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Idh mutant glioma

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https://www.readbyqxmd.com/read/29156679/remote-intracranial-recurrence-of-idh-mutant-gliomas-is-associated-with-tp53-mutations-and-an-8q-gain
#1
Shunsuke Nakae, Takema Kato, Kazuhiro Murayama, Hikaru Sasaki, Masato Abe, Masanobu Kumon, Tadashi Kumai, Kei Yamashiro, Joji Inamasu, Mitsuhiro Hasegawa, Hiroki Kurahashi, Yuichi Hirose
Most IDH mutant gliomas harbor either 1p/19q co-deletions or TP53 mutation; 1p/19q co-deleted tumors have significantly better prognoses than tumors harboring TP53 mutations. To investigate the clinical factors that contribute to differences in tumor progression of IDH mutant gliomas, we classified recurrent tumor patterns based on MRI and correlated these patterns with their genomic characterization. Accordingly, in IDH mutant gliomas (N = 66), 1p/19 co-deleted gliomas only recurred locally, whereas TP53 mutant gliomas recurred both locally and in remote intracranial regions...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29140606/mr-textural-analysis-on-t2-flair-images-for-the-prediction-of-true-oligodendroglioma-by-the-2016-who-genetic-classification
#2
Wenting Rui, Yan Ren, Yin Wang, Xinyi Gao, Xiao Xu, Zhenwei Yao
BACKGROUND: The genetic status of 1p/19q is important for differentiating oligodendroglioma, isocitrate-dehydrogenase (IDH)-mutant, and 1p/19q-codeleted from diffuse astrocytoma, IDH-mutant according to the 2016 World Health Organization (WHO) criteria. PURPOSE: To assess the value of magnetic resonance textural analysis (MRTA) on T2 fluid-attenuated inversion recovery (FLAIR) images for making a genetically integrated diagnosis of true oligodendroglioma by WHO guidelines...
November 15, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/29122763/prediction-of-idh1-mutation-and-1p-19q-codeletion-status-using-preoperative-mr-imaging-phenotypes-in-lower-grade-gliomas
#3
Y W Park, K Han, S S Ahn, S Bae, Y S Choi, J H Chang, S H Kim, S-G Kang, S-K Lee
BACKGROUND AND PURPOSE: WHO grade II gliomas are divided into three classes: isocitrate dehydrogenase (IDH)-wildtype, IDH-mutant and no 1p/19q codeletion, and IDH-mutant and 1p/19q-codeleted. Different molecular subtypes have been reported to have prognostic differences and different chemosensitivity. Our aim was to evaluate the predictive value of imaging phenotypes assessed with the Visually AcceSAble Rembrandt Images lexicon for molecular classification of lower grade gliomas. MATERIALS AND METHODS: MR imaging scans of 175 patients with lower grade gliomas with known IDH1 mutation and 1p/19q-codeletion status were included (78 grade II and 97 grade III) in the discovery set...
November 9, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/29089260/design-synthesis-and-biological-activity-of-3-pyrazine-2-yl-oxazolidin-2-ones-as-novel-potent-and-selective-inhibitors-of-mutant-isocitrate-dehydrogenase-1
#4
Tianfang Ma, Fangxia Zou, Stefan Pusch, Lijun Yang, Qihua Zhu, Yungen Xu, Yueqing Gu, Andreas von Deimling, Xiaoming Zha
Isocitrate dehydrogenases (IDHs) catalyze the oxidative decarboxylation of isocitrate to alpha-ketoglutarate (α-KG) generating carbon dioxide and NADPH/NADH. Evidence suggests that the specific mutations in IDH1 are critical to the growth and reproduction of some tumor cells such as gliomas and acute myeloid leukemia, emerging as an attractive antitumor target. In order to discovery potent new mutant IDH1 inhibitors, we designed, synthesized and evaluated a series of allosteric mIDH1 inhibitors harboring the scaffold of 3-pyrazine-2-yl-oxazolidin-2-ones...
October 13, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29054837/altered-metabolic-landscape-in-idh-mutant-gliomas%C3%A2-affects-phospholipid-energy-and-oxidative-stress-pathways
#5
Fred Fack, Saverio Tardito, Guillaume Hochart, Anais Oudin, Liang Zheng, Sabrina Fritah, Anna Golebiewska, Petr V Nazarov, Amandine Bernard, Ann-Christin Hau, Olivier Keunen, William Leenders, Morten Lund-Johansen, Jonathan Stauber, Eyal Gottlieb, Rolf Bjerkvig, Simone P Niclou
Heterozygous mutations in NADP-dependent isocitrate dehydrogenases (IDH) define the large majority of diffuse gliomas and are associated with hypermethylation of DNA and chromatin. The metabolic dysregulations imposed by these mutations, whether dependent or not on the oncometabolite D-2-hydroxyglutarate (D2HG), are less well understood. Here, we applied mass spectrometry imaging on intracranial patient-derived xenografts of IDH-mutant versus IDH wild-type glioma to profile the distribution of metabolites at high anatomical resolution in situ This approach was complemented by in vivo tracing of labeled nutrients followed by liquid chromatography-mass spectrometry (LC-MS) analysis...
October 20, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29053887/low-foxg1-and-high-olig-2-labelling-indices-define-a-prognostically-favorable-subset-in-idh-mutant-gliomas
#6
Sarah Schäfer, Felix Behling, Marco Skardelly, Marilin Koch, Ines Ott, Frank Paulsen, Ghazaleh Tabatabai, Jens Schittenhelm
AIMS: Previous data suggest that expression of transcription factors FoxG1 and Olig-2 can separate hotspot H3F3A-mutant tumors in pediatric glioma. We evaluated their prognostic potential and feasibility for identifying H3F3A-mutant tumors among IDH-mutant/wildtype gliomas. METHODS: Immunohistochemistry of FoxG1/Olig-2 and ATRX in 471 cases of diffuse gliomas and molecular determination of IDH, H3F3A, MGMT and 1p/19 codeletion status. RESULTS: Mean percentage of FoxG1 positive tumor cells increased from 17% in WHO grade II to over 21% in grade III to 37% in grade IV tumors, while mean Olig-2 indices decreased from 29% to 28% to 17% respectively...
October 20, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29050068/-diagnostic-and-prognostic-roles-of-loss-of-cic-protein-expression-in-oligodendroglial-tumors
#7
C C Liu, L Y Zhang, L M Wang, D D Wang, Y J Fu, Y N Cai, D H Lu, Y S Piao
Objective: To investigate the usefulness of loss of CIC expression as the prescreening detection of 1p/19q co-deletion in the diagnosis of oligodendroglial tumors and its prognostic implication. Methods: The retrospective study included 113 oligodendroglial tumors diagnosed in the Department of Pathology, Xuanwu Hospital, Capital Medical University. Expression of CIC protein was detected by immunohistochemistry, and the 1p/19q co-deletion by fluorescence in situ hybridization in all the tumors; and the correlation of the loss of protein and 1p/19q co-deletion with prognosis was assessed...
October 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29040662/molecular-subtyping-of-tumors-from-patients-with-familial-glioma
#8
Vanessa Y Ruiz, Corinne E Praska, Georgina Armstrong, Thomas M Kollmeyer, Seiji Yamada, Paul A Decker, Matthew L Kosel, Jeanette E Eckel-Passow, The Gliogene Consortium, Daniel H Lachance, Matthew N Bainbridge, Beatrice S Melin, Melissa L Bondy, Robert B Jenkins
BACKGROUND: Single-gene mutation syndromes account for some familial glioma (FG); however, they make up only a small fraction of glioma families. Gliomas can be classified into 3 major molecular subtypes based on IDH mutation and 1p/19q co-deletion. We hypothesized that the prevalence of molecular subtypes might differ in familial versus sporadic gliomas, and that tumors in the same family should have the same molecular subtype. METHODS: Participants in the FG study (Gliogene) provided samples for germline DNA analysis...
October 10, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29036500/glioma-cpg-island-methylator-phenotype-g-cimp-biological-and-clinical-implications
#9
Tathiane M Malta, Camila F de Souza, Thais S Sabedot, Tiago C Silva, Maritza Q S Mosella, Steven N Kalkanis, James Snyder, Ana Valeria B Castro, Houtan Noushmehr
Gliomas are a heterogeneous group of brain tumors with distinct biological and clinical properties. Despite advances in surgical techniques and clinical regimens, treatment of high-grade glioma remains challenging and carries dismal rates of therapeutic success and overall survival. Challenges include the molecular complexity of gliomas, as well as inconsistencies in histopathological grading, resulting in an inaccurate prediction of disease progression and failure in the use of standard therapy. The updated 2016 World Health Organization (WHO) classification of tumors of the central nervous system reflects a refinement of tumor diagnostics by integrating the genotypic and phenotypic features, thereby narrowing the defined subgroups...
September 26, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29031038/isocitrate-dehydrogenase-mutations-are-better-prognostic-marker-than-o6-methylguanine-dna-methyltransferase-promoter-methylation-in-glioblastomas-a-retrospective-single-centre-molecular-genetics-study-of-gliomas
#10
M Houdova Megova, J Drábek, Z Dwight, R Trojanec, V Koudeláková, J Vrbková, O Kalita, S Mlcochova, M Rabcanova, M Hajdúch
BACKGROUND: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are a promising prognostic biomarker of gliomas. The purpose of our study was to examine the clinical prognostic properties of IDH1/2 mutations in a glioma patient cohort from the Czech Republic using an improved platform for simple and reliable IDH genotyping. MATERIAL AND METHODS: We retrospectively analyzed a group of 145 glioma patients by testing for the three most frequent IDH mutations, IDH1 R132H, IDH1 R132C, and IDH2 R172K, through the competitive amplification of differentially melting amplicons (CADMA) polymerase chain reaction (PCR)...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29016839/prognostic-relevance-of-genetic-alterations-in-diffuse-lower-grade-gliomas
#11
Kosuke Aoki, Hideo Nakamura, Hiromichi Suzuki, Keitaro Matsuo, Keisuke Kataoka, Teppei Shimamura, Kazuya Motomura, Fumiharu Ohka, Satoshi Shiina, Takashi Yamamoto, Yasunobu Nagata, Tetsuichi Yoshizato, Masahiro Mizoguchi, Tatsuya Abe, Yasutomo Momii, Yoshihiro Muragaki, Reiko Watanabe, Ichiro Ito, Masashi Sanada, Hironori Yajima, Naoya Morita, Ichiro Takeuchi, Satoru Miyano, Toshihiko Wakabayashi, Seishi Ogawa, Atsushi Natsume
Background: Diffuse lower-grade gliomas (LGGs) are genetically classified into 3 distinct subtypes based on isocitrate dehydrogenase (IDH) mutation status and codeletion of chromosome 1p and 19q (1p/19q). However, the subtype-specific effects of additional genetic lesions on survival are largely unknown. Methods: Using Cox proportional hazards regression modeling, we investigated the subtype-specific effects of genetic alterations and clinicopathological factors on survival in each LGG subtype, in a Japanese cohort of LGG cases fully genotyped for driver mutations and copy number variations associated with LGGs (n = 308)...
July 18, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28983683/in-vivo-metabolic-profiles-as-determined-by-31-p-and-short-te-1-h-mr-spectroscopy-no-difference-between-patients-with-idh-wildtype-and-idh-mutant-gliomas
#12
Katharina J Wenger, Elke Hattingen, Kea Franz, Joachim Steinbach, Oliver Bähr, Ulrich Pilatus
PURPOSE: Previous ex vivo spectroscopic data from tissue samples revealed differences in phospholipid metabolites between isocitrate dehydrogenase mutated (IDHmut) and IDH wildtype (IDHwt) gliomas. We investigated whether these changes can be found in vivo using (1)H-decoupled (31)P magnetic resonance spectroscopic imaging (MRSI) with 3D chemical shift imaging (CSI) at 3 T in patients with low and high-grade gliomas. METHODS: The study included 33 prospectively enrolled, mostly untreated patients who met spectral quality criteria according to the World Health Organization (WHO II n = 7, WHO III n = 17, WHO IV n = 9; 25 patients IDHmut, 8 patients IDHwt)...
October 5, 2017: Clinical Neuroradiology
https://www.readbyqxmd.com/read/28980701/isocitrate-dehydrogenase-mutant-glioma-evolving-clinical-and-therapeutic-implications
#13
REVIEW
Julie J Miller, Helen A Shih, Ovidiu C Andronesi, Daniel P Cahill
The metabolic genes isocitrate dehydrogenase 1 (IDH1) and IDH2 are commonly mutated in low-grade glioma and in a subset of glioblastoma. These mutations co-occur with other recurrent molecular alterations, including 1p/19q codeletions and tumor suppressor protein 53 (TP53) and alpha thalassemia/mental retardation (ATRX) mutations, which together help to define a molecular signature that aids in the classification of gliomas and helps to better predict clinical behavior. A confluence of research suggests that glioma development in IDH-mutant and IDH wild-type tumors is driven by different oncogenic processes and responds differently to current treatment paradigms...
December 1, 2017: Cancer
https://www.readbyqxmd.com/read/28958143/reclassification-of-mixed-oligoastrocytic-tumors-using-a-genetically-integrated-diagnostic-approach
#14
Seong-Ik Kim, Yujin Lee, Jae-Kyung Won, Chul-Kee Park, Seung Hong Choi, Sung-Hye Park
Background: Mixed gliomas, such as oligoastrocytomas (OA), anaplastic oligoastrocytomas, and glioblastomas with an oligodendroglial component (GBMO) are defined as tumors composed of a mixture of two distinct neoplastic cell types, astrocytic and oligodendroglial. Recently, mutations ATRX and TP53, and codeletion of 1p/19q are shown to be genetic hallmarks of astrocytic and oligodendroglial tumors, respectively. Subsequent molecular analyses of mixed gliomas preferred the reclassification to either oligodendroglioma or astrocytoma...
September 29, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28956184/reliable-diagnosis-of-idh-mutant-glioblastoma-by-2-hydroxyglutarate-detection-a-study-by-3-t-magnetic-resonance-spectroscopy
#15
Manabu Natsumeda, Kunio Motohashi, Hironaka Igarashi, Takanori Nozawa, Hideaki Abe, Yoshihiro Tsukamoto, Ryosuke Ogura, Masayasu Okada, Tsutomu Kobayashi, Hiroshi Aoki, Hitoshi Takahashi, Akiyoshi Kakita, Kouichirou Okamoto, Tsutomu Nakada, Yukihiko Fujii
We have previously reported that reliable detection of 2-hydroxyglutarate (2HG) in isocitrate dehydrogenase (IDH)-mutant WHO grade 2 and 3 gliomas is possible utilizing 3.0-T single-voxel magnetic resonance spectroscopy (SVMRS). We set out to determine whether the same method could be applied to detect 2HG in IDH-mutant glioblastoma. Forty-four patients harboring glioblastoma underwent pre-operative MRS evaluation to detect 2HG and other metabolites. Presence of IDH-mutations was determined by IDH1 R132H immunohistochemical analysis and DNA sequencing of surgically obtained tissues...
September 27, 2017: Neurosurgical Review
https://www.readbyqxmd.com/read/28945860/the-role-of-extent-of-resection-in-idh1-wild-type-or-mutant-low-grade-gliomas
#16
Toral Patel, Evan D Bander, Rachael A Venn, Tiffany Powell, Gustav Young-Min Cederquist, Peter M Schaefer, Luis A Puchi, Akbarshakh Akhmerov, Shahiba Ogilvie, Anne S Reiner, Nelson Moussazadeh, Viviane Tabar
BACKGROUND: Maximizing extent of resection (EOR) improves outcomes in adults with World Health Organization (WHO) grade II low-grade gliomas (LGG). However, recent studies demonstrate that LGGs bearing a mutation in the isocitrate dehydrogenase 1 (IDH1) gene are a distinct molecular and clinical entity. It remains unclear whether maximizing EOR confers an equivalent clinical benefit in IDH mutated (mtIDH) and IDH wild-type (wtIDH) LGGs. OBJECTIVE: To assess the impact of EOR on malignant progression-free survival (MPFS) and overall survival (OS) in mtIDH and wtIDH LGGs...
July 27, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28901965/anaplastic-gliomas-in-adults-an-update
#17
Cristina Izquierdo, Bastien Joubert, François Ducray
PURPOSE OF REVIEW: The current review summarizes recent advances on the oncogenesis, classification and treatment of adult anaplastic gliomas. RECENT FINDINGS: According to the 2016 WHO classification, three main molecular subgroups of adult diffuse anaplastic gliomas can be distinguished based on the 1p/19q codeletion and isocitrate dehydrogenase (IDH) mutation status. In the future, this classification may be further refined based on the telomerase reverse transcriptase promoter and alpha thalassemia/mental retardation syndrome X-linked mutation status, gene expression, DNA methylation and genomic profiling...
November 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28871469/imaging-correlates-for-the-2016-update-on-who-classification-of-grade-ii-iii-gliomas-implications-for-idh-1p-19q-and-atrx-status
#18
Rachel L Delfanti, David E Piccioni, Jason Handwerker, Naeim Bahrami, AnithaPriya Krishnan, Roshan Karunamuni, Jona A Hattangadi-Gluth, Tyler M Seibert, Ashwin Srikant, Karra A Jones, Vivian S Snyder, Anders M Dale, Nathan S White, Carrie R McDonald, Nikdokht Farid
The 2016 World Health Organization Classification of Tumors of the Central Nervous System incorporates the use of molecular information into the classification of brain tumors, including grade II and III gliomas, providing new prognostic information that cannot be delineated based on histopathology alone. We hypothesized that these genomic subgroups may also have distinct imaging features. A retrospective single institution study was performed on 40 patients with pathologically proven infiltrating WHO grade II/III gliomas with a pre-treatment MRI and molecular data on IDH, chromosomes 1p/19q and ATRX status...
September 4, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28866063/spinal-cord-astrocytoma-with-isocitrate-dehydrogenase-1-gene-mutation
#19
Keisuke Takai, Shota Tanaka, Takashi Sota, Akitake Mukasa, Takashi Komori, Makoto Taniguchi
BACKGROUND: In 2016, the World Health Organization updated its classification of tumors, adding genetic profiles to the conventional histopathologic typing. CASE DESCRIPTION: The authors present herein the first case of a 44-year-old female with isocitrate dehydrogenase-mutant World Health Organization grade II diffuse spinal astrocytoma diagnosed on the basis of both histopathologic and genetic findings. CONCLUSIONS: The present case underscores the significant role of a molecular genetic analysis in the differential diagnosis of intramedullary spinal gliomas...
September 1, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28851427/the-frequency-and-prognostic-effect-of-tert-promoter-mutation-in-diffuse-gliomas
#20
Yujin Lee, Jaemoon Koh, Seong-Ik Kim, Jae Kyung Won, Chul-Kee Park, Seung Hong Choi, Sung-Hye Park
Mutations in the telomerase reverse transcriptase gene promoter (TERTp) are common in glioblastomas (GBMs) and oligodendrogliomas (ODGs), and therefore, have a key role in tumorigenesis and may be of prognostic value. However, the extent of their prognostic importance in various gliomas is controversial. We studied 168 patients separated into five groups: Group 1: 65 patients with ODG carrying an IDH1 or IDH2 mutation (IDH-mutant) and 1p/19q-codeletion, Group 2: 23 patients with anaplastic astrocytoma (AA), IDH-mutant, Group 3: 13 patients with GBM, IDH-mutant, Group 4: 15 patients with AA, IDH-wildtype (WT), and Group 5: 52 patients with GBM, IDH-WT...
August 29, 2017: Acta Neuropathologica Communications
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