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https://www.readbyqxmd.com/read/28444195/dna-methylome-analysis-reveals-distinct-epigenetic-patterns-of-ascending-aortic-dissection-and-bicuspid-aortic-valve
#1
Sun Pan, Hao Lai, Yiru Shen, Charles Breeze, Stephan Beck, Tao Hong, Chunsheng Wang, Andrew E Teschendorff
Epigenetics may mediate the effects of environmental risk factors on disease, including heart disease. Thus, measuring the DNA methylome offers the opportunity to identify novel disease biomarkers and novel insights into disease mechanisms. The DNA methylation landscape of ascending aortic dissection (AD) and bicuspid aortic valve (BAV) with aortic aneurysmal dilatation remain uncharacterized. The present study aimed to explore the genome-wide DNA methylation landscape underpinning these two diseases. Methods and results: We used Illumina 450k DNA methylation beadarrays to analyze 21 ascending aorta samples, including 10 cases with AD, 5 with BAV and 6 healthy controls...
April 19, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28442560/obesity-and-menopause-modify-the-epigenomic-profile-of-breast-cancer
#2
Ana B Crujeiras, Angel Díaz-Lagares, Olafur A Stefansson, Manuel Macias, Juan Sandoval, Juan Cueva, Rafael López-López, Sebastian Moran, Jon G Jonasson, Laufey Tryggvadottir, Elinborg Olafsdottir, Francisco J Tinahones, Marcos C Carreira, Felipe F Casanueva, Manel Esteller
Obesity is a high risk factor for breast cancer. This relationship could be marked by a specific methylome. The current work was aimed to explore the impact of obesity and menopausal status on variation in breast cancer methylomes. Data from Infinium 450K array-based methylomes of 64 breast tumor were coupled with information on BMI and menopausal status. Additionally, DNA methylation results were validated in 18 non-tumor and 81 tumor breast samples. Breast tumors arising in either pre- or postmenopausal women stratified by BMI or menopausal status alone were not associated with a specific DNA methylation pattern...
April 25, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28439722/dna-methylation-age-acceleration-is-associated-with-disease-duration-and-age-at-onset-in-c9orf72-patients
#3
Ming Zhang, Maria Carmela Tartaglia, Danielle Moreno, Christine Sato, Paul McKeever, Anna Weichert, Julia Keith, Janice Robertson, Lorne Zinman, Ekaterina Rogaeva
The repeat expansion in C9orf72 is the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia. C9orf72 patients present with a wide range in disease duration and age of onset. The strongest risk factor for both syndromes is aging, which was linked to DNA methylation (DNAm) age based on the cumulative assessment of the methylation levels of 353 CpGs included on the genome-wide 450k BeadChip. DNAm age may reflect biological age better than chronological age. We conducted a genome-wide blood DNA methylation study of 46 unrelated C9orf72 patients...
April 24, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28428831/cord-blood-hematopoietic-cells-from-preterm-infants-display-altered-dna-methylation-patterns
#4
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/28427179/comprehensive-mapping-of-the-effects-of-azacitidine-on-dna-methylation-repressive-permissive-histone-marks-and-gene-expression-in-primary-cells-from-patients-with-mds-and-mds-related-disease
#5
Magnus Tobiasson, Hani Abdulkadir, Andreas Lennartsson, Shintaro Katayama, Francesco Marabita, Ayla De Paepe, Mohsen Karimi, Kaarel Krjutskov, Elisabet Einarsdottir, Michael Grövdal, Monika Jansson, Asmaa Ben Azenkoud, Lina Corddedu, Sören Lehmann, Karl Ekwall, Juha Kere, Eva Hellström-Lindberg, Johanna Ungerstedt
Azacitidine (Aza) is first-line treatment for patients with high-risk myelodysplastic syndromes (MDS), although its precise mechanism of action is unknown. We performed the first study to globally evaluate the epigenetic effects of Aza on MDS bone marrow progenitor cells assessing gene expression (RNA seq), DNA methylation (Illumina 450k) and the histone modifications H3K18ac and H3K9me3 (ChIP seq). Aza induced a general increase in gene expression with 924 significantly upregulated genes but this increase showed no correlation with changes in DNA methylation or H3K18ac, and only a weak association with changes in H3K9me3...
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423542/dna-methylation-intratumor-heterogeneity-in-localized-lung-adenocarcinomas
#6
Kelly Quek, Jun Li, Marcos Estecio, Jiexin Zhang, Junya Fujimoto, Emily Roarty, Latasha Little, Chi-Wan Chow, Xingzhi Song, Carmen Behrens, Taiping Chen, William N William, Stephen Swisher, John Heymach, Ignacio Wistuba, Jianhua Zhang, Andrew Futreal, Jianjun Zhang
Cancers are composed of cells with distinct molecular and phenotypic features within a given tumor, a phenomenon termed intratumor heterogeneity (ITH). Previously, we have demonstrated genomic ITH in localized lung adenocarcinomas; however, the nature of methylation ITH in lung cancers has not been well investigated. In this study, we generated methylation profiles of 48 spatially separated tumor regions from 11 localized lung adenocarcinomas and their matched normal lung tissues using Illumina Infinium Human Methylation 450K BeadChip array...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421459/rapid-progression-to-glioblastoma-in-a-subset-of-idh-mutated-astrocytomas-a-genome-wide-analysis
#7
Timothy E Richardson, Matija Snuderl, Jonathan Serrano, Matthias A Karajannis, Adriana Heguy, Dwight Oliver, Jack M Raisanen, Elizabeth A Maher, Edward Pan, Samuel Barnett, Chunyu Cai, Amyn A Habib, Robert M Bachoo, Kimmo J Hatanpaa
According to the recently updated World Health Organization (WHO) classification (2016), grade II-III astrocytomas are divided into IDH-wildtype and IDH-mutant groups, the latter being significantly less aggressive in terms of both progression-free and total survival. We identified a small cohort of WHO grade II-III astrocytomas that harbored the IDH1 R132H mutation, as confirmed by both immunohistochemistry and molecular sequence analysis, which nonetheless had unexpectedly rapid recurrence and subsequent progression to glioblastoma...
April 18, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28415743/survival-differences-of-cimp-subtypes-integrated-with-cna-information-in-human-breast-cancer
#8
Huihan Wang, Weili Yan, Shumei Zhang, Yue Gu, Yihan Wang, Yanjun Wei, Hongbo Liu, Fang Wang, Qiong Wu, Yan Zhang
CpG island methylator phenotype of breast cancer is associated with widespread aberrant methylation at specified CpG islands and distinct patient outcomes. However, the influence of copy number contributing to the prognosis of tumors with different CpG island methylator phenotypes is still unclear. We analyzed both genetic (copy number) and epigenetic alterations in 765 breast cancers from The Cancer Genome Atlas data portal and got a panel of 15 biomarkers for copy number and methylation status evaluation...
March 14, 2017: Oncotarget
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/28387568/non-linear-patterns-in-age-related-dna-methylation-may-reflect-cd4-t-cell-differentiation
#10
Nicholas D Johnson, Howard W Wiener, Alicia K Smith, Shota Nishitani, Devin M Absher, Donna K Arnett, Stella Aslibekyan, Karen N Conneely
DNA methylation (DNAm) is an important epigenetic process involved in the regulation of gene expression. While many studies have identified thousands of loci associated with age, few have differentiated between linear and non-linear DNAm trends with age. Non-linear trends could indicate early- or late-life gene regulatory processes. Using data from the Illumina 450K array on 336 human peripheral blood samples, we identified 21 CpG sites that associated with age (P<1.03E-7) and exhibited changing rates of DNAm change with age (P<1...
April 7, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28379302/cnanalysis450k-an-r-package-for-comparative-analysis-of-450k-epic-illumina-methylation-array-derived-copy-number-data
#11
Maximilian Knoll, Jürgen Debus, Amir Abdollahi
Motivation: Detailed copy number (CN) variation data can be obtained from 450k or EPIC Illumina methylation assays. However, the effects of different preprocessing strategies (normalization, transformation and selection of gain/loss cutoff values) on variant calling have not been evaluated systematically. Results: We provide an R package which allows to directly compare any preprocessed CN data. It provides its own CN alteration detection methodology: segments are identified through detection of changes in variance of CN data and are subsequently filtered for significance...
March 30, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28364215/dna-methylation-age-is-elevated-in-breast-tissue-of-healthy-women
#12
Mary E Sehl, Jill E Henry, Anna Maria Storniolo, Patricia A Ganz, Steve Horvath
BACKGROUND: Limited evidence suggests that female breast tissue ages faster than other parts of the body according to an epigenetic biomarker of aging known as the "epigenetic clock." However, it is unknown whether breast tissue samples from healthy women show a similar accelerated aging effect relative to other tissues, and what could drive this acceleration. The goal of this study is to validate our initial finding of advanced DNA methylation (DNAm) age in breast tissue, by directly comparing it to that of peripheral blood tissue from the same individuals, and to do a preliminary assessment of hormonal factors that could explain the difference...
March 31, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28360945/epigenetic-signatures-of-gestational-diabetes-mellitus-on-cord-blood-methylation
#13
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/28344890/suppression-of-indoleamine-2-3-dioxygenase-1-expression-by-promoter-hypermethylation-in-er-positive-breast-cancer
#14
Dyah L Dewi, Soumya R Mohapatra, Saioa Blanco Cabañes, Isabell Adam, Luis F Somarribas Patterson, Bianca Berdel, Masroor Kahloon, Loreen Thürmann, Stefanie Loth, Katharina Heilmann, Dieter Weichenhan, Oliver Mücke, Ines Heiland, Pauline Wimberger, Jan Dominik Kuhlmann, Karl-Heinz Kellner, Sarah Schott, Christoph Plass, Michael Platten, Clarissa Gerhäuser, Saskia Trump, Christiane A Opitz
Kynurenine formation by tryptophan-catabolic indoleamine-2,3-dioxygenase 1 (IDO1) plays a key role in tumor immune evasion and inhibition of IDO1 is efficacious in preclinical models of breast cancer. As the response of breast cancer to immune checkpoint inhibitors may be limited, a better understanding of the expression of additional targetable immunomodulatory pathways is of importance. We therefore investigated the regulation of IDO1 expression in different breast cancer subtypes. We identified estrogen receptor α (ER) as a negative regulator of IDO1 expression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28330812/molecular-evidence-for-differential-long-term-outcomes-of-early-life-severe-acute-malnutrition
#15
Allan Sheppard, Sherry Ngo, Xiaoling Li, Michael Boyne, Debbie Thompson, Anthony Pleasants, Peter Gluckman, Terrence Forrester
BACKGROUND: Severe acute malnutrition (SAM) in infants may present as one of two distinct syndromic forms: non-edematous (marasmus), with severe wasting and no nutritional edema; or edematous (kwashiorkor) with moderately severe wasting. These differences may be related to developmental changes prior to the exposure to SAM and phenotypic changes appear to persist into adulthood with differences between the two groups. We examined whether the different response to SAM and subsequent trajectories may be explained by developmentally-induced epigenetic differences...
March 8, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28298607/human-herpesvirus-6b-induces-hypomethylation-on-chromosome-17p13-3-correlating-with-increased-gene-expression-and-virus-integration
#16
Elin Engdahl, Nicky Dunn, Pitt Niehusmann, Sarah Wideman, Peter Wipfler, Albert J Becker, Tomas J Ekström, Malin Almgren, Anna Fogdell-Hahn
Human herpesvirus 6B (HHV-6B) is a neurotropic beta-herpesvirus that achieves latency by integrating its genome into host cell chromosomes. Several viruses can induce epigenetic modifications in their host cells, but no study has investigated the epigenetic modifications induced by HHV-6B. This study analyzed methylation with Illumina 450K array comparing HHV-6B infected and uninfected Molt-3 T cells three days post infection. Bisulfite pyrosequencing was used to validate Illumina results and investigate methylation over time in vitro Expression of genes was investigated using qPCR, and virus integration was investigated with PCR...
March 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28284085/detection-of-turner-syndrome-using-x-chromosome-inactivation-specific-differentially-methylated-cpg-sites-a-pilot-study
#17
Qiang Zhang, Xiaohong Guo, Tian Tian, Teng Wang, Qiaoli Li, Lei Wang, Yun Liu, Qinghe Xing, Lin He, Xinzhi Zhao
BACKGROUND: Early diagnosis of Turner syndrome (TS) may improve preventive measures and treatment. X-chromosome inactivation specific differentially methylated CpG sites (XIDMSs) that are high methylated in inactive X chromosomes (Xi) and unmethylated in active X chromosomes (Xa) may be potential makers for TS detection. METHODS: The candidate XIDMSs were screened from 9 male and 12 female DNA samples with normal karyotypes using the Illumina 450k array and validated by bisulfite sequencing PCR and pyrosequencing assay...
March 8, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28271161/dna-methylation-profiling-reveals-the-presence-of-population-specific-signatures-correlating-with-phenotypic-characteristics
#18
Anil K Giri, Soham Bharadwaj, Priyanka Banerjee, Shraddha Chakraborty, Vaisak Parekatt, Donaka Rajashekar, Abhishek Tomar, Aarthi Ravindran, Analabha Basu, Nikhil Tandon, Dwaipayan Bharadwaj
Phenotypic characteristics are known to vary substantially among different ethnicities around the globe. These variations are mediated by number of stochastic events and cannot be attributed to genetic architecture alone. DNA methylation is a well-established mechanism that sculpts our epigenome influencing phenotypic variation including disease manifestation. Since DNA methylation is an important determinant for health issues of a population, it demands a thorough investigation of the natural differences in genome wide DNA methylation patterns across different ethnic groups...
March 7, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28270869/epigenome-wide-discovery-and-evaluation-of-leukocyte-dna-methylation-markers-for-the-detection-of-colorectal-cancer-in-a-screening-setting
#19
Jonathan Alexander Heiss, Hermann Brenner
BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. If detected at an early stage, prognosis is good. Despite increasing evidence for the benefits of implemented screening programs, such as screening colonoscopy, compliance is rather low. Hence there is demand for non-invasive tests for the early detection of CRC with high acceptance in population-wide screening. The objective of this study was to identify and evaluate leukocyte DNA methylation patterns as a potential biomarker for early detection of CRC...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28259012/dna-methylome-analysis-identifies-accelerated-epigenetic-ageing-associated-with-postmenopausal-breast-cancer-susceptibility
#20
Srikant Ambatipudi, Steve Horvath, Flavie Perrier, Cyrille Cuenin, Hector Hernandez-Vargas, Florence Le Calvez-Kelm, Geoffroy Durand, Graham Byrnes, Pietro Ferrari, Liacine Bouaoun, Athena Sklias, Véronique Chajes, Kim Overvad, Gianluca Severi, Laura Baglietto, Françoise Clavel-Chapelon, Rudolf Kaaks, Myrto Barrdahl, Heiner Boeing, Antonia Trichopoulou, Pagona Lagiou, Androniki Naska, Giovanna Masala, Claudia Agnoli, Silvia Polidoro, Rosario Tumino, Salvatore Panico, Martijn Dollé, Petra H M Peeters, N Charlotte Onland-Moret, Torkjel M Sandanger, Therese H Nøst, Elisabete Weiderpass, J Ramón Quirós, Antonio Agudo, Miguel Rodriguez-Barranco, José María Huerta Castaño, Aurelio Barricarte, Ander Matheu Fernández, Ruth C Travis, Paolo Vineis, David C Muller, Elio Riboli, Marc Gunter, Isabelle Romieu, Zdenko Herceg
AIM OF THE STUDY: A vast majority of human malignancies are associated with ageing, and age is a strong predictor of cancer risk. Recently, DNA methylation-based marker of ageing, known as 'epigenetic clock', has been linked with cancer risk factors. This study aimed to evaluate whether the epigenetic clock is associated with breast cancer risk susceptibility and to identify potential epigenetics-based biomarkers for risk stratification. METHODS: Here, we profiled DNA methylation changes in a nested case-control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (n = 960) using the Illumina HumanMethylation 450K BeadChip arrays and used the Horvath age estimation method to calculate epigenetic age for these samples...
April 2017: European Journal of Cancer
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