title: The global DNA methylation surrogate LINE-1 methylation is correlated with MGMT promoter methylation and is a better prognostic factor for glioma.
abstract: Gliomas are the most frequently occurring primary brain tumor in the central nervous system of adults. Glioblastoma multiformes (GBMs, WHO grade 4) have a dismal prognosis despite the use of the alkylating agent, temozolomide (TMZ), and even low grade gliomas (LGGs, WHO grade 2) eventually transform to malignant secondary GBMs. Although GBM patients benefit from promoter hypermethylation of the O(6)-methylguanine-DNA methyltransferase (MGMT) that is the main determinant of resistance to TMZ, recent studies suggested that MGMT promoter methylation is of prognostic as well as predictive significance for the efficacy of TMZ. Glioma-CpG island methylator phenotype (G-CIMP) in the global genome was shown to be a significant predictor of improved survival in patients with GBM. Collectively, we hypothesized that MGMT promoter methylation might reflect global DNA methylation. Additionally in LGGs, the significance of MGMT promoter methylation is still undetermined. In the current study, we aimed to determine the correlation between clinical, genetic, and epigenetic profiles including LINE-1 and different cancer-related genes and the clinical outcome in newly diagnosed 57 LGG and 54 GBM patients. Here, we demonstrated that (1) IDH1/2 mutation is closely correlated with MGMT promoter methylation and 1p/19q codeletion in LGGs, (2) LINE-1 methylation levels in primary and secondary GBMs are lower than those in LGGs and normal brain tissues, (3) LINE-1 methylation is proportional to MGMT promoter methylation in gliomas, and (4) higher LINE-1 methylation is a favorable prognostic factor in primary GBMs, even compared to MGMT promoter methylation. As a global DNA methylation marker, LINE-1 may be a promising marker in gliomas.
authors.affiliation: Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: Fumiharu
authors.initials: F
authors.lastname: Ohka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Natsume
authors.forename: Kazuya
authors.initials: K
authors.lastname: Motomura
authors.forename: Yugo
authors.initials: Y
authors.lastname: Kishida
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kondo
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Abe
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakasu
authors.forename: Hiroki
authors.initials: H
authors.lastname: Namba
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakai
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukui
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Momota
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Iwami
authors.forename: Sayano
authors.initials: S
authors.lastname: Kinjo
authors.forename: Maki
authors.initials: M
authors.lastname: Ito
authors.forename: Masazumi
authors.initials: M
authors.lastname: Fujii
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Wakabayashi
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D017931:DNA Primers; D045643:DNA Repair Enzymes / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D017931:DNA Primers; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes