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Dis Markers. 2018 May 20;2018:5975216. doi: 10.1155/2018/5975216. eCollection 2018.

MEGF10, a Glioma Survival-Associated Molecular Signature, Predicts IDH Mutation Status.

Li G1,2, Wang Z1,2, Zhang C2, Liu X1,2, Yang F1, Sun L1, Liang J1, Hu H1,2, Liu Y2, You G2, Bao Z2, Zhang W2, Wang Z1,2, Jiang T1,2,3,4,5.

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Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China.
China National Clinical Research Center for Neurological Diseases, Beijing, China.
Chinese Glioma Genome Atlas Network (CGGA), Beijing, China.


Glioma is the most common primary brain tumor with various genetic alterations; among which, IDH mutation is the most common mutation and plays an important role in glioma early development, especially in lower grade glioma (LGG, WHO II-III). Previous studies have found that IDH mutation is tightly associated with extensive methylation across whole genome in glioma. To further investigate the role of IDH, we obtained methylation data of 777 samples from CGGA (Chinese Glioma Genome Atlas) and TCGA (The Cancer Genome Atlas) with IDH mutation status available. A package compiled under R language called Tspair was used as the main analytic tool to find potential probes that were significantly affected by IDH mutation. As a result, we found one pair of probes, cg06940792 and cg26025891, which was capable of predicting IDH mutation status precisely. The hypermethylated probe was cg06940792, designed in the promoter region of MEGF10, while the hypomethylated probe was cg26025891, designed in the promoter region of PSTPIP1. Survival analysis proved that hypermethylation or low expression of MEGF10 indicated a favorable prognosis in 983 glioma samples. Moreover, gene ontology analysis demonstrated that MEGF10 was associated with cell migration, cell proliferation, and regulation of apoptosis in glioma. All findings above can be validated in three other independent cohorts. In a word, our results suggested that methylation level and mRNA expression of MEGF10 in glioma were not only correlated with IDH mutation but also associated with clinical outcome of patients, providing potential guide for future dissection of IDH role in glioma.

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