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Idh mutant glioma

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https://www.readbyqxmd.com/read/28730141/extracellular-vesicles-as-modulators-of-tumor-microenvironment-and-disease-progression-in-glioma
#1
REVIEW
Abir Mondal, Divya Kumari Singh, Suchismita Panda, Anjali Shiras
Diffuse gliomas are lethal tumors of the central nervous system (CNS) characterized by infiltrative growth, aggressive nature, and therapeutic resistance. The recent 2016 WHO classification for CNS tumors categorizes diffuse glioma into two major types that include IDH wild-type glioblastoma, which is the predominant type and IDH-mutant glioblastoma, which is less common and displays better prognosis. Recent studies suggest presence of a distinct cell population with stem cell features termed as glioma stem cells (GSCs) to be causal in driving tumor growth in glioblastoma...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28714279/predicting-idh-mutation-status-in-grade-ii-gliomas-using-amide-proton-transfer-weighted-aptw-mri
#2
Shanshan Jiang, Tianyu Zou, Charles G Eberhart, Maria A V Villalobos, Hye-Young Heo, Yi Zhang, Yu Wang, Xianlong Wang, Hao Yu, Yongxing Du, Peter C M van Zijl, Zhibo Wen, Jinyuan Zhou
PURPOSE: To assess the amide proton transfer-weighted (APTw) MRI features of isocitrate dehydrogenase (IDH)-wildtype and IDH-mutant grade II gliomas and to test the hypothesis that the APTw signal is a surrogate imaging marker for identifying IDH mutation status preoperatively. METHODS: Twenty-seven patients with pathologically confirmed low-grade glioma, who were previously scanned at 3T, were retrospectively analyzed. The Mann-Whitney test was used to evaluate relationships between APTw intensities for IDH-mutant and IDH-wildtype groups, and receiver operator characteristic (ROC) analysis was used to assess the diagnostic performance of APTw...
July 16, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28705010/isocitrate-dehydrogenase-mutation-as-a-therapeutic-target-in-gliomas
#3
Catherine H Han, Tracy T Batchelor
Isocitrate dehydrogenases (IDH) are important enzymes that catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG), producing NADPH in the process. More than 80% of low-grade gliomas and secondary glioblastoma (GBM) harbor an IDH mutation. IDH mutations involve the catalytic pocket of the enzyme and lead to a neomorphic ability to produce 2-hydroxyglutarate (2HG) while oxidizing NADPH to NADP+. 2HG is considered as an 'oncometabolite' which is thought to be responsible for many, if not all, biologic effects of IDH mutations...
June 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28679024/multi-pronged-proteomic-analysis-to-study-the-glioma-pathobiology-using-cerebrospinal-fluid-samples
#4
Nikita Gahoi, Darpan Malhotra, Aliasgar Moiyadi, Santosh G Varma, Mayuri N Gandhi, Sanjeeva Srivastava
PURPOSE: Gliomas are one of the most aggressive and lethal brain tumors arising from neoplastic transformation of astrocytes and oligodendrocytes. In this study, we have carried out a comprehensive quantitative analysis of proteome level differences in cerebrospinal fluid (CSF) across different grades of gliomas for a better understanding of glioma pathobiology. EXPERIMENTAL DESIGN: Glioma patients were diagnosed by radiology and histochemistry- based analyses. Differential proteomic analysis of high (n = 12) and low (n = 8) grade gliomas, and control (n = 3) samples was performed by using two complementary quantitative proteomic approaches; 2D-DIGE and iTRAQ...
July 5, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28674742/characterization-of-gliomas-from-morphology-to-molecules
#5
Sean P Ferris, Jeffrey W Hofmann, David A Solomon, Arie Perry
This article reviews the histologic and molecular characterization of gliomas, including the new "integrated diagnoses" of the World Health Organization Classification, 2016 edition. The entities reviewed within include diffuse gliomas (astrocytoma, oligodendroglioma, glioblastoma), as well as circumscribed and low-grade gliomas (angiocentric glioma, pilocytic astrocytoma, subependymal giant cell astrocytoma, pleomorphic xanthoastrocytoma, pilomyxoid astrocytoma, ependymoma, myxopapillary ependymoma, and subependymoma)...
July 4, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28640698/pediatric-gliomas-current-concepts-on-diagnosis-biology-and-clinical-management
#6
Dominik Sturm, Stefan M Pfister, David T W Jones
Gliomas are the most common CNS tumors in children and adolescents, and they show an extremely broad range of clinical behavior. The majority of pediatric gliomas present as benign, slow-growing lesions classified as grade I or II by the WHO classification of CNS tumors. These pediatric low-grade gliomas (LGGs) are fundamentally different from IDH-mutant LGGs occurring in adults, because they rarely undergo malignant transformation and show excellent overall survival under current treatment strategies. However, a significant fraction of gliomas develop over a short period of time and progress rapidly and are therefore classified as WHO grade III or IV high-grade gliomas (HGGs)...
July 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28621624/use-of-telomerase-promoter-mutations-to-mark-specific-molecular-subsets-with-reciprocal-clinical-behavior-in-idh-mutant-and-idh-wild-type-diffuse-gliomas
#7
Cemaliye B Akyerli, Şirin Yüksel, Özge Can, E Zeynep Erson-Omay, Yavuz Oktay, Erdal Coşgun, Ege Ülgen, Yiğit Erdemgil, Aydın Sav, Andreas von Deimling, Murat Günel, M Cengiz Yakıcıer, M Necmettin Pamir, Koray Özduman
OBJECTIVE Recent studies have established that hemispheric diffuse gliomas may be grouped into subsets on the basis of molecular markers; these subsets are loosely correlated with the histopathological diagnosis but are strong predictors of clinical tumor behavior. Based on an analysis of molecular and clinical parameters, the authors hypothesized that mutations of the telomerase promoter (TERTp-mut) mark separate oncogenic programs among isocitrate dehydrogenase 1 and/or 2 (IDH) mutant (IDH-mut) and IDH wild-type (IDH-wt) diffuse gliomas independent of histopathology or WHO grade...
June 16, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28592714/the-2016-who-classification-of-tumours-of-the-central-nervous-system-the-major-points-of-revision
#8
Takashi Komori
The updated 2016 edition of the World Health Organization (WHO) Classification of Tumours of the Central Nervous System (CNS) uses molecular parameters and the histology to define the main tumor categories for the first time. This represents a shift from the traditional principle of using neuropathological diagnoses, which are primarily based on the microscopic features, to using molecularly-oriented diagnoses. Major restructuring was made with regard to diffuse gliomas, medulloblastomas and other embryonal tumors...
June 8, 2017: Neurologia Medico-chirurgica
https://www.readbyqxmd.com/read/28549927/molecular-classification-of-adult-diffuse-gliomas-conflicting-idh1-idh2-atrx-and-1p-19q-results
#9
Leomar Y Ballester, Jason T Huse, Guilin Tang, Gregory N Fuller
Until recently, the diagnosis of brain tumors was primarily based on microscopic examination of hematoxylin and eosin (H&E) stained tissue sections. The updated World Health Organization (WHO) classification of tumours of the central nervous system (CNS) incorporates genetic alterations into the classification system, with the goal of creating more homogenous disease categories with greater prognostic value. Hence, under the new classification system the diagnosis of diffuse gliomas incorporates the evaluation of mutations in the IDH1 and IDH2 genes and simultaneous deletion of chromosomes 1p and 19...
May 23, 2017: Human Pathology
https://www.readbyqxmd.com/read/28535583/molecular-testing-of-brain-tumor
#10
REVIEW
Sung-Hye Park, Jaekyung Won, Seong-Ik Kim, Yujin Lee, Chul-Kee Park, Seung-Ki Kim, Seung-Hong Choi
The World Health Organization (WHO) classification of central nervous system (CNS) tumors was revised in 2016 with a basis on the integrated diagnosis of molecular genetics. We herein provide the guidelines for using molecular genetic tests in routine pathological practice for an accurate diagnosis and appropriate management. While astrocytomas and IDH-mutant (secondary) glioblastomas are characterized by the mutational status of IDH, TP53 , and ATRX , oligodendrogliomas have a 1p/19q codeletion and mutations in IDH, CIC , FUBP1 , and the promoter region of telomerase reverse transcriptase ( TERTp )...
May 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28531337/correlation-of-immune-phenotype-with-idh-mutation-in-diffuse-glioma
#11
Anna Sophie Berghoff, Barbara Kiesel, Georg Widhalm, Dorothee Wilhelm, Orsolya Rajky, Sebastian Kurscheid, Philip Kresl, Adelheid Wöhrer, Christine Marosi, Monika E Hegi, Matthias Preusser
Background: Tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) are targets of immune checkpoint inhibitors. Methods: Forty-three World Health Organization (WHO) grade II/III gliomas (39 IDH-mutant [mut], 4 IDH-wildtype [wt]) and 14 IDH-mut glioblastomas (GBM) were analyzed for TIL (CD3+; PD1+) infiltration and PD-L1 expression. Results were compared with the data of a previously published series of 117 IDH-wt glioblastomas. PD-L1 gene expression levels were evaluated in 677 diffuse gliomas grades II-IV from The Cancer Genome Atlas (TCGA) database...
May 20, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28498812/structure-based-discovery-of-clomifene-as-a-potent-inhibitor-of-cancer-associated-mutant-idh1
#12
Mengzhu Zheng, Weiguang Sun, Suyu Gao, Shanshan Luan, Dan Li, Renqi Chen, Qian Zhang, Lixia Chen, Jiangeng Huang, Hua Li
Isocitrate dehydrogenase (IDH) plays an indispensable role in the tricarboxylic acid cycle, and IDH mutations are present in nearly 75% of glioma and 20% of acute myeloid leukemia. One IDH1R132H inhibitor (clomifene citrate) was found by virtual screening method, which can selectively suppress mutant enzyme activities in vitro and in vivo with a dose-dependent manner. The molecular docking indicated that clomifene occupied the allosteric site of the mutant IDH1. Enzymatic kinetics also demonstrated that clomifene inhibited mutant enzyme in a non-competitive manner...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28467778/somatostatin-receptor-2a-in-gliomas-association-with-oligodendrogliomas-and-favourable-outcome
#13
Aida Kiviniemi, Maria Gardberg, Katri Kivinen, Jussi P Posti, Ville Vuorinen, Jussi Sipilä, Melissa Rahi, Matti Sankinen, Heikki Minn
Somatostatin receptor subtype 2A (SSTR2A) is a potential therapeutic target in gliomas. Data on SSTR2A expression in different glioma entities, however, is particularly conflicting. Our objective was to characterize SSTR2A status and explore its impact on survival in gliomas classified according to the specific molecular signatures of the updated WHO classification. In total, 184 glioma samples were retrospectively analyzed for SSTR2A expression using immunohistochemistry with monoclonal antibody UMB-1. Double staining with CD68 was used to exclude microglia and macrophages from analyses...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28465358/mutant-idh1-regulates-the-tumor-associated-immune-system-in-gliomas
#14
Nduka M Amankulor, Youngmi Kim, Sonali Arora, Julia Kargl, Frank Szulzewsky, Mark Hanke, Daciana H Margineantu, Aparna Rao, Hamid Bolouri, Jeff Delrow, David Hockenbery, A McGarry Houghton, Eric C Holland
Gliomas harboring mutations in isocitrate dehydrogenase 1/2 (IDH1/2) have the CpG island methylator phenotype (CIMP) and significantly longer patient survival time than wild-type IDH1/2 (wtIDH1/2) tumors. Although there are many factors underlying the differences in survival between these two tumor types, immune-related differences in cell content are potentially important contributors. In order to investigate the role of IDH mutations in immune response, we created a syngeneic pair mouse model for mutant IDH1 (muIDH1) and wtIDH1 gliomas and demonstrated that muIDH1 mice showed many molecular and clinical similarities to muIDH1 human gliomas, including a 100-fold higher concentration of 2-hydroxygluratate (2-HG), longer survival time, and higher CpG methylation compared with wtIDH1...
April 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28450436/noninvasive-assessment-of-idh-mutational-status-in-world-health-organization-grade-ii-and-iii-astrocytomas-using-dwi-and-dsc-pwi-combined-with-conventional-mr-imaging
#15
Z Xing, X Yang, D She, Y Lin, Y Zhang, D Cao
BACKGROUND AND PURPOSE: Isocitrate dehydrogenase (IDH) has been shown to have both diagnostic and prognostic implications in gliomas. The purpose of this study was to examine whether DWI and DSC-PWI combined with conventional MR imaging could noninvasively predict IDH mutational status in World Health Organization grade II and III astrocytomas. MATERIALS AND METHODS: We retrospectively reviewed DWI, DSC-PWI, and conventional MR imaging in 42 patients with World Health Organization grade II and III astrocytomas...
April 27, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28434111/idh-mutation-and-1p19q-codeletion-distinguish-two-radiological-patterns-of-diffuse-low-grade-gliomas
#16
Amélie Darlix, Jérémy Deverdun, Nicolas Menjot de Champfleur, Florence Castan, Sonia Zouaoui, Valérie Rigau, Michel Fabbro, Yordanka Yordanova, Emmanuelle Le Bars, Luc Bauchet, Catherine Gozé, Hugues Duffau
Diffuse low-grade gliomas (DLGG) prognosis is variable, depending on several factors, including the isocitrate dehydrogenase (IDH) mutation and the 1p19q codeletion. A few studies suggested associations between these parameters and tumor radiological characteristics including topography. Our aim was analyzing the correlations between the IDH and 1p19q statuses and the tumor intracerebral distribution (at the lobar and voxel levels), volume, and borders. We conducted a retrospective, monocentric study on a consecutive series of 198 DLGG patients...
April 22, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28421459/rapid-progression-to-glioblastoma-in-a-subset-of-idh-mutated-astrocytomas-a-genome-wide-analysis
#17
Timothy E Richardson, Matija Snuderl, Jonathan Serrano, Matthias A Karajannis, Adriana Heguy, Dwight Oliver, Jack M Raisanen, Elizabeth A Maher, Edward Pan, Samuel Barnett, Chunyu Cai, Amyn A Habib, Robert M Bachoo, Kimmo J Hatanpaa
According to the recently updated World Health Organization (WHO) classification (2016), grade II-III astrocytomas are divided into IDH-wildtype and IDH-mutant groups, the latter being significantly less aggressive in terms of both progression-free and total survival. We identified a small cohort of WHO grade II-III astrocytomas that harbored the IDH1 R132H mutation, as confirmed by both immunohistochemistry and molecular sequence analysis, which nonetheless had unexpectedly rapid recurrence and subsequent progression to glioblastoma...
April 18, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28392842/dna-methylation-signatures-for-2016-who-classification-subtypes-of-diffuse-gliomas
#18
Yashna Paul, Baisakhi Mondal, Vikas Patil, Kumaravel Somasundaram
BACKGROUND: Glioma is the most common of all primary brain tumors with poor prognosis and high mortality. The 2016 World Health Organization classification of the tumors of central nervous system uses molecular parameters in addition to histology to redefine many tumor entities. The new classification scheme divides diffuse gliomas into low-grade glioma (LGG) and glioblastoma (GBM) as per histology. LGGs are further divided into isocitrate dehydrogenase (IDH) wild type or mutant, which is further classified into either oligodendroglioma that harbors 1p/19q codeletion or diffuse astrocytoma that has an intact 1p/19q loci but enriched for ATRX loss and TP53 mutation...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28360267/decoupling-genetics-lineages-and-microenvironment-in-idh-mutant-gliomas-by-single-cell-rna-seq
#19
Andrew S Venteicher, Itay Tirosh, Christine Hebert, Keren Yizhak, Cyril Neftel, Mariella G Filbin, Volker Hovestadt, Leah E Escalante, McKenzie L Shaw, Christopher Rodman, Shawn M Gillespie, Danielle Dionne, Christina C Luo, Hiranmayi Ravichandran, Ravindra Mylvaganam, Christopher Mount, Maristela L Onozato, Brian V Nahed, Hiroaki Wakimoto, William T Curry, A John Iafrate, Miguel N Rivera, Matthew P Frosch, Todd R Golub, Priscilla K Brastianos, Gad Getz, Anoop P Patel, Michelle Monje, Daniel P Cahill, Orit Rozenblatt-Rosen, David N Louis, Bradley E Bernstein, Aviv Regev, Mario L Suvà
Tumor subclasses differ according to the genotypes and phenotypes of malignant cells as well as the composition of the tumor microenvironment (TME). We dissected these influences in isocitrate dehydrogenase (IDH)-mutant gliomas by combining 14,226 single-cell RNA sequencing (RNA-seq) profiles from 16 patient samples with bulk RNA-seq profiles from 165 patient samples. Differences in bulk profiles between IDH-mutant astrocytoma and oligodendroglioma can be primarily explained by distinct TME and signature genetic events, whereas both tumor types share similar developmental hierarchies and lineages of glial differentiation...
March 31, 2017: Science
https://www.readbyqxmd.com/read/28353033/a-novel-all-in-one-intraoperative-genotyping-system-for-idh1-mutant-glioma
#20
Fumiharu Ohka, Akane Yamamichi, Michihiro Kurimoto, Kazuya Motomura, Kuniaki Tanahashi, Hiromichi Suzuki, Kosuke Aoki, Shoichi Deguchi, Lushun Chalise, Masaki Hirano, Akira Kato, Yusuke Nishimura, Masahito Hara, Yukinari Kato, Toshihiko Wakabayashi, Atsushi Natsume
IDH1 gene mutation has been demonstrated to be an oncogenic driver in a majority of lower-grade gliomas (LGGs). In contrast to other central nervous neoplasms and normal brain tissue without IDH1 mutation, almost 80% of LGGs exhibit IDH1 mutation. Therefore, expeditious detection of IDH1 mutation is useful, not only for intraoperative diagnosis of these gliomas but also for determination of the border between the tumor and normal brain tissue. In this study, we established a rapid genotyping assay with a simple DNA extraction method, involving only incubation of the tumor specimen with Tris-EDTA buffer, which can be easily performed in an operating room...
April 2017: Brain Tumor Pathology
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