title: Methylation associated genes contribute to the favorable prognosis of gliomas with isocitrate dehydrogenase 1 mutation.
abstract: Gliomas, the most common primary brain tumors, are characterized by isocitrate dehydrogenase 1 mutation (IDH1-M). High mutation frequency of IDH1 indicates it's promoting role in tumorgenesis. However, the observation that patients with IDH1-M have better survival comparing with patients with IDH1 wild-type (IDH1-W) suggests that this alteration has other significant beneficial features for patients. Currently, temozolomide (TMZ) is a standard of care for patients which play a major role in DNA methylation that is similar with the role of IDH1-M in genome-wide methylation. In this study, we collected 323 gliomas samples with genome-wide methylation microarray, 502 samples with genome-wide mRNA expression microarray and 295 samples with RNA-seq. By significance analysis of microarray (SAM), we identified 18 genes which are hypermethylation and low expression in samples with IDH1-M comparing with IDH1-W (FDR<0.01). Furthermore, 18 candidate genes were downregulated in TMZ-treated samples. Finally, we obtained two candidate genes, F3 and RBP1. Survival analysis showed that hypermethylation or low expression of the two genes indicated a favorable prognosis, which was consistent with IDH1-M and administration of TMZ in glioma patients. F3 and RBP1 were further validated by qPCR on an independent validation cohort containing 145 samples. Our data suggest that these candidate genes were suppressed by TMZ or IDH1-M induced hypermethylation, resulting in the favorable prognosis of patients with gliomas.
authors.affiliation: Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University Beijing 100050, China ; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University Beijing 100050, China ; Chinese Glioma Cooperative Group (CGCG) China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University Beijing 100050, China ; Chinese Glioma Cooperative Group (CGCG) China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University Beijing 100050, China ; Chinese Glioma Cooperative Group (CGCG) China.
authors.forename: Chuanbao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University Beijing 100050, China ; Chinese Glioma Cooperative Group (CGCG) China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University Beijing 100050, China ; Chinese Glioma Cooperative Group (CGCG) China.
authors.forename: Mingyang
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University Beijing 100050, China ; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University Beijing 100050, China ; Brain Tumor Center, Beijing Institute for Brain Disorders Beijing 100069, China ; Chinese Glioma Cooperative Group (CGCG) China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University Beijing 100050, China ; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University Beijing 100050, China ; Brain Tumor Center, Beijing Institute for Brain Disorders Beijing 100069, China ; Chinese Glioma Cooperative Group (CGCG) China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
keywords: Gliomas; IDH1 mutation; RNA microarray; RNA-Seq; methylation microarray; temozolomide