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Global Analysis of LncRNAs in Gliomas and Glioblastomas

Each year, over 15,000 patients will die from brain cancer. Long noncoding RNAs (lncRNAs) are a new regulatory entity that has large effects on cell physiology and have recently been recognized for their functional role in cancer. To better understand the role of lncRNAs in brain cancer, we identified and characterized all of the long non‐coding RNAs (lncRNAs) in both grade II and III gliomas as wells as grade IV glioblastomas (GBM). We determined the expression of all lncRNAs in over 750 brain cancer and normal brain tissue RNA‐seq datasets from the Cancer Genome Atlas (TCGA) and other publicly available datasets. Over a thousand lncRNAs were induced or repressed in gliomas and GBMs relative to normal brains. Interestingly, lncRNA expression profiles distinguished the three glioma subtypes (IDH1/2 wt, IDH1/2 mutant and IDH1/2 mutant with 1p19q deletion) and the four subtypes of GBM (Classical, Mesenchymal, Neural and Proneural). Using a multivariate Cox regression survival model, we identified several hundred lncRNAs that predict patient survival independent of grade, patient age or IDH1/2 mutational status. Compared to two published studies of lncRNAs in cancer (Yan et al. Cancer Cell 28:529–540 and Iyer et al. Nat Genetics 47:199–208), this is the first comprehensive profiling of lncRNAs in gliomas and GBMs correlating expression to tumor subtype and prognosis.