Abstract
BACKGROUND: Isocitrate dehydrogenase 1 (IDH1) mutation is a frequent event in low-grade gliomas as well as secondary glioblastomas. Mutated IDH1 can induce genome-wide transcriptional alterations that may contribute to gliomagenesis. Long non-coding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis in a number of neoplastic conditions including glioma. Our previous works suggested that aberrant expressions of specific lncRNAs may play important roles in tumor initiation and progression.1 In the present study, we further investigated changes in lncRNA expression profile associated with IDH1 mutation. METHODS: We performed lncRNA profiling analysis of publicly available glioma microarray data using our previously reported mining approach. We compared the differential lncRNA expression profiles between mutant-type and wild-type IDH1 samples in both glioblastoma and oligodendroglioma. RESULTS: We identified distinct sets of dysregulated lncRNAs that were associated with IDH1 mutation in glioblastomas and oligodendrogliomas. Hierarchical clustering revealed that IDH1-mutant tumors clustered together and were clearly distinguishable from IDH1-wild-type samples. Interestingly, glioblastoma and oligodendroglioma also shared a specific set of lncRNA alterations, suggesting common and early transcriptional alterations. We also found that IDH1-mutation-associated lncRNA alterations exhibited a tumor grade-dependent pattern that was associated with differences in clinical outcomes. CONCLUSION: The identification of IDH1-mutation-associated lncRNAs provided further evidence in support of the important roles of lncRNA in glioma pathogenesis. The approach may improve the understanding of the pathogenesis of gliomas with different IDH1 gene mutation status. References: 1. Zhang X, Sun S, Lam KF, Kiang KMY, Pu JKS, Ho ASW, Lui WM, Gung CF, Leung GKK. A long non-coding RNA signature in glioblastoma multiforme predicts survival.