Evidence map›Paper›PMID 30460631›Full record

ArticleJournal of neuro-oncology2019

Characterization of iPSCs derived from low grade gliomas revealed early regional chromosomal amplifications during gliomagenesis.

Zhong Liu, Pulin Che, Juan J Mercado, James R Hackney, Gregory K Friedman, Cheng Zhang, Zhiying You, Xinyang Zhao, Qiang Ding, Kitai Kim and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuro-oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.7field-weighted citation impact, top 27% 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

13 citing papers in PubMed, 14 citations in OpenAlex.

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  11. Structure and Emerging Functions of LRCH Proteins in Leukocyte Biology.Frontiers in cell and developmental biology · 2020
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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

17 authors at 5 institutions in 1 country.

Zhong LiuDepartment of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Pulin CheDepartment of Neurology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Juan J MercadoDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
James R HackneyDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Gregory K FriedmanDepartment of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Cheng ZhangDepartment of Molecular Pharmacology & Experimental Therapeutics, Center for Individualized Medicine, Mayo Clinic College of Medicine, Rochester, MN, 55904, USA.
Zhiying YouDepartment of Medicine, University of Colorado Denver-Anschutz Medical Campus, Denver, CO, 80045, USA.
Xinyang ZhaoDepartment of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Qiang DingDepartment of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Kitai KimCancer Biology and Genetics Program, The Center for Cell Engineering, The Center for Stem Cell Biology, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute for Cancer Research, New York, NY, USA.
Hu LiDepartment of Molecular Pharmacology & Experimental Therapeutics, Center for Individualized Medicine, Mayo Clinic College of Medicine, Rochester, MN, 55904, USA.
Xiaoguang LiuDepartment of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
James M MarkertDepartment of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Burt NaborsDepartment of Neurology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
G Yancey GillespieDepartment of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Rui ZhaoDepartment of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA. ruizhao@uab.edu.ORCID http://orcid.org/0000-0003-3769-6550
Xiaosi HanDepartment of Neurology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA. xhan@uab.edu.ORCID http://orcid.org/0000-0003-2985-8580
University of Alabama at Birmingham · USMayo Clinic · USMemorial Sloan Kettering Cancer Center · USUniversity of Alabama at Birmingham Hospital · USUniversity of Colorado Anschutz Medical Campus · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
The Role of FAK-related-non-kinase (FRNK) in Lung FibrosisR01HL085324 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI DING, QIANG · 2007 to 2016
$3.9M
Explore the APOE e4-mediated p53 activation in Alzheimer's DiseaseR01OD026594 · OD · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ZHAO, RUI · 2019 to 2022
$1.7M
Targeting PRMT5 in Cancer Initiating Cells as a New Therapy for GlioblastomaR01NS095626 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI HAN, XIAOSI · 2015 to 2019
$1.6M
The Role of ZFP36 in Control of IPFR01HL127338 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI DING, QIANG · 2016 to 2019
$1.5M
Hematopoietic potential of histocompatible embryonic stem cell linesR00HL093212 · NHLBI · SLOAN-KETTERING INST CAN RESEARCH · PI KIM, KITAI · 2012 to 2014
$717k
Modeling low-grade gliomas using human pluripotent stem cellsR21NS106430 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI HAN, XIAOSI, ZHAO, RUI · 2018 to 2019
$408k
National Heart, Lung, and Blood Institute (US) HL085324National Heart, Lung, and Blood Institute (US) HL127338NCI NIH HHS P30 CA008748NHLBI NIH HHS R00 HL093212NIH HHS R01 OD026594NINDS NIH HHS R01 NS095626NINDS NIH HHS R01NS095626NINDS NIH HHS R21 NS106430NINDS NIH HHS R21NS106430University of Alabama at Birmingham Faculty Development Grant Program award
6 · The paper itself

Abstract

introductionIDH1 mutation has been identified as an early genetic event driving low grade gliomas (LGGs) and it has been proven to exerts a powerful epigenetic effect. Cells containing IDH1 mutation are refractory to epigenetical reprogramming to iPSC induced by expression of Yamanaka transcription factors, a feature that we employed to study early genetic amplifications or deletions in gliomagenesis.

methodsWe made iPSC clones from freshly surgically resected IDH1 mutant LGGs by forced expression of Yamanaka transcription factors. We sequenced the IDH locus and analyzed the genetic composition of multiple iPSC clones by array-based comparative genomic hybridization (aCGH).

resultsWe hypothesize that the primary cell pool isolated from LGG tumor contains a heterogeneous population consisting tumor cells at various stages of tumor progression including cells with early genetic lesions if any prior to acquisition of IDH1 mutation. Because cells containing IDH1 mutation are refractory to reprogramming, we predict that iPSC clones should originate only from LGG cells without IDH1 mutation, i.e. cells prior to acquisition of IDH1 mutation. As expected, we found that none of the iPSC clones contains IDH1 mutation. Further analysis by aCGH of the iPSC clones reveals that they contain regional chromosomal amplifications which are also present in the primary LGG cells.

conclusionsThese results indicate that there exists a subpopulation of cells harboring gene amplification but without IDH1 mutation in the LGG primary cell pool. Further analysis of TCGA LGG database demonstrates that these regional chromosomal amplifications are also present in some cases of low grade gliomas indicating they are reoccurring lesions in glioma albeit at a low frequency. Taken together, these data suggest that regional chromosomal alterations may exist prior to the acquisition of IDH mutations in at least some cases of LGGs.

Indexed as

Gene AmplificationAdultBrain NeoplasmsChromosome AberrationsClone CellsGliomaHumansInduced Pluripotent Stem CellsIsocitrate DehydrogenaseMaleIDH1 protein, humanIsocitrate DehydrogenaseGliomagenesisIDH1Induced pluripotent stem cellsLow-grade gliomaRegional chromosomal amplification

Identifiers

PMID30460631
PMCPMC6344247
OpenAlexW2900509015

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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.