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Clinical Epigenetics

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https://www.readbyqxmd.com/read/28228863/medulloblastoma-and-ependymoma-cells-display-increased-levels-of-5-carboxylcytosine-and-elevated-tet1-expression
#1
Ashley Ramsawhook, Lara Lewis, Beth Coyle, Alexey Ruzov
BACKGROUND: Alteration of DNA methylation (5-methylcytosine, 5mC) patterns represents one of the causes of tumorigenesis and cancer progression. Tet proteins can oxidise 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine (5caC). Although the roles of these oxidised forms of 5mC (oxi-mCs) in cancer pathogenesis are still largely unknown, there are indications that they may be involved in the mechanisms of malignant transformation. Thus, reduction of 5hmC content represents an epigenetic hallmark of human tumours, and according to our recent report, 5caC is enriched in a proportion of breast cancers and gliomas...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28203307/epigenetic-strategies-to-reverse-drug-resistance-in-heterogeneous-multiple-myeloma
#2
REVIEW
Mark E Issa, Farnaz Sedigheh Takhsha, Chandra Sekhar Chirumamilla, Claudina Perez-Novo, Wim Vanden Berghe, Muriel Cuendet
Multiple myeloma (MM) is a hematological malignancy, which remains incurable because most patients eventually relapse or become refractory to current treatments. Due to heterogeneity within the cancer cell microenvironment, cancer cell populations employ a dynamic survival strategy to chemotherapeutic treatments, which frequently results in a rapid acquisition of therapy resistance. Besides resistance-conferring genetic alterations within a tumor cell population selected during drug treatment, recent findings also reveal non-mutational mechanisms of drug resistance, involving a small population of "cancer stem cells" (CSCs) which are intrinsically more refractory to the effects of a variety of anticancer drugs...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28194238/epigenome-wide-association-study-ewas-on-lipids-the-rotterdam-study
#3
Kim V E Braun, Klodian Dhana, Paul S de Vries, Trudy Voortman, Joyce B J van Meurs, Andre G Uitterlinden, Albert Hofman, Frank B Hu, Oscar H Franco, Abbas Dehghan
BACKGROUND: DNA methylation is a key epigenetic mechanism that is suggested to be associated with blood lipid levels. We aimed to identify CpG sites at which DNA methylation levels are associated with blood levels of triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol in 725 participants of the Rotterdam Study, a population-based cohort study. Subsequently, we sought replication in a non-overlapping set of 760 participants...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28191262/maternal-intake-of-methyl-group-donors-affects-dna-methylation-of-metabolic-genes-in-infants
#4
Sara Pauwels, Manosij Ghosh, Radu Corneliu Duca, Bram Bekaert, Kathleen Freson, Inge Huybrechts, Sabine A S Langie, Gudrun Koppen, Roland Devlieger, Lode Godderis
BACKGROUND: Maternal nutrition during pregnancy and infant nutrition in the early postnatal period (lactation) are critically involved in the development and health of the newborn infant. The Maternal Nutrition and Offspring's Epigenome (MANOE) study was set up to assess the effect of maternal methyl-group donor intake (choline, betaine, folate, methionine) on infant DNA methylation. Maternal intake of dietary methyl-group donors was assessed using a food-frequency questionnaire (FFQ)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28191261/global-dna-methylation-levels-are-altered-by-modifiable-clinical-manipulations-in-assisted-reproductive-technologies
#5
Jayashri Ghosh, Christos Coutifaris, Carmen Sapienza, Monica Mainigi
BACKGROUND: We analyzed placental DNA methylation levels at repeated sequences (LINE1 elements) and all CCGG sites (the LUMA assay) to study the effect of modifiable clinical or laboratory procedures involved in in vitro fertilization. We included four potential modifiable factors: oxygen tension during embryo culture, fresh embryo transfer vs frozen embryo transfer, intracytoplasmic sperm injection (ICSI) vs conventional insemination or day 3 embryo transfer vs day 5 embryo transfer...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28184257/an-empirically-driven-data-reduction-method-on-the-human-450k-methylation-array-to-remove-tissue-specific-non-variable-cpgs
#6
Rachel D Edgar, Meaghan J Jones, Wendy P Robinson, Michael S Kobor
BACKGROUND: Population based epigenetic association studies of disease and exposures are becoming more common with the availability of economical genome-wide technologies for interrogation of the methylome, such as the Illumina 450K Human Methylation Array (450K). Often, the expected small number of differentially methylated cytosine-guanine pairs (CpGs) in studies of the human methylome presents a statistical challenge, as the large number of CpGs measured on the 450K necessitates careful multiple test correction...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28184256/immunomethylomic-approach-to-explore-the-blood-neutrophil-lymphocyte-ratio-nlr-in-glioma-survival
#7
John K Wiencke, Devin C Koestler, Lucas A Salas, Joseph L Wiemels, Ritu P Roy, Helen M Hansen, Terri Rice, Lucie S McCoy, Paige M Bracci, Annette M Molinaro, Karl T Kelsey, Margaret R Wrensch, Brock C Christensen
BACKGROUND: Differentially methylated regions (DMRs) within DNA isolated from whole blood can be used to estimate the proportions of circulating leukocyte subtypes. We use the term "immunomethylomics" to describe the application of these immune lineage DMRs to studying leukocyte profiles. Here, we applied this approach to peripheral blood DNA from 72 glioma patients with molecularly defined brain tumors, representing common patient groups with defined characteristic survival times and risk factors...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28174608/genome-wide-dna-methylation-profile-identified-a-unique-set-of-differentially-methylated-immune-genes-in-oral-squamous-cell-carcinoma-patients-in-india
#8
Baidehi Basu, Joyeeta Chakraborty, Aditi Chandra, Atul Katarkar, Jadav Ritesh Kumar Baldevbhai, Debjit Dhar Chowdhury, Jay Gopal Ray, Keya Chaudhuri, Raghunath Chatterjee
BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the common malignancies in Southeast Asia. Epigenetic changes, mainly the altered DNA methylation, have been implicated in many cancers. Considering the varied environmental and genotoxic exposures among the Indian population, we conducted a genome-wide DNA methylation study on paired tumor and adjacent normal tissues of ten well-differentiated OSCC patients and validated in an additional 53 well-differentiated OSCC and adjacent normal samples...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28174607/pitx3-dna-methylation-is-an-independent-predictor-of-overall-survival-in-patients-with-head-and-neck-squamous-cell-carcinoma
#9
Verena Sailer, Emily Eva Holmes, Heidrun Gevensleben, Diane Goltz, Freya Dröge, Alina Franzen, Jörn Dietrich, Glen Kristiansen, Friedrich Bootz, Andreas Schröck, Dimo Dietrich
BACKGROUND: Molecular biomarkers assisting risk-group assignment and subsequent treatment stratification are urgently needed for patients with squamous cell cancer of the head and neck region (HNSCC). Aberrant methylation is a frequent event in cancer and, therefore, a promising source for potential biomarkers. Here, the methylation status of the paired-like homeodomain transcription factor 3 (PITX3) was evaluated in HNSCC. METHODS: Using a quantitative real-time PCR, PITX3 methylation was assessed in a cohort of 326 HNSCC patients treated for localized or locally advanced disease (training cohort)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28168006/individual-cpg-sites-that-are-associated-with-age-and-life-expectancy-become-hypomethylated-upon-aging
#10
Yan Zhang, Jan Hapala, Hermann Brenner, Wolfgang Wagner
BACKGROUND: There is a growing interest in simple molecular biomarkers for biological aging. Age-associated DNA methylation (DNAm) changes at specific CG dinucleotides can be combined into epigenetic age predictors to estimate chronological age-and the deviation of chronological and predicted age (∆age) seems to be associated with all-cause mortality. In this study, we have further validated this association and analyzed whether or not individual age-associated CG-dinucleotides (CpGs) are related to life expectancy...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28163793/uromark-a-urinary-biomarker-assay-for-the-detection-of-bladder-cancer
#11
Andrew Feber, Pawan Dhami, Liqin Dong, Patricia de Winter, Wei Shen Tan, Mónica Martínez-Fernández, Dirk S Paul, Antony Hynes-Allen, Sheida Rezaee, Pratik Gurung, Simon Rodney, Ahmed Mehmood, Felipe Villacampa, Federico de la Rosa, Charles Jameson, Kar Keung Cheng, Maurice P Zeegers, Richard T Bryan, Nicholas D James, Jesus M Paramio, Alex Freeman, Stephan Beck, John D Kelly
BACKGROUND: Bladder cancer (BC) is one of the most common cancers in the western world and ranks as the most expensive to manage, due to the need for cystoscopic examination. BC shows frequent changes in DNA methylation, and several studies have shown the potential utility of urinary biomarkers by detecting epigenetic alterations in voided urine. The aim of this study is to develop a targeted bisulfite next-generation sequencing assay to diagnose BC from urine with high sensitivity and specificity...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28149335/cdh22-hypermethylation-is-an-independent-prognostic-biomarker-in-breast-cancer
#12
Esperanza Martín-Sánchez, Saioa Mendaza, Ane Ulazia-Garmendia, Iñaki Monreal-Santesteban, Alicia Córdoba, Francisco Vicente-García, Idoia Blanco-Luquin, Susana De La Cruz, Ana Aramendia, David Guerrero-Setas
BACKGROUND: Cadherin-like protein 22 (CDH22) is a transmembrane glycoprotein involved in cell-cell adhesion and metastasis. Its role in cancer is controversial because it has been described as being upregulated in colorectal cancer, whereas it is downregulated in metastatic melanoma. However, its status in breast cancer (BC) is unknown. The purpose of our study was to determine the molecular status and clinical value of CDH22 in BC. RESULTS: We observed by immunohistochemistry that the level of CDH22 expression was lower in BC tissues than in their matched adjacent-to-tumour and non-neoplastic tissues from reduction mammoplasties...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28149334/epigenome-wide-association-study-of-dna-methylation-in-panic-disorder
#13
Mihoko Shimada-Sugimoto, Takeshi Otowa, Taku Miyagawa, Tadashi Umekage, Yoshiya Kawamura, Miki Bundo, Kazuya Iwamoto, Mamoru Tochigi, Kiyoto Kasai, Hisanobu Kaiya, Hisashi Tanii, Yuji Okazaki, Katsushi Tokunaga, Tsukasa Sasaki
BACKGROUND: Panic disorder (PD) is considered to be a multifactorial disorder emerging from interactions among multiple genetic and environmental factors. To date, although genetic studies reported several susceptibility genes with PD, few of them were replicated and the pathogenesis of PD remains to be clarified. Epigenetics is considered to play an important role in etiology of complex traits and diseases, and DNA methylation is one of the major forms of epigenetic modifications. In this study, we performed an epigenome-wide association study of PD using DNA methylation arrays so as to investigate the possibility that different levels of DNA methylation might be associated with PD...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28149333/the-epigenomic-basis-of-common-diseases
#14
Euan J Rodger, Aniruddha Chatterjee
A report of the 6(th) Epigenomics of Common Diseases Conference held at the Wellcome Genome Campus in Hinxton, Cambridge, UK, on 1-4 November 2016.
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28149332/the-immunomodulatory-anticancer-agent-rrx-001-induces-an-interferon-response-through-epigenetic-induction-of-viral-mimicry
#15
Hongjuan Zhao, Shoucheng Ning, Rosalie Nolley, Jan Scicinski, Bryan Oronsky, Susan J Knox, Donna M Peehl
BACKGROUND: RRx-001, a dinitroazetidine derivative, is a novel anticancer agent currently in phase II clinical trials. It mediates immunomodulatory effects either directly through polarization of tumor associated macrophages or indirectly through vascular normalization and increased T-lymphocyte infiltration. With multiple additional mechanisms of action including upregulation of oxidative stress, depletion of GSH and NADPH, anti-angiogenesis and epigenetic modulation, RRx-001 is being studied as a radio- and chemo-sensitizer to resensitize tumors to prior therapy and to prime tumors to respond to radiation, chemotherapy and immunotherapy in combination therapy studies...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28149331/combining-omics-data-to-identify-genes-associated-with-allergic-rhinitis
#16
Andréanne Morin, Michel Laviolette, Tomi Pastinen, Louis-Philippe Boulet, Catherine Laprise
Allergic rhinitis is a common chronic disorder characterized by immunoglobulin E-mediated inflammation. To identify new genes associated with this trait, we performed genome- and epigenome-wide association studies and linked marginally significant CpGs located in genes or its promoter and SNPs located 1 Mb from the CpGs, by identifying cis methylation quantitative trait loci (mQTL). This approach relies on functional cellular aspects rather than stringent statistical correction. We were able to identify one gene with significant cis-mQTL for allergic rhinitis, caudal-type homeobox 1 (CDX1)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28149330/what-s-in-a-name-context-dependent-significance-of-global-methylation-measures-in-human-health-and-disease
#17
Regan Vryer, Richard Saffery
The study of DNA methylation in development and disease has 'exploded' as a field in recent years, with three major classes of measurement now routine. These encompass (i) locus-specific, (ii) genome-scale/wide and (iii) 'global' methylation approaches. Measures of global methylation refer to the level of 5-methylcytosine (5mC) content in a sample relative to total cytosine. Despite this, several other measures are often referred to as 'global', with the underlying assumption that they accurately reflect 5mC content...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28149329/improved-results-of-line-1-methylation-analysis-in-formalin-fixed-paraffin-embedded-tissues-with-the-application-of-a-heating-step-during-the-dna-extraction-process
#18
Xianyu Wen, Seorin Jeong, Younghoon Kim, Jeong Mo Bae, Nam Yun Cho, Jung Ho Kim, Gyeong Hoon Kang
BACKGROUND: Formalin-fixed, paraffin-embedded (FFPE) tissues are important resources for profiling DNA methylation changes and for studying a variety of diseases. However, formalin fixation introduces inter-strand crosslinking, which might cause incomplete bisulfite conversion of unmethylated cytosines, which might lead to falsely elevated measurements of methylation levels in pyrosequencing assays. Long interspersed nucleotide element-1 (LINE-1) is a major constituent of repetitive transposable DNA elements, and its methylation is referred to correlates with global DNA methylation...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/27999621/promoter-hypermethylation-of-shox2-and-sept9-is-a-potential-biomarker-for-minimally-invasive-diagnosis-in-adenocarcinomas-of-the-biliary-tract
#19
V Branchi, P Schaefer, A Semaan, A Kania, P Lingohr, J C Kalff, N Schäfer, G Kristiansen, D Dietrich, H Matthaei
BACKGROUND: Biliary tract carcinoma (BTC) is a fatal malignancy which aggressiveness contrasts sharply with its relatively mild and late clinical presentation. Novel molecular markers for early diagnosis and precise treatment are urgently needed. The purpose of this study was to evaluate the diagnostic and prognostic value of promoter hypermethylation of the SHOX2 and SEPT9 gene loci in BTC. METHODS: Relative DNA methylation of SHOX2 and SEPT9 was quantified in tumor specimens and matched normal adjacent tissue (NAT) from 71 BTC patients, as well as in plasma samples from an independent prospective cohort of 20 cholangiocarcinoma patients and 100 control patients...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27980696/characterization-of-tet-and-idh-gene-expression-in-chronic-lymphocytic-leukemia-comparison-with-normal-b-cells-and-prognostic-significance
#20
Michaël Van Damme, Emerence Crompot, Nathalie Meuleman, Marie Maerevoet, Philippe Mineur, Dominique Bron, Laurence Lagneaux, Basile Stamatopoulos
BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common hematological malignancy in western countries, characterized by a heterogeneous clinical course. Although genetic studies have identified chromosomal aberrations or specific mutations, epigenetic changes have been poorly characterized in CLL. METHODS: We assessed ten-eleven translocations (TET) 1, 2, and 3, isocitrate dehydrogenase (IDH) 1, and 2 messenger RNA (mRNA) expression using real-time PCR on purified leukemic B cells from 214 CLL patients (median follow-up = 75 months, range 1-380), normal peripheral blood B cells (n = 20), and umbilical cord blood B cells (n = 21)...
2016: Clinical Epigenetics
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