Evidence mapPaperPMID 36044040Full record

ArticleNeuro-oncology2023

In vivo functional characterization of EGFR variants identifies novel drivers of glioblastoma.

Kwanha Yu, Kathleen Kong, Brittney Lozzi, Estefania Luna-Figueroa, Alexis Cervantes, Rachel Curry, Carrie A Mohila, Ganesh Rao, Ali Jalali, Gordon B Mills and 2 more

Open access · greenAbstract read
In one paragraph

Article in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.2field-weighted citation impact, top 54% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Article
  2. Article
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

12 authors at 3 institutions in 1 country.

Kwanha YuCenter for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, 77030, USA.
Kathleen KongCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, 77030, USA.
Brittney LozziCenter for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, 77030, USA.
Estefania Luna-FigueroaCenter for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, 77030, USA.
Alexis CervantesCenter for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, 77030, USA.
Rachel CurryCenter for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, 77030, USA.
Carrie A MohilaDepartment of Pathology, Texas Children's Hospital, Houston, TX, 77030, USA.
Ganesh RaoCenter for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, 77030, USA.
Ali JalaliDepartment of Neurosurgery, Baylor College of Medicine, Houston, TX, 77030, USA.
Gordon B MillsDepartment of Cell, Developmental and Cancer Biology, Knight Cancer Institute, Oregon Health Science University, Portland, OR 97239, USA.
Kenneth L ScottDepartment of Human and Molecular Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.
Benjamin DeneenCenter for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, 77030, USA.
Baylor College of Medicine · USOregon Health & Science University · USTexas Children's Hospital · US

Funding

Training In Cell and Gene TherapyT32HL092332 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI MALCOLM K. BRENNER, Bruno Di Stefano · 2008 to 2026
$6.9M
Integrative bioinformatics and functional characterization of oncogenic driver aberrations in cancerU01CA217842 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DENEEN, BENJAMIN, MILLS, GORDON B. · 2017 to 2021
$3.6M
Systematic Characterization and Targeting of Neomorphic Drivers in CancerU01CA281902 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Benjamin Deneen, Han Liang · 2023 to 2026
$3.5M
MOLECULAR DISSECTION OF SEIZURE MICROENVIRONMENT IN MALIGNANT GLIOMAR01CA223388 · NCI · BAYLOR COLLEGE OF MEDICINE · PI DENEEN, BENJAMIN, NOEBELS, JEFFREY · 2018 to 2022
$3.5M
Cellular and Molecular Mechanisms of GBM InfiltrationR01NS124093 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI Benjamin Deneen, Ganesh Rao · 2022 to 2026
$1.6M
Role of POT1 mutations in glioma initiationK08NS110976 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI JALALI, ALI · 2019 to 2023
$880k
Functional Genomics of High Grade GliomaR50CA252125 · NCI · BAYLOR COLLEGE OF MEDICINE · PI YU, KWANHA · 2020 to 2024
$761k
NCI NIH HHS R01 CA223388NCI NIH HHS R50 CA252125NCI NIH HHS U01 CA217842NCI NIH HHS U01 CA281902NHLBI NIH HHS T32 HL092332NINDS NIH HHS K08 NS110976NINDS NIH HHS R01 NS124093
6 · The paper itself

Abstract

backgroundGlioblastoma is the most common and aggressive primary brain tumor. Large-scale sequencing initiatives have cataloged its mutational landscape in hopes of elucidating mechanisms driving this deadly disease. However, a major bottleneck in harnessing this data for new therapies is deciphering "driver" and "passenger" events amongst the vast volume of information.

methodsWe utilized an autochthonous, in vivo screening approach to identify driver, EGFR variants. RNA-Seq identified unique molecular signatures of mouse gliomas across these variants, which only differ by a single amino acid change. In particular, we identified alterations to lipid metabolism, which we further validated through an unbiased lipidomics screen.

resultsOur screen identified A289I as the most potent EGFR variant, which has previously not been characterized. One of the mechanisms through which A289I promotes gliomagenesis is to alter cellular triacylglycerides through MTTP. Knockout of Mttp in mouse gliomas, reduces gliomagenesis in multiple models.

conclusionsEGFR variants that differ by a single amino acid residue differentially promote gliomagenesis. Among the identified mechanism that drives glioma growth include lipid metabolism through MTTP. Understanding triacylglyceride accumulation may present a prospective therapeutic pathway for this deadly disease.

Indexed as

Brain NeoplasmsGlioblastomaGliomaAnimalsErbB ReceptorsMiceMice, KnockoutMutationErbB ReceptorsEGFR variantsGlioblastomalipid metabolismmouse models

Identifiers

PMID36044040
PMCPMC10013639
OpenAlexW4293835641

What Socratic holds

Textmetadata
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 Socratic graph.