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
Department of Radiological, Oncological and Anatomo-Pathological Sciences, University Sapienza of Rome, Rome, Italy.
Unit of Biology and Genetics, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Oncotarget. 2018 Feb 12;9(17):13807-13821. doi: 10.18632/oncotarget.24480. eCollection 2018 Mar 2.
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 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 the methylation alterations of some CpG islands. Furthermore, we evaluated the expression levels of selected differentially methylated genes and identified two biomarkers, one, , related to the tumor localization and the other, , as tumoral biomarker.
毛细胞型星形细胞瘤（PA）是儿科患者中最常见的胶质瘤，可发生于不同部位。染色体改变大多位于7q34染色体，其中包含癌基因，进而激活丝裂原活化蛋白激酶途径。尽管已经报道了来自不同部位的PA的基因和表观遗传改变，但表观遗传改变在PA发生发展中的作用仍不清楚。本研究的目的是调查独特的甲基化模式是否可以定义生物学上相关的PA组。通过Illumina Infinium HumanMethylation27 BeadChips对20例PA和4例正常脑样本进行了综合DNA甲基化分析。我们确定了不同的甲基化谱，其特征在于来自不同部位（幕下与幕上）以及3岁之前和之后发病的肿瘤的PA。这些结果表明，PA可能与肿瘤起源于区域特异性细胞的特定脑部位有关。我们鉴定并验证了一些CpG岛的甲基化改变。此外，我们评估了选定的差异甲基化基因的表达水平，并鉴定了两种生物标志物，一种与肿瘤定位有关，另一种作为肿瘤生物标志物。
