<i>IDH1</i>-Mutation in Diffuse Gliomas in Persons Age 55 Years and Over

Robinson, Chase F.; Kleinschmidt‐DeMasters, Bette K.

doi:10.1093/jnen/nlw112

Cited by 28 publications

(24 citation statements)

References 8 publications

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“…Of the six patients without available IDH status, all were age ≥55 years at the time of diagnosis. Recent reports suggest that <7% of patients age ≥55 years have IDH mutations on IHC 53 , 54 and an even smaller proportion (<1%) of patients in this age group will have a non-canonical mutation on sequencing after negative IHC 54 . Given the age criterion, there is a high likelihood that the patients who did not undergo IDH testing in our cohort were IDH -wild-type, rather than IDH -mutant.…”

Section: Discussionmentioning

confidence: 99%

Probing tumor microenvironment in patients with newly diagnosed glioblastoma during chemoradiation and adjuvant temozolomide with functional MRI

Vakulenko‐Lagun

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et al. 2018

Sci Rep

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Functional MRI may identify critical windows of opportunity for drug delivery and distinguish between early treatment responders and non-responders. Using diffusion-weighted, dynamic contrast-enhanced, and dynamic susceptibility contrast MRI, as well as pro-angiogenic and pro-inflammatory blood markers, we prospectively studied the physiologic tumor-related changes in fourteen newly diagnosed glioblastoma patients during standard therapy. 153 MRI scans and blood collection were performed before chemoradiation (baseline), weekly during chemoradiation (week 1–6), monthly before each cycle of adjuvant temozolomide (pre-C1-C6), and after cycle 6. The apparent diffusion coefficient, volume transfer coefficient (Ktrans), and relative cerebral blood volume (rCBV) and flow (rCBF) were calculated within the tumor and edema regions and compared to baseline. Cox regression analysis was used to assess the effect of clinical variables, imaging, and blood markers on progression-free (PFS) and overall survival (OS). After controlling for additional covariates, high baseline rCBV and rCBF within the edema region were associated with worse PFS (microvessel rCBF: HR = 7.849, p = 0.044; panvessel rCBV: HR = 3.763, p = 0.032; panvessel rCBF: HR = 3.984; p = 0.049). The same applied to high week 5 and pre-C1 Ktrans within the tumor region (week 5 Ktrans: HR = 1.038, p = 0.003; pre-C1 Ktrans: HR = 1.029, p = 0.004). Elevated week 6 VEGF levels were associated with worse OS (HR = 1.034; p = 0.004). Our findings suggest a role for rCBV and rCBF at baseline and Ktrans and VEGF levels during treatment as markers of response. Functional imaging changes can differ substantially between tumor and edema regions, highlighting the variable biologic and vascular state of tumor microenvironment during therapy.

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Section: Discussionmentioning

confidence: 99%

Probing tumor microenvironment in patients with newly diagnosed glioblastoma during chemoradiation and adjuvant temozolomide with functional MRI

Vakulenko‐Lagun

Emblem

et al. 2018

Sci Rep

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“…In our study, only 2.4% (3/124) of the gliomas had IDH2 mutations. The vast majority of IDH mutated gliomas occur in patients younger than 55 years (Parsons et al, 2008; Robinson & Kleinschmidt‐DeMasters, 2017). In our study, only 9.5% (2/21) of patients with IDH mutated gliomas were older than 55 years.…”

Section: Discussionmentioning

confidence: 99%

“…The IDH and TERTp mutation status is often taken into consideration in molecular classification studies of gliomas (Kim et al, 2018; Pekmezci et al, 2017). Patients with IDH and TERTp glioma mutations have the best prognosis whereas only IDH mutation patients and only TERTp mutation patients have the worst prognosis (Robinson & Kleinschmidt‐DeMasters, 2017). Our study showed similar results.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of the isocitrate dehydrogenase gene and telomerase reverse transcriptase promoter mutations in gliomas in Chinese patients

Ji²,

Shi

et al. 2020

Brain and Behavior

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Objectives To explore the characteristics of IDH and TERT promoter mutations in gliomas in Chinese patients. Methods A total of 124 Chinese patients with gliomas were enrolled to study the frequencies of mutations in isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase promoter (TERTp). Among the 124 patients, 59 patients were enrolled to study the classification of gliomas based on mutations in IDH and TERTp. Results Isocitrate dehydrogenase mutations are positively correlated with a good prognosis but mutations in TERTp cannot predict prognoses independently. The combined analysis of the mutations of IDH and TERTp can predict the prognosis more accurately. Patients with IDH and TERTp glioma mutations have the best prognosis, followed by only IDH mutation patients and only TERTp mutation patients, which have the worst prognosis. IDH and TERTp mutations occur frequently in males, younger patients or lower‐grade patients. In contrast, only TERTp mutations occur frequently in females, older patients or higher‐grade patients. Conclusions Patients with IDH and TERTp glioma mutations have the best prognosis, and only IDH mutation patients and only TERTp mutation patients have the worst prognosis. Moreover, the molecular classification of gliomas by mutations of IDH and TERTp is not suitable for pediatric patients.

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“…Mutation in the metabolic enzyme isocitrate dehydrogenase 1 (mIDH1) at active site residue R132H occur in ~20-25% of infiltrative gliomas ( 40 , 312 , 313 ). The mutation leads to gain-of-function catalytic activity that converts α-ketoglutarate (αKG) to the onco-metabolite (R)-2-hydroxyglutarate ((R)-2-HG) ( 40 , 314 , 315 ).…”

Section: Novel Targets and Strategies To Stimulate Anti-glioma Immune Responsementioning

confidence: 99%

Genetic Alterations in Gliomas Remodel the Tumor Immune Microenvironment and Impact Immune-Mediated Therapies

et al. 2021

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High grade gliomas are malignant brain tumors that arise in the central nervous system, in patients of all ages. Currently, the standard of care, entailing surgery and chemo radiation, exhibits a survival rate of 14-17 months. Thus, there is an urgent need to develop new therapeutic strategies for these malignant brain tumors. Currently, immunotherapies represent an appealing approach to treat malignant gliomas, as the pre-clinical data has been encouraging. However, the translation of the discoveries from the bench to the bedside has not been as successful as with other types of cancer, and no long-lasting clinical benefits have been observed for glioma patients treated with immune-mediated therapies so far. This review aims to discuss our current knowledge about gliomas, their molecular particularities and the impact on the tumor immune microenvironment. Also, we discuss several murine models used to study these therapies pre-clinically and how the model selection can impact the outcomes of the approaches to be tested. Finally, we present different immunotherapy strategies being employed in clinical trials for glioma and the newest developments intended to harness the immune system against these incurable brain tumors.

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IDH1-Mutation in Diffuse Gliomas in Persons Age 55 Years and Over

Cited by 28 publications

References 8 publications

Probing tumor microenvironment in patients with newly diagnosed glioblastoma during chemoradiation and adjuvant temozolomide with functional MRI

Probing tumor microenvironment in patients with newly diagnosed glioblastoma during chemoradiation and adjuvant temozolomide with functional MRI

Characteristics of the isocitrate dehydrogenase gene and telomerase reverse transcriptase promoter mutations in gliomas in Chinese patients

Genetic Alterations in Gliomas Remodel the Tumor Immune Microenvironment and Impact Immune-Mediated Therapies

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