Recent developments and future directions in adult lower-grade gliomas: Society for Neuro-Oncology (SNO) and European Association of Neuro-Oncology (EANO) consensus (original) (raw)
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Neuro-oncology, 2022
Isocitrate dehydrogenase (IDH) mutant gliomas are the most common adult, malignant primary brain tumors diagnosed in patients younger than 50, constituting an important cause of morbidity and mortality. In recent years, there has been significant progress in understanding the molecular pathogenesis and biology of these tumors, sparking multiple efforts to improve their diagnosis and treatment. In this consensus review from the Society for Neuro-Oncology (SNO), the current diagnosis and management of IDH-mutant gliomas will be discussed. In addition, novel therapies, such as targeted molecular therapies and immunotherapies, will be reviewed. Current challenges and future directions for research will be discussed.
International journal of oncology, 2012
Reliable prognostic biomarkers of grade II gliomas remain unclear. This study aimed to examine the role of mutations of isocitrate dehydrogenase (IDH1/2), 1p/19q co-deletion, and clinicopathological factors in patients with grade II glioma who were primarily treated with radiotherapy or chemoradiotherapy after surgery. Seventy-two consecutive patients, including 49 cases of diffuse astrocytomas (DA), 4 oligodendrogliomas (OL) and 19 oligoastrocytomas (OA), who underwent treatment from 1991 to 2010 at a single institution were examined. The overall survival (OS) of the DA patients (8.3 years) was significantly shorter than that of the OL and OA patients (11.7 years). IDH1/2 mutations were found in 46.9% of the DA patients and 82.6% of the OL and OA patients. The progression-free survival (PFS) and OS of the patients with IDH1/2 mutations (8.4 and 16.3 years) were significantly longer than those of the patients without IDH1/2 mutations (3.3 and 4.5 years). Among the patients with IDH1...
Isocitrate dehydrogenase 1 and 2 mutations in gliomas
Journal of neuroscience research, 2014
Over the past few years, new biomarkers have allowed a deeper insight into gliomagenesis and facilitated the identification of possible targets for glioma therapy. Isocitrate dehydrogenase (IDH) 1 and IDH2 mutations have been shown to be promising biomarkers for monitoring disease prognosis and predicting the response to treatment. This review summarizes recent findings in this field. Web of Science, Science Direct, and PubMed online databases were used to search for publications investigating the role of IDH in glioma. References were identified by searching for the keywords "IDH1 or IDH2 and glioma and diagnostic or predictive or prognostic" in papers published from January, 2008, to April, 2014. Only papers in English were reviewed. Publications available only as an abstract were not included. IDH1/2 mutations are tightly associated with grade II and III gliomas and secondary glioblastomas, with better prognosis and production of a recently described oncometabolite, 2-h...
A population-based study of low-grade gliomas and mutated isocitrate dehydrogenase 1 (IDH1)
Journal of Neuro-Oncology, 2013
High-grade gliomas have a dismal prognosis, and prognostic factors are needed to optimize treatment algorithms. In this study we identified clinical prognostic factors as well as the prognostic value of isocitrate dehydrogenase 1 (IDH1) status in a population-based group of patients with high-grade gliomas. Using the Danish Cancer Registry and the Danish Pathology Databank we identified 359 patients: 234 had WHO grade IV gliomas, 58 had WHO grade III gliomas, and 67 were diagnosed clinically. Mutated IDH1 was predominantly observed in oligodendroglial tumors (WHO grade III). Patients with mutated IDH1 had a significantly better outcome than patients with wildtype IDH1: 2-year OS 59% and 18%, respectively (HR 0.38, 95% CI 0.21-0.68). However, when adjusting for other prognostic factors, IDH1 status was not a significant independent prognostic factor (HR=0.58, 95% CI 0.32-1.07). Young age, absence of neurological deficit, performance status 0-1, tumor not crossing the midline, and receiving post-surgical treatment were significant independent indicators of a good prognosis in multivariate analysis. In conclusion: This population-based study could not demonstrate IDH1 status to be an independent prognostic factor in high-grade gliomas when adjusting for the effect of classic prognostic factors.
2021
Adult glioma; IDH1/2 mutated gliomas; Immunohistochemistry; Isocitratedehydrogenase 1 and 2 genes Isocitrate dehydrogenase 1 and 2 mutations are known to be early events in gliomagenesis and have a definite role in tumor progression.Isocitrate dehydrogenase1/2 mutation status is considered to be one of the most powerful independent positive predictor of outcome amongst all molecular markers described in association with gliomas. The inclusion of this parameter in the 2016 update of the World Health Organization Classification of Tumors of The Central Nervous System reinforced its importance in glioma classification and prognostication. As a result, now there is enough evidence to prove that Isocitrate dehydrogenase-mutant and Isocitrate dehydrogenasewildtypegliomas are two biologically distinct categories of gliomas with likely different pathways of tumorigenesis,different clinical outcomes, and respond differently to similar treatment strategies. Increasing knowledge aboutthe role ...
Molecular Diagnosis & Therapy, 2014
Background and Objective IDH1 (isocitrate dehydrogenase 1) is a potential biomarker and drug target. Genomic and epigenetic data on astrocytoma have demonstrated that the IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Furthermore, recent studies have also indicated that a mutant IDH1 inhibitor induced demethylation of histone H3K9me3 and expression of genes associated with gliogenic differentiation. As the presence of the p.R132H mutation in the IDH1 gene seems to be a more powerful prognostic marker than O 6 -methylguanine-DNA methyltransferase promoter status, we evaluated the presence of IDH1 mutation in Polish patients with astrocytoma, glioblastoma, oligoastrocytoma, ganglioglioma, oligodendroglioma, and ependymoma. Methods The IDH1 mutation status at codon 132 was determined using a mouse monoclonal antibody specific for the R132H mutation, direct sequencing, and
New insights into glioma classification based on isocitrate dehydrogenase 1 and 2 gene status
Brain tumor pathology, 2011
In glioma, mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) genes have been receiving attention. IDH1/2 mutations are frequently found in grade II and III gliomas. These genetic alterations occur very early in gliomagenesis and strongly predict favorable outcome in patients with high-grade gliomas. Despite the evolution of studies on this topic, the underlying mechanism of the IDH1/2 mutations remains unknown. Here, we briefly review the current knowledge of IDH1/2 and discuss molecular diagnostics based on IDH1/2 gene status.
The Role of IDH1 and IDH2 Mutations in Malignant Gliomas
Tumors of the Central Nervous System, Volume 2, 2011
A recent study identified mutations in the active sites of isocitrate dehydrogenase 1 and 2 (IDH1and IDH2) genes in several types of glioma. All mutations affected a single amino acid located in the binding site of isocitrate (R132 of IDH1 and R172 of IDH2). We analyzed the genomic region spanning wild-type R132 of IDH1 and R172 of IDH2 by direct sequencing in 125 glial tumors. A total of 39 IDH1 mutations and one IDH2 mutation were observed. IDH1 and IDH2 mutations were frequently present in astrocytic and oligodendroglial tumors. However, primary glioblastomas were characterized by a low frequency of mutations (5%) at amino acid position 132 of IDH1. Mutations of IDH1 and IDH2 genes were significantly associated with improved outcome in patients with anaplastic astrocytomas. IDH1 and IDH2 mutations seem to play an important role in early tumor progression of specific types of glioma and might arise from a common glial precursor. The infrequency of IDH1 mutation in primary glioblastomas revealed that these subtypes are entities that are genetically distinct from other glial tumors. Analyses of IDH1 and IDH2 status have significant utility for diagnosis and treatment of patients with gliomas.
IDH1 mutations are present in the majority of common adult gliomas but rare in primary glioblastomas
Neuro-Oncology, 2009
We screened exon 4 of the gene isocitrate dehydrogenase 1 (NADP+), soluble (IDH1) for mutations in 596 primary intracranial tumors of all major types. Codon 132 mutation was seen in 54% of astrocytomas and 65% of oligodendroglial tumors but in only 6% of glioblastomas (3% of primary and 50% of secondary glioblastomas). There were no mutations in any other type of tumor studied. While mutations in the tumor protein p53 gene (TP53) and total 1p/19q deletions were mutually exclusive, IDH1 mutations were strongly correlated with these genetic abnormalities. All four types of mutant IDH1 proteins showed decreased enzymatic activity. The data indicate that IDH1 mutation combined with either TP53 mutation or total 1p/19q loss is a frequent and early change in the majority of oligodendroglial tumors, diffuse astrocytomas, anaplastic astrocytomas, and secondary glioblastomas but not in primary glioblastomas.