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

Li MY, Wang YY, Cai JQ, Zhang CB, Wang KY, Cheng W, Liu YW, Zhang W, Jiang T - PLoS ONE (2015)

Bottom Line: Notably, isocitrate dehydrogenase 1 mutation was found to be a significant prognostic factor in patients with oligodendrogliomas, but not in patients with astrocytomas.Chemotherapy did not provide a survival benefit in patients with isocitrate dehydrogenase 1-mutated tumors.Isocitrate dehydrogenase 1 mutation was highly associated with O 6-methylguanine DNA methyltransferase promoter methylation and TP53 mutation.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier Analysis of Overall Survival and Progression-free Survival in Patients with IDH1-mutated and Wild-type Gliomas.Comparison of (A) overall survival (OS) and (B) progression-free survival (PFS) between patients with IDH1-mutated (IDH1 MT) and wild-type (IDH1 WT) grade II gliomas. Comparison of (C) OS and (D) PFS among patients with IDH1 MT grade II oligodendrogliomas (O), oliogoastrocytomas (OA), and atrocytomas (A). (E) A comparison of OS between patients with IDH1 MT or IDH1 WT grade II O or OA. (F) A comparison of OS between patients with IDH1 MT or IDH1 WT grade II As.
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pone.0130872.g001: Kaplan-Meier Analysis of Overall Survival and Progression-free Survival in Patients with IDH1-mutated and Wild-type Gliomas.Comparison of (A) overall survival (OS) and (B) progression-free survival (PFS) between patients with IDH1-mutated (IDH1 MT) and wild-type (IDH1 WT) grade II gliomas. Comparison of (C) OS and (D) PFS among patients with IDH1 MT grade II oligodendrogliomas (O), oliogoastrocytomas (OA), and atrocytomas (A). (E) A comparison of OS between patients with IDH1 MT or IDH1 WT grade II O or OA. (F) A comparison of OS between patients with IDH1 MT or IDH1 WT grade II As.

Mentions: The study cohort consisted of 417 patients with grade II gliomas. Of the 417 patients, 309 and 108 patients had IDH1-mutated and wild-tumors, respectively. OS was significantly longer in patients with IDH1-mutated tumors than in patients with IDH1 wild-type tumors (log-rank test, p = 0.015; Fig 1A). Although PFS was longer in patients with IDH1-mutated tumors than in patients with IDH1 wild-type tumors, this difference was not significant (log-rank test, p = 0.095; Fig 1B). Histological subtype influenced the prognostic effect of IDH1 mutation (log-rank test: OS p = 0.005, PFS p = 0.008; Fig 1C and 1D). IDH1 mutation was associated with better OS in patients with oligoastrocytomas or oligodendrogliomas (p = 0.047; Fig 1E), but not in patients with astrocytomas (p = 0.124; Fig 1F).


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

Li MY, Wang YY, Cai JQ, Zhang CB, Wang KY, Cheng W, Liu YW, Zhang W, Jiang T - PLoS ONE (2015)

Kaplan-Meier Analysis of Overall Survival and Progression-free Survival in Patients with IDH1-mutated and Wild-type Gliomas.Comparison of (A) overall survival (OS) and (B) progression-free survival (PFS) between patients with IDH1-mutated (IDH1 MT) and wild-type (IDH1 WT) grade II gliomas. Comparison of (C) OS and (D) PFS among patients with IDH1 MT grade II oligodendrogliomas (O), oliogoastrocytomas (OA), and atrocytomas (A). (E) A comparison of OS between patients with IDH1 MT or IDH1 WT grade II O or OA. (F) A comparison of OS between patients with IDH1 MT or IDH1 WT grade II As.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482584&req=5

pone.0130872.g001: Kaplan-Meier Analysis of Overall Survival and Progression-free Survival in Patients with IDH1-mutated and Wild-type Gliomas.Comparison of (A) overall survival (OS) and (B) progression-free survival (PFS) between patients with IDH1-mutated (IDH1 MT) and wild-type (IDH1 WT) grade II gliomas. Comparison of (C) OS and (D) PFS among patients with IDH1 MT grade II oligodendrogliomas (O), oliogoastrocytomas (OA), and atrocytomas (A). (E) A comparison of OS between patients with IDH1 MT or IDH1 WT grade II O or OA. (F) A comparison of OS between patients with IDH1 MT or IDH1 WT grade II As.
Mentions: The study cohort consisted of 417 patients with grade II gliomas. Of the 417 patients, 309 and 108 patients had IDH1-mutated and wild-tumors, respectively. OS was significantly longer in patients with IDH1-mutated tumors than in patients with IDH1 wild-type tumors (log-rank test, p = 0.015; Fig 1A). Although PFS was longer in patients with IDH1-mutated tumors than in patients with IDH1 wild-type tumors, this difference was not significant (log-rank test, p = 0.095; Fig 1B). Histological subtype influenced the prognostic effect of IDH1 mutation (log-rank test: OS p = 0.005, PFS p = 0.008; Fig 1C and 1D). IDH1 mutation was associated with better OS in patients with oligoastrocytomas or oligodendrogliomas (p = 0.047; Fig 1E), but not in patients with astrocytomas (p = 0.124; Fig 1F).

Bottom Line: Notably, isocitrate dehydrogenase 1 mutation was found to be a significant prognostic factor in patients with oligodendrogliomas, but not in patients with astrocytomas.Chemotherapy did not provide a survival benefit in patients with isocitrate dehydrogenase 1-mutated tumors.Isocitrate dehydrogenase 1 mutation was highly associated with O 6-methylguanine DNA methyltransferase promoter methylation and TP53 mutation.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus