Epigenetically defined therapeutic targeting in H3.3G34R/V high-grade gliomas.

Animals Brain Neoplasms / genetics Epigenesis, Genetic Glioma / genetics Glycine Histones / metabolism Humans Mice

Journal

Science translational medicine
ISSN: 1946-6242
Titre abrégé: Sci Transl Med
Pays: United States
ID NLM: 101505086

Informations de publication

Date de publication:
13 Oct 2021
Historique:
entrez: 13 10 2021
pubmed: 14 10 2021
medline: 3 11 2021
Statut: ppublish

Résumé

High-grade gliomas with arginine or valine substitutions of the histone H3.3 glycine-34 residue (H3.3G34R/V) carry a dismal prognosis, and current treatments, including radiotherapy and chemotherapy, are not curative. Because H3.3G34R/V mutations reprogram epigenetic modifications, we undertook a comprehensive epigenetic approach using ChIP sequencing and ChromHMM computational analysis to define therapeutic dependencies in H3.3G34R/V gliomas. Our analyses revealed a convergence of epigenetic alterations, including (i) activating epigenetic modifications on histone H3 lysine (K) residues such as H3K36 trimethylation (H3K36me3), H3K27 acetylation (H3K27ac), and H3K4 trimethylation (H3K4me3); (ii) DNA promoter hypomethylation; and (iii) redistribution of repressive histone H3K27 trimethylation (H3K27me3) to intergenic regions at the

Identifiants

DOI: 10.1126/scitranslmed.abf7860 PMID: 34644147 PMC: PMC8783551
pubmed: 34644147
doi: 10.1126/scitranslmed.abf7860
pmc: PMC8783551
mid: NIHMS1769316
doi:

Substances chimiques

Histones 0
Glycine TE7660XO1C

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

eabf7860

Subventions

Organisme : NINDS NIH HHS
ID : K08 NS099427
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA258346
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA260735
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS110572
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007863
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009676
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA214955
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA096832
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA234416
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007315
Pays : United States

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Auteurs

Stefan R Sweha (SR)

Laboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA.
ORCID: 0000-0002-1807-6770

Chan Chung (C)

Laboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea.
ORCID: 0000-0003-0510-8996

Siva Kumar Natarajan (SK)

Laboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Molecular and Cellular Pathology Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
ORCID: 0000-0002-9663-079X

Pooja Panwalkar (P)

Laboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
ORCID: 0000-0001-7223-0452

Matthew Pun (M)

Laboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Cellular and Molecular Biology Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Medical Scientist Training Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
ORCID: 0000-0002-4766-4301

Amer Ghali (A)

Laboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
ORCID: 0000-0001-9580-587X

Jill Bayliss (J)

Laboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
ORCID: 0000-0002-7995-5584

Drew Pratt (D)

Laboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
ORCID: 0000-0003-3583-8308

Anand Shankar (A)

Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Visweswaran Ravikumar (V)

Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
ORCID: 0000-0003-4670-3898

Arvind Rao (A)

Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
ORCID: 0000-0002-9613-426X

Marcin Cieslik (M)

Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Kari Wilder-Romans (K)

Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Andrew J Scott (AJ)

Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
ORCID: 0000-0002-0835-4888

Daniel R Wahl (DR)

Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Selin Jessa (S)

Quantitative Life Sciences, McGill University, Montreal, Quebec H3A 2A7, Canada.
Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada.
ORCID: 0000-0003-4192-6523

Claudia L Kleinman (CL)

Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada.
Department of Human Genetics, McGill University, Montreal, Quebec H3A 0C7, Canada.

Nada Jabado (N)

Department of Human Genetics, McGill University, Montreal, Quebec H3A 0C7, Canada.
Department of Pediatrics, McGill University, and Research Institute of McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.
ORCID: 0000-0003-2485-3692

Alan Mackay (A)

Division of Molecular Pathology and Cancer Therapeutics, Institute of Cancer Research, London SM2 5NG, UK.
ORCID: 0000-0003-3323-4017

Chris Jones (C)

Division of Molecular Pathology and Cancer Therapeutics, Institute of Cancer Research, London SM2 5NG, UK.
ORCID: 0000-0001-8118-2296

Daniel Martinez (D)

Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
ORCID: 0000-0002-4723-9989

Mariarita Santi (M)

Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Alexander R Judkins (AR)

Department of Pathology, Children's Hospital of Los Angeles, Los Angeles, CA 90027, USA.
ORCID: 0000-0002-9242-3769

Viveka Nand Yadav (VN)

Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Tingting Qin (T)

Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Timothy N Phoenix (TN)

Division of Pharmaceutical Sciences, College of Pharmacy, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
ORCID: 0000-0003-4771-4003

Carl J Koschmann (CJ)

Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Suzanne J Baker (SJ)

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
ORCID: 0000-0002-5833-472X

Arul M Chinnaiyan (AM)

Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Michigan Center for Translational Pathology, Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109, USA.
ORCID: 0000-0001-9282-3415

Sriram Venneti (S)

Laboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
ORCID: 0000-0001-9764-0423

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Epigenetically defined therapeutic targeting...
questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs du cerveau › Epigenetically defined therapeutic targeting...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Epigenetically defined therapeutic targeting...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Gliome › Epigenetically defined therapeutic targeting...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Glycine › Epigenetically defined therapeutic targeting...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Histone › Epigenetically defined therapeutic targeting...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Epigenetically defined therapeutic targeting...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Epigenetically defined therapeutic targeting...