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

PLoS One

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Beijing Neurosurgical Institute, Capital Medical University, Beijing, China; Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China.

Published: April 2016

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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482584PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0130872PLOS

Publication Analysis

Top Keywords

isocitrate dehydrogenase
56
dehydrogenase mutation
24
low-grade gliomas
20
isocitrate
14
dehydrogenase
13
6-methylguanine dna
12
dna methyltransferase
12
methyltransferase promoter
12
promoter methylation
12
tp53 mutation
12

Similar Publications

IDH1 mutation inhibits differentiation of astrocytes and glioma cells with low oxoglutarate dehydrogenase expression by disturbing α-ketoglutarate-related metabolism and epigenetic modification.

Life Metab

April 2024

State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.

Isocitrate dehydrogenase (IDH) mutations frequently occur in lower-grade gliomas and secondary glioblastomas. Mutant IDHs exhibit a gain-of-function activity, leading to the production of D-2-hydroxyglutarate (D-2HG) by reducing α-ketoglutarate (α-KG), a central player in metabolism and epigenetic modifications. However, the role of α-KG homeostasis in IDH-mutated gliomagenesis remains elusive.

View Article and Find Full Text PDF

Growth inhibition by ppc deletion is rescued by isocitrate dehydrogenase mutations in Escherichia coli.

FEMS Microbiol Lett

January 2025

Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka 565-0871, Japan.

Phosphoenolpyruvate carboxylase encoded by ppc catalyzes the anaplerotic reaction of oxaloacetate in the TCA cycle in Escherichia coli. Deletion of ppc does not prevent the cells from replenishing oxaloacetate via the glyoxylate shunt, but the ppc-deletion strain almost did not grow on glucose. In the present study, we obtained evolved strains by deleting both ppc and mutS to increase the mutation rate and investigated the mechanisms for improving growth by analyzing the mutated genes.

View Article and Find Full Text PDF

HNF4α inhibits the malignancy of intrahepatic cholangiocarcinoma by suppressing the Wnt signaling pathway.

Transl Oncol

January 2025

Department of Gastroenterology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Shanghai 200003, China. Electronic address:

Previous studies have demonstrated that intrahepatic cholangiocarcinoma (ICC) may derive from transdifferentiation of hepatocytes, so transforming ICC cells into hepatocytes could be a potential strategy for treating ICC. Hepatocyte nuclear factor 4α (HNF4α), a master transcription factor in the liver, has been demonstrated to induce the differentiation of hepatocellular carcinoma, while its effects on ICC remains unclear. Ivosidenib, an isocitrate dehydrogenase 1 (IDH1) inhibitor, is a novel targeted drug for ICC patients.

View Article and Find Full Text PDF

Infectious Spleen and Kidney Necrosis Virus ORF093R and ORF102R Regulate Glutamate Metabolic Reprogramming to Support Virus Proliferation by Interacting with c-Myc.

Int J Mol Sci

January 2025

Ministry of Agriculture and Rural Affairs, Key Laboratory of Aquatic Animal Immune Technology, Key Laboratory of fishery Drug Development, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510380, China.

Glutamine metabolism is essential for infectious spleen and kidney necrosis virus (ISKNV) replication. Glutaminase 1 (GLS1), the key enzyme of the glutamine metabolism, and c-Myc positively regulate ISKNV infection, while c-Myc is closely correlated with GLS1. However, the regulatory mechanism among ISKNV, c-Myc and glutamine metabolism remains unclear.

View Article and Find Full Text PDF

Glioblastoma (GBM) is an aggressive brain tumor characterized by extensive metabolic reprogramming that drives tumor growth and therapeutic resistance. Key metabolic pathways, including glycolysis, lactate production, and lipid metabolism, are upregulated to sustain tumor survival in the hypoxic and nutrient-deprived tumor microenvironment (TME), while glutamine and tryptophan metabolism further contribute to the aggressive phenotype of GBM. These metabolic alterations impair immune cell function, leading to exhaustion and stress in CD8+ and CD4+ T cells while favoring immunosuppressive populations such as regulatory T cells (Tregs) and M2-like macrophages.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!