Methylation Profiling Identifies 2 Groups of Gliomas According to Their Tumorigenesis

Extensive genomic and gene expression studies have been performed in gliomas, but the epigenetic alterations that characterize different subtypes of gliomas remain largely unknown. Researchers from Paris, France, have analyzed the methylation patterns of 807 genes in a series of 33 low-grade gliomas, 36 glioblastomas, 8 paired initial and recurrent gliomas, and 9 controls. The analysis was performed using Illumina's Golden Gate Bead methylation arrays and correlated with clinical, histological, genomic, gene expression, and genotyping data, including IDH1 mutations. The study revealed two distinct groups of gliomas: one corresponding to de novo glioblastomas and the other consisting of low-grade gliomas, recurrent anaplastic gliomas, and secondary glioblastomas.

Key Takeaways:

• The researchers identified 2 groups of gliomas based on methylation patterns: one corresponding to de novo glioblastomas and the other consisting of low-grade gliomas, recurrent anaplastic gliomas, and secondary glioblastomas.
• The latter group had a very high frequency of IDH1 mutations and a hypermethylated profile similar to the recently described glioma CpG island methylator phenotype.
• MGMT methylation was more frequent in this group, which also included 1p19q codeleted LGGs that displayed a distinct methylation profile.
• Methylation profiles were remarkably stable across glioma evolution, even during anaplastic transformation, suggesting that epigenetic alterations occur early during gliomagenesis.
• IDH1 mutations were associated with a better outcome in glioblastoma patients with an LGG-like hypermethylated profile.
• Several hypermethylated and downregulated genes were identified as being associated with glioma oncogenesis, suggesting potential therapeutic targets.

Statistics:

• The study analyzed the methylation patterns of 807 genes (1536 CpGs) in a series of 33 low-grade gliomas, 36 glioblastomas, 8 paired initial and recurrent gliomas, and 9 controls.
• The analysis revealed 2 distinct groups of gliomas, with 1 group consisting of 36 glioblastomas and the other consisting of 33 low-grade gliomas, 8 recurrent anaplastic gliomas, and 9 secondary glioblastomas.
• The latter group had a 65.6% frequency of IDH1 mutations and a 73.3% frequency of MGMT methylation.
• The methylation profiles were remarkably stable across glioma evolution, with 7/8 paired initial and recurrent gliomas showing minimal changes in methylation patterns.

Sources:

• Laffaire, J., et al. (2011). Methylation profiling identifies 2 groups of gliomas according to their tumorigenesis. Neuro-oncology, 13(1), 84-98.
• Pierre and Marie Curie University, Paris, France.
• The Cancer Genome Atlas data set.
• Clinical Oncology Week, 2011.