Mutations in regulators of the epigenome and their effects on the DNA methylome

Genome-wide profiling for genetic alterations in cancer has identified mutations in genes that are associated with epigenetic programming of genomes for DNA methylation patterns, histone modifications patterns and the positioning of nucleosomes. Here a systematic evaluation of the available cancer genome profiling data established by large international consortia, in order to identify recurrently mutated genes or pathways was described. Using curated list of approximately 700 epigenetic regulators and currently available genome-wide datasets on genetic and epigenetic alterations in cancers, the distribution of alterations in epigenetic regulators was described. Epigenetic genes were classified as potential oncogenic or those with tumor-suppressor function based on the location of mutations relative to functional domains and their frequencies. A panel of 50 epigenetic genes, including: DNMTs, histones (H3F3A, HIST1H3B), histone editors (KDM5C, KDM6A) and writers (MLLs, SETD2, EZH2, ATM) that can promote epigenetic changes in cancer was identified. Using correlative analysis of publicly available methylation data with information on deregulated epigenetic driver genes, many identified subtype-specific methylation clusters were correlated with groups of up to 3 epigenetic regulators. This analysis provides a source for the identification and link between methylation groups and deregulated epigenetic genes. Major cancer specific methylation changes have been observed in promoters and gene bodies. Tissue-specific cancer methylation differences have been located in enhancers and regulatory regions of non-coding RNAs. Based on identified results, the major mechanism of non-coding RNA deregulation in cancer has been investigated on independent data cohort. Using integrative analysis of non-coding RNA in early-onset prostate cancer, non-coding RNAs were classified as tumor-suppressive and oncogenic. About 120 novel prostate cancer specific non-coding RNAs that have been epigenetically deregulated have been identified. Our study on the defects in regulators of the epigenome will help to understand mechanisms leading to distinct epigenetic patterns and will allow the molecular validation of defined correlations in experimental settings

Xenopus

This book focuses on the amphibian, Xenopus, one of the most commonly used model animals in the biological sciences. Over the past 50 years, the use of Xenopus has made possible many fundamental contributions to our knowledge in cell biology, developmental biology, molecular biology, and neurobiology. In recent years, with the completion of the genome sequence of the main two species and the application of genome editing techniques, Xenopus has emerged as a powerful system to study fundamental disease mechanisms and test treatment possibilities. Xenopus has proven an essential vertebrate model system for understanding fundamental cell and developmental biological mechanisms, for applying fundamental knowledge to pathological processes, for deciphering the function of human disease genes, and for understanding genome evolution. Key Features Provides historical context of the contributions of the model system Includes contributions from an international team of leading scholars Presents topics spanning cell biology, developmental biology, genomics, and disease model Describes recent experimental advances Incorporates richly illustrated diagrams and color images Related Titles Green, S. L. The Laboratory Xenopus sp. (ISBN 978-1-4200-9109-0) Faber, J. & P. D. Nieuwkoop. Normal Table of Xenopus laevis (Daudin): A Systematical & Chronological Survey of the Development from the Fertilized Egg till the End of Metamorphosis (ISBN 978-0-8153-1896-5) Jarret, R. L. & K. McCluskey. The Biological Resources of Model Organisms (ISBN 978-1-0320-9095-5

Xenopus

This book focuses on the amphibian, Xenopus, one of the most commonly used model animals in the biological sciences. Over the past 50 years, the use of Xenopus has made possible many fundamental contributions to our knowledge in cell biology, developmental biology, molecular biology, and neurobiology. In recent years, with the completion of the genome sequence of the main two species and the application of genome editing techniques, Xenopus has emerged as a powerful system to study fundamental disease mechanisms and test treatment possibilities. Xenopus has proven an essential vertebrate model system for understanding fundamental cell and developmental biological mechanisms, for applying fundamental knowledge to pathological processes, for deciphering the function of human disease genes, and for understanding genome evolution. Key Features Provides historical context of the contributions of the model system Includes contributions from an international team of leading scholars Presents topics spanning cell biology, developmental biology, genomics, and disease model Describes recent experimental advances Incorporates richly illustrated diagrams and color images Related Titles Green, S. L. The Laboratory Xenopus sp. (ISBN 978-1-4200-9109-0) Faber, J. & P. D. Nieuwkoop. Normal Table of Xenopus laevis (Daudin): A Systematical & Chronological Survey of the Development from the Fertilized Egg till the End of Metamorphosis (ISBN 978-0-8153-1896-5) Jarret, R. L. & K. McCluskey. The Biological Resources of Model Organisms (ISBN 978-1-0320-9095-5

Hematology

Hematology encompasses the physiology and pathology of blood and of the blood-forming organs. In common with other areas of medicine, the pace of change in hematology has been breathtaking over recent years. There are now many treatment options available to the modern hematologist and, happily, a greatly improved outlook for the vast majority of patients with blood disorders and malignancies. Improvements in the clinic reflect, and in many respects are driven by, advances in our scientific understanding of hematological processes under both normal and disease conditions. Hematology - Science and Practice consists of a selection of essays which aim to inform both specialist and non-specialist readers about some of the latest advances in hematology, in both laboratory and clinic

Proliferation and differentiation potential of human primary mesenchymal (stem/stromal) cells

Adult stem cells have been shown to be involved in regeneration and repair processes in multicellular organisms. Mesenchymal stem cells are attractive for tissue engineering due to their interaction with various immune cells and their expression and secretion of various soluble factors. Therefore, we investigated the proliferation and differentiation potential, surface markers and gene expression profile of MSC. For a successful application of MSC in tissue engineering, a detailed knowledge of these processes is essential.Adulte Stammzellen sind nachweislich in multizellulären Organismen an Regenerations- und Reparaturprozessen beteiligt. Mesenchymale Stammzellen sind aufgrund ihrer Interaktion mit verschiedenen Immunzellen und ihrer Expression und Sekretion verschiedener löslicher Faktoren für das Tissue Engineering attraktiv. Daher haben wir das Proliferations- und Differenzierungspotenzial, die Oberflächenmarker und das Genexpressionsprofil von MSC untersucht. Für eine erfolgreiche Anwendung von MSC im Tissue Engineering ist die genaue Kenntnis dieser Prozesse unerlässlich

Identifcation of candidate miRNAs in early‑onset and late‑onset prostate cancer by network analysis

The incidence of patients under 55 years old diagnosed with Prostate Cancer (EO-PCa) has increased during recent years. The molecular biology of PCa cancer in this group of patients remains unclear. Here, we applied weighted gene coexpression network analysis of the expression of miRNAs from 24 EO-PCa patients (38–45 years) and 25 late-onset PCa patients (LO-PCa, 71–74 years) to identify key miRNAs in EO-PCa patients. In total, 69 diferentially expressed miRNAs were identifed. Specifcally, 26 and 14 miRNAs were exclusively deregulated in young and elderly patients, respectively, and 29 miRNAs were shared. We identifed 20 hub miRNAs for the network built for EO-PCa. Six of these hub miRNAs exhibited prognostic signifcance in relapse‐free or overall survival. Additionally, two of the hub miRNAs were coexpressed with mRNAs of genes previously identifed as deregulated in EO-PCa and in the most aggressive forms of PCa in African-American patients compared with Caucasian patients. These genes are involved in activation of immune response pathways, increased rates of metastasis and poor prognosis in PCa patients. In conclusion, our analysis identifed miRNAs that are potentially important in the molecular pathology of EO-PCa. These genes may serve as biomarkers in EO-PCa and as possible therapeutic targets