TTYH3 Sirna (H): Sc-89544
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245 E L Woodward et al. Genetic changes in anaplastic 24:5 209–220 Research thyroid cancer Genomic complexity and targeted genes in anaplastic thyroid cancer cell lines Eleanor L Woodward1, Andrea Biloglav1, Naveen Ravi1, Minjun Yang1, Lars Ekblad2, Johan Wennerberg3 and Kajsa Paulsson1 1Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden Correspondence 2Division of Oncology and Pathology, Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden should be addressed 3Division of Otorhinolaryngology/Head and Neck Surgery, Clinical Sciences, Lund University and Skåne to K Paulsson University Hospital, Lund, Sweden Email [email protected] Abstract Anaplastic thyroid cancer (ATC) is a highly malignant disease with a very short median Key Words survival time. Few studies have addressed the underlying somatic mutations, and the f thyroid genomic landscape of ATC thus remains largely unknown. In the present study, we f molecular genetics have ascertained copy number aberrations, gene fusions, gene expression patterns, f gene expression and mutations in early-passage cells from ten newly established ATC cell lines using single nucleotide polymorphism (SNP) array analysis, RNA sequencing and whole exome sequencing. The ATC cell line genomes were highly complex and displayed signs of replicative stress and genomic instability, including massive aneuploidy and frequent Endocrine-Related Cancer Endocrine-Related breakpoints in the centromeric regions and in fragile sites. Loss of heterozygosity involving whole chromosomes was common, but there were no signs of previous near- haploidisation events or chromothripsis. A total of 21 fusion genes were detected, including six predicted in-frame fusions; none were recurrent. -
Molecular Targeting and Enhancing Anticancer Efficacy of Oncolytic HSV-1 to Midkine Expressing Tumors
University of Cincinnati Date: 12/20/2010 I, Arturo R Maldonado , hereby submit this original work as part of the requirements for the degree of Doctor of Philosophy in Developmental Biology. It is entitled: Molecular Targeting and Enhancing Anticancer Efficacy of Oncolytic HSV-1 to Midkine Expressing Tumors Student's name: Arturo R Maldonado This work and its defense approved by: Committee chair: Jeffrey Whitsett Committee member: Timothy Crombleholme, MD Committee member: Dan Wiginton, PhD Committee member: Rhonda Cardin, PhD Committee member: Tim Cripe 1297 Last Printed:1/11/2011 Document Of Defense Form Molecular Targeting and Enhancing Anticancer Efficacy of Oncolytic HSV-1 to Midkine Expressing Tumors A dissertation submitted to the Graduate School of the University of Cincinnati College of Medicine in partial fulfillment of the requirements for the degree of DOCTORATE OF PHILOSOPHY (PH.D.) in the Division of Molecular & Developmental Biology 2010 By Arturo Rafael Maldonado B.A., University of Miami, Coral Gables, Florida June 1993 M.D., New Jersey Medical School, Newark, New Jersey June 1999 Committee Chair: Jeffrey A. Whitsett, M.D. Advisor: Timothy M. Crombleholme, M.D. Timothy P. Cripe, M.D. Ph.D. Dan Wiginton, Ph.D. Rhonda D. Cardin, Ph.D. ABSTRACT Since 1999, cancer has surpassed heart disease as the number one cause of death in the US for people under the age of 85. Malignant Peripheral Nerve Sheath Tumor (MPNST), a common malignancy in patients with Neurofibromatosis, and colorectal cancer are midkine- producing tumors with high mortality rates. In vitro and preclinical xenograft models of MPNST were utilized in this dissertation to study the role of midkine (MDK), a tumor-specific gene over- expressed in these tumors and to test the efficacy of a MDK-transcriptionally targeted oncolytic HSV-1 (oHSV). -
Genomic Profiling of Primary Histiocytic Sarcoma Reveals Two Molecular
Hystiocyte DIsordes ARTICLE Genomic profiling of primary histiocytic Ferrata Storti Foundation sarcoma reveals two molecular subgroups Caoimhe Egan,1 Alina Nicolae,1 Justin Lack,2 Hye-Jung Chung,1 Shannon Skarshaug,1 Thu Anh Pham,1 Winnifred Navarro,1 Zied Abdullaev,1 Nadine S. Aguilera, 3 Liqiang Xi,1 Svetlana Pack,1 Stefania Pittaluga,1 Elaine S. Jaffe1 and Mark Raffeld1 1Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD; 2NIAID Collaborative Bioinformatics Resource (NCBR), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD and 3 Haematologica 2020 University of Virginia Health System, Charlottesville, VA, USA Volume 105(4):951-960 ABSTRACT istiocytic sarcoma is a rare malignant neoplasm that may occur de novo or in the context of a previous hematologic malignancy or Hmediastinal germ cell tumor. Here, we performed whole exome sequencing and RNA-sequencing (RNA-Seq) on 21 archival cases of pri- mary histiocytic sarcoma. We identified a high number of genetic alter- ations within the RAS/RAF/MAPK pathway in 21 of 21 cases, with alter- ations in NF1 (6 of 21), MAP2K1 (5 of 21), PTPN11 (4 of 21), BRAF (4 of 21), KRAS (4 of 21), NRAS (1 of 21), and LZTR1 (1 of 21), including single cases with homozygous deletion of NF1, high-level amplification of PTPN11, and a novel TTYH3-BRAF fusion. Concurrent NF1 and PTPN11 mutations were present in 3 of 21 cases, and 5 of 7 cases with alterations in NF1 and/or PTPN11 had disease involving the gastrointestinal tract. Following unsuper- vised clustering of gene expression data, cases with NF1 and/or PTPN11 abnormalities formed a distinct tumor subgroup. -
Modifiers of Beta-Amyloid Metabolism and Deposition in Mouse Models of Alzheimer’S Disease
MODIFIERS OF BETA-AMYLOID METABOLISM AND DEPOSITION IN MOUSE MODELS OF ALZHEIMER’S DISEASE by STEFANIE SCHRUMP Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy Dissertation Adviser: Bruce Lamb, Ph.D. Department of Genetics CASE WESTERN RESERVE UNIVERSITY August, 2011 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of Stefanie Elaine Schrump______________________________________ candidate for the Doctor of Philosophy degree *. (signed) Mitch Drumm_______________________________________ (chair of the committee) Bruce Lamb_________________________________________ Anna Mitchell_______________________________________ Gary Landreth_______________________________________ ___________________________________________________ (date) May 9, 2011____________ *We also certify that written approval has been obtained for any proprietary material contained therein. 2 Copyright © 2011 by Stefanie E. Schrump All rights reserved 3 This thesis is dedicated to my children, the greatest accomplishments of my life. 4 TABLE OF CONTENTS Chapter 1: Introduction and Research Aims………………………………….16 Introduction to Alzheimer’s Disease Alzheimer’s Disease Hallmarks Alzheimer’s Disease Epidemiology APP, Abeta and the Amyloid Hypothesis Mouse Models of Alzheimer’s Disease Research Aims Chapter 2: Gene-Environment Interactions Influence Beta-Amyloid Metabolism in Mice…………………………………………………..60 Abstract Introduction Materials and Methods Results Discussion Chapter 3: The Role of -
Epigenome-Wide DNA Methylation Profiling in Progressive
ARTICLE DOI: 10.1038/s41467-018-05325-y OPEN Epigenome-wide DNA methylation profiling in Progressive Supranuclear Palsy reveals major changes at DLX1 Axel Weber 1, Sigrid C. Schwarz2,3, Jörg Tost 4, Dietrich Trümbach5, Pia Winter1, Florence Busato4, Pawel Tacik6,7, Anita C. Windhorst8, Maud Fagny4, Thomas Arzberger3,9,10, Catriona McLean11, John C. van Swieten12, Johannes Schwarz2, Daniela Vogt Weisenhorn3,5,13, Wolfgang Wurst3,5,13,14, Till Adhikary15, Dennis W. Dickson 6, Günter U. Höglinger 2,3,14 & Ulrich Müller 1 1234567890():,; Genetic, epigenetic, and environmental factors contribute to the multifactorial disorder progressive supranuclear palsy (PSP). Here, we study epigenetic changes by genome-wide analysis of DNA from postmortem tissue of forebrains of patients and controls and detect significant (P < 0.05) methylation differences at 717 CpG sites in PSP vs. controls. Four- hundred fifty-one of these sites are associated with protein-coding genes. While differential methylation only affects a few sites in most genes, DLX1 is hypermethylated at multiple sites. Expression of an antisense transcript of DLX1, DLX1AS, is reduced in PSP brains. The amount of DLX1 protein is increased in gray matter of PSP forebrains. Pathway analysis suggests that DLX1 influences MAPT-encoded Tau protein. In a cell system, overexpression of DLX1 results in downregulation of MAPT while overexpression of DLX1AS causes upregulation of MAPT. Our observations suggest that altered DLX1 methylation and expression contribute to pathogenesis of PSP by influencing MAPT. 1 Institute of Human Genetics, Justus-Liebig-Universität, Gießen 35392, Germany. 2 Department of Neurology, Technische Universität München, Munich 81377, Germany. 3 German Center for Neurodegenerative Diseases (DZNE), Munich 81377, Germany.