Impact of IDH Mutations, the 1p/19q Co-Deletion and the G-CIMP Status on Alternative Splicing in Diffuse Gliomas

By generating protein diversity, alternative splicing provides an important oncogenic pathway. Isocitrate dehydrogenase (IDH) 1 and 2 mutations and 1p/19q co-deletion have become crucial for the novel molecular classification of diffuse gliomas, which also incorporates DNA methylation profiling. In this study, we have carried out a bioinformatics analysis to examine the impact of the IDH mutation, as well as the 1p/19q co-deletion and the glioma CpG island methylator phenotype (G-CIMP) status on alternative splicing in a cohort of 662 diffuse gliomas from The Cancer Genome Atlas (TCGA). We identify the biological processes and molecular functions affected by alternative splicing in the various glioma subgroups and provide evidence supporting the important contribution of alternative splicing in modulating epigenetic regulation in diffuse gliomas. Targeting the genes and pathways affected by alternative splicing might provide novel therapeutic opportunities against gliomas.

Automated summary

By generating protein diversity, alternative splicing plays an important role in oncogenesis. The IDH1 and IDH2 mutations, as well as the 1p/19q co-deletion, have become crucial for the molecular classification of diffuse gliomas, which also considers DNA methylation profiling. This study demonstrates the impact of IDH mutation, 1p/19q co-deletion, and glioma CpG island methylator phenotype (G-CIMP) on alternative splicing in diffuse gliomas from The Cancer Genome Atlas (TCGA). The findings suggest that alternative splicing contributes to epigenetic regulation in diffuse gliomas and targeting the genes and pathways affected by alternative splicing may offer potential therapeutic opportunities against gliomas.