Isocitrate dehydrogenase 1 Gene Mutation Is Associated with Prognosis in Clinical Low-Grade Gliomas

Isocitrate dehydrogenase 1 gene mutations are found in most World Health Organization grade II and III gliomas and secondary glioblastomas. Isocitrate dehydrogenase 1 mutations are known to have prognostic value in high-grade gliomas. However, their prognostic significance in low-grade gliomas remai...

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Published in:PloS one 2015-06, Vol.10 (6), p.e0130872-e0130872
Main Authors: Li, Ming-Yang, Wang, Yin-Yan, Cai, Jin-Quan, Zhang, Chuan-Bao, Wang, Kuan-Yu, Cheng, Wen, Liu, Yan-Wei, Zhang, Wei, Jiang, Tao
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Astrocytoma
Biomarkers
Brain cancer
Brain research
Brain tumors
Cancer genetics
Chemotherapy
Chi-square test
Dehydrogenase
Dehydrogenases
Deoxyribonucleic acid
DNA
DNA methylation
DNA methyltransferase
DNA Modification Methylases - genetics
DNA Repair Enzymes - genetics
Female
Frontal lobe
Gene mutation
Genes
Genetic aspects
Genetic factors
Genomes
Genomics
Glioma
Glioma - enzymology
Glioma - genetics
Glioma - pathology
Gliomas
Hazards
Hospitals
Humans
Isocitrate dehydrogenase
Isocitrate Dehydrogenase - genetics
Kaplan-Meier Estimate
Li, Yang
Male
Medical prognosis
Methylation
Methylguanine
Middle Aged
Molecular chains
Mutation
Neurosurgery
p53 Protein
Patients
Point mutation
Polymerase chain reaction
Prognosis
Promoter Regions, Genetic - genetics
Radiation therapy
Regression analysis
Studies
Survival
Tumor proteins
Tumor Suppressor Proteins - genetics
Tumors
Young Adult
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Summary:Isocitrate dehydrogenase 1 gene mutations are found in most World Health Organization grade II and III gliomas and secondary glioblastomas. Isocitrate dehydrogenase 1 mutations are known to have prognostic value in high-grade gliomas. However, their prognostic significance in low-grade gliomas remains controversial. We determined the predictive and prognostic value of isocitrate dehydrogenase 1 status in low-grade gliomas. The association of isocitrate dehydrogenase 1 status with clinicopathological and genetic factors was also evaluated. Clinical information and genetic data including isocitrate dehydrogenase 1 mutation, O 6-methylguanine DNA methyltransferase promoter methylation, 1p/19q chromosome loss, and TP53 mutation of 417 low-grade gliomas were collected from the Chinese Glioma Genome Atlas database. Kaplan-Meier and Cox proportional hazards regression analyses were performed to evaluate the prognostic effect of clinical characteristics and molecular biomarkers. Isocitrate dehydrogenase 1 mutation was identified as an independent prognostic factor for overall, but not progression-free, survival. Notably, isocitrate dehydrogenase 1 mutation was found to be a significant prognostic factor in patients with oligodendrogliomas, but not in patients with astrocytomas. Furthermore, O 6-methylguanine DNA methyltransferase promoter methylation (p = 0.017) and TP53 mutation (p < 0.001), but not 1p/19q loss (p = 0.834), occurred at a higher frequency in isocitrate dehydrogenase 1-mutated tumors than in isocitrate dehydrogenase 1 wild-type tumors. Younger patient age (p = 0.041) and frontal lobe location (p = 0.010) were significantly correlated with isocitrate dehydrogenase 1 mutation. Chemotherapy did not provide a survival benefit in patients with isocitrate dehydrogenase 1-mutated tumors. Isocitrate dehydrogenase 1 mutation was an independent prognostic factor in low-grade gliomas, whereas it showed no predictive value for chemotherapy response. Isocitrate dehydrogenase 1 mutation was highly associated with O 6-methylguanine DNA methyltransferase promoter methylation and TP53 mutation.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0130872