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Clinical Epigenetics

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https://www.readbyqxmd.com/read/30005706/loss-of-maternal-eed-results-in-postnatal-overgrowth
#1
Lexie Prokopuk, Jessica M Stringer, Craig R White, Rolf H A M Vossen, Stefan J White, Ana S A Cohen, William T Gibson, Patrick S Western
BACKGROUND: Investigating how epigenetic information is transmitted through the mammalian germline is the key to understanding how this information impacts on health and disease susceptibility in offspring. EED is essential for regulating the repressive histone modification, histone 3 lysine 27 tri-methylation (H3K27me3) at many developmental genes. RESULTS: In this study, we used oocyte-specific Zp3-Cre recombinase (Zp3Cre) to delete Eed specifically in mouse growing oocytes, permitting the study of EED function in oocytes and the impact of depleting EED in oocytes on outcomes in offspring...
July 13, 2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/30005700/differentially-methylated-loci-in-nafld-cirrhosis-are-associated-with-key-signaling-pathways
#2
Glenn S Gerhard, Ivana Malenica, Lorida Llaci, Xin Chu, Anthony T Petrick, Christopher D Still, Johanna K DiStefano
Altered DNA methylation events contribute to the pathogenesis and progression of metabolic disorders, including nonalcoholic fatty liver disease (NAFLD). Investigations of global DNA methylation patterns in liver biopsies representing severe NAFLD fibrosis have been limited. We used the HumanMethylation 450K BeadChip to analyze genome-wide methylation in patients with biopsy-proven grade 3/4 NAFLD fibrosis/cirrhosis (N = 14) and age- and sex-matched controls with normal histology (N = 15). We identified 208 CpG islands (CGIs), including 99 hypomethylated and 109 hypermethylated CGIs, showing statistically significant evidence (adjusted P value < 0...
July 13, 2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/30005692/vitamin-c-increases-5-hydroxymethylcytosine-level-and-inhibits-the-growth-of-bladder-cancer
#3
Ding Peng, Guangzhe Ge, Yanqing Gong, Yonghao Zhan, Shiming He, Bao Guan, Yifan Li, Ziying Xu, Han Hao, Zhisong He, Gengyan Xiong, Cuijian Zhang, Yue Shi, Yuanyuan Zhou, Weimin Ci, Xuesong Li, Liqun Zhou
BACKGROUND: 5-Hydroxymethylcytosine (5hmC) is converted from 5-methylcytosine (5mC) by a group of enzymes termed ten-eleven translocation (TET) family dioxygenases. The loss of 5hmC has been identified as a hallmark of most types of cancer and is related to tumorigenesis and progression. However, the role of 5hmC in bladder cancer is seldom investigated. Vitamin C was recently reported to induce the generation of 5hmC by acting as a cofactor for TET dioxygenases. In this study, we explored the role of 5hmC in bladder cancer and the therapeutic efficacy of vitamin C in increasing the 5hmC pattern...
July 13, 2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/30002740/identification-and-validation-of-sry-box-containing-gene-family-member-sox30-methylation-as-a-prognostic-and-predictive-biomarker-in-myeloid-malignancies
#4
Jing-Dong Zhou, Yu-Xin Wang, Ting-Juan Zhang, Xi-Xi Li, Yu Gu, Wei Zhang, Ji-Chun Ma, Jiang Lin, Jun Qian
Background: Methylation-associated SOX family genes have been proved to be involved in multiple essential processes during carcinogenesis and act as potential biomarkers for cancer diagnosis, staging, prediction of prognosis, and monitoring of response to therapy. Herein, we revealed SOX30 methylation and its clinical implication in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Results: In the discovery stage, we identified that SOX30 methylation, a frequent event in AML, was negatively associated with SOX30 expression and correlated with overall survival (OS) and leukemia-free survival (LFS) in cytogenetically normal AML among SOX family members from The Cancer Genome Atlas (TCGA) datasets...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29991969/promoter-methylation-of-the-mgat3-and-bach2-genes-correlates-with-the-composition-of-the-immunoglobulin-g-glycome-in-inflammatory-bowel-disease
#5
Marija Klasić, Dora Markulin, Aleksandar Vojta, Ivana Samaržija, Ivan Biruš, Paula Dobrinić, Nicholas T Ventham, Irena Trbojević-Akmačić, Mirna Šimurina, Jerko Štambuk, Genadij Razdorov, Nicholas A Kennedy, Jack Satsangi, Ana M Dias, Salome Pinho, Vito Annese, Anna Latiano, Renata D'Inca, Gordan Lauc, Vlatka Zoldoš
Background: Many genome- and epigenome-wide association studies (GWAS and EWAS) and studies of promoter methylation of candidate genes for inflammatory bowel disease (IBD) have demonstrated significant associations between genetic and epigenetic changes and IBD. Independent GWA studies have identified genetic variants in the BACH2 , IL6ST , LAMB1 , IKZF1 , and MGAT3 loci to be associated with both IBD and immunoglobulin G (IgG) glycosylation. Methods: Using bisulfite pyrosequencing, we analyzed CpG methylation in promoter regions of these five genes from peripheral blood of several hundred IBD patients and healthy controls (HCs) from two independent cohorts, respectively...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29991968/correction-to-fetal-growth-is-associated-with-cpg-methylation-in-the-p2-promoter-of-the-igf1-gene
#6
Catherine Le Stunff, Anne-Laure Castell, Nicolas Todd, Clémence Mille, Marie-Pierre Belot, Nathalie Frament, Sylvie Brailly-Tabard, Alexandra Benachi, Delphine Fradin, Pierre Bougnères
[This corrects the article DOI: 10.1186/s13148-018-0489-9.].
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29988684/a-panel-of-dna-methylation-markers-for-the-detection-of-prostate-cancer-from-fv-and-dre-urine-dna
#7
Igor Brikun, Deborah Nusskern, Andrew Decatus, Eric Harvey, Lin Li, Diha Freije
Background: Early screening for prostate cancer (PCA) remains controversial because of overdiagnosis and overtreatment of clinically insignificant cancers. Even though a number of diagnostic tests have been developed to improve on PSA testing, there remains a need for a more informative non-invasive test for PCA. The objective of this study is to identify a panel of DNA methylation markers suitable for a non-invasive diagnostic test from urine DNA collected following a digital rectal exam (DRE) and/or from first morning void (FV)...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29988473/dna-methylation-of-imprinted-genes-at-birth-is-associated-with-child-weight-status-at-birth-1-year-and-3-years
#8
Sarah Gonzalez-Nahm, Michelle A Mendez, Sara E Benjamin-Neelon, Susan K Murphy, Vijaya K Hogan, Diane L Rowley, Cathrine Hoyo
Background: This study assessed the associations between nine differentially methylated regions (DMRs) of imprinted genes in DNA derived from umbilical cord blood leukocytes in males and females and (1) birth weight for gestational age z score, (2) weight-for-length (WFL) z score at 1 year, and (3) body mass index (BMI) z score at 3 years. Methods: We conducted multiple linear regression in n  = 567 infants at birth, n  = 288 children at 1 year, and n  = 294 children at 3 years from the Newborn Epigenetics Study (NEST)...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29988283/paternal-sepsis-induces-alterations-of-the-sperm-methylome-and-dampens-offspring-immune-responses-an-animal-study
#9
Katharina Bomans, Judith Schenz, Sandra Tamulyte, Dominik Schaack, Markus Alexander Weigand, Florian Uhle
Background: Sepsis represents the utmost severe consequence of infection, involving a dysregulated and self-damaging immune response of the host. While different environmental exposures like chronic stress or malnutrition have been well described to reprogram the germline and subsequently offspring attributes, the intergenerational impact of sepsis as a tremendous immunological stressor has not been examined yet. Methods: Polymicrobial sepsis in 12-week-old male C57BL/6 mice was induced by cecal ligation and puncture (CLP), followed by a mating of the male survivors (or appropriate sham control animals) 6 weeks later with healthy females...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29983835/long-non-coding-rnas-implications-in-targeted-diagnoses-prognosis-and-improved-therapeutic-strategies-in-human-non-and-triple-negative-breast-cancer
#10
REVIEW
Rubén Rodríguez Bautista, Alette Ortega Gómez, Alfredo Hidalgo Miranda, Alejandro Zentella Dehesa, Cynthia Villarreal-Garza, Federico Ávila-Moreno, Oscar Arrieta
Triple-negative breast cancer (TNBC) has been clinically difficult to manage because of tumor aggressiveness, cellular and histological heterogeneity, and molecular mechanisms' complexity. All this in turn leads us to evaluate that tumor biological behavior is not yet fully understood. Additionally, the heterogeneity of tumor cells represents a great biomedicine challenge in terms of the complex molecular-genetical-transcriptional and epigenetical-mechanisms, which have not been fully elucidated on human solid tumors...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29983834/epigenetic-signature-of-preterm-birth-in-adult-twins
#11
Qihua Tan, Shuxia Li, Morten Frost, Marianne Nygaard, Mette Soerensen, Martin Larsen, Kaare Christensen, Lene Christiansen
Background: Preterm birth is a leading cause of perinatal mortality and long-term health consequences. Epigenetic mechanisms may have been at play in preterm birth survivors, and these could be persistent and detrimental to health later in life. Methods: We performed a genome-wide DNA methylation profiling in adult twins of premature birth to identify genomic regions under differential epigenetic regulation in 144 twins with a median age of 33 years (age range 30-36)...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29983833/epigenetic-gestational-age-acceleration-a-prospective-cohort-study-investigating-associations-with-familial-sociodemographic-and-birth-characteristics
#12
Jasmine N Khouja, Andrew J Simpkin, Linda M O'Keeffe, Kaitlin H Wade, Lotte C Houtepen, Caroline L Relton, Matthew Suderman, Laura D Howe
Background: Gestational age at delivery is associated with health and social outcomes. Recently, cord blood DNA methylation data has been used to predict gestational age. The discrepancy between gestational age predicted from DNA methylation and determined by ultrasound or last menstrual period is known as gestational age acceleration. This study investigated associations of sex, socioeconomic status, parental behaviours and characteristics and birth outcomes with gestational age acceleration...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29983832/h3k27-acetylation-and-gene-expression-analysis-reveals-differences-in-placental-chromatin-activity-in-fetal-growth-restriction
#13
N D Paauw, A T Lely, J A Joles, A Franx, P G Nikkels, M Mokry, B B van Rijn
Background: Posttranslational modification of histone tails such as histone 3 lysine 27 acetylation (H3K27ac) is tightly coupled to epigenetic regulation of gene expression. To explore whether this is involved in placenta pathology, we probed genome-wide H3K27ac occupancy by chromatin immunoprecipitation sequencing (ChIP-seq) in healthy placentas and placentas from pathological pregnancies with fetal growth restriction (FGR). Furthermore, we related specific acetylation profiles of FGR placentas to gene expression changes...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29983831/dna-methylation-and-repressive-h3k9-and-h3k27-trimethylation-in-the-promoter-regions-of-pd-1-ctla-4-tim-3-lag-3-tigit-and-pd-l1-genes-in-human-primary-breast-cancer
#14
Varun Sasidharan Nair, Haytham El Salhat, Rowaida Z Taha, Anne John, Bassam R Ali, Eyad Elkord
Background: High expression of immune checkpoints in tumor microenvironment plays significant roles in inhibiting anti-tumor immunity, which is associated with poor prognosis and cancer progression. Major epigenetic modifications in both DNA and histone could be involved in upregulation of immune checkpoints in cancer. Methods: Expressions of different immune checkpoint genes and PD-L1 were assessed using qRT-PCR, and the underlying epigenetic modifications including CpG methylation and repressive histone abundance were determined using bisulfite sequencing, and histone 3 lysine 9 trimethylation (H3K9me3) and histone 3 lysine 27 trimethylation (H3K27me3) chromatin immunoprecipitation assays (ChIP), respectively...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29977410/vitamin-d-status-and-epigenetic-based-mortality-risk-score-strong-independent-and-joint-prediction-of-all-cause-mortality-in-a-population-based-cohort-study
#15
Xu Gao, Yan Zhang, Ben Schöttker, Hermann Brenner
Background: Vitamin D deficiency and insufficiency have been established to be strongly associated with increased overall mortality and deaths from specific aging-related diseases. Recently, an epigenetic "mortality risk score" (MS) based on whole blood DNA methylation at the 10 most prominent mortality-related cytosine-phosphate-guanine (CpG) sites has also been found to be highly related to all-cause mortality. This study aimed to explore whether vitamin D status, defined by serum 25-hydroxyvitamin D [25(OH)D] concentrations, is associated with the MS and to what extent both indicators are individually and jointly capable of predicting all-cause mortality in a general population sample of older adults...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29951132/acute-leukemia-cells-resistant-to-pi3k-mtor-inhibition-display-upregulation-of-p2ry14-expression
#16
Kinjal Shah, Sausan A Moharram, Julhash U Kazi
The PI3K/mTOR pathway is the second most frequently deregulated pathway in a majority of cancers such as breast cancer, lung cancer, and melanomas as well as leukemia. Mutations in the genes coding for receptor tyrosine kinases (RTKs) and G-protein-coupled receptors (GPCRs) are quite common in all forms of acute leukemia. This can be a major cause of deregulation of the PI3K-mTOR pathway. To understand how cells display resistance to the dual PI3K/mTOR inhibitor, we used a panel of 25 acute leukemia cell lines...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29951131/type-2-diabetes-and-cardiometabolic-risk-may-be-associated-with-increase-in-dna-methylation-of-fkbp5
#17
Robin Ortiz, Joshua J Joseph, Richard Lee, Gary S Wand, Sherita Hill Golden
Background: Subclinical hypercortisolism and hypothalamic-pituitary-adrenal (HPA) axis dysfunction are associated with type 2 diabetes (T2DM), cardiovascular disease, and metabolic dysfunction. Intronic methylation of FKBP5 has been implicated as a potential indicator of chronic cortisol exposure. Our overall objective in this study was to determine the association of chronic cortisol exposure, measured via percent methylation of FKBP5 at intron 2, with percent glycosylated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-cholesterol), waist circumference (WC), and body mass index (BMI), in a clinic-based sample of 43 individuals with T2DM...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29946375/differentially-methylated-regions-in-t-cells-identify-kidney-transplant-patients-at-risk-for-de-novo-skin-cancer
#18
Fleur S Peters, Annemiek M A Peeters, Pooja R Mandaviya, Joyce B J van Meurs, Leo J Hofland, Jacqueline van de Wetering, Michiel G H Betjes, Carla C Baan, Karin Boer
Background: Cutaneous squamous cell carcinoma (cSCC) occurs 65-200 times more in immunosuppressed organ transplant patients than in the general population. T cells, which are targeted by the given immunosuppressive drugs, are involved in anti-tumor immune surveillance and are functionally regulated by DNA methylation. Prior to kidney transplantation, we aim to discover differentially methylated regions (DMRs) in T cells involved in de novo post-transplant cSCC development. Methods: We matched 27 kidney transplant patients with a future de novo cSCC after transplantation to 27 kidney transplant patients without cSCC and studied genome-wide DNA methylation of T cells prior to transplantation...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29946374/rs10732516-polymorphism-at-the-igf2-h19-locus-associates-with-genotype-specific-effects-on-placental-dna-methylation-and-birth-weight-of-newborns-conceived-by-assisted-reproductive-technology
#19
Heidi Marjonen, Pauliina Auvinen, Hanna Kahila, Olga Tšuiko, Sulev Kõks, Airi Tiirats, Triin Viltrop, Timo Tuuri, Viveca Söderström-Anttila, Anne-Maria Suikkari, Andres Salumets, Aila Tiitinen, Nina Kaminen-Ahola
Background: Assisted reproductive technology (ART) has been associated with low birth weight of fresh embryo transfer (FRESH) derived and increased birth weight of frozen embryo transfer (FET)-derived newborns. Owing to that, we focused on imprinted insulin-like growth factor 2 ( IGF2 )/ H19 locus known to be important for normal growth. This locus is regulated by H19 imprinting control region (ICR) with seven binding sites for the methylation-sensitive zinc finger regulatory protein (CTCF)...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29946373/assessment-of-new-hdac-inhibitors-for-immunotherapy-of-malignant-pleural-mesothelioma
#20
Douae Bensaid, Thibaut Blondy, Sophie Deshayes, Virginie Dehame, Philippe Bertrand, Marc Grégoire, Mohammed Errami, Christophe Blanquart
Background: Malignant pleural mesothelioma (MPM) is a very rare and highly aggressive cancer of the pleura associated in most cases with asbestos exposure. To date, no really efficient treatments are available for this pathology. Recently, it has been shown that epigenetic drugs, particularly DNA methylation or histone acetylation modulating agents, could be very efficient in terms of cytotoxicity for several types of cancer cells. We previously showed that a hypomethylating agent (decitabine) and a histone deacetylase inhibitor (HDACi) (valproic acid (VPA)) combination was immunogenic and led to the induction of an anti-tumor immune response in a mice model of mesothelioma...
2018: Clinical Epigenetics
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