title: Significance of IDH mutations varies with tumor histology, grade, and genetics in Japanese glioma patients.
abstract: Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are found frequently in malignant gliomas and are likely involved in early gliomagenesis. To understand the prevalence of these mutations and their relationship to other genetic alterations and impact on prognosis for Japanese glioma patients, we analyzed 250 glioma cases. Mutations of IDH1 and IDH2 were found in 73 (29%) and 2 (1%) cases, respectively. All detected mutations were heterozygous, and most mutations were an Arg132His (G395A) substitution. IDH mutations were frequent in oligodendroglial tumors (37/52, 71%) and diffuse astrocytomas (17/29, 59%), and were less frequent in anaplastic astrocytomas (8/29, 28%) and glioblastomas (13/125, 10%). The pilocytic astrocytomas and gangliogliomas did not have either mutation. Notably, 28 of 30 oligodendroglial tumors harboring the 1p/19q co-deletion also had an IDH mutation, and these alterations were significantly correlated (P < 0.001). The association between TP53 and IDH mutation was significant in diffuse astrocytomas (P = 0.0018). MGMT promoter methylation was significantly associated with IDH mutation in grade 2 (P < 0.001) and grade 3 (P = 0.02) gliomas. IDH mutation and 1p/19q co-deletion were independent favorable prognostic factors for patients with grade 3 gliomas. For patients with grade 3 gliomas and without 1p/19q co-deletion, IDH mutation was strongly associated with increased progression-free survival (P < 0.0001) and overall survival (P < 0.0001), but no such marked correlation was observed with grade 2 gliomas or glioblastomas. Therefore, IDH mutation would be most useful when assessing prognosis of patients with grade 3 glioma with intact 1p/19q; anaplastic astrocytomas account for most of these grade 3 gliomas.
authors.affiliation: Department of Neurosurgery, University of Tokyo, Tokyo, Japan. mukasa-nsu@umin.ac.jp
authors.forename: Akitake
authors.initials: A
authors.lastname: Mukasa
authors.forename: Shunsaku
authors.initials: S
authors.lastname: Takayanagi
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Saito
authors.forename: Junji
authors.initials: J
authors.lastname: Shibahara
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tabei
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Furuya
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ide
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Narita
authors.forename: Ryo
authors.initials: R
authors.lastname: Nishikawa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ueki
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Saito
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human