Genetic Biomarkers of Glial Brain Tumors: Idh1 and Idh2 Mutations

Прокудин, М. Ю.; Мартынов, Б. В.; Svistov, D. V.; Litvinenko, I. V.; Имянитов, Е. Н.; Чирский, В. С.; Бушуров, С Е; Iakovenko, Andrei; Чемодакова, К. А.; Клиценко, О. А.; Горустович, О. А.; Медведева, Г. Ф.; Bulatov, A R

doi:10.21294/1814-4861-2020-19-4-59-66

Cited by 4 publications

(1 citation statement)

References 16 publications

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“…et al, фармакорезистентность наблюдется у 22 % пациентов при наличии мутации IDH1/2 и у 12 % пациентов при отсутствии данной мутации (IDH wildtype). По результатам собственных исследований установлено, что присутствие мутаций в генах IDH1/2 ассоциировано с локализацией глиальных опухолей в лобной и теменной долях головного мозга и с клиническими прогностическими факторами: более молодым возрастом начала заболевания, присутствием в клинической картине эпилептических приступов [22]. Для пациентов с наличием мутаций IDH1/2 характерно более благоприятное течение заболевания (более высокие длительность безрецидивного периода и продолжительность жизни).…”

Section: Russian Military Medicalunclassified

Antiepileptic therapy algorithms in patients with primary and metastatic brain tumors

Prokudin,

Litvinenko,

Rumуantseva

et al. 2023

Russian Military Medical Academy Reports

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Up to date the brain tumors incidence keeps growing worldwide. Epilepsy and epileptic seizures are one of the most common clinical features of brain tumors. The aim of the study was to invent the algorithms antiepileptic treatment of patients with primary and metastatic brain tumors based on literature data. We searched eLIBRARY, PubMed databases by keywords. We concluded, that preventive antiepileptic drugs administration in patients with primary or metastatic brain lesions does not lower the risk of acute symptomatic postoperative seizures or epilepsy incidence, and therefore should not be recommended. Experts’ opinion states that in patients with brain tumors even one unprovoked seizure makes it feasible to initiate antiepileptic drugs therapy as soon as possible. In case of two or more unprovoked episodes (with over 24 hours difference) the diagnosis of “epilepsy” is legitimate and antiepileptic therapy should be started. The treating physician’s choice of antiepileptic therapy is based on type of seizures, age and sex of the patient, the comorbidity and potential antiepileptic drugs pharmacokinetic interactions with other drugs (including chemotherapy), in particular, one should avoid the use of liver microsomal-inducing antiepileptic drugs. The presented algorithms provide the decision-making guidelines in case of intraoperative focal seizures, acute symptomatic seizures and status epilepticus occurrence in early postoperative period.

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Section: Russian Military Medicalunclassified

Antiepileptic therapy algorithms in patients with primary and metastatic brain tumors

Prokudin,

Litvinenko,

Rumуantseva

et al. 2023

Russian Military Medical Academy Reports

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Clinical prognostic factors in patients with diffuse gliomas of the brain

Prokudin,

Martynov,

Litvinenko

et al. 2024

Russian Military Medical Academy Reports

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BACKGROUND: Diffuse gliomas of the brain represent a heterogeneous group, which differs in age of the disease onset, histologic characteristics, tumor grade, molecular genetic markers and prognosis. AIM: of the present study is to identify the factors, which affect the duration of the relapse-free period and life expectancy in patients with diffuse brain gliomas, based on a comprehensive analysis of clinical syndromes and symptoms. MATERIALS AND METHODS: The study was carried out at the Departments of Neurosurgery and Nerve Diseases of the S.M. Kirov Military Medical Academy (Saint Petersburg, Russia). It included 390 in-patients with diffuse brain gliomas who underwent treatment over the periods of 2014–2022 and 2004–2006. Age at time of diagnosis was 45.26 ± 15.72 years old. The study included 218 (55.9%) male and 172 (44.1%) female patients. It was a single-centre prospective study. RESULTS: of the author’s research. Favourable demographic factors include the age range of 18–39 (relapse-free period duration p 0.01, life expectancy p 0.001) and female sex (relapse-free period p = 0.02, life expectancy p = 0.03). Prognostically favourable clinical manifestations include epileptic seizures before surgery (relapse-free period p 0.01, life expectancy p 0.02); unfavourable clinical manifestations are pyramidal syndrome (relapse-free period p 0.01, life expectancy p 0.001), sensitive disorders (relapse-free period p = 0.045–0.12, life expectancy p = 0.09–0.17), speech pathology (relapse-free period p 0.02, life expectancy p = 0.02–0.12) and cerebellar syndrome (relapse-free period p 0.02, life expectancy p 0.001). Clinical signs such as headache, nausea and vomiting, asthenia, diffuse neurological symptoms, craniocerebral nerve involvement and visual impairment do not affect (p 0.05) the outcomes of the patients with diffuse brain gliomas. CONCLUSION: Thus, favourable demographic prognostic factors include female sex and age range of 18–39, favourable clinical prognostic factors include epileptic seizures before surgery. Unfavourable clinical prognostic factors include presence of motor, sensory disorders, speech impairment and cerebellar syndrome.

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Can the metabolic characteristics of diffuse glioma on <sup>11</sup>C-methionine PET/CT serve as a marker of its IDH status? Cross sectional study

Skvortsova,

Savintseva,

Gurchin

et al. 2024

Lučevaâ diagn. ter.

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INTRODUCTION: Since 2016, molecular markers, in particular, mutations in isocitrate dehydrogenase (IDH) 1 and 2, have been introduced as a classifying feature of cerebral gliomas that provided superior prognostication. The search for non-invasive biomarkers of the molecular profile of gliomas is necessary to improve the quality of preoperative diagnostics, identify patients with good and poor prognosis and determine treatment tactics.OBJECTIVE: Was to study the relationship between the IDH genotype of diffuse cerebral gliomas and metabolic biomarkers according to the results of PET/CT with [11C]methionine.MATERIALS AND METHOD: The results of PET/CT with 11C-methionine were identified to a retrospective analysis of 260 patients aged 18 to 75 years (median 40 years) with untreated cerebral glioma. Based on histological and molecular genetic studies of the surgical material including the determination of a mutation in the isocitrate dehydrogenase 1 (IDH1132H) gene, diffuse gliomas were classified according to the 2016 WHO classification of CNS tumors. Metabolic biomarkers included the calculation of tumor-to-brain ratio of 11С-methionine (TBRmax, TBRpeak and TBRmean) as well as the metabolic tumor volume (MTV). Statistics. Non-parametric tests were performed to compare the differences among patient groups. ROC curve analysis was performed to screen the optimal parameter and its best cutoff value for the discrimination of glioma genotype. All data analyses were performed using “Statistica 10,0” and “MedCalc” ststistical software. p-values less than 0.05 were considered statistically significant.RESULTS: According to the 2016 WHO classification astrocytic and oligodendroglial tumors of the adult type were divided into three groups: astrocytic gliomas with a mutation in the IDH1 gene (IDH1 mut) (n=95), astrocytic gliomas without a mutation in the IDH1 gene (IDH1 wild type — IDH1 wt) (n=103), and IDH1-mutant oligodendrogliomas (n=62). Significant differences in all ratios between the three molecular groups of gliomas were established. TBRmax cutoff of 2.27 differentiated between IDH1 wt and IDH1 mut gliomas with a sensitivity of 61% and a specificity of 77% (area under curve — AUC 0.752). When considering subgroups of gliomas that are homogeneous in terms of the IDH1 status or Grade, the dependence of TBR on the glioma histotype and grading was additionally established. In IDH1 mut oligodendrogliomas, TBR was significantly higher than in mutant astrocytomas, and in IDH1 wt astrocytomas, significant differences in TBR were established between Grade 2 and Grade 3–4. TBRmax was not a predictor of glioma type according to the WHO 2016 classification due to significant overlap of individual of TBR values. But TBRmax allowed diagnosing a cluster of malignant gliomas, including glioblastoma and astrocytoma Grade 3 IDH wt, as well as oligodendroglioma Grade 3 IDH1 mut, with a sensitivity of 65% and a specificity of 89% (AUC 0.848) at a cutoff of TBR=2.7. A strong correlation between the three tumor-to-brain ratios allows any ratio to be used in diagnostics. There were no significant differences in MTV between molecular types of gliomas.DISCUSSION: Distinguishing glioma types based on the 2016 WHO classification of the CNS tumors on the basis of 11Cmethionine uptake seems to be not reliable due to many factors that affect its uptake. In astrocytomas high TBR is associated with malignant grade and wild type IDH1 gene. However, the lack of differences in TBR between these astrocytomas and Grade 3 IDH1-mutant oligodendrogliomas does not allow one to predict the IDH1 status of the tumor in the absence of other radiological signs of the glioma histotype. The absence of differences in TBR between Grade 2 and Grade 3 astrocytomas IDH1 mut supports the view that they are considered as a single subgroup of lower grade gliomas. CONCLUSION: PET/CT with 11C-methionine has limited potential to assess the IDH status of diffuse gliomas. High TBR is associated with malignant glioma with wild-type IDH1 gene or oligodendroglial structure.

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Genetic Biomarkers of Glial Brain Tumors: Idh1 and Idh2 Mutations

Cited by 4 publications

References 16 publications

Antiepileptic therapy algorithms in patients with primary and metastatic brain tumors

Antiepileptic therapy algorithms in patients with primary and metastatic brain tumors

Clinical prognostic factors in patients with diffuse gliomas of the brain

Can the metabolic characteristics of diffuse glioma on <sup>11</sup>C-methionine PET/CT serve as a marker of its IDH status? Cross sectional study

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