A Study of Histone H2B Mutations in Cancer PDF Download

Author: 劉嘉賢
Publisher:
ISBN:
Category : Medical sciences
Languages : en
Pages : 117

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Author: Dong Fang
Publisher: Springer Nature
ISBN: 9811581045
Category : Medical
Languages : en
Pages : 102

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Book Description
This book focuses on histone mutations, especially those mutations closely related to cancer. Genetic mutations and epigenetic alterations contribute to the development of a variety of cancers: recent genetic studies have identified e.g. H3K27M and H3G34R/V mutation in over 75% of DIPG cases, H3.3K36M mutation in more than 90% of chondroblastoma cases, and H3G34W/L mutation in over 90% of giant cell tumors of bone. Given the high incidence and tumorigenesis effects of histone H3 mutations, they are also referred to as oncohistones. This book highlights the advances made in the area over the past 10 years, and offers a state-of-the-art summary of epigenetic alternation, gene expression, protein structure, drug discovery, immunotherapy, and mouse modeling of histone H3 mutations in various tumors. Chiefly intended to provide researchers and graduate students with an overall picture of these mutations, it will also be of interest to researchers in basic oncology, clinical oncology, and epigenetics, as well as academics and clinical oncology practitioners.

Author: Shelley L. Berger
Publisher: Springer Science & Business Media
ISBN: 354037633X
Category : Science
Languages : en
Pages : 223

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Book Description
Methylation of DNA at cytosine residues as well as post-translational modifications of histones, including phosphorylation, acetylation, methylation and ubiquitylation, contribute to the epigenetic information carried by chromatin. These changes play an important role in the regulation of gene expression by modulating the access of regulatory factors to the DNA. The use of a combination of biochemical, genetic and structural approaches has allowed demonstration of the role of chromatin structure in transcriptional control. The structure of nucleosomes has been elucidated and enzymes involved in DNA or histone modifications have been extensively characterized. Since deregulation of epigenetic marks has been reported in many cancers, a better understanding of the underlying molecular mechanisms bears the promise that new drug targets may soon be found. The newest developments in this quickly developing field are presented in this book.

Author: Nisha Kabir
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

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"Histone proteins have vital roles in the regulation of gene expression during development, where dysregulation of this processes results in diseases such as cancer and neurological disorders. Pediatric high-grade glioma (pHGG) is a highly aggressive cancer with a two-year survival rate of less than 30%. With the advent of whole genome sequencing, recurrent somatic mutations in histone H3 proteins and common co-occurring partner mutations have been identified to drive a subset of cancer. Histone H3 lysine 27 to methionine (H3K27M) cause a subset of pHGGs occurring in the brain midline in younger children, while mutations in glycine 34 to arginine or valine (G34R/V) cause another subset of pHGGs occurring in the cerebral cortex of adolescents and young adults. Histone H3 mutants also drive cancer outside of the brain, where mutations in glycine 34 to tryptophan (G34W) cause over 90% of giant cell tumors of bone (GCTB) in adults. The restricted pattern of histone mutations with anatomical location and age of incidence in brain tumors gave rise to the hypothesis that histone mutations only occurring in a specific developmental window and cellular context give rise to cancer. While the cellular context is known for these tumors, how the mutations subsequently impact cell identity along differentiation are not well characterized. In this thesis, I study the transcriptomic effect of H3 and partner mutations on cellular identity using in silico integrative analysis of genome-wide transcriptomic data from model systems and normal references of the developing brain at single-cell resolution. I will use a variety computational methods to map genome-wide transcriptomic data to normal references to infer changes to cell identity in disease states. First, I study the role of partner mutations in a kinase, ACVR1, in the context of mutant H3 K27M. Gene expression profiling shows that mutations in ACVR1 impact cellular identity in distinct ways depending on the histone context. Second, I study the effect of H3.3 K27M mutations using cell lines subjected to differentiation experiments and orthotopic xenograft models using an isogenic system. In vivo K27M-KO experiments show a difference in cell state towards oligodendrocyte and astrocyte lineages, while in vitro K27M-KO experiments show upregulation of extracellular matrix and cellular adhesion gene programs. Third, I study the transcriptomic effects of germline heterozygous H3.3 G34R/V/W mutations in murine models. Germline G34 mutants have surprising tissue specificity; G34R mutants cause progressive neuronal loss coupled to increased immune infiltration in the brain, while G34W mutants cause an unhealthy obesity phenotype with decreased expression of PPARG, a master regulator of adipocyte differentiation. Together, this work provides insight into changes in cell identity and neurological abnormalities induced by H3 mutations at the level of transcription. This represents an important step in characterizing the cellular contexts of these disease states for the development of therapeutics"--

Author: Aamir Ahmad
Publisher: Springer Nature
ISBN: 3030203018
Category : Medical
Languages : en
Pages : 427

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Resistance to therapies, both targeted and systemic, and metastases to distant organs are the underlying causes of breast cancer-associated mortality. The second edition of Breast Cancer Metastasis and Drug Resistance brings together some of the leading experts to comprehensively understand breast cancer: the factors that make it lethal, and current research and clinical progress. This volume covers the following core topics: basic understanding of breast cancer (statistics, epidemiology, racial disparity and heterogeneity), metastasis and drug resistance (bone metastasis, trastuzumab resistance, tamoxifen resistance and novel therapeutic targets, including non-coding RNAs, inflammatory cytokines, cancer stem cells, ubiquitin ligases, tumor microenvironment and signaling pathways such as TRAIL, JAK-STAT and mTOR) and recent developments in the field (epigenetic regulation, microRNAs-mediated regulation, novel therapies and the clinically relevant 3D models). Experts also discuss the advances in laboratory research along with their translational and clinical implications with an overarching goal to improve the diagnosis and prognosis, particularly that of breast cancer patients with advanced disease.

Author: Domenico Coppola
Publisher: Springer Science & Business Media
ISBN: 904813725X
Category : Medical
Languages : en
Pages : 317

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This book offers a comprehensive update on mechanisms of tumorigenesis. The first portion discusses pediatric cancer, the influence of environmental factors and oncogene activity in tumorigenesis; the second portion is structured by organ site for easy access.

Author: Jerry L. Workman
Publisher: Springer Science & Business Media
ISBN: 1461486246
Category : Medical
Languages : en
Pages : 594

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Book Description
​​​​​​​​​​​​​While there has been an increasing number of books on various aspects of epigenetics, there has been a gap over the years in books that provide a comprehensive understanding of the fundamentals of chromatin. ​Chromatin is the combination of DNA and proteins that make up the genetic material of chromosomes. Its primary function is to package DNA to fit into the cell, to strengthen the DNA to prevent damage, to allow mitosis and meiosis, and to control the expression of genes and DNA replication. The audience for this book is mainly newly established scientists ​and graduate students. Rather than going into the more specific areas of recent research on chromatin the chapters in this book give a strong, updated groundwork about the topic. Some the fundamentals that this book will cover include the structure of chromatin and biochemistry and the enzyme complexes that manage it.

Author: Cesar Lopez-Camarillo
Publisher: CRC Press
ISBN: 1466576774
Category : Medical
Languages : en
Pages : 426

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Book Description
MicroRNA (miRNA) biology is a cutting-edge topic in basic as well as biomedical research. This is a specialized book focusing on the current understanding of the role of miRNAs in the development, progression, invasion, and metastasis of diverse types of cancer. It also reviews their potential for applications in cancer diagnosis, prognosis, and th

Author: David W. FitzSimons
Publisher: John Wiley & Sons
ISBN: 0470717785
Category : Science
Languages : en
Pages : 192

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The Novartis Foundation Series is a popular collection of the proceedings from Novartis Foundation Symposia, in which groups of leading scientists from a range of topics across biology, chemistry and medicine assembled to present papers and discuss results. The Novartis Foundation, originally known as the Ciba Foundation, is well known to scientists and clinicians around the world.

Author: Renato Paro
Publisher: Springer Nature
ISBN: 3030686701
Category : Science
Languages : en
Pages : 215

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Book Description
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