دورية أكاديمية
Metabolic Regulation of the Epigenome Drives Lethal Infantile Ependymoma.
العنوان: | Metabolic Regulation of the Epigenome Drives Lethal Infantile Ependymoma. |
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المؤلفون: | Michealraj KA; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Kumar SA; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1L7, Canada., Kim LJY; Division of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA., Cavalli FMG; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Przelicki D; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1L7, Canada., Wojcik JB; Department of Biochemistry and Biophysics and Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Delaidelli A; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC V6T 1Z2, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z2, Canada., Bajic A; Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada., Saulnier O; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., MacLeod G; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada., Vellanki RN; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada., Vladoiu MC; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1L7, Canada., Guilhamon P; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Ong W; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1L7, Canada., Lee JJY; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1L7, Canada., Jiang Y; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Holgado BL; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Rasnitsyn A; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada., Malik AA; Centre for Molecular and Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada., Tsai R; Centre for Molecular and Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada., Richman CM; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada., Juraschka K; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1L7, Canada., Haapasalo J; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Wang EY; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada., De Antonellis P; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Suzuki H; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Farooq H; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Balin P; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1L7, Canada., Kharas K; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1L7, Canada., Van Ommeren R; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1L7, Canada., Sirbu O; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada., Rastan A; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Krumholtz SL; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Ly M; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1L7, Canada., Ahmadi M; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada., Deblois G; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada., Srikanthan D; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1L7, Canada., Luu B; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Loukides J; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Wu X; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Garzia L; Cancer Research Program, McGill University Health Centre Research Institute, Montreal, QC H4A 3J1, Canada., Ramaswamy V; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Division of Haematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada., Kanshin E; Institute for Research in Immunology and Cancer (IRIC), Department of Medicine, Université de Montréal, Montréal, QC H3C 3J7, Canada., Sánchez-Osuna M; Institute for Research in Immunology and Cancer (IRIC), Department of Medicine, Université de Montréal, Montréal, QC H3C 3J7, Canada., El-Hamamy I; Computational Biology Program, Adaptive Oncology Theme, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada., Coutinho FJ; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Prinos P; Structural Genomics Consortium, University of Toronto, 101 College Street, MaRS Centre, South Tower, Toronto, ON M5G 1L7, Canada., Singh S; Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Surgery, McMaster University, Hamilton, ON L8S 4K1, Canada., Donovan LK; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Daniels C; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Schramek D; Centre for Molecular and Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada., Tyers M; Institute for Research in Immunology and Cancer (IRIC), Department of Medicine, Université de Montréal, Montréal, QC H3C 3J7, Canada., Weiss S; Hotchkiss Brain Institute, Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada., Stein LD; Computational Biology Program, Adaptive Oncology Theme, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada., Lupien M; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada., Wouters BG; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada., Garcia BA; Department of Biochemistry and Biophysics and Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Arrowsmith CH; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Structural Genomics Consortium, University of Toronto, 101 College Street, MaRS Centre, South Tower, Toronto, ON M5G 1L7, Canada., Sorensen PH; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC V6T 1Z2, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z2, Canada., Angers S; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada; Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada., Jabado N; Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; Department of Pediatrics, McGill University, The Research Institute of the McGill University Health Center, Montreal, QC H4A 3J1, Canada., Dirks PB; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada; Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON M5G 1L7, Canada., Mack SC; Texas Children's Hospital Cancer Center, Department of Pediatrics, Baylor College of Medicine, Dan L. Duncan Cancer Center, Houston, TX 77030, USA. Electronic address: stephen.mack@bcm.edu., Agnihotri S; Department of Neurological Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. Electronic address: sameer.agnihotri@gmail.com., Rich JN; Division of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA. Electronic address: drjeremyrich@gmail.com., Taylor MD; The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON M5G 1L7, Canada. Electronic address: mdt.cns@gmail.com. |
المصدر: | Cell [Cell] 2020 Jun 11; Vol. 181 (6), pp. 1329-1345.e24. Date of Electronic Publication: 2020 May 22. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 0413066 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4172 (Electronic) Linking ISSN: 00928674 NLM ISO Abbreviation: Cell Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Cambridge, Ma : Cell Press Original Publication: Cambridge, MIT Press. |
مواضيع طبية MeSH: | Ependymoma/*genetics , Ependymoma/*metabolism , Epigenome/*genetics , Infratentorial Neoplasms/*genetics , Infratentorial Neoplasms/*metabolism, Animals ; Brain Neoplasms/genetics ; Brain Neoplasms/metabolism ; Cell Line ; Cell Proliferation/genetics ; DNA Methylation/genetics ; Epigenomics/methods ; Histones/genetics ; Histones/metabolism ; Humans ; Infant ; Lysine/genetics ; Lysine/metabolism ; Male ; Mice, Inbred C57BL ; Mutation/genetics |
مستخلص: | Posterior fossa A (PFA) ependymomas are lethal malignancies of the hindbrain in infants and toddlers. Lacking highly recurrent somatic mutations, PFA ependymomas are proposed to be epigenetically driven tumors for which model systems are lacking. Here we demonstrate that PFA ependymomas are maintained under hypoxia, associated with restricted availability of specific metabolites to diminish histone methylation, and increase histone demethylation and acetylation at histone 3 lysine 27 (H3K27). PFA ependymomas initiate from a cell lineage in the first trimester of human development that resides in restricted oxygen. Unlike other ependymomas, transient exposure of PFA cells to ambient oxygen induces irreversible cellular toxicity. PFA tumors exhibit a low basal level of H3K27me3, and, paradoxically, inhibition of H3K27 methylation specifically disrupts PFA tumor growth. Targeting metabolism and/or the epigenome presents a unique opportunity for rational therapy for infants with PFA ependymoma. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020 Elsevier Inc. All rights reserved.) |
التعليقات: | Comment in: Mol Cell. 2020 Jun 18;78(6):999-1001. (PMID: 32559429) Comment in: Dev Cell. 2020 Jul 20;54(2):134-136. (PMID: 32693052) |
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معلومات مُعتمدة: | R01 CA169117 United States CA NCI NIH HHS; R01 CA159859 United States CA NCI NIH HHS; R01 CA148699 United States CA NCI NIH HHS; United Kingdom WT_ Wellcome Trust; R01 NS087913 United States NS NINDS NIH HHS; R35 CA197718 United States CA NCI NIH HHS; R01 CA154130 United States CA NCI NIH HHS; F30 CA203101 United States CA NCI NIH HHS; R01 CA171652 United States CA NCI NIH HHS; R01 NS089272 United States NS NINDS NIH HHS |
فهرسة مساهمة: | Keywords: cancer metabolism; ependymoma; epigenetics; hindbrain development; microenvironment; paediatric cancer |
المشرفين على المادة: | 0 (Histones) K3Z4F929H6 (Lysine) |
تواريخ الأحداث: | Date Created: 20200524 Date Completed: 20210104 Latest Revision: 20240113 |
رمز التحديث: | 20240113 |
مُعرف محوري في PubMed: | PMC10782558 |
DOI: | 10.1016/j.cell.2020.04.047 |
PMID: | 32445698 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1097-4172 |
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DOI: | 10.1016/j.cell.2020.04.047 |