Research Papers:

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, Cincia Cameli, Elena Bacchelli, Manuela Badiali, Antonella Arcella, Isabella Morra, Felice Giangaspero and Patrizia Zavattari _

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Oncotarget. 2018; 9:13807-13821. https://doi.org/10.18632/oncotarget.24480

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Manila Antonelli1,*, Antonio Fadda2,*, Eleonora Loi2, Loredana Moi2,3, Cesare Zavattari4, Pia Sulas5, Davide Gentilini6,7, Cinzia Cameli8, Elena Bacchelli8, Manuela Badiali3, Antonella Arcella9, Isabella Morra10, Felice Giangaspero1,9 and Patrizia Zavattari2

1Department of Radiological, Oncological and Anatomo-Pathological Sciences, University Sapienza of Rome, Rome, Italy

2Unit of Biology and Genetics, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy

3Bone Marrow Transplantation Unit, Microcitemico Children's Hospital, Cagliari, Italy

4Independent Researcher, Machine Learning, Lucca, Italy

5Unit of Oncology and Molecular Pathology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy

6Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy

7Bioinformatics and Statistical Genomics Unit, Istituto Auxologico Italiano IRCCS, Cusano Milanino, Milan, Italy

8Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy

9IRCCS Neuromed, Pozzilli, Italy

10Department of Pathology OIRM-S, Anna Hospital, A.O.U. City of Health and Science, Turin, Italy

*These authors contributed equally to this work

Correspondence to:

Patrizia Zavattari, email: pzavattari@unica.it

Keywords: pilocytic astrocytomas; methylome alteration; topographic and tumor biomarkers; gene expression alteration; human methylation beadchips

Received: October 19, 2017     Accepted: January 31, 2018     Published: February 12, 2018


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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