Methylation profiling identifies 2 groups of gliomas according to their tumorigenesis
Open Access
- 5 October 2010
- journal article
- Published by Oxford University Press (OUP) in Neuro-Oncology
- Vol. 13 (1), 84-98
- https://doi.org/10.1093/neuonc/noq110
Abstract
Extensive genomic and gene expression studies have been performed in gliomas, but the epigenetic alterations that characterize different subtypes of gliomas remain largely unknown. Here, we analyzed the methylation patterns of 807 genes (1536 CpGs) in a series of 33 low-grade gliomas (LGGs), 36 glioblastomas (GBMs), 8 paired initial and recurrent gliomas, and 9 controls. This analysis was performed with Illumina's Golden Gate Bead methylation arrays and was correlated with clinical, histological, genomic, gene expression, and genotyping data, including IDH1 mutations. Unsupervised hierarchical clustering resulted in 2 groups of gliomas: a group corresponding to de novo GBMs and a group consisting of LGGs, recurrent anaplastic gliomas, and secondary GBMs. When compared with de novo GBMs and controls, this latter group was characterized by a very high frequency of IDH1 mutations and by a hypermethylated profile similar to the recently described glioma CpG island methylator phenotype. MGMT methylation was more frequent in this group. Among the LGG cluster, 1p19q codeleted LGG displayed a distinct methylation profile. A study of paired initial and recurrent gliomas demonstrated that methylation profiles were remarkably stable across glioma evolution, even during anaplastic transformation, suggesting that epigenetic alterations occur early during gliomagenesis. Using the Cancer Genome Atlas data set, we demonstrated that GBM samples that had an LGG-like hypermethylated profile had a high rate of IDH1 mutations and a better outcome. Finally, we identified several hypermethylated and downregulated genes that may be associated with LGG and GBM oncogenesis, LGG oncogenesis, 1p19q codeleted LGG oncogenesis, and GBM oncogenesis.Keywords
This publication has 65 references indexed in Scilit:
- Identification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of GliomaCancer Cell, 2010
- Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1Cancer Cell, 2010
- Mammalian MagT1 and TUSC3 are required for cellular magnesium uptake and vertebrate embryonic developmentProceedings of the National Academy of Sciences, 2009
- Expression, mutation and copy number analysis of platelet-derived growth factor receptor A (PDGFRA) and its ligand PDGFA in gliomasBritish Journal of Cancer, 2009
- Epigenetic Control of the Invasion-promoting MT1-MMP/MMP-2/TIMP-2 Axis in Cancer CellsJournal of Biological Chemistry, 2009
- Comprehensive genomic characterization defines human glioblastoma genes and core pathwaysNature, 2008
- The 2007 WHO Classification of Tumours of the Central Nervous SystemActa Neuropathologica, 2007
- Highly parallel genomic assaysNature Reviews Genetics, 2006
- Quantitative analysis of associations between DNA hypermethylation, hypomethylation, and DNMT RNA levels in ovarian tumorsOncogene, 2006
- High-throughput DNA methylation profiling using universal bead arraysGenome Research, 2006