Epigenetic Alterations In Oncogenesis

The purpose of this book is to provide an up to date review of the nature and consequences of epigenetic changes in cancer. Epigenetics literally means “above” genetics, and consists of heritable gene expression or other phenotypic states not accounted for by DNA base sequence. Epigenetic changes are now known to make a large contribution to various aspects of tumorigenesis. These changes include alterations in global and promoter specific DNA methylation, activating and repressive histone modifications, and changes in higher order chromatin structures. Each of these topics will be covered in this book.

The purpose of this book is to provide an up to date review of the nature and consequences of epigenetic changes in cancer. Epigenetics literally means “above” genetics, and consists of heritable gene expression or other phenotypic states not accounted for by DNA base sequence. Epigenetic changes are now known to make a large contribution to various aspects of tumorigenesis. These changes include alterations in global and promoter specific DNA methylation, activating and repressive histone modifications, and changes in higher order chromatin structures. Each of these topics will be covered in this book.

Overall, this book illustrates the complexities of the regulation and deregulation of genes mediated through epigenetics in the development and progression of human malignancies. All the articles have been carefully chosen to represent several cancer systems with state of our knowledge on the role of epigenetic deregulation of microRNAs (miRNAs) and their target mRNAs along with epigenetic deregulation of mRNAs. This book also illustrates the role of several dietary agents, collectively called nutraceuticals or natural agents in modulating the epigenetic reprogramming of miRNAs and mRNAs for the prevention and/or treatment of human malignancies. It is well known that genetic aberrations, especially inherited through parents (somatic genetic alterations) contribute to the development of less than 10% of all cancer yet epigenetic alterations in genes especially through selective methylation and acetylation appears to be responsible for the development and progression of the vast majority of all cancers. Therefore, understanding the role of epigenetics in the regulation of genes especially through deregulated expression of miRNAs as presented in this book will allow scientists to devise targeted therapeutic strategies for re-expression of the lost genes or down-regulate the genes that are over-expressed in order to eradicate cancer. It is hoped that targeting epigenetics will not only target cancer cells but it will also target the tumor microenvironment (more like the entire tumor environment such as the entire host) for achieving better treatment outcomes for patients diagnosed with cancer which will lead to achieve the long-term objective for complete eradication of cancer. This book contains fifteen chapters which begins with the concept of systems and network biology for investigating the epigenetics of cancer followed by a series of articles on the role of miRNAs and their target genes in the biology of pancreatic cancer and other cancers such as breast, kidney, prostate and and colon. Since it is becoming increasingly clear that cancer stem cells (CSCs) are important in the development and progression of cancer, and CSCs are important in therapeutic resistance, treatment failure and tumor recurrence, thus the importance of CSCs and epigenetics has been highlighted by a very timely article on epigenetic variations of stem cell markers in cancer including miRNAs. Moreover, just targeting heterogeneous cancer cell populations may not be optimal to eradicate tumors and for which one must take a holistic approach for developing drugs that could also target the tumor microenvironment and tumor dormancy that are regulated through epigenetics. Keeping abreast with this thought process the concluding chapter provides a concept towards curative cancer therapy with maspin, which could be a unique window of opportunity to target tumor dormancy. Therefore, it suggest that targeting the tumor dormancy and the tumor microenvironment using novel therapeutics specifically by targeting epigenetics would become the future of medicine.

This volume explores the epigenetic alterations and their association with various human cancers. Considering one of human cancer as an example, individual chapters are focused on defining the role of epigenetic regulators and underlying mechanisms in cancer growth and progression. Epigenetic alteration including DNA methylation, histone modification, nucleosome positioning and non-coding RNAs expression are involved in a complex network of regulating expression of oncogenes and tumor suppressor genes and constitute an important event of the multistep process of carcinogenesis. Recent advances in the understanding of the epigenetic regulation and detailed information of these epigenetic changes in various cancers provide new avenues of advancements in diagnostics, prognostics, and therapies of this highly fatal disease.

Anomalous epigenetic patterns touch many areas of study including biomedical, scientific, and industrial. With perspectives from international experts, this resource offers an all-inclusive overview of epigenetics, which bridge DNA information and function by regulating gene expression without modifying the DNA sequence itself. Epigenetics, in its

In Epigenetic Regulation of Cancer, a series of volumes from the International Review of Cell and Molecular Biology series, various experts in epigenetics critically cover multiple facets of cancer-associated epigenetic alterations, including the impact of epigenetic deregulation in all steps of oncogenesis as well as promising strategies to therapeutically target cancer-associated epigenetic deregulation. This collection aims at expanding our knowledge on this exciting field of investigation and providing fresh insights as a basis for further investigations that will hopefully translate into an improved clinical management of patients with cancer. The collection provides accurate and critical review articles from invited experts on the selected topic Each review provides the newest insights and remarks on multiple subjects of the topic The volume offers a broad range of perspectives on detailed features

During the past few decades, it has become increasingly apparent that heredity is not the sole determining factor in disease development, such as cancer. This landmark work covers a wide array of aspects in the relatively new area of epigenetics, ranging from its role in the basic mechanisms of tumorigenesis, to the newest epigenetic drugs being developed and used for cancer therapy. Cancer Epigenetics presents in-depth discussions of DNA methylation alterations, histone and RNA modifications, and nucleosome remodeling, which are all intimately involved in the formation of tumors. It also analyzes metabolic influences on cancer epigenetics and advances in epigenetic cancer gene therapy. Discusses the Latest Advances in the Role of Epigenetics in Tumor Initiation, Progression, and Metastasis With stand-alone chapters written by research pioneers in the field, this definitive resource covers— DNA methylation and cancer Histone modifications in cancer Emerging areas of cancer epigenetics Epigenetics in the diagnosis, prognosis, and therapy of cancer Future directions in epigenetic cancer research Bringing together different topics into a single compilation, this text is a prime resource for those with interests ranging from the basic mechanisms of tumor biology to cancer therapy. It also serves as a core textbook for advanced courses with a focus on genetic diseases, molecular biology, and/or cancer. This seminal work answers the call for a thorough and authoritative reference that covers the critical and contemporary aspects of this revolutionary field.

Epigenetics, which deals with the study of heritable gene expression that takes place independent of changes in DNA sequence, and optogenetics, which deals with the study of genes expressed under the influence of light, are two emerging areas of study and research that have contributed immensely to our current knowledge of mechanisms and disease processes in humans. These disciplines are interrelated in the broader picture of biology and one can be used to change or modify the other. The complexity of the techniques involved in these disciplines often leads to a lack of proper understanding by researchers from other disciplines and the scientific community at large. As such, this book provides simple and easy-to-follow explanations of some of the most exciting areas of research in these disciplines.