Download or read book Genome wide Approaches for Discovery of Novel Genetic and Epigenetic Events in Gastrointestinal Cancer written by Ryan E Fecteau and published by . This book was released on 2015 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer is a disease caused by the sequential acquisition of genetic and epigenetic changes that transform a normal cell into an ungovernable malignancy. Advances in technologies to interrogate these changes on a genome-wide scale have reshaped our understanding of this disease and rapidly expanded the field of cancer genomics. The objective of the projects described herein was to adapt high-throughput methods to discover and characterize novel genetic and epigenetic events in gastrointestinal cancers with the intention of translational application. Three primary studies comprise the body of this thesis. In the first, we identify recurrent mutations in the oncogene GNAS found by sequencing of the colorectal cancer genome. Targeted pyrosequencing of GNAS in a colon cancer tumor cohort established a mutation frequency in colorectal cancer of around 2%. By comparing GNAS mutation status with clinical and pathologic data, we found that GNAS mutations associate with a distinct class of colon cancers that are characterized by concomitant KRAS or BRAF mutations, by location in the proximal colon, and by a unique association with a villous morphology. The second study applied a targeted next generation sequencing approach, whole exome sequencing, to identify a germ-line susceptibility variant in a familial syndrome of Barrett's esophagus and esophageal adenocarcinoma. Sequencing revealed a private variant in the uncharacterized gene VSIG10L that segregated with disease in a large familial Barrett's esophagus family and functional studies suggested the discovered variant disrupted maturation of the normal esophageal epithelium. Lastly, we describe using reduced representation bisulfite sequencing to examine the colon cancer methylome for candidate methylated biomarker loci. Preliminary data from this work has identified 3 candidate methylated DNA biomarkers for potential use in detection of colorectal cancer in patient plasma. Cumulatively, these studies have identified a rare mutation in colon cancer associated with a unique molecular phenotype, a private germ-line variant predisposing to familial Barrett's esophagus and adenocarcinoma, and candidate methylated biomarkers for detection and monitoring of colon cancer, all of which are of potential clinical importance.
Download or read book Discovery of Novel Epigenetic Mechanisms of Carcinogenesis by Genome wide Profiling of Non coding Regulatory Elements written by Batool Akhtar-Zaidi and published by . This book was released on 2013 with total page 135 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetic mechanisms are of paramount importance in cancer. Historically, epigenetic studies of cancer have focused on aberrant DNA methylation events. Far less is known about the role of histone modifications in epigenetic mechanisms of human cancers, and of disease in general. There are a number of reasons why histone modifications are especially important to investigate in the context of tumor formation. While DNA methylation contributes to stable gene silencing and formation of heterochromatin, histone modifications are associated with much more dynamic gene expression patterns. Importantly, histone modifications are also informative of the activity states of distal regulatory elements. Therefore we can use these epigenetic marks to study important regions of the cancer genome that are key regulators of transcription with unprecedented resolution and accuracy. In this work, in-depth studies of epigenetic features of both promoters and distal enhancer elements are described, in each case enabled by distinct histone modifications that are chromatin "signatures" of promoter and enhancer elements, respectively. We show that in colon cancer, the presence of the H3K4me3 active mark is associated with resistance to silencing associated with DNA methylation. We further show evidence that in colon cancer, DNA hypermethylation is likely a relatively rare event at CpG-islands, and that most CpG-islands are probably silenced by alternative mechanisms, specifically the acquisition of repressive histone marks. With respect to distal regulatory elements, enhancer elements are especially attractive candidates to study in cancer, a disease of widespread and heterogeneous aberrant transcription, because they are under normal circumstances drivers of cellular identity and associated global gene expression programs. We report the discovery of thousands of Variant Enhancer Loci, or VELs, which have gained or lost H3K4me1 at enhancer elements in colon cancer samples. We show that VELs are tightly linked to the in vivo colon cancer transcriptome, and furthermore are enriched at colon cancer susceptibility SNPs. We propose that the model describing gene dysregulation in cancer be revised to now include epigenetic dysregulation at enhancer elements as an important mechanism in cancer-specific gene expression.
Download or read book Genetics of Colorectal Cancer written by John D. Potter and published by Springer. This book was released on 2008-12-08 with total page 309 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetic susceptibility refers to how variations in a person’s genes increase or decrease his or her susceptibility to environmental factors, such as chemicals, radiation and lifestyle (diet and smoking). This volume will explore the latest findings in the area of genetic susceptibility to gastrointestinal cancers, focusing on molecular epidemiology, DNA repair, and gene-environment interactions to identify factors that affect the incidence of GI cancers. Topics will include germline susceptibility, including Mendelian patterns of inheritance and gene-environment interactions that lead to cancer etiology.
Download or read book DNA Methylation and Complex Human Disease written by Michel Neidhart and published by Academic Press. This book was released on 2015-08-11 with total page 546 pages. Available in PDF, EPUB and Kindle. Book excerpt: DNA Methylation and Complex Human Disease reviews the possibilities of methyl-group-based epigenetic biomarkers of major diseases, tailored epigenetic therapies, and the future uses of high-throughput methylome technologies. This volume includes many pertinent advances in disease-bearing research, including obesity, type II diabetes, schizophrenia, and autoimmunity. DNA methylation is also discussed as a plasma and serum test for non-invasive screening, diagnostic and prognostic tests, as compared to biopsy-driven gene expression analysis, factors which have led to the use of DNA methylation as a potential tool for determining cancer risk, and diagnosis between benign and malignant disease. Therapies are at the heart of this volume and the possibilities of DNA demethylation. In cancer, unlike genetic mutations, DNA methylation and histone modifications are reversible and thus have shown great potential in the race for effective treatments. In addition, the authors present the importance of high-throughput methylome analysis, not only in cancer, but also in non-neoplastic diseases such as rheumatoid arthritis. Discusses breaking biomarker research in major disease families of current health concern and research interest, including obesity, type II diabetes, schizophrenia, and autoimmunity Summarizes advances not only relevant to cancer, but also in non-neoplastic disease, currently an emerging field Describes wholly new concepts, including the linking of metabolic pathways with epigenetics Provides translational researchers with the knowledge of both basic research and clinic applications of DNA methylation in human diseases
Download or read book Hereditary Colorectal Cancer written by Laura Valle and published by Springer. This book was released on 2018-05-04 with total page 494 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides information on a wide variety of issues ranging from genetics to clinical description of the syndromes, genetic testing and counseling, and clinical management including surveillance, surgical and prophylactic interventions, and chemoprevention. Moreover, current hot issues, such as the identification of novel causal genes and the challenges we face, and the relevance of cancer risk modifiers, both genetic and environmental, are also discussed. This reference book is great for geneticists, oncologists, genetic counselors, researchers, clinicians, surgeons and nurses dedicated to, or interested in, hereditary cancer. The best and most recognized experts in the field have contributed to this project, guaranteeing updated information, accuracy and the discussion of topical issues.
Download or read book Epigenetic Therapy of Cancer written by Michael Lübbert and published by Springer Science & Business Media. This book was released on 2013-12-12 with total page 332 pages. Available in PDF, EPUB and Kindle. Book excerpt: The growing knowledge about disturbances of epigenetic gene regulation in hematopoietic stem cell disorders is now being translated into treatment approaches that target the epigenetic defects pharmacologically. This book first presents the latest evidence regarding the epigenetic regulation of hematopoietic stem cell differentiation and hemoglobin production. The significance of DNA methylation abnormalities in hematopoietic disorders and of epigenetic disturbances in lung cancer and other solid tumors is then discussed. A major part of the book, however, relates specifically to the translation of basic research and drug development to clinical applications, and in this context both present and future clinical strategies are considered. Individual chapters are devoted to the use of DNA hypomethylating agents and chromatin-modifying agents, and the treatment of hematologic malignancies and solid tumors by means of epigenetic agents is discussed in detail.
Download or read book Prevention and Early Detection of Colorectal Cancer written by Graeme P. Young and published by W.B. Saunders Company. This book was released on 1996 with total page 410 pages. Available in PDF, EPUB and Kindle. Book excerpt: This is an overview of the issues involved in prevention and early detection of colorectal cancer providing up-to-date, practical advice for clinicians. Possible management strategies for those at risk are provided, taking into account the biological principles of colorectal cancer development, epidemiological data and emerging genetic information, as well as social and environmental factors.
Download or read book How Tobacco Smoke Causes Disease written by United States. Public Health Service. Office of the Surgeon General and published by . This book was released on 2010 with total page 728 pages. Available in PDF, EPUB and Kindle. Book excerpt: This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.
Download or read book Telomeres and Telomerase in Cancer written by Keiko Hiyama and published by Springer Science & Business Media. This book was released on 2009-03-18 with total page 375 pages. Available in PDF, EPUB and Kindle. Book excerpt: Telomerase, an enzyme that maintains telomeres and endows eukaryotic cells with immortality, was first discovered in tetrahymena in 1985. In 1990s, it was proven that this enzyme also plays a key role in the infinite proliferation of human cancer cells. Now telomere and telomerase are widely accepted as important factors involved in cancer biology, and as promising diagnostic tools and therapeutic targets. Recently, role of telomerase in “cancer stem cells” has become another attractive story. Until now, there are several good books on telomere and telomerase focusing on biology in ciliates, yeasts, and mouse or basic sciences in human, providing basic scientists or students with updated knowledge.
Download or read book Recent Advancements in Biomarkers and Early Detection of Gastrointestinal Cancers written by Pallaval Veera Bramhachari and published by Springer Nature. This book was released on 2020-07-21 with total page 238 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book describes various novel biomarkers for the early diagnosis of gastrointestinal (GI) cancers. It also highlights recent advances in understanding the role of molecular markers and biomarkers, such as volatile biomarkers, serum biomarkers, predictive and prognostic molecular markers for the early detection of GI cancers. Further, it discusses novel biomarkers, including circulating microRNAs, serum microRNA and plasma microRNA in GI cancer. The book presents breakthrough technologies like ultra-sensitive nano-chips, nanosensors, nanodevices, biosensors, electrochemical biosensors, optical biosensors, DNA biosensors, synthetic biology devices, and 'omics' technologies for the early diagnosis of gastrointestinal cancer. In addition it examines the potential of genome-wide association studies, big data analytics, computation biology, systems biology, and nanotechnology for early diagnostics and therapeutics for gastrointestinal cancer, with a focus on personalized cancer treatment. The book is a valuable source for researchers and clinicians engaged in detection and diagnosis of gastrointestinal cancers.
Download or read book Introduction to Epigenetics written by Renato Paro and published by Springer Nature. This book was released on 2021-03-23 with total page 215 pages. Available in PDF, EPUB and Kindle. Book excerpt: This open access textbook leads the reader from basic concepts of chromatin structure and function and RNA mechanisms to the understanding of epigenetics, imprinting, regeneration and reprogramming. The textbook treats epigenetic phenomena in animals, as well as plants. Written by four internationally known experts and senior lecturers in this field, it provides a valuable tool for Master- and PhD- students who need to comprehend the principles of epigenetics, or wish to gain a deeper knowledge in this field. After reading this book, the student will: Have an understanding of the basic toolbox of epigenetic regulation Know how genetic and epigenetic information layers are interconnected Be able to explain complex epigenetic phenomena by understanding the structures and principles of the underlying molecular mechanisms Understand how misregulated epigenetic mechanisms can lead to disease
Download or read book Epigenetics in Human Disease written by Trygve Tollefsbol and published by Academic Press. This book was released on 2012-07-26 with total page 617 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetics is one of the fastest growing fields of sciences, illuminating studies of human diseases by looking beyond genetic make-up and acknowledging that outside factors play a role in gene expression. The goal of this volume is to highlight those diseases or conditions for which we have advanced knowledge of epigenetic factors such as cancer, autoimmune disorders and aging as well as those that are yielding exciting breakthroughs in epigenetics such as diabetes, neurobiological disorders and cardiovascular disease. Where applicable, attempts are made to not only detail the role of epigenetics in the etiology, progression, diagnosis and prognosis of these diseases, but also novel epigenetic approaches to the treatment of these diseases. Chapters are also presented on human imprinting disorders, respiratory diseases, infectious diseases and gynecological and reproductive diseases. Since epigenetics plays a major role in the aging process, advances in the epigenetics of aging are highly relevant to many age-related human diseases. Therefore, this volume closes with chapters on aging epigenetics and breakthroughs that have been made to delay the aging process through epigenetic approaches. With its translational focus, this book will serve as valuable reference for both basic scientists and clinicians alike. Comprehensive coverage of fundamental and emergent science and clinical usage Side-by-side coverage of the basis of epigenetic diseases and their treatments Evaluation of recent epigenetic clinical breakthroughs
Download or read book Molecular Epidemiology written by Paul A. Schulte and published by Academic Press. This book was released on 2012-12-02 with total page 609 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book will serve as a primer for both laboratory and field scientists who are shaping the emerging field of molecular epidemiology. Molecular epidemiology utilizes the same paradigm as traditional epidemiology but uses biological markers to identify exposure, disease or susceptibility. Schulte and Perera present the epidemiologic methods pertinent to biological markers. The book is also designed to enumerate the considerations necessary for valid field research and provide a resource on the salient and subtle features of biological indicators.
Download or read book Epigenetics of Aging written by Trygve O. Tollefsbol and published by Springer Science & Business Media. This book was released on 2009-11-11 with total page 462 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent studies have indicated that epigenetic processes may play a major role in both cellular and organismal aging. These epigenetic processes include not only DNA methylation and histone modifications, but also extend to many other epigenetic mediators such as the polycomb group proteins, chromosomal position effects, and noncoding RNA. The topics of this book range from fundamental changes in DNA methylation in aging to the most recent research on intervention into epigenetic modifications to modulate the aging process. The major topics of epigenetics and aging covered in this book are: 1) DNA methylation and histone modifications in aging; 2) Other epigenetic processes and aging; 3) Impact of epigenetics on aging; 4) Epigenetics of age-related diseases; 5) Epigenetic interventions and aging: and 6) Future directions in epigenetic aging research. The most studied of epigenetic processes, DNA methylation, has been associated with cellular aging and aging of organisms for many years. It is now apparent that both global and gene-specific alterations occur not only in DNA methylation during aging, but also in several histone alterations. Many epigenetic alterations can have an impact on aging processes such as stem cell aging, control of telomerase, modifications of telomeres, and epigenetic drift can impact the aging process as evident in the recent studies of aging monozygotic twins. Numerous age-related diseases are affected by epigenetic mechanisms. For example, recent studies have shown that DNA methylation is altered in Alzheimer’s disease and autoimmunity. Other prevalent diseases that have been associated with age-related epigenetic changes include cancer and diabetes. Paternal age and epigenetic changes appear to have an effect on schizophrenia and epigenetic silencing has been associated with several of the progeroid syndromes of premature aging. Moreover, the impact of dietary or drug intervention into epigenetic processes as they affect normal aging or age-related diseases is becoming increasingly feasible.
Download or read book The Genetic Basis of Human Cancer written by Kenneth W. Kinzler and published by McGraw Hill Professional. This book was released on 2002 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: -- Current coverage of diagnosis and treatment on a wide spectrum of active cancer research.
Download or read book DNA Methylation and Cancer Therapy written by Moshe Szyf and published by Springer Science & Business Media. This book was released on 2005-01-20 with total page 264 pages. Available in PDF, EPUB and Kindle. Book excerpt: NA methylation has bewildered molecular biologists since Hotchkiss discovered it almost six decades ago (Hotchkiss RDJ. Biol Cem 1948; 175:315-332). The fact that the chemical structure of our D genome consists of two components that are covalently bound, the genetic information that is replicated by the DNA replication machinery ana DNA methylation that is maintainea by independent enzymatic machinery, has redictably stimulated the imagination and curiosity of generations of mo Edular biologists. An obvious question was whether DNA methylation was a bearer of additional information to the genetic information and what was the nature of this information? It was tempting to speculate that DNA me thylation applied some form of control over programming of the genome s expression profile. Once techniques to probe the methylation profile of whole genomes as well as specific genes became available, it became clear that DNA methylation patterns are gene and tissue specific and that patterns of gene expression correlate with patterns of methylation. DNA methylation pat terns emerged as the only component of the chemical structure of DNA that exhibited tissue and cell specificity. This data seemingly provided an attrac tively simple explanation for the longstanding dilemma of how could one identical genome manifest itself in so many different forms in multicellular organisms? The DNA methylation pattern has thus become the only known factor to confer upon DNA a unique cellular identity.
Download or read book Handbook of Nutrition Diet and Epigenetics written by Vinood B. Patel and published by Springer. This book was released on 2019-02-27 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This multivolume reference work addresses the fact that the well being of humankind is predicated not only on individuals receiving adequate nutrition but also on their genetic makeup. The work includes more than 100 chapters organized in the following major sections: Introduction and Overview; Epigenetics of Organs and Diseases in Relation to Diet and Nutrition; Detailed Processes in Epigenetics of Diet and Nutrition; Modulating Epigenetics with Diet and Nutrition; and Practical Techniques. While it is well known that genes may encode proteins responsible for structural and dynamic components, there is an increasing body of evidence to suggest that nutrition itself may alter the way in which genes are expressed via the process of epigenetics. This is where chemically imposed alteration in the DNA sequence occurs or where the functional expression of DNA is modulated. This may include changes in DNA methylation, non-coding RNA, chromatin, histone acetylation or methylation, and genomic imprinting. Knowledge regarding the number of dietary components that impact on epigenetic processes is increasing almost daily. Marshalling all the information on the complex relationships between diet, nutrition, and epigenetic processes is somewhat difficult due to the wide myriad of material. It is for this reason that the present work has been compiled.
