Integrated DNA methylation analysis identifies topographical and tumoral biomarkers in pilocytic astrocytomas

Manila Antonelli, Antonio Fadda, Eleonora Loi, Loredana Moi, Cesare Zavattari, Pia Sulas, Davide Gentilini, Cinzia Cameli, Elena Bacchelli, Manuela Badiali, Antonella Arcella, Isabella Morra, Felice Giangaspero, Patrizia Zavattari

Research output: Contribution to journalArticle

Abstract

Pilocytic astrocytoma (PA) is the most common glioma in pediatric patients and occurs in different locations. Chromosomal alterations are mostly located at chromosome 7q34 comprising the BRAF oncogene with consequent activation of the mitogen-activated protein kinase pathway. Although genetic and epigenetic alterations characterizing PA from different localizations have been reported, the role of epigenetic alterations in PA development is still not clear. The aim of this study was to investigate whether distinctive methylation patterns may define biologically relevant groups of PAs. Integrated DNA methylation analysis was performed on 20 PAs and 4 normal brain samples by Illumina Infinium HumanMethylation27 BeadChips. We identified distinct methylation profiles characterizing PAs from different locations (infratentorial vs supratentorial) and tumors with onset before and after 3 years of age. These results suggest that PA may be related to the specific brain site where the tumor arises from region-specific cells of origin. We identified and validated in silico the methylation alterations of some CpG islands. Furthermore, we evaluated the expression levels of selected differentially methylated genes and identified two biomarkers, one, IRX2, related to the tumor localization and the other, TOX2, as tumoral biomarker.

Original languageEnglish
Pages (from-to)13807-13821
Number of pages15
JournalOncotarget
Volume9
Issue number17
DOIs
Publication statusPublished - Mar 2 2018

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Astrocytoma
DNA Methylation
Biomarkers
Methylation
Epigenomics
Supratentorial Neoplasms
CpG Islands
Mitogen-Activated Protein Kinases
Oncogenes
Brain Neoplasms
Glioma
Computer Simulation
Chromosomes
Pediatrics
Brain
Genes
Neoplasms

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Antonelli, M., Fadda, A., Loi, E., Moi, L., Zavattari, C., Sulas, P., ... Zavattari, P. (2018). Integrated DNA methylation analysis identifies topographical and tumoral biomarkers in pilocytic astrocytomas. Oncotarget, 9(17), 13807-13821. https://doi.org/10.18632/oncotarget.24480

Integrated DNA methylation analysis identifies topographical and tumoral biomarkers in pilocytic astrocytomas. / Antonelli, Manila; Fadda, Antonio; Loi, Eleonora; Moi, Loredana; Zavattari, Cesare; Sulas, Pia; Gentilini, Davide; Cameli, Cinzia; Bacchelli, Elena; Badiali, Manuela; Arcella, Antonella; Morra, Isabella; Giangaspero, Felice; Zavattari, Patrizia.

In: Oncotarget, Vol. 9, No. 17, 02.03.2018, p. 13807-13821.

Research output: Contribution to journalArticle

Antonelli, M, Fadda, A, Loi, E, Moi, L, Zavattari, C, Sulas, P, Gentilini, D, Cameli, C, Bacchelli, E, Badiali, M, Arcella, A, Morra, I, Giangaspero, F & Zavattari, P 2018, 'Integrated DNA methylation analysis identifies topographical and tumoral biomarkers in pilocytic astrocytomas', Oncotarget, vol. 9, no. 17, pp. 13807-13821. https://doi.org/10.18632/oncotarget.24480
Antonelli, Manila ; Fadda, Antonio ; Loi, Eleonora ; Moi, Loredana ; Zavattari, Cesare ; Sulas, Pia ; Gentilini, Davide ; Cameli, Cinzia ; Bacchelli, Elena ; Badiali, Manuela ; Arcella, Antonella ; Morra, Isabella ; Giangaspero, Felice ; Zavattari, Patrizia. / Integrated DNA methylation analysis identifies topographical and tumoral biomarkers in pilocytic astrocytomas. In: Oncotarget. 2018 ; Vol. 9, No. 17. pp. 13807-13821.
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AB - Pilocytic astrocytoma (PA) is the most common glioma in pediatric patients and occurs in different locations. Chromosomal alterations are mostly located at chromosome 7q34 comprising the BRAF oncogene with consequent activation of the mitogen-activated protein kinase pathway. Although genetic and epigenetic alterations characterizing PA from different localizations have been reported, the role of epigenetic alterations in PA development is still not clear. The aim of this study was to investigate whether distinctive methylation patterns may define biologically relevant groups of PAs. Integrated DNA methylation analysis was performed on 20 PAs and 4 normal brain samples by Illumina Infinium HumanMethylation27 BeadChips. We identified distinct methylation profiles characterizing PAs from different locations (infratentorial vs supratentorial) and tumors with onset before and after 3 years of age. These results suggest that PA may be related to the specific brain site where the tumor arises from region-specific cells of origin. We identified and validated in silico the methylation alterations of some CpG islands. Furthermore, we evaluated the expression levels of selected differentially methylated genes and identified two biomarkers, one, IRX2, related to the tumor localization and the other, TOX2, as tumoral biomarker.

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