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

Adolescent Astrocytoma / diagnosis Brain Neoplasms / diagnosis Cell Line, Tumor Child Child, Preschool Cohort Studies Female Gene Expression Profiling / methods Histone Code / physiology Histone-Lysine N-Methyltransferase / biosynthesis Humans Infant Male Methylation Methyltransferases / biosynthesis Prognosis Repressor Proteins / biosynthesis
H3K9me3 Histone methylation Pediatric astrocytomas SUV39H1 Survival

Journal

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
ISSN: 1878-7479
Titre abrégé: Neurotherapeutics
Pays: United States
ID NLM: 101290381

Informations de publication

Date de publication:
07 2021
Historique:
accepted: 07 07 2021
pubmed: 24 7 2021
medline: 4 3 2022
entrez: 23 7 2021
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1007/s13311-021-01090-x PMID: 34296393 PMC: PMC8609021
pubmed: 34296393
doi: 10.1007/s13311-021-01090-x
pii: 10.1007/s13311-021-01090-x
pmc: PMC8609021
doi:

Substances chimiques

Repressor Proteins 0
SUV39H1 protein, human EC 2.1.1.
Methyltransferases EC 2.1.1.-
Histone-Lysine N-Methyltransferase EC 2.1.1.43

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2073-2090

Informations de copyright

© 2021. The American Society for Experimental NeuroTherapeutics, Inc.

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Auteurs

Alexia Klonou (A)

Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Athens, Greece.

Penelope Korkolopoulou (P)

First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.

Antonios N Gargalionis (AN)

Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Athens, Greece.

Dimitrios S Kanakoglou (DS)

First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.

Hector Katifelis (H)

Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.

Maria Gazouli (M)

Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.

Sarantis Chlamydas (S)

Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Athens, Greece.

Andreas Mitsios (A)

Department of Neurosurgery, Agia Sofia' Children's Hospital, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.

Theodosis Kalamatianos (T)

Department of Neurosurgery, 'Evangelismos' Hospital, Medical School, National and Kapodistrian University of Athens, 10676, Athens, Greece.

George Stranjalis (G)

Department of Neurosurgery, 'Evangelismos' Hospital, Medical School, National and Kapodistrian University of Athens, 10676, Athens, Greece.

Marios S Themistocleous (MS)

Department of Neurosurgery, Agia Sofia' Children's Hospital, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.

Kostas A Papavassiliou (KA)

Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Athens, Greece.

Spyros Sgouros (S)

Department of Pediatric Neurosurgery, 'Mitera' Children's Hospital, Medical School, National and Kapodistrian University of Athens, 15123, Athens, Greece.

Athanasios G Papavassiliou (AG)

Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Athens, Greece. papavas@med.uoa.gr.

Christina Piperi (C)

Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Athens, Greece. cpiperi@med.uoa.gr.
ORCID: 0000-0002-2701-0618

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Classifications MeSH

Recherchemedicale.com › Personnes › Tranches d'âge › Adolescent › Histone Mark Profiling in Pediatric...
Recherchemedicale.com › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Gliome › Astrocytome › Histone Mark Profiling in Pediatric...
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Recherchemedicale.com › Enzymes et coenzymes › Enzymes › Transferases › One-carbon group transferases › Methyltransferases › Protein Methyltransferases › Histone méthyltransférases › Histone-lysine N-methyltransferase › Histone Mark Profiling in Pediatric...
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