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Cancer epigenomics

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https://www.readbyqxmd.com/read/28937658/extracellular-vesicle-associated-rna-as-a-carrier-of-epigenetic-information
#1
REVIEW
Carlo Maria Di Liegro, Gabriella Schiera, Italia Di Liegro
Post-transcriptional regulation of messenger RNA (mRNA) metabolism and subcellular localization is of the utmost importance both during development and in cell differentiation. Besides carrying genetic information, mRNAs contain cis-acting signals (zip codes), usually present in their 5'- and 3'-untranslated regions (UTRs). By binding to these signals, trans-acting factors, such as RNA-binding proteins (RBPs), and/or non-coding RNAs (ncRNAs), control mRNA localization, translation and stability. RBPs can also form complexes with non-coding RNAs of different sizes...
September 22, 2017: Genes
https://www.readbyqxmd.com/read/28934561/epigenetic-mechanisms-regulating-adaptive-responses-to-targeted-kinase-inhibitors-in-cancer
#2
Steven P Angus, Jon S Zawistowski, Gary L Johnson
Although targeted inhibition of oncogenic kinase drivers has achieved remarkable patient responses in many cancers, the development of resistance has remained a significant challenge. Numerous mechanisms have been identified, including the acquisition of gatekeeper mutations, activating pathway mutations, and copy number loss or gain of the driver or alternate nodes. These changes have prompted the development of kinase inhibitors with increased selectivity, use of second-line therapeutics to overcome primary resistance, and combination treatment to forestall resistance...
September 15, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28934364/the-histone-variant-macroh2a-confers-functional-robustness-to-the-intestinal-stem-cell-compartment
#3
Ryan James Cedeno, Angela Nakauka-Ddamba, Maryam Yousefi, Stephanie Sterling, Nicolae Adrian Leu, Ning Li, John R Pehrson, Christopher Joachim Lengner
A stem cell's epigenome directs cell fate during development, homeostasis, and regeneration. Epigenetic dysregulation can lead to inappropriate cell fate decisions, aberrant cell function, and even cancer. The histone variant macroH2A has been shown to influence gene expression, guide cell fate, and safeguard against genotoxic stress. Interestingly, mice lacking functional macroH2A histones (hereafter referred to as macroH2A DKO) are viable and fertile; yet suffer from increased perinatal death and reduced weight and size compared to wildtype (WT)...
2017: PloS One
https://www.readbyqxmd.com/read/28933651/characterization-of-h3-3k36m-as-a-tool-to-study-h3k36-methylation-in-cancer-cells
#4
Saumya M Sankaran, Or Gozani
Recurrent mutations at key lysine residues in the histone variant H3.3 are thought to play an etiologic role in the development of distinct subsets of pediatric gliomas and bone and cartilage cancers. H3.3K36M is one such mutation that was originally identified in chondroblastomas, and its expression in these tumors contributes to oncogenic reprogramming by triggering global depletion of dimethylation and trimethylation at H3K36 with a concomitant increase in the levels of H3K27 trimethylation. H3.3K36M expression can also cause epigenomic changes in cell types beyond chondrocytic cells...
September 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28926427/dna-methylation-targeted-drugs
#5
Elodie M Da Costa, Gabrielle McInnes, Annie Beaudry, Noël J-M Raynal
Targeting DNA hypermethylation, using nucleoside analogs, is an efficient approach to reprogram cancer cell epigenome leading to reduced proliferation, increased differentiation, recognition by the immune system, and ultimately cancer cell death. DNA methyltransferase inhibitors have been approved for the treatment of myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myelogenous leukemia. To improve clinical efficacy and overcome mechanisms of drug resistance, a second generation of DNA methyltransferase inhibitors has been designed and is currently in clinical trials...
September 2017: Cancer Journal
https://www.readbyqxmd.com/read/28919981/regulation-of-cancer-epigenomes-with-a-histone-binding-synthetic-transcription-factor
#6
David B Nyer, Rene M Daer, Daniel Vargas, Caroline Hom, Karmella A Haynes
Chromatin proteins have expanded the mammalian synthetic biology toolbox by enabling control of active and silenced states at endogenous genes. Others have reported synthetic proteins that bind DNA and regulate genes by altering chromatin marks, such as histone modifications. Previously, we reported the first synthetic transcriptional activator, the "Polycomb-based transcription factor" (PcTF) that reads histone modifications through a protein-protein interaction between the polycomb chromodomain motif and trimethylated lysine 27 of histone H3 (H3K27me3)...
2017: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/28915241/the-relative-contribution-of-dna-methylation-and-genetic-variants-on-protein-biomarkers-for-human-diseases
#7
Muhammad Ahsan, Weronica E Ek, Mathias Rask-Andersen, Torgny Karlsson, Allan Lind-Thomsen, Stefan Enroth, Ulf Gyllensten, Åsa Johansson
Associations between epigenetic alterations and disease status have been identified for many diseases. However, there is no strong evidence that epigenetic alterations are directly causal for disease pathogenesis. In this study, we combined SNP and DNA methylation data with measurements of protein biomarkers for cancer, inflammation or cardiovascular disease, to investigate the relative contribution of genetic and epigenetic variation on biomarker levels. A total of 121 protein biomarkers were measured and analyzed in relation to DNA methylation at 470,000 genomic positions and to over 10 million SNPs...
September 15, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28912888/sulforaphane-induced-cell-cycle-arrest-and-senescence-are-accompanied-by-dna-hypomethylation-and-changes-in-microrna-profile-in-breast-cancer-cells
#8
Anna Lewinska, Jagoda Adamczyk-Grochala, Anna Deregowska, Maciej Wnuk
Cancer cells are characterized by genetic and epigenetic alterations and phytochemicals, epigenetic modulators, are considered as promising candidates for epigenetic therapy of cancer. In the present study, we have investigated cancer cell fates upon stimulation of breast cancer cells (MCF-7, MDA-MB-231, SK-BR-3) with low doses of sulforaphane (SFN), an isothiocyanate. SFN (5-10 µM) promoted cell cycle arrest, elevation in the levels of p21 and p27 and cellular senescence, whereas at the concentration of 20 µM, apoptosis was induced...
2017: Theranostics
https://www.readbyqxmd.com/read/28905855/new-insights-into-the-epigenetics-of-inflammatory-rheumatic-diseases
#9
REVIEW
Esteban Ballestar, Tianlu Li
Over the past decade, awareness of the importance of epigenetic alterations in the pathogenesis of rheumatic diseases has grown in parallel with a general recognition of the fundamental role of epigenetics in the regulation of gene expression. Large-scale efforts to generate genome-wide maps of epigenetic modifications in different cell types, as well as in physiological and pathological contexts, illustrate the increasing recognition of the relevance of epigenetics. To date, although several reports have demonstrated the occurrence of epigenetic alterations in a wide range of inflammatory rheumatic conditions, epigenomic information is rarely used in a clinical setting...
September 14, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28904641/histone-code-and-long-non-coding-rnas-lncrnas-aberrations-in-lung-cancer-implications-in-the-therapy-response
#10
REVIEW
Abril Marcela Herrera-Solorio, Leonel Armas-López, Oscar Arrieta, Joaquín Zúñiga, Patricia Piña-Sánchez, Federico Ávila-Moreno
Respiratory diseases hold several genome, epigenome, and transcriptional aberrations as a cause of the accumulated damage promoted by, among others, environmental risk factors. Such aberrations can also come about as an adaptive response when faced with therapeutic oncological drugs. In epigenetic terms, aberrations in DNA methylation patterns, histone code marks balance, and/or chromatin-remodeling complexes recruitment, among Polycomb Repressive Complex-2 (PRC2) versus Trithorax (TRX) Activator Complex, have been proposed to be affected by several previously characterized functional long non-coding RNAs (lncRNAs)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28903418/histone-modification-alteration-coordinated-with-acquisition-of-promoter-dna-methylation-during-epstein-barr-virus-infection
#11
Sayaka Funata, Keisuke Matsusaka, Ryota Yamanaka, Shogo Yamamoto, Atsushi Okabe, Masaki Fukuyo, Hiroyuki Aburatani, Masashi Fukayama, Atsushi Kaneda
Aberrant DNA hypermethylation is a major epigenetic mechanism to inactivate tumor suppressor genes in cancer. Epstein-Barr virus positive gastric cancer is the most frequently hypermethylated tumor among human malignancies. Herein, we performed comprehensive analysis of epigenomic alteration during EBV infection, by Infinium HumanMethylation 450K BeadChip for DNA methylation and ChIP-sequencing for histone modification alteration during EBV infection into gastric cancer cell line MKN7. Among 7,775 genes with increased DNA methylation in promoter regions, roughly half were "DNA methylation-sensitive" genes, which acquired DNA methylation in the whole promoter regions and thus were repressed...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28898697/chronic-cigarette-smoke-induced-epigenomic-changes-precede-sensitization-of-bronchial-epithelial-cells-to-single-step-transformation-by-kras-mutations
#12
Michelle Vaz, Stephen Y Hwang, Ioannis Kagiampakis, Jillian Phallen, Ashwini Patil, Heather M O'Hagan, Lauren Murphy, Cynthia A Zahnow, Edward Gabrielson, Victor E Velculescu, Hariharan P Easwaran, Stephen B Baylin
We define how chronic cigarette smoke-induced time-dependent epigenetic alterations can sensitize human bronchial epithelial cells for transformation by a single oncogene. The smoke-induced chromatin changes include initial repressive polycomb marking of genes, later manifesting abnormal DNA methylation by 10 months. At this time, cells exhibit epithelial-to-mesenchymal changes, anchorage-independent growth, and upregulated RAS/MAPK signaling with silencing of hypermethylated genes, which normally inhibit these pathways and are associated with smoking-related non-small cell lung cancer...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28898692/smoke-induced-changes-to-the-epigenome-provide-fertile-ground-for-oncogenic-mutation
#13
Susan J Clark, Peter L Molloy
How genetic and epigenetic events synergize to generate the oncogenic state is not well understood. In this issue of Cancer Cell, Vaz et al. provide compelling evidence that exposure to chronic cigarette smoke causes progressive epigenetic alterations that prime for key genetic events to drive the development of lung cancer.
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28893800/vhl-deficiency-drives-enhancer-activation-of-oncogenes-in-clear-cell-renal-cell-carcinoma
#14
Xiaosai Yao, Jing Tan, Kevin Junliang Lim, Joanna Koh, Wen Fong Ooi, Zhimei Li, Dachuan Huang, Manjie Xing, Yang Sun Chan, James Zhengzhong Qu, Su Ting Tay, Giovani Wijaya, Yue Ning Lam, Jing Han Hong, Ai Ping Lee-Lim, Peiyong Guan, Michelle Shu Wen Ng, Cassandra Zhengxuan He, Joyce Suling Lin, Tannistha Nandi, Aditi Qamra, Chang Xu, Swe Swe Myint, James O J Davies, Jian Yuan Goh, Gary Loh, Bryan C Tan, Steven G Rozen, Qiang Yu, Iain Bee Huat Tan, Christopher Wai Sam Cheng, Shang Li, Kenneth Tou En Chang, Puay Hoon Tan, David Lawrence Silver, Alexander Lezhava, Gertrud Steger, Jim R Hughes, Bin Tean Teh, Patrick Tan
Protein-coding mutations in clear cell renal cell carcinoma (ccRCC) have been extensively characterized, frequently involving inactivation of the von Hippel Lindau (VHL) tumor suppressor. Roles for non-coding cis-regulatory aberrations in ccRCC tumorigenesis, however, remain unclear. Analyzing 10 primary tumor/normal pairs and 9 cell lines across 79 chromatin profiles, we observed pervasive enhancer malfunction in ccRCC, with cognate enhancer-target genes associated with tissue-specific aspects of malignancy...
September 11, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28891455/epigenetic-biomarkers-for-risk-assessment-of-particulate-matter-associated-lung-cancer
#15
Arpit Bhargava, Neha Bunkar, Aniket Aglawe, Kailash Chand Pandey, Rajnarayan Tiwari, Koel Chaudhury, Irina Yu Goryacheva, Pradyumna Kumar Mishra
BACKGROUND: Particulate matter directly emitted into the air by sources such as combustion processes and windblown dust, or formed in the atmosphere by transformation of emitted gases are the major contributors to air pollution that triggers a diverse array of human pathologies including lung cancer. The mortality in lung cancer is usually high as the disease is not symptomatic at its early treatable stage. Moreover, available methods for screening are costly and mainly rely on imaging techniques which lack sufficient sensitivity and specificity...
September 10, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28890207/whole-genome-dna-methylation-profiling-of-oral-cancer-in-ethnic-population-of-meghalaya-north-east-india-reveals-novel-genes
#16
Shngainlang Khongsti, Frederick A Lamare, Neizekhotuo Brian Shunyu, Sahana Ghosh, Arindam Maitra, Srimoyee Ghosh
Oral Squamous Cell Carcinoma (OSCC) is a serious and one of the most common and highly aggressive malignancies. Epigenetic factors such as DNA methylation have been known to be implicated in a number of cancer etiologies. The main objective of this study was to investigate physiognomies of Promoter DNA methylation patterns associated with oral cancer epigenome with special reference to the ethnic population of Meghalaya, North East India. The present study identifies 27,205 CpG sites and 3811 regions that are differentially methylated in oral cancer when compared to matched normal...
September 7, 2017: Genomics
https://www.readbyqxmd.com/read/28889778/genotoxicity-testing-progress-and-prospects-for-the-next-decade
#17
Hasan Turkez, Mehmet E Arslan, Ozlem Ozdemir
Genotoxicity and mutagenicity analyses have a significant role in the identification of hazard effects of therapeutic drugs, cosmetics, agrochemicals, industrial compounds, food additives, natural toxins and nanomaterials for regulatory purposes. To evaluate mutagenicity or genotoxicity, different in vitro and in vivo methodologies exert various genotoxicological endpoints such as point mutations, changes in number and structure of chromosomes. Areas covered: This review covered the basics of genotoxicity and in vitro/in vivo methods for determining of genetic damages...
September 10, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28871255/signaling-to-the-epigenome-new-insights-into-the-roles-of-nuclear-signaling-kinases-in-the-context-of-the-immune-system-and-cancer
#18
EDITORIAL
Pek Siew Lim, Kum Kum Khanna, Sudha Rao
No abstract text is available yet for this article.
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28862667/epigenetic-alterations-in-human-papillomavirus-associated-cancers
#19
REVIEW
David Soto, Christine Song, Margaret E McLaughlin-Drubin
Approximately 15-20% of human cancers are caused by viruses, including human papillomaviruses (HPVs). Viruses are obligatory intracellular parasites and encode proteins that reprogram the regulatory networks governing host cellular signaling pathways that control recognition by the immune system, proliferation, differentiation, genomic integrity, and cell death. Given that key proteins in these regulatory networks are also subject to mutation in non-virally associated diseases and cancers, the study of oncogenic viruses has also been instrumental to the discovery and analysis of many fundamental cellular processes, including messenger RNA (mRNA) splicing, transcriptional enhancers, oncogenes and tumor suppressors, signal transduction, immune regulation, and cell cycle control...
September 1, 2017: Viruses
https://www.readbyqxmd.com/read/28860502/bi-directional-and-shared-epigenomic-signatures-following-proton-and-56-fe-irradiation
#20
Soren Impey, Timothy Jopson, Carl Pelz, Amanuel Tafessu, Fatema Fareh, Damian Zuloaga, Tessa Marzulla, Lara-Kirstie Riparip, Blair Stewart, Susanna Rosi, Mitchell S Turker, Jacob Raber
The brain's response to radiation exposure is an important concern for patients undergoing cancer therapy and astronauts on long missions in deep space. We assessed whether this response is specific and prolonged and is linked to epigenetic mechanisms. We focused on the response of the hippocampus at early (2-weeks) and late (20-week) time points following whole body proton irradiation. We examined two forms of DNA methylation, cytosine methylation (5mC) and hydroxymethylation (5hmC). Impairments in object recognition, spatial memory retention, and network stability following proton irradiation were observed at the two-week time point and correlated with altered gene expression and 5hmC profiles that mapped to specific gene ontology pathways...
August 31, 2017: Scientific Reports
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