Use Of Epigenetics Research Articles

Epigenetics and Cancer: A Comprehensive Review

Cancer is a disease with extraordinary clinical significance, with much of medical research being devoted to it. Innumerable factors are relevant in fully understanding cancer but the epigenetic aspect stands out. Epigenetics is the study of changes, often germ-line, to the genome affecting the gene expression by silencing certain genes and modifying the gene expression. The three primary mechanisms for epigenetic changes are DNA methylation, histone modification and non-coding RNA (ncRNA) associated gene silencing. While epigenetics is a pivotal mechanism for the regular maintenance of a myriad of processes- including in cell differentiation and adaptability- aberrant epigenetic changes can lead to depreciated/altered gene function which may ultimately culminate in cancer. Consequently, the connection between epigenetics and cancer has been intensely studied over the past two decades and has generated substantial clinical data attesting to the efficacy of epigenetics as a viable approach to understand cancer progression or therapy. In this review, we look at the fundamental epigenetic principles, the changes in the epigenome which can often be a precursor to cancer, analyse the increasingly important role of epigenetics in decoding carcinogenesis, explore the latest advancements in use of epigenetics in cancer therapy and how the reversible nature of these epigenetic changes have changed the way we approach cancer therapy.

Heart Failure in Breast Cancer Survivors: Focus on Early Detection and Novel Biomarkers.

Breast cancer survival rate has greatly improved in the last two decades due to the emergence of next-generation anti-cancer agents. However, cardiotoxicity remains a significant adverse effect arising from traditional and emerging chemotherapies as well as targeted therapies for breast cancer patients. In this review, we will discuss cardiotoxicities of both traditional and emerging therapies for breast cancer. We will discuss current practices to detect cardiotoxicity of these therapies with the focus on new and emerging biomarkers. We will then focus on 'omics approaches, especially the use of epigenetics to discover novel biomarkers and therapeutics to mitigate cardiotoxicity. Significant cardiotoxicities of conventional chemotherapies remain and new and unpredictable new forms of cardiac and/or vascular toxicity emerge with the surge in novel and targeted therapies. Yet, there is no clear guidance on detection of cardiotoxicity, except for significant left ventricular systolic dysfunction, and even then, there is no uniform definition of what constitutes cardiotoxicity. The gold standard for detection of cardiotoxicity involves a serial echocardiography in conjunction with blood-based biomarkers to detect early subclinical cardiac dysfunction. However, the ability of these tests to detect early disease remains limited and not all forms of toxicity are detectable with these modalities. There is an unprecedented need to discover novel biomarkers that are sensitive and specific for early detection of subclinical cardiotoxicity. In that space, novel echocardiographic techniques, such as strain, are becoming more common-place and new biomarkers, discovered by epigenetic approaches, seem to become promising alternatives or adjuncts to conventional non-specific cardiac biomarkers.

Epigenetics for Crop Improvement in Times of Global Change.

Simple SummaryResearch on plant epigenetics aims to understand how endogenous, biotic, and abiotic factors regulate plant development and growth independent of changes in the genome sequence. Often, the epigenetic changes are heritable across generations and modulate plant growth and crop tolerance, particularly in response to environmental stimuli. To take advantage of epigenetic adaptation, recent research has focused on implementing targeted epigenetic diversity to engineer plants that harbour advantageous traits for optimal crop production. Epigenetics has the potential to provide a powerful toolbox for crop breeders; however, most mechanistic studies are based on information from model plant species due to the challenges that arise when working with crops. Here, we summarise the contribution of epigenetics to optimising crop adaptation in response to climate change and overview potential future applications as well as challenges.Epigenetics has emerged as an important research field for crop improvement under the on-going climatic changes. Heritable epigenetic changes can arise independently of DNA sequence alterations and have been associated with altered gene expression and transmitted phenotypic variation. By modulating plant development and physiological responses to environmental conditions, epigenetic diversity—naturally, genetically, chemically, or environmentally induced—can help optimise crop traits in an era challenged by global climate change. Beyond DNA sequence variation, the epigenetic modifications may contribute to breeding by providing useful markers and allowing the use of epigenome diversity to predict plant performance and increase final crop production. Given the difficulties in transferring the knowledge of the epigenetic mechanisms from model plants to crops, various strategies have emerged. Among those strategies are modelling frameworks dedicated to predicting epigenetically controlled-adaptive traits, the use of epigenetics for in vitro regeneration to accelerate crop breeding, and changes of specific epigenetic marks that modulate gene expression of traits of interest. The key challenge that agriculture faces in the 21st century is to increase crop production by speeding up the breeding of resilient crop species. Therefore, epigenetics provides fundamental molecular information with potential direct applications in crop enhancement, tolerance, and adaptation within the context of climate change.

Plant Responses to Abiotic Stresses and Rhizobacterial Biostimulants: Metabolomics and Epigenetics Perspectives.

In response to abiotic stresses, plants mount comprehensive stress-specific responses which mediate signal transduction cascades, transcription of relevant responsive genes and the accumulation of numerous different stress-specific transcripts and metabolites, as well as coordinated stress-specific biochemical and physiological readjustments. These natural mechanisms employed by plants are however not always sufficient to ensure plant survival under abiotic stress conditions. Biostimulants such as plant growth-promoting rhizobacteria (PGPR) formulation are emerging as novel strategies for improving crop quality, yield and resilience against adverse environmental conditions. However, to successfully formulate these microbial-based biostimulants and design efficient application programs, the understanding of molecular and physiological mechanisms that govern biostimulant-plant interactions is imperatively required. Systems biology approaches, such as metabolomics, can unravel insights on the complex network of plant-PGPR interactions allowing for the identification of molecular targets responsible for improved growth and crop quality. Thus, this review highlights the current models on plant defence responses to abiotic stresses, from perception to the activation of cellular and molecular events. It further highlights the current knowledge on the application of microbial biostimulants and the use of epigenetics and metabolomics approaches to elucidate mechanisms of action of microbial biostimulants.

APPLICATIONS OF EPIGENETICS IN FORENSIC INVESTIGATIONS: A BRIEF REVIEW

Forensic science is a discipline that has the capacity to be merged with every promise to offer a solution to a criminal investigation to help the legal system. Epigenetics is a branch of genetics that deals with the study of environmental interaction with the genome. The emerging field of forensic epigenetics has a variety of applications in criminal investigations. It provides an addictive tool to solve criminal activity-related issues. In this review, we have showcased the brief use of epigenetics to sort out forensic-related issues and help the legal system. We have briefly taken a snapshot of genetics, epigenetics, and application of epigenetics in forensic science that how it could offer solutions to queries of forensic nature. Also, potential future developments in the field and their probable impact have been anticipated. It has many potential applications which are still to be explored. It complements forensic science at many potential levels.

The Role of Epigenetics in the Chronic Sinusitis with Nasal Polyp.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and heterogeneous inflammatory disease. The underlying epigenetic mechanisms and treatment of CRSwNP are partially understood. Of the different epigenetic changes in CRSwNP, histone deacetylases (HDACs), methylation of DNA, and the levels of miRNA are widely studied. Here, we review the human studies of epigenetic mechanisms in CRSwNP. The promoters of COL18A1, PTGES, PLAT, and TSLP genes are hypermethylated in CRSwNP compared with those of controls, while the promoters of PGDS, ALOX5AP, LTB4R, IL-8, and FZD5 genes are hypomethylated in CRSwNP. Promoter hypermethylation suppresses the gene expression, while promoter hypomethylation increases the gene expression. Studies have shown the elevation in the levels of HDAC2, HDAC4, and H3K4me3 in CRSwNP. In CRSwNP patients, there is also an upregulation of certain miRNAs including miR-125b, miR-155, miR-19a, miR-142-3p, and miR-21 and downregulation of miR-4492. Epigenetics takes part in the immunology of CRSwNP and may give rise to endotypes of CRSwNP. Both HDAC2 and the miRNA including miR-18a, miR-124a, and miR-142-3p may take function in the regulation of glucocorticoid resistance. HDAC inhibitors and KDM2B have shown effectiveness in decreasing nasal polyp, and DNA methyltransferase (DNMT) or HDAC inhibitors may have a potential efficacy for the treatment of CRSwNP. Recent advances in the epigenetics of CRSwNP have led to the identification of several potential therapeutic targets for this disease. The use of epigenetics may provide novel and effective biomarkers and therapies for the treatment of nasal polyp.

Assisted migration vs. close-to-nature forestry: what are the prospects for tree populations under climate change?

Abstract Climate change is currently perceived as the most important challenge faced globally by ecosystems and human society. The predicted changes of temperature and precipitation patterns are expected to alter the environmental conditions to which forest trees in Europe are adapted, and expose them to new pests and pathogens. This would unavoidably lead to a huge loss of ecosystem services provided to society, and at the local scale may potentially endanger the very existence of forests. In this study, we reviewed biological background and limits of mechanisms by which tree populations may cope with climate change: adaptation by natural selection, gene flow, epigenetic phenomena and phenotypic plasticity, as well as forest management strategies, which rely on these mechanisms. We argue that maintaining genetic diversity is important in the long-term view but natural selection cannot ensure sufficiently rapid response to environmental change. On the other hand, epigenetic memory effects may change adaptively relevant traits within a single generation, while close-to-nature forestry practices are the basic requirement to make use of epigenetics. Assisted migration, as a frequently suggested mitigation option, relies primarily on the knowledge gained from provenance research; the review analyses potential pitfalls of this strategy. We suggest that all approaches, i.e., leaving a part of forests without management, close-to-nature forestry, and transfer of forest reproductive materials from sources presumably adapted to future climates are combined across the landscape in an integrative manner.

Epigenetic Barcodes for Detection of Adulterated Plants and Plant-Derived Products.

In this chapter, we report a possible alternative use of epigenetics by applying methylation-sensitive amplified fragment length polymorphisms (MS-AFLP) to saffron traceability. Saffron is the most expensive plant-derived product in the world and one of the most frequently adulterated. One of the most frequent adulteration is by adding to saffron stigmas different parts of the saffron flower itself to increase volumes. While DNA is the same in all the parts of the plant, the epigenetic state can vary according to the organ and/or tissue of origin, making it possible to discriminate the stigmas from the other parts of saffron flower. In the subsequent method, the protocol to carry out a MS-AFLP analysis of saffron DNA methylation patterns is described.

Epigenetic research in multiple sclerosis: progress, challenges, and opportunities.

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system. MS likely results from a complex interplay between predisposing causal gene variants (the strongest influence coming from HLA class II locus) and environmental risk factors such as smoking, infectious mononucleosis, and lack of sun exposure/vitamin D. However, little is known about the mechanisms underlying MS development and progression. Moreover, the clinical heterogeneity and variable response to treatment represent additional challenges to a comprehensive understanding and efficient treatment of disease. Epigenetic processes, such as DNA methylation and histone posttranslational modifications, integrate influences from the genes and the environment to regulate gene expression accordingly. Studying epigenetic modifications, which are stable and reversible, may provide an alternative approach to better understand and manage disease. We here aim to review findings from epigenetic studies in MS and further discuss the challenges and clinical opportunities arising from epigenetic research, many of which apply to other diseases with similar complex etiology. A growing body of evidence supports a role of epigenetic processes in the mechanisms underlying immune pathogenesis and nervous system dysfunction in MS. However, disparities between studies shed light on the need to consider possible confounders and methodological limitations for a better interpretation of the data. Nevertheless, translational use of epigenetics might offer new opportunities in epigenetic-based diagnostics and therapeutic tools for a personalized care of MS patients.

Epigenetic regulation in bladder cancer: development of new prognostic targets and therapeutic implications

Epigenetic and genetic alterations contribute to cancer initiation and progression. Epigenetics refers to heritable alterations in gene expression without DNA sequence changes. Epigenetic changes include reversible alterations in DNA methylation, chromatin modification, nucleosome positioning, and non-coding RNA profiles. In bladder cancer, many epigenetic changes have been reported to exhibit correlation with cancer progression and malignances. In particular, both DNA hypermethylation and hypomethylation have been reported to be associated with higher bladder cancer rates or advanced tumor stages. The association of changes in histone modifying enzyme expression with bladder cancer stages has been extensively studied. MicroRNA (miRNA) expression also has been studied in bladder cancer diagnosis and disease progression. The use of epigenetics for the diagnosis of and therapeutic target screening in bladder cancer is an emerging and rapidly evolving field. The reversible nature of epigenetic changes may facilitate additional therapeutic options in the future.

Epigenetic regulation in bladder cancer: development of new prognostic targets and therapeutic implications

: Epigenetic and genetic alterations contribute to cancer initiation and progression. Epigenetics refers to heritable alterations in gene expression without DNA sequence changes. Epigenetic changes include reversible alterations in DNA methylation, chromatin modification, nucleosome positioning, and non-coding RNA profiles. In bladder cancer, many epigenetic changes have been reported to exhibit correlation with cancer progression and malignances. In particular, both DNA hypermethylation and hypomethylation have been reported to be associated with higher bladder cancer rates or advanced tumor stages. The association of changes in histone modifying enzyme expression with bladder cancer stages has been extensively studied. MicroRNA (miRNA) expression also has been studied in bladder cancer diagnosis and disease progression. The use of epigenetics for the diagnosis of and therapeutic target screening in bladder cancer is an emerging and rapidly evolving field. The reversible nature of epigenetic changes may facilitate additional therapeutic options in the future.

Introduction to the Special Section on Epigenetics.

Epigenetics provides the opportunity to revolutionize our understanding of the role of genetics and the environment in explaining human behavior, although the use of epigenetics to study human behavior is just beginning. In this introduction, the authors present the basics of epigenetics in a way that is designed to make this exciting field accessible to a wide readership. The authors describe the history of human behavioral epigenetic research in the context of other disciplines and graphically illustrate the burgeoning of research in the application of epigenetic methods and principles to the study of human behavior. The role of epigenetics in normal embryonic development and the influence of biological and environmental factors altering behavior through epigenetic mechanisms and developmental programming are discussed. Some basic approaches to the study of epigenetics are reviewed. The authors conclude with a discussion of challenges and opportunities, including intervention, as the field of human behavioral epigenetics continue to grow.

Shu Wang

Angewandte Chemie International EditionVolume 55, Issue 17 p. 5120-5120 Author ProfileFree Access Shu Wang First published: 17 December 2015 https://doi.org/10.1002/anie.201511263AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract “My favorite drink is Chinese black tea. My favorite reaction is natural DNA synthesis ...” This and more about Shu Wang can be found on page 5120. 1 Table 1. Shu Wang Date of birth: April 5, 1972 Position: Professor, Institute of Chemistry, Chinese Academy of Sciences E-mail: wangshu@iccas.ac.cn Homepage: http://wangshu.iccas.ac.cn Education: 1994 BSc, Hebei University 1994–1999 PhD with Prof. Wenting Hua, Peking University 1999–2001 Postdoctoral associate with Prof. Yuliang Li and Prof. Daoben Zhu, Institute of Chemistry, Chinese Academy of Sciences 2001–2004 Postdoctoral associate with Prof. Guillermo C. Bazan, University of California, Santa Barbara Awards: 2006 Chinese Chemical Society Award for Young Chemists; 2007 National Natural Science Funds for Distinguished Young Scholars; 2011 Chinese Chemical Society–Royal Society of Chemistry Prize for Young Chemists; 2011 12th National Award for Youth in Science and Technology Research: Functional organic conjugated molecules, synthesis, assembly, biosensors, imaging Hobbies: Badminton, music, and cooking My favorite drink is Chinese black tea. My favorite reaction is natural DNA synthesis. The principal aspects of my personality are I am rigorous and lively. If I had one year of paid leave I would go back to my hometown and enjoy the country life with my parents. If I could be a piece of lab equipment, I would be a flash chromatography column. The biggest challenge facing scientists is to find a new way for drug discovery to combat tumor and pathogen-cell resistance to drugs. Looking back over my career, I can say my achievements are beyond my expectations. The most important future applications of my research are the early diagnosis and treatment of disease. In a spare hour, I will find a quiet place to have a sleep. My favorite time of day is the night when I read or write papers. The most important thing I learned from my parents is perseverance, patience, and dedication. My 5 top papers: References 1“A Supramolecular Antibiotic Switch for Antibacterial Regulation”: H. T. Bai, H. Yuan, C. Nie, B. Wang, F. Lv, L. Liu, S. Wang, Angew. Chem. Int. Ed. 2015, 54, 13208; Wiley Online LibraryCASPubMedWeb of Science®Google ScholarAngew. Chem. 2015, 127, 13406. (A new strategy for fighting bacterial resistance to antibiotics.) Wiley Online LibraryGoogle Scholar 2“Cationic Oligo(p-phenylene vinylene) Materials for Combatting Drug Resistance of Cancer Cells by Light Manipulation”: B. Wang, H. Yuan, Z. Liu, C. Nie, L. Liu, F. Lv, Y. Wang, S. Wang, Adv. Mater. 2014, 26, 5986. (A feasible methodology for recovering the activity of already established anticancer drugs in resistant cells.) Wiley Online LibraryCASPubMedWeb of Science®Google Scholar 3“Multiplex Detection of DNA Mutations by the Fluorescence Fingerprint Spectrum Technique”: J. Song, J. Zhang, F. Lv, Y. Cheng, B. Wang, L. Feng, L. Liu, S. Wang, Angew. Chem. Int. Ed. 2013, 52, 13020; Wiley Online LibraryCASPubMedWeb of Science®Google ScholarAngew. Chem. 2013, 125, 13258. (A proof-of-concept for conjugated polymer-based multistep FRET for rapid and sensitive sensing.) Wiley Online LibraryGoogle Scholar 4“Detection and differential diagnosis of colon cancer by a cumulative analysis of promoter methylation technique”: Q. Yang, D. Ying, W. Wu, C. Zhu, H. Chong, J. Lu, D. Yu, L. Liu, F. Lv, S. Wang, Nat. Commun. 2012, 3, 1206. (The use of epigenetics in differential tumor diagnosis.) CrossrefCASPubMedWeb of Science®Google Scholar 5“Chemical Molecule-Induced Light-Activated System for Anticancer and Antifungal Activities”: H. Yuan, H. Chong, B. Wang, C. Zhu, L. Liu, Q. Yang, F. Lv, S. Wang, J. Am. Chem. Soc. 2012, 134, 13184. (A smart photodynamic therapy system activated by molecules instead of an external light source.) CrossrefCASPubMedWeb of Science®Google Scholar Volume55, Issue17April 18, 2016Pages 5120-5120 ReferencesRelatedInformation

Abstract IA09: Imaging to guide genomics and epigenomics of glioma

Abstract Genomic analysis of cancer is typically conducted at a single time point and on a single piece of tumor tissue without knowledge of its original context within the heterogeneous tumor. Glioma tissue biopsies guided by distinct physiologic and metabolic imaging parameters can enrich for tumor regions with elevated levels of cycling cells, differences in blood vessels, and increased presence of hypoxic regions, and an increased probability of malignant transformation. An imaging guided approach to biopsy allows the tumor genomic and transcriptome evolution to be focused on malignant transformation. I will describe the use of novel quantitative imaging methods to guide biopsies to biologically distinct regions of brain tumors for targeted genomic, epigenomic and transcriptome analysis. The clonal evolution of tumor cell populations can be reconstructed from patterns of genetic alterations. In contrast, tumor epigenetic states are reversible and sensitive to the tumor microenvironment, presumably precluding the use of epigenetics to discover the clonal and sub-clonal evolution of tumors. We recently used mutation patterns to learn how low grade brain tumors evolve over time, and also discovered that temozolomide treatment of LGG is associated with TMZ-induced hypermutation and malignant progression to GBM (BE Johnson et al, Science, 2014). I will present an update to these results, and our follow up analysis of the spatial and temporal dynamics of DNA methylation in this clinically and genetically characterized cohort and in imaging guided biopsies. Citation Format: Joseph F. Costello. Imaging to guide genomics and epigenomics of glioma. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr IA09.

Past, present, and future of epigenetics applied to livestock breeding.

This article reviews the concept of Lamarckian inheritance and the use of the term epigenetics in the field of animal genetics. Epigenetics was first coined by Conrad Hal Waddington (1905–1975), who derived the term from the Aristotelian word epigenesis. There exists some controversy around the word epigenetics and its broad definition. It includes any modification of the expression of genes due to factors other than mutation in the DNA sequence. This involves DNA methylation, post-translational modification of histones, but also linked to regulation of gene expression by non-coding RNAs, genome instabilities or any other force that could modify a phenotype. There is little evidence of the existence of transgenerational epigenetic inheritance in mammals, which may commonly be confounded with environmental forces acting simultaneously on an individual, her developing fetus and the germ cell lines of the latter, although it could have an important role in the cellular energetic status of cells. Finally, we review some of the scarce literature on the use of epigenetics in animal breeding programs.

Epigenetics and Child Psychiatry: Ethical and Legal Issues.

Epigenetics has the potential to revolutionize diagnosis and treatment in psychiatry, especially child psychiatry, as it may offer the opportunity for early detection and prevention, as well as development of new treatments. As with the previous introduction of genetic research in psychiatry, there is also the problem of unrealistic expectations and new legal and ethical problems. This article reviews the potential contributions and problems of epigenetic research in child psychiatry. Previous legal and ethical issues in genetic research serve as a guide to those in epigenetic research. Recommendations for safeguards and guidelines on the use of epigenetics with children and adolescents are outlined based on the identified issues.

EG-07 * CELL CYCLE SIGNATURE AND TUMOR PHYLOGENY ARE ENCODED IN THE EVOLUTIONARY DYNAMICS OF DNA METHYLATION IN GLIOMA

The clonal evolution of tumor cell populations can be reconstructed from patterns of genetic alterations. In contrast, tumor epigenetic states, including DNA methylation, are reversible and sensitive to the tumor microenvironment, presumably precluding the use of epigenetics to discover tumor phylogeny. Here we examined the spatial and temporal dynamics of DNA methylation in a clinically and genetically characterized cohort of IDH1-mutant low-grade gliomas and their patient-matched recurrences. WHO grade II gliomas are diffuse, infiltrative tumors that frequently recur and may undergo malignant progression to a higher grade with a worse prognosis. The extent to which epigenetic alterations contribute to the evolution of low-grade gliomas, including malignant progression, is unknown. While all gliomas in the cohort exhibited the hypermethylation signature associated with IDH1 mutation, low-grade gliomas that underwent malignant progression to high-grade glioblastoma (GBM) had a unique signature of DNA hypomethylation enriched for active enhancers, as well as sites of age-related hypermethylation in the brain. Genes with promoter hypomethylation and concordant transcriptional upregulation during evolution to GBM were enriched in cell cycle function, evolving in concert with genetic alterations that deregulate the G1/S cell cycle checkpoint. Despite the plasticity of tumor epigenetic states, phyloepigenetic trees robustly recapitulated phylogenetic trees derived from somatic mutations in the same patients. These findings highlight widespread co-dependency of genetic and epigenetic events throughout the clonal evolution of initial and recurrent glioma.

CLONAL EVOLUTION OF GLIOMAS IS ENCODED IN THE EVOLUTIONARY DYNAMICS OF DNA METHYLATION

BACKGROUND: The clonal evolution of tumor cell populations can be reconstructed from patterns of genetic alterations. In contrast, tumor epigenetic states are reversible and sensitive to the tumor microenvironment, presumably precluding the use of epigenetics to discover the clonal and sub-clonal evolution of tumors. We recently used mutation patterns to learn how low grade gliomas evolve over time, and also discovered that temozolomide treatment of LGG is associated with TMZ-induced hypermutation and malignant progression to GBM (BE Johnson et al, Science, 2014). METHODS: We used exome and RNA sequencing, DNA methylation arrays, along with computational analysis to construct phylogenetic and phyloepigenetic relationships among co-evolving tumor cell populations. RESULTS: Here we examined the spatial and temporal dynamics of DNA methylation in our clinically and genetically characterized cohort of IDH1-mutant low-grade gliomas and their patient-matched recurrences. While all tumors exhibited the hypermethylation signature associated with IDH1 mutation, low-grade gliomas that underwent spontaneous or temozolomide-associated malignant progression to high-grade glioblastoma multiforme (GBM) had a unique signature of DNA hypomethylation enriched for both active enhancers, and sites of age-related hypermethylation in the brain. Genes with promoter hypomethylation and concordant transcriptional upregulation during evolution to GBM were enriched in cell cycle function, evolving in concert with genetic alterations that deregulate the G1/S cell cycle checkpoint. Despite the plasticity of tumor epigenetic states, phyloepigenetic relationships robustly recapitulated phylogenetic patterns inferred from somatic mutations in the same patients. CONCLUSIONS: These findings highlight widespread co-dependency of genetic and epigenetic events throughout the clonal evolution of initial and recurrent gliomas.

Cancer Epigenetics: New Therapies and New Challenges

Cancer is nowadays considered to be both a genetic and an epigenetic disease. The most well studied epigenetic modification in humans is DNA methylation; however it becomes increasingly acknowledged that DNA methylation does not work alone, but rather is linked to other modifications, such as histone modifications. Epigenetic abnormalities are reversible and as a result novel therapies that work by reversing epigenetic effects are being increasingly explored. The biggest clinical impact of epigenetic modifying agents in neoplastic disorders thus far has been in haematological malignancies, and the efficacy of DNMT inhibitors and HDAC inhibitors in blood cancers clearly attests to the principle that therapeutic modification of the cancer cell epigenome can produce clinical benefit. This paper will discuss the most well studied epigenetic modifications and how these are linked to cancer, will give a brief overview of the clinical use of epigenetics as biomarkers, and will focus in more detail on epigenetic drugs and their use in solid and blood cancers.

Update on the epidemiology and genetics of myopic refractive error

While myopia is an increasingly common refractive error worldwide, its prevalence is greatest in urbanized regions in east Asia. Myopia is a complex multifactorial ocular disorder governed by both genetic and environmental factors and possibly their interplay. Evidence for a genetic role in myopia has been derived from studies of syndromal myopia, familial correlation studies and linkage analyses. More recently, candidate gene and genome-wide association studies have been utilized. However, a high proportion of the heritability of myopia remains unexplained. Most genetic discoveries have been for high myopia, with the search for genes underpinning myopia of lesser severity yielding fewer positive associations. This may soon change with the use of next-generation sequencing, as well as the use of epigenetics and proteomic approaches.