Evidence map›Paper›PMID 31085178›Full record

ArticleCancer cell2019

Pervasive H3K27 Acetylation Leads to ERV Expression and a Therapeutic Vulnerability in H3K27M Gliomas.

Brian Krug, Nicolas De Jay, Ashot S Harutyunyan, Shriya Deshmukh, Dylan M Marchione, Paul Guilhamon, Kelsey C Bertrand, Leonie G Mikael, Melissa K McConechy, Carol C L Chen and 18 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 133 papers.

0numbers the graph read from it
0cells of the map it votes in
133citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

133 citing papers in PubMed.

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73 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors.

Brian KrugDepartment of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada.
Nicolas De JayDepartment of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; Lady Davis Research Institute, Jewish General Hospital, Montreal, QC H3T 1E2, Canada.
Ashot S HarutyunyanDepartment of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada.
Shriya DeshmukhDepartment of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada.
Dylan M MarchioneDepartment of Biochemistry and Biophysics, and Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Paul GuilhamonPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A8, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
Kelsey C BertrandDepartment of Pediatrics, Division of Hematology and Oncology, Texas Children's Cancer and Hematology Centers, Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Leonie G MikaelDepartment of Pediatrics, McGill University, The Research Institute of the McGill University Health Center, Montreal, QC H4A 3J1, Canada.
Melissa K McConechyDepartment of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada.
Carol C L ChenDepartment of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada.
Sima KhazaeiDepartment of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada.
Robert F KoncarDepartment of Neurological Surgery, Children's Hospital, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA.
Sameer AgnihotriDepartment of Neurological Surgery, Children's Hospital, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA.
Damien FauryDepartment of Pediatrics, McGill University, The Research Institute of the McGill University Health Center, Montreal, QC H4A 3J1, Canada.
Benjamin EllezamDepartment of Pathology, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montréal, QC H3T 1C5, Canada.
Alexander G WeilDepartment of Pediatric Neurosurgery, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montréal, QC H3T 1C5, Canada.
Josie Ursini-SiegelLady Davis Research Institute, Jewish General Hospital, Montreal, QC H3T 1E2, Canada.
Daniel D De CarvalhoPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Peter B DirksDepartment of Surgery and Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Peter W LewisDepartment of Biomolecular Chemistry, School of Medicine and Public Health and Wisconsin Institute for Discovery, University of Wisconsin, Madison, WI 53715, USA.
Paolo SalomoniNuclear Function in CNS Pathophysiology, German Center for Neurodegenerative Diseases, 53127 Bonn, Germany.
Mathieu LupienPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A8, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
Cheryl ArrowsmithDepartment of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Paul F LaskoDepartment of Biology, McGill University, Montreal, QC H3A 1B1, Canada.
Benjamin A GarciaDepartment of Biochemistry and Biophysics, and Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Claudia L KleinmanDepartment of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; Lady Davis Research Institute, Jewish General Hospital, Montreal, QC H3T 1E2, Canada. Electronic address: claudia.kleinman@mcgill.ca.
Nada JabadoDepartment 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. Electronic address: nada.jabado@mcgill.ca.
Stephen C MackDepartment of Pediatrics, Division of Hematology and Oncology, Texas Children's Cancer and Hematology Centers, Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: scmack@bcm.edu.

Funding

Shared Resources Core 2: Quantitative Proteomics CoreP01CA196539 · NCI · ROCKEFELLER UNIVERSITY · PI MUIR, TOM · 2015 to 2024
$17.6M
NRSA Training CoreTL1TR001880 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI MEAGHER, EMMA ANNE · 2016 to 2025
$10.0M
STRUCTURAL BIOLOGY TRAINING PROGRAMT32GM008275 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI WAND, A. JOSHUA · 1988 to 2018
$6.0M
Viral modulation of epitranscriptomic mechanismsR01AI118891 · NIAID · WASHINGTON UNIVERSITY · PI GARCIA, BENJAMIN A, WEITZMAN, MATTHEW D. · 2015 to 2025
$5.4M
Understanding the Role of Combinatorial Histone PTM PatternsR01GM110174 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI GARCIA, BENJAMIN A · 2014 to 2017
$1.3M
CIHR EP1-120608CIHR FDN-154307CIHR MOP-286756CIHR PJT-156086NCATS NIH HHS TL1 TR001880NCI NIH HHS P01 CA196539NIAID NIH HHS R01 AI118891NIGMS NIH HHS R01 GM110174NIGMS NIH HHS T32 GM008275
6 · The paper itself

Abstract

High-grade gliomas defined by histone 3 K27M driver mutations exhibit global loss of H3K27 trimethylation and reciprocal gain of H3K27 acetylation, respectively shaping repressive and active chromatin landscapes. We generated tumor-derived isogenic models bearing this mutation and show that it leads to pervasive H3K27ac deposition across the genome. In turn, active enhancers and promoters are not created de novo and instead reflect the epigenomic landscape of the cell of origin. H3K27ac is enriched at repeat elements, resulting in their increased expression, which in turn can be further amplified by DNA demethylation and histone deacetylase inhibitors providing an exquisite therapeutic vulnerability. These agents may therefore modulate anti-tumor immune responses as a therapeutic modality for this untreatable disease.

Indexed as

AcetylationBrain NeoplasmsCell Line, TumorChromatinEnhancer Elements, GeneticEpigenomicsGene Expression Regulation, NeoplasticGliomaHistone Deacetylase InhibitorsHistonesHumansMutationChromatinHistone Deacetylase InhibitorsHistonesenhancerepigenetic therapyH3K27acH3K27Mpediatric high-grade gliomarepetitive elementviral mimicry

Identifiers

PMID31085178
PMCPMC6521975

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.