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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.

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