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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 According to IDH1 Status and Adjuvant Treatment.A comparison of (A) overall survival (OS) and (B) progression-free survival (PFS) between patients with IDH1 wild-type (IDH1 WT) grade II gliomas who received radiotherapy (RT) or radiotherapy plus chemotherapy (RT+CT). A comparison of (C) OS and (D) PFS between patients with IDH1-mutated (IDH1 MT) grade II gliomas who received RT or RT+CT. For the IDH1 WT group, PFS and OS were longer in patients who underwent RT compared with those who underwent RT+CT (p = 0.002). For the IDH1 MT group, PFS and OS were not significantly different between patients who underwent RT or RT+CT (p = 0.194).
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pone.0130872.g002: Kaplan-Meier Analysis of Overall Survival and Progression-free Survival According to IDH1 Status and Adjuvant Treatment.A comparison of (A) overall survival (OS) and (B) progression-free survival (PFS) between patients with IDH1 wild-type (IDH1 WT) grade II gliomas who received radiotherapy (RT) or radiotherapy plus chemotherapy (RT+CT). A comparison of (C) OS and (D) PFS between patients with IDH1-mutated (IDH1 MT) grade II gliomas who received RT or RT+CT. For the IDH1 WT group, PFS and OS were longer in patients who underwent RT compared with those who underwent RT+CT (p = 0.002). For the IDH1 MT group, PFS and OS were not significantly different between patients who underwent RT or RT+CT (p = 0.194).

Mentions: MGMT promoter methylation status could be determined in 83 tumors. MGMT promoter methylation was present in 48 (58%) tumors (Table 2). Strikingly, of the 48 tumors with MGMT promoter methylation, 42 (87%) were IDH1-mutated tumors, whereas only 6 (13%) were IDH1 wild-type tumors (chi square test, p = 0.017). The proportion of patients with TP53 mutations was higher in the IDH1 mutation group than in the IDH1 wild-type group (36% [81/226] vs. 9% [7/80]; chi square test, p < 0.001). The frequency of 1p/19q deletion was not significantly different between the IDH1 mutation and wild-type groups (30% vs. 31%; chi square test, p = 0.834). Furthermore, in the IDH1 wild-type group, OS and PFS were significantly longer in patients who underwent radiotherapy than those who underwent radiotherapy plus chemotherapy (p = 0.002 and p = 0.003, respectively). In contrast, OS and PFS were not significantly different between patients who received radiotherapy or radiotherapy plus chemotherapy in the IDH1 mutation group (p = 0.194 and p = 0.137, respectively; Fig 2).


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 According to IDH1 Status and Adjuvant Treatment.A comparison of (A) overall survival (OS) and (B) progression-free survival (PFS) between patients with IDH1 wild-type (IDH1 WT) grade II gliomas who received radiotherapy (RT) or radiotherapy plus chemotherapy (RT+CT). A comparison of (C) OS and (D) PFS between patients with IDH1-mutated (IDH1 MT) grade II gliomas who received RT or RT+CT. For the IDH1 WT group, PFS and OS were longer in patients who underwent RT compared with those who underwent RT+CT (p = 0.002). For the IDH1 MT group, PFS and OS were not significantly different between patients who underwent RT or RT+CT (p = 0.194).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0130872.g002: Kaplan-Meier Analysis of Overall Survival and Progression-free Survival According to IDH1 Status and Adjuvant Treatment.A comparison of (A) overall survival (OS) and (B) progression-free survival (PFS) between patients with IDH1 wild-type (IDH1 WT) grade II gliomas who received radiotherapy (RT) or radiotherapy plus chemotherapy (RT+CT). A comparison of (C) OS and (D) PFS between patients with IDH1-mutated (IDH1 MT) grade II gliomas who received RT or RT+CT. For the IDH1 WT group, PFS and OS were longer in patients who underwent RT compared with those who underwent RT+CT (p = 0.002). For the IDH1 MT group, PFS and OS were not significantly different between patients who underwent RT or RT+CT (p = 0.194).
Mentions: MGMT promoter methylation status could be determined in 83 tumors. MGMT promoter methylation was present in 48 (58%) tumors (Table 2). Strikingly, of the 48 tumors with MGMT promoter methylation, 42 (87%) were IDH1-mutated tumors, whereas only 6 (13%) were IDH1 wild-type tumors (chi square test, p = 0.017). The proportion of patients with TP53 mutations was higher in the IDH1 mutation group than in the IDH1 wild-type group (36% [81/226] vs. 9% [7/80]; chi square test, p < 0.001). The frequency of 1p/19q deletion was not significantly different between the IDH1 mutation and wild-type groups (30% vs. 31%; chi square test, p = 0.834). Furthermore, in the IDH1 wild-type group, OS and PFS were significantly longer in patients who underwent radiotherapy than those who underwent radiotherapy plus chemotherapy (p = 0.002 and p = 0.003, respectively). In contrast, OS and PFS were not significantly different between patients who received radiotherapy or radiotherapy plus chemotherapy in the IDH1 mutation group (p = 0.194 and p = 0.137, respectively; Fig 2).

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