Dataset Information

Isocitrate dehydrogenase 1 (IDH1) mutant gliomas demonstrate a distinct global CpG island methylation profile compared to IDH1 wildtype gliomas using MRSE

ABSTRACT: In order to identify other molecular aberrations that may cooperate with IDH1R132MUT in gliomagenesis, we performed CpG-island methylation profiling analysis using MSRE (Tran et al. Front. Neurosci. 3:57. Doi: 10.3389/neuro.15.005.2009) on a subset of IDH1R132MUT and IDH1R132WT GBMs and found a distinct pattern of CpG island hypermethylation that was detected in all GBMs and lower grade gliomas with IDH1R132MUT. While absent from nearly all IDH1R132WT glioma, the methylation pattern in IDH1R132MUT GBMs shows similarity to the recently reported CpG island methylator phenotype (CIMP) found to be tightly associated with IDH1R132MUT gliomas(Noushmehr et al. Cancer Cell, Volume 17, Issue 5, 18 May 2010, Pages 510-522, ISSN 1535-6108, DOI: 10.1016/j.ccr.2010.03.017).

ORGANISM(S): Homo sapiens

PROVIDER: GSE28271 | GEO | 2011/10/25

SECONDARY ACCESSION(S): PRJNA139265

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:The p90 ribosomal S6 kinase (RSK) family, a downstream target of Ras/extracellular signal-regulated kinase (ERK) signaling, can mediate cross-talk with the mammalian target of rapamycin complex 1 (mTORC1) pathway. As RSK connects two oncogenic pathways in gliomas, we investigated the protein levels of the RSK isoforms RSK1-4 in non-tumoral brain (NB) and grade I-IV gliomas. RSK4 expression was not detected in any brain tissues, whereas RSK3 expression was very low, with GBMs demonstrating the lowest RSK3 protein levels. When compared to NB or low-grade gliomas (LGG), a group of glioblastomas (RSK1hi) that excluded long-survivor cases expressed higher levels of RSK1. No difference was observed in RSK2 median-expression levels among NB and gliomas; however, high levels of RSK2 in glioblastomas (GBM) were associated with worse survival. RSK1hi and, to a lesser extent, RSK2hi GBMs, showed higher levels of phosphorylated RSK, which indicates RSK activation. Transcriptome analysis indicated that most RSK1hi GBMs belonged to the mesenchymal subtype, and RSK1 expression strongly correlated with gene expression signature of immune infiltrates, in particular of activated-natural killer cells and M2 macrophages. In an independent cohort, we confirmed that RSK1hi GBMs exclude long-survivors, and RSK1 expression was associated with high protein levels of the mesenchymal subtype marker LAPTM5, as well as with high expression of CD68, which indicated the presence of infiltrating immune cells. An RSK1 signature was obtained based on differentially expressed mRNAs and validated in public glioma datasets. Enrichment of RSK1 signature followed glioma progression, recapitulating RSK1 protein expression, and was associated with worse survival not only in GBM but also in LGG. In conclusion, both RSK1 and RSK2 associate with glioma malignity, but displaying isoform-specific peculiarities. The progression-dependent expression and association with immune infiltration, suggests RSK1 as a potential progression marker and therapeutic target for gliomas.

Dataset Information

Isocitrate dehydrogenase 1 (IDH1) mutant gliomas demonstrate a distinct global CpG island methylation profile compared to IDH1 wildtype gliomas using MRSE

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure