title: Mutation analysis of IDH1 in paired gliomas revealed IDH1 mutation was not associated with malignant progression but predicted longer survival.
abstract: Recurrence and progression to higher grade lesions are characteristic behaviors of gliomas. Though IDH1 mutation frequently occurs and is considered as an early event in gliomagenesis, little is known about its role in the recurrence and progression of gliomas. We therefore analysed IDH1 and IDH2 status at codon 132 of IDH1 and codon 172 of IDH2 by direct sequencing and anti-IDH1-R132H immunohistochemistry in 53 paired samples and their recurrences, including 29 low-grade gliomas, 16 anaplastic gliomas and 8 Glioblastomas. IDH1/IDH2 mutation was detected in 32 primary tumors, with 25 low-grade gliomas and 6 anaplastic gliomas harboring IDH1 mutation and 1 low-grade glioma harboring IDH2 mutation. All of the paired tumors showed consistent IDH1 and IDH2 status. Patients were analyzed according to IDH1 status and tumor-related factors. Malignant progression at recurrence was noted in 22 gliomas and was not associated with IDH1 mutation. Survival analysis revealed patients with IDH1 mutated gliomas had a significantly longer progression-free survival (PFS) and overall survival (OS). In conclusion, this study demonstrated a strong tendency of IDH1/IDH2 status being consistent during progression of glioma. IDH1 mutation was not a predictive marker for malignant progression and it was a potential prognostic marker for gliomas of Chinese patients.
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
authors.forename: Aden Ka-Yin
authors.initials: AK
authors.lastname: Chan
authors.forename: Zhi Yong
authors.initials: ZY
authors.lastname: Qin
authors.forename: Ling Chao
authors.initials: LC
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Jesse Chung-Sean
authors.initials: JC
authors.lastname: Pang
authors.forename: Hiu Ming
authors.initials: HM
authors.lastname: Li
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
authors.forename: Ho-Keung
authors.initials: HK
authors.lastname: Ng
authors.forename: Liang Fu
authors.initials: LF
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020125:Mutation, Missense; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D055815:Young Adult
chemical_list: C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human