Evidence map›Paper›PMID 34296393›Full record

ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2021

Histone Mark Profiling in Pediatric Astrocytomas Reveals Prognostic Significance of H3K9 Trimethylation and Histone Methyltransferase SUV39H1.

Alexia Klonou, Penelope Korkolopoulou, Antonios N Gargalionis, Dimitrios S Kanakoglou, Hector Katifelis, Maria Gazouli, Sarantis Chlamydas, Andreas Mitsios, Theodosis Kalamatianos, George Stranjalis and 5 more

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

Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

8 citing papers in PubMed, 13 citations in OpenAlex.

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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

15 authors at 1 institution in 1 country.

Alexia KlonouDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Athens, Greece.
Penelope KorkolopoulouFirst Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.
Antonios N GargalionisDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Athens, Greece.
Dimitrios S KanakoglouFirst Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.
Hector KatifelisLaboratory of Biology, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.
Maria GazouliLaboratory of Biology, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.
Sarantis ChlamydasDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Athens, Greece.
Andreas MitsiosDepartment of Neurosurgery, Agia Sofia' Children's Hospital, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.
Theodosis KalamatianosDepartment of Neurosurgery, 'Evangelismos' Hospital, Medical School, National and Kapodistrian University of Athens, 10676, Athens, Greece.
George StranjalisDepartment of Neurosurgery, 'Evangelismos' Hospital, Medical School, National and Kapodistrian University of Athens, 10676, Athens, Greece.
Marios S ThemistocleousDepartment of Neurosurgery, Agia Sofia' Children's Hospital, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.
Kostas A PapavassiliouDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Athens, Greece.
Spyros SgourosDepartment of Pediatric Neurosurgery, 'Mitera' Children's Hospital, Medical School, National and Kapodistrian University of Athens, 15123, Athens, Greece.
Athanasios G PapavassiliouDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Athens, Greece. papavas@med.uoa.gr.
Christina PiperiDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Athens, Greece. cpiperi@med.uoa.gr.ORCID http://orcid.org/0000-0002-2701-0618
National and Kapodistrian University of Athens · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alterations in global histone methylation regulate gene expression and participate in cancer onset and progression. The profile of histone methylation marks in pediatric astrocytomas is currently understudied with limited data on their distribution among grades. The global expression patterns of repressive histone marks H3K9me3, H3K27me3, and H4K20me3 and active H3K4me3 and H3K36me3 along with their writers SUV39H1, SETDB1, EZH2, MLL2, and SETD2 were investigated in 46 pediatric astrocytomas and normal brain tissues. Associations between histone marks and modifying enzymes with clinicopathological characteristics and disease-specific survival were studied along with their functional impact in proliferation and migration of pediatric astrocytoma cell lines using selective inhibitors in vitro. Upregulation of histone methyltransferase gene expression and deregulation of histone code were detected in astrocytomas compared to normal brain tissues, with higher levels of SUV39H1, SETDB1, and SETD2 as well as H4K20me3 and H3K4me3 histone marks. Pilocytic astrocytomas exhibited lower MLL2 levels compared to diffusely infiltrating tumors indicating a differential pattern of epigenetic regulator expression between the two types of astrocytic neoplasms. Moreover, higher H3K9me3, H3K36me3, and SETDB1 expression was detected in grade IIΙ/IV compared to grade II astrocytomas. In univariate analysis, elevated H3K9me3 and MLL2 and diminished SUV39H1 expression adversely affected survival. Upon multivariate survival analysis, only SUV39H1 expression was revealed as an independent prognostic factor of adverse significance. Treatment of pediatric astrocytoma cell lines with SUV39H1 inhibitor reduced proliferation and cell migration. Our data implicate H3K9me3 and SUV39H1 in the pathobiology of pediatric astrocytomas, with SUV39H1 yielding prognostic information independent of other clinicopathologic variables.

Indexed as

Gene Expression ProfilingAdolescentAstrocytomaBrain NeoplasmsCell Line, TumorChildChild, PreschoolCohort StudiesFemaleHistone CodeHistone-Lysine N-MethyltransferaseHumansInfantMaleMethylationMethyltransferasesHistone-Lysine N-MethyltransferaseMethyltransferasesRepressor ProteinsSUV39H1 protein, humanH3K9me3Histone methylationPediatric astrocytomasSurvivalSUV39H1

Identifiers

PMID34296393
PMCPMC8609021
OpenAlexW3185540348

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.