigenetics
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