Evidence map›Paper›PMID 24997139›Full record

ArticleNeuro-oncology2014

Genome-wide methylation profiling identifies an essential role of reactive oxygen species in pediatric glioblastoma multiforme and validates a methylome specific for H3 histone family 3A with absence of G-CIMP/isocitrate dehydrogenase 1 mutation.

Prerana Jha, Irene Rosita Pia Patric, Sudhanshu Shukla, Pankaj Pathak, Jagriti Pal, Vikas Sharma, Sivaarumugam Thinagararanjan, Vani Santosh, Vaishali Suri, Mehar Chand Sharma and 5 more

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In one paragraph

Article in Neuro-oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it

0cells of the map it votes in

19citing papers in PubMed

2.3field-weighted citation impact, top 12% 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

19 citing papers in PubMed, 33 citations in OpenAlex.

Uncovering the Role of Small and Intermediate-Length Non-Coding RNAs in Glioma Pathogenesis and Prognosis.Cancers · 2026
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Cold atmospheric plasma stabilizes mismatch repair for effective, uniform treatment of diverse colorectal cancer cell types.Scientific reports · 2024
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Potential targets and treatments affect oxidative stress in gliomas: An overview of molecular mechanisms.Frontiers in pharmacology · 2022
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Therapeutic Targets in Diffuse Midline Gliomas-An Emerging Landscape.Cancers · 2021
Review
Effect of Cold Atmospheric Plasma on Epigenetic Changes, DNA Damage, and Possibilities for Its Use in Synergistic Cancer Therapy.International journal of molecular sciences · 2021
Review
Epigenomics and immunotherapeutic advances in pediatric brain tumors.NPJ precision oncology · 2021
Review
Recent Trends of microRNA Significance in Pediatric Population Glioblastoma and Current Knowledge of Micro RNA Function in Glioblastoma Multiforme.International journal of molecular sciences · 2020
Review
Total DNA Methylation Changes Reflect Random Oxidative DNA Damage in Gliomas.Cells · 2019
Article
Potential Epigenetic-Based Therapeutic Targets for Glioma.Frontiers in molecular neuroscience · 2018
Review
Significance of H3K27M mutation with specific histomorphological features and associated molecular alterations in pediatric high-grade glial tumors.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2018
Article
Expression of p53 & epidermal growth factor receptor in glioblastoma.The Indian journal of medical research · 2017
Article
Molecular Testing of Brain Tumor.Journal of pathology and translational medicine · 2017
Review
Precision medicine in pediatric oncology: Lessons learned and next steps.Pediatric blood & cancer · 2017
Review
Cancer Stem Cell Hierarchy in Glioblastoma Multiforme.Frontiers in surgery · 2016
Review
Modulation of microRNA editing, expression and processing by ADAR2 deaminase in glioblastoma.Genome biology · 2015
Article
Differential Epigenetic Effects of Atmospheric Cold Plasma on MCF-7 and MDA-MB-231 Breast Cancer Cells.PloS one · 2015
Article
A sensitive and specific histopathologic prognostic marker for H3F3A K27M mutant pediatric glioblastomas.Acta neuropathologica · 2014
Article
Therapeutic approach beyond conventional temozolomide for newly diagnosed glioblastoma: Review of the present evidence and future direction.Indian journal of medical and paediatric oncology : official journal of Indian Society of Medical & Paediatric Oncology
Review
Indian data on central nervous tumors: A summary of published work.South Asian journal of cancer
Review

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

15 authors at 3 institutions in 1 country.

Prerana JhaDepartment of Pathology, All India Institute of Medical Sciences, New Delhi, India (P.J., P.P., VI.S., VA.S., M.C.S., C.S.); Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India (I.R.P.P., S.S., J.P., S.T., K.S.); Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, India (VAI.S.); Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India (A.A.); Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India (A.S., D.G.).

Irene Rosita Pia PatricDepartment of Pathology, All India Institute of Medical Sciences, New Delhi, India (P.J., P.P., VI.S., VA.S., M.C.S., C.S.); Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India (I.R.P.P., S.S., J.P., S.T., K.S.); Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, India (VAI.S.); Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India (A.A.); Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India (A.S., D.G.).

Sudhanshu ShuklaDepartment of Pathology, All India Institute of Medical Sciences, New Delhi, India (P.J., P.P., VI.S., VA.S., M.C.S., C.S.); Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India (I.R.P.P., S.S., J.P., S.T., K.S.); Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, India (VAI.S.); Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India (A.A.); Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India (A.S., D.G.).

Pankaj PathakDepartment of Pathology, All India Institute of Medical Sciences, New Delhi, India (P.J., P.P., VI.S., VA.S., M.C.S., C.S.); Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India (I.R.P.P., S.S., J.P., S.T., K.S.); Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, India (VAI.S.); Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India (A.A.); Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India (A.S., D.G.).

Jagriti PalDepartment of Pathology, All India Institute of Medical Sciences, New Delhi, India (P.J., P.P., VI.S., VA.S., M.C.S., C.S.); Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India (I.R.P.P., S.S., J.P., S.T., K.S.); Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, India (VAI.S.); Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India (A.A.); Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India (A.S., D.G.).

Vikas SharmaDepartment of Pathology, All India Institute of Medical Sciences, New Delhi, India (P.J., P.P., VI.S., VA.S., M.C.S., C.S.); Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India (I.R.P.P., S.S., J.P., S.T., K.S.); Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, India (VAI.S.); Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India (A.A.); Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India (A.S., D.G.).

Sivaarumugam ThinagararanjanDepartment of Pathology, All India Institute of Medical Sciences, New Delhi, India (P.J., P.P., VI.S., VA.S., M.C.S., C.S.); Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India (I.R.P.P., S.S., J.P., S.T., K.S.); Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, India (VAI.S.); Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India (A.A.); Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India (A.S., D.G.).

Vani SantoshDepartment of Pathology, All India Institute of Medical Sciences, New Delhi, India (P.J., P.P., VI.S., VA.S., M.C.S., C.S.); Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India (I.R.P.P., S.S., J.P., S.T., K.S.); Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, India (VAI.S.); Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India (A.A.); Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India (A.S., D.G.).

Vaishali SuriDepartment of Pathology, All India Institute of Medical Sciences, New Delhi, India (P.J., P.P., VI.S., VA.S., M.C.S., C.S.); Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India (I.R.P.P., S.S., J.P., S.T., K.S.); Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, India (VAI.S.); Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India (A.A.); Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India (A.S., D.G.).

Mehar Chand SharmaDepartment of Pathology, All India Institute of Medical Sciences, New Delhi, India (P.J., P.P., VI.S., VA.S., M.C.S., C.S.); Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India (I.R.P.P., S.S., J.P., S.T., K.S.); Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, India (VAI.S.); Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India (A.A.); Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India (A.S., D.G.).

Arimappamagan ArivazhaganDepartment of Pathology, All India Institute of Medical Sciences, New Delhi, India (P.J., P.P., VI.S., VA.S., M.C.S., C.S.); Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India (I.R.P.P., S.S., J.P., S.T., K.S.); Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, India (VAI.S.); Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India (A.A.); Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India (A.S., D.G.).

Ashish SuriDepartment of Pathology, All India Institute of Medical Sciences, New Delhi, India (P.J., P.P., VI.S., VA.S., M.C.S., C.S.); Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India (I.R.P.P., S.S., J.P., S.T., K.S.); Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, India (VAI.S.); Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India (A.A.); Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India (A.S., D.G.).

Deepak GuptaDepartment of Pathology, All India Institute of Medical Sciences, New Delhi, India (P.J., P.P., VI.S., VA.S., M.C.S., C.S.); Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India (I.R.P.P., S.S., J.P., S.T., K.S.); Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, India (VAI.S.); Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India (A.A.); Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India (A.S., D.G.).

Kumaravel SomasundaramDepartment of Pathology, All India Institute of Medical Sciences, New Delhi, India (P.J., P.P., VI.S., VA.S., M.C.S., C.S.); Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India (I.R.P.P., S.S., J.P., S.T., K.S.); Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, India (VAI.S.); Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India (A.A.); Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India (A.S., D.G.).

Chitra SarkarDepartment of Pathology, All India Institute of Medical Sciences, New Delhi, India (P.J., P.P., VI.S., VA.S., M.C.S., C.S.); Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India (I.R.P.P., S.S., J.P., S.T., K.S.); Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, India (VAI.S.); Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India (A.A.); Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India (A.S., D.G.).

All India Institute of Medical Sciences · INIndian Institute of Science Bangalore · INNational Institute of Mental Health and Neurosciences · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPediatric glioblastoma multiforme (GBM) is rare, and there is a single study, a seminal discovery showing association of histone H3.3 and isocitrate dehydrogenase (IDH)1 mutation with a DNA methylation signature. The present study aims to validate these findings in an independent cohort of pediatric GBM, compare it with adult GBM, and evaluate the involvement of important functionally altered pathways.

methodsGenome-wide methylation profiling of 21 pediatric GBM cases was done and compared with adult GBM data (GSE22867). We performed gene mutation analysis of IDH1 and H3 histone family 3A (H3F3A), status evaluation of glioma cytosine-phosphate-guanine island methylator phenotype (G-CIMP), and Gene Ontology analysis. Experimental evaluation of reactive oxygen species (ROS) association was also done.

resultsDistinct differences were noted between methylomes of pediatric and adult GBM. Pediatric GBM was characterized by 94 hypermethylated and 1206 hypomethylated cytosine-phosphate-guanine (CpG) islands, with 3 distinct clusters, having a trend to prognostic correlation. Interestingly, none of the pediatric GBM cases showed G-CIMP/IDH1 mutation. Gene Ontology analysis identified ROS association in pediatric GBM, which was experimentally validated. H3F3A mutants (36.4%; all K27M) harbored distinct methylomes and showed enrichment of processes related to neuronal development, differentiation, and cell-fate commitment.

conclusionsOur study confirms that pediatric GBM has a distinct methylome compared with that of adults. Presence of distinct clusters and an H3F3A mutation-specific methylome indicate existence of epigenetic subgroups within pediatric GBM. Absence of IDH1/G-CIMP status further indicates that findings in adult GBM cannot be simply extrapolated to pediatric GBM and that there is a strong need for identification of separate prognostic markers. A possible role of ROS in pediatric GBM pathogenesis is demonstrated for the first time and needs further evaluation.

Indexed as

DNA MethylationAdultBrain NeoplasmsCell Line, TumorChildChild, PreschoolCpG IslandsFemaleGlioblastomaHistonesHumansIsocitrate DehydrogenaseMaleMutationReactive Oxygen SpeciesHistonesIDH1 protein, humanIsocitrate DehydrogenaseReactive Oxygen SpeciesG-CIMPH3F3AIDH1methylationpediatric GBMreactive oxygen species (ROS)

Identifiers

PMID24997139

DOI10.1093/neuonc/nou113

PMCPMC4232083

OpenAlexW2102083739

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