Evidence map›Paper›PMID 32303840›Full record

ArticleActa neuropathologica2020

Pediatric bithalamic gliomas have a distinct epigenetic signature and frequent EGFR exon 20 insertions resulting in potential sensitivity to targeted kinase inhibition.

Gourish Mondal, Julieann C Lee, Ajay Ravindranathan, Javier E Villanueva-Meyer, Quynh T Tran, Sariah J Allen, Jairo Barreto, Rohit Gupta, Pamela Doo, Jessica Van Ziffle and 32 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 1 pooled it
6.7field-weighted citation impact, top 2% of its field
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

55 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.

  1. Molecular Biomarker Testing for the Diagnosis of Diffuse Gliomas.Archives of pathology & laboratory medicine · 2022
    Guideline
  2. Clinical, molecular, and surgical predictors of outcome in non-DIPG pediatric diffuse midline gliomas: A collaborative retrospective analysis.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

42 authors at 9 institutions in 1 country.

Gourish MondalDepartment of Pathology, University of California, San Francisco, CA, USA.
Julieann C LeeDepartment of Pathology, University of California, San Francisco, CA, USA.
Ajay RavindranathanDepartment of Pathology, University of California, San Francisco, CA, USA.
Javier E Villanueva-MeyerDepartment of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
Quynh T TranDepartment of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA.
Sariah J AllenDepartment of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA.
Jairo BarretoDepartment of Pathology, University of California, San Francisco, CA, USA.
Rohit GuptaDepartment of Pathology, University of California, San Francisco, CA, USA.
Pamela DooInstitute for Human Genetics, University of California, San Francisco, CA, USA.
Jessica Van ZiffleDepartment of Pathology, University of California, San Francisco, CA, USA.
Courtney OnoderaDepartment of Pathology, University of California, San Francisco, CA, USA.
Patrick DevineDepartment of Pathology, University of California, San Francisco, CA, USA.
James P GrenertDepartment of Pathology, University of California, San Francisco, CA, USA.
David SamuelDepartment of Hematology/Oncology, Valley Children's Hospital, Madera, CA, USA.
Rong LiDepartment of Pathology, Children's of Alabama, Birmingham, AL, USA.
Laura K MetrockDepartment of Pediatric Hematology/Oncology, University of Alabama, Birmingham, AL, USA.
Lee-Way JinDepartment of Pathology, University of California Davis Medical Center, Sacramento, CA, USA.
Reuben AntonyDivision of Pediatric Hematology/Oncology, Department of Pediatrics, University of California Davis Medical Center, Sacramento, CA, USA.
Mouied AlashariDepartment of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA.
Samuel CheshierDepartment of Neurosurgery, University of Utah School of Medicine, Salt Lake City, UT, USA.
Nicholas S WhippleDivision of Pediatric Hematology/Oncology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
Carol BruggersDivision of Pediatric Hematology/Oncology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
Corey RaffelDepartment of Neurological Surgery, University of California, San Francisco, CA, USA.
Nalin GuptaDepartment of Neurological Surgery, University of California, San Francisco, CA, USA.
Cassie N KlineDivision of Pediatric Hematology/Oncology, Department of Pediatrics, University of California, San Francisco, CA, USA.
Alyssa ReddyDepartment of Neurology, University of California, San Francisco, CA, USA.
Anu BanerjeeDivision of Pediatric Hematology/Oncology, Department of Pediatrics, University of California, San Francisco, CA, USA.
Matthew D HallDepartment of Radiation Oncology, Miami Cancer Institute, Miami, FL, USA.
Minesh P MehtaDepartment of Radiation Oncology, Miami Cancer Institute, Miami, FL, USA.
Ziad KhatibDivision of Hematology/Oncology, Department of Pediatrics, Nicklaus Children's Hospital, Miami, FL, USA.
Ossama M MaherDivision of Hematology/Oncology, Department of Pediatrics, Nicklaus Children's Hospital, Miami, FL, USA.
Carole BrathwaiteDepartment of Pathology, Nicklaus Children's Hospital, Miami, FL, USA.
Melike PekmezciDepartment of Pathology, University of California, San Francisco, CA, USA.
Joanna J PhillipsDepartment of Pathology, University of California, San Francisco, CA, USA.
Andrew W BollenDepartment of Pathology, University of California, San Francisco, CA, USA.
Tarik TihanDepartment of Pathology, University of California, San Francisco, CA, USA.
John T LucasDepartment of Radiation Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
Alberto BroniscerDivision of Pediatric Hematology/Oncology, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Mitchel S BergerDepartment of Neurological Surgery, University of California, San Francisco, CA, USA.
Arie PerryDepartment of Pathology, University of California, San Francisco, CA, USA.
Brent A OrrDepartment of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA.
David A SolomonDepartment of Pathology, University of California, San Francisco, CA, USA. david.solomon@ucsf.edu.ORCID http://orcid.org/0000-0003-4571-7999
University of California, San Francisco · USSt. Jude Children's Research Hospital · USUniversity of Utah · USMiami Children's Hospital · USUniversity of California Davis Medical Center · USChildren's Hospital Central California · USChildren's of Alabama · USUniversity of Alabama at Birmingham · USUniversity of Pittsburgh · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
Tissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2002 to 2026
$57.4M
Research Training in Childhood CancerT32CA128583 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Eric Alejandro Sweet-Cordero · 2007 to 2026
$6.0M
Cohesin gene mutations in tumorigenesisDP5OD021403 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SOLOMON, DAVID A. · 2015 to 2019
$2.0M
NCI NIH HHS P30 CA021765NCI NIH HHS P50 CA097257NCI NIH HHS T32 CA128583NIH HHS DP5 OD021403ODCDC CDC HHS DP5 OD021403
6 · The paper itself

Abstract

Brain tumors are the most common solid tumors of childhood, and the genetic drivers and optimal therapeutic strategies for many of the different subtypes remain unknown. Here, we identify that bithalamic gliomas harbor frequent mutations in the EGFR oncogene, only rare histone H3 mutation (in contrast to their unilateral counterparts), and a distinct genome-wide DNA methylation profile compared to all other glioma subtypes studied to date. These EGFR mutations are either small in-frame insertions within exon 20 (intracellular tyrosine kinase domain) or missense mutations within exon 7 (extracellular ligand-binding domain) that occur in the absence of accompanying gene amplification. We find these EGFR mutations are oncogenic in primary astrocyte models and confer sensitivity to specific tyrosine kinase inhibitors dependent on location within the kinase domain or extracellular domain. We initiated treatment with targeted kinase inhibitors in four children whose tumors harbor EGFR mutations with encouraging results. This study identifies a promising genomically-tailored therapeutic strategy for bithalamic gliomas, a lethal and genetically distinct brain tumor of childhood.

Indexed as

AdolescentAntineoplastic AgentsBrain NeoplasmsCarcinoma, Non-Small-Cell LungChildChild, PreschoolEpigenesis, GeneticErbB ReceptorsFemaleGliomaHumansLung NeoplasmsMaleMutationProtein Kinase InhibitorsAntineoplastic AgentsEGFR protein, humanErbB ReceptorsProtein Kinase InhibitorsAfatinibBithalamic gliomaDiffuse midline gliomaEGFRErlotinibHistone H3Molecular neuropathologyOsimertinibPediatric cancerTrametinibTyrosine kinase inhibitor

Identifiers

PMID32303840
PMCPMC7792550
OpenAlexW3016386208

What OpenQuestion holds

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Registered trials

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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.