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diffuse astrocytoma IDH mutant

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https://www.readbyqxmd.com/read/29777252/noninvasively-evaluating-the-grading-and-idh1-mutation-status-of-diffuse-gliomas-by-three-dimensional-pseudo-continuous-arterial-spin-labeling-and-diffusion-weighted-imaging
#1
Tingting Liu, Guang Cheng, Xiaowei Kang, Yibin Xi, Yuanqiang Zhu, Kai Wang, Chao Sun, Jing Ye, Ping Li, Hong Yin
PURPOSE: To noninvasively evaluate the value of three-dimensional pseudo-continuous arterial spin labeling (3D pCASL) and diffusion-weighted imaging (DWI) in diffuse gliomas grading as well as isocitrate dehydrogenase (IDH) 1 mutation status. METHODS: Fifty-six patients with pathologically confirmed diffuse gliomas with preoperative 3D pCASL and DWI were enrolled in this study. The Student's t test and Mann-Whitney U test were used to evaluate differences in parameters of DWI and 3D pCASL between low and high grade as well as between mutant and wild-type IDH1 diffuse gliomas; receiver operator characteristic (ROC) analysis was used to assess the diagnostic performance...
May 18, 2018: Neuroradiology
https://www.readbyqxmd.com/read/29720725/inhibition-of-gpr158-by-microrna-449a-suppresses-neural-lineage-of-glioma-stem-progenitor-cells-and-correlates-with-higher-glioma-grades
#2
Ningning Li, Ying Zhang, Kastytis Sidlauskas, Matthew Ellis, Ian Evans, Paul Frankel, Joanne Lau, Tedani El-Hassan, Loredana Guglielmi, Jessica Broni, Angela Richard-Loendt, Sebastian Brandner
To identify biomarkers for glioma growth, invasion and progression, we used a candidate gene approach in mouse models with two complementary brain tumour phenotypes, developing either slow-growing, diffusely infiltrating gliomas or highly proliferative, non-invasive primitive neural tumours. In a microRNA screen we first identified microRNA-449a as most significantly differentially expressed between these two tumour types. miR-449a has a target dependent effect, inhibiting cell growth and migration by downregulation of CCND1 and suppressing neural phenotypes by inhibition of G protein coupled-receptor (GPR) 158...
May 3, 2018: Oncogene
https://www.readbyqxmd.com/read/29687258/novel-improved-grading-system-s-for-idh-mutant-astrocytic-gliomas
#3
Mitsuaki Shirahata, Takahiro Ono, Damian Stichel, Daniel Schrimpf, David E Reuss, Felix Sahm, Christian Koelsche, Annika Wefers, Annekathrin Reinhardt, Kristin Huang, Philipp Sievers, Hiroaki Shimizu, Hiroshi Nanjo, Yusuke Kobayashi, Yohei Miyake, Tomonari Suzuki, Jun-Ichi Adachi, Kazuhiko Mishima, Atsushi Sasaki, Ryo Nishikawa, Melanie Bewerunge-Hudler, Marina Ryzhova, Oksana Absalyamova, Andrey Golanov, Peter Sinn, Michael Platten, Christine Jungk, Frank Winkler, Antje Wick, Daniel Hänggi, Andreas Unterberg, Stefan M Pfister, David T W Jones, Martin van den Bent, Monika Hegi, Pim French, Brigitta G Baumert, Roger Stupp, Thierry Gorlia, Michael Weller, David Capper, Andrey Korshunov, Christel Herold-Mende, Wolfgang Wick, David N Louis, Andreas von Deimling
According to the 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 CNS WHO), IDH-mutant astrocytic gliomas comprised WHO grade II diffuse astrocytoma, IDH-mutant (AIIIDHmut ), WHO grade III anaplastic astrocytoma, IDH-mutant (AAIIIIDHmut ), and WHO grade IV glioblastoma, IDH-mutant (GBMIDHmut ). Notably, IDH gene status has been made the major criterion for classification while the manner of grading has remained unchanged: it is based on histological criteria that arose from studies which antedated knowledge of the importance of IDH status in diffuse astrocytic tumor prognostic assessment...
April 23, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29676695/huge-heterogeneity-in-survival-in-a-subset-of-adult-patients-with-resected-wild-type-isocitrate-dehydrogenase-status-who-grade-ii-astrocytomas
#4
Gaëtan Poulen, Catherine Gozé, Valérie Rigau, Hugues Duffau
OBJECTIVE World Health Organization grade II gliomas are infiltrating tumors that inexorably progress to a higher grade of malignancy. However, the time to malignant transformation is quite unpredictable at the individual patient level. A wild-type isocitrate dehydrogenase (IDH-wt) molecular profile has been reported as a poor prognostic factor, with more rapid progression and a shorter survival compared with IDH-mutant tumors. Here, the oncological outcomes of a series of adult patients with IDH-wt, diffuse, WHO grade II astrocytomas (AII) who underwent resection without early adjuvant therapy were investigated...
April 20, 2018: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29615461/molecular-diagnosis-of-diffuse-gliomas-through-sequencing-of-cell-free-circulating-tumour-dna-from-cerebrospinal-fluid
#5
Francisco Martínez-Ricarte, Regina Mayor, Elena Martínez-Sáez, Carlota Rubio-Pérez, Estela Pineda, Esteban Cordero, Marta Cicuéndez, Maria A Poca, Nuria Lopez-Bigas, Santiago Ramón Y Cajal, María Vieito, Joan Carles, Josep Tabernero, Ana Vivancos, Soledad Gallego, Francesc Graus, Juan Sahuquillo, Joan Seoane
PURPOSE: Diffuse gliomas are the most common primary tumour of the brain and include different subtypes with diverse prognosis. The genomic characterization of diffuse gliomas facilitates their molecular diagnosis. The anatomical localization of diffuse gliomas complicates access to tumour specimens for diagnosis, in some cases incurring high-risk surgical procedures and stereotactic biopsies. Recently, cell-free circulating tumour DNA (ctDNA) has been identified in the cerebrospinal fluid (CSF) of patients with brain malignancies...
April 3, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29613896/neoplastic-myelopathies
#6
Jing Wu, Surabhi Ranjan
PURPOSE OF REVIEW: This article discusses the diagnosis and management of neoplasms that affect the spinal cord as well as spinal cord disorders that can occur due to cancer treatments. RECENT FINDINGS: Neoplastic myelopathies are uncommon neurologic disorders but cause significant morbidity when they occur. Primary spinal cord tumors can be classified into intramedullary, intradural extramedullary, or extradural tumors. Diffuse gliomas and ependymal tumors are the most common intramedullary tumors...
April 2018: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/29590424/the-t2-flair-mismatch-sign-as-an-imaging-marker-for-non-enhancing-idh-mutant-1p-19q-intact-lower-grade-glioma-a-validation-study
#7
Martinus P G Broen, Marion Smits, Maarten M J Wijnenga, Hendrikus J Dubbink, Monique H M E Anten, Olaf E M G Schijns, Jan Beckervordersandforth, Alida A Postma, Martin J van den Bent
Background: The purpose of this study was to assess the reproducibility of the previously described T2-FLAIR mismatch sign as a specific imaging marker in non-enhancing isocitrate dehydrogenase (IDH) mutant, 1p/19q non-codeleted lower grade glioma (LGG), encompassing both diffuse and anaplastic astrocytoma. Methods: MR scans (n=154) from three separate databases with genotyped LGG were evaluated by two independent reviewers to assess (i) presence/absence of "T2-FLAIR mismatch" sign and (ii) presence/absence of homogenous signal on T2WI...
March 26, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29527387/-idh1-atrx-and-braf-v600e-mutation-in-astrocytic-tumors-and-their-significance-in-patient-outcome-in-north-indian-population
#8
Debajyoti Chatterjee, Bishan Dass Radotra, Narendra Kumar, Rakesh Kumar Vasishta, Sunil Kumar Gupta
Background: According to the current World Health Organization (WHO) classification of central nervous system (CNS) tumors (2016), histological diagnosis of gliomas should be supplemented by molecular information. This study was carried out to determine the frequency of isocitrate dehydrogenase 1 ( IDH 1), ATRX , and BRAF V600E mutations in different grade astrocytomas and their prognostic value. Methods: Eighty cases of astrocytoma (15 pilocytic astrocytoma, 25 diffuse astrocytoma, 15 anaplastic astrocytoma, and 25 glioblastoma) with follow-up information were analyzed using immunohistochemistry for IDH1 mutant protein, ATRX, p53, and BRAF...
2018: Surgical Neurology International
https://www.readbyqxmd.com/read/29444314/diffuse-astrocytoma-idh-wildtype-a-dissolving-diagnosis
#9
Martin Hasselblatt, Mohammed Jaber, David Reuss, Oliver Grauer, Annkatrin Bibo, Stephanie Terwey, Uta Schick, Heinrich Ebel, Thomas Niederstadt, Walter Stummer, Andreas von Deimling, Werner Paulus
The histological and molecular features and even the mere existence of diffuse astrocytoma, IDH-wildtype, remain unclear. We therefore examined 212 diffuse astrocytomas (grade II WHO) in adults using IDH1(R132H) immunohistochemistry followed by IDH1/IDH2 sequencing and neuroimaging review. DNA methylation status and copy number profiles were assessed by Infinium HumanMethylation450k BeadChip. Only 25/212 patients harbored tumors without IDH1/IDH2 hotspot mutations and without contrast enhancement. By DNA methylation profiling, 10/25 tumors were classified as glioblastoma, IDH-wildtype, and an additional 7 cases could not be classified using methylome analysis, but showed genetic characteristics of glioblastoma...
February 9, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29258767/immunohistochemical-comparative-analysis-of-gfap-map-2-nogo-a-olig-2-and-wt-1-expression-in-who-2016-classified-neuroepithelial-tumours-and-their-prognostic-value
#10
David Emanuel Schwab, Guilherme Lepski, Christian Borchers, Katrin Trautmann, Frank Paulsen, Jens Schittenhelm
Immunohistochemistry is routinely used in differential diagnosis of tumours of the central nervous system (CNS). The latest 2016 WHO 2016 revision now includes molecular data such as IDH mutation and 1p/19q codeletion thus restructuring glioma classification. Direct comparative information between commonly used immunohistochemical markers for glial tumours GFAP, MAP - 2, NOGO - A, OLIG - 2 and WT - 1 concerning quality and quantity of expression and their relation to the new molecular markers are lacking. We therefore compared the immunohistochemical staining results of all five antibodies in 34 oligodendrogliomas, 106 ependymomas and 423 astrocytic tumours...
January 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29218432/the-2016-revision-of-the-who-classification-of-central-nervous-system-tumours-retrospective-application-to-a-cohort-of-diffuse-gliomas
#11
Te Whiti Rogers, Gurvinder Toor, Katharine Drummond, Craig Love, Kathryn Field, Rebecca Asher, Alpha Tsui, Michael Buckland, Michael Gonzales
The classification of central nervous system tumours has more recently been shaped by a focus on molecular pathology rather than histopathology. We re-classified 82 glial tumours according to the molecular-genetic criteria of the 2016 revision of the World Health Organization (WHO) Classification of Tumours of the Central Nervous System. Initial diagnoses and grading were based on the morphological criteria of the 2007 WHO scheme. Because of the impression of an oligodendroglial component on initial histological assessment, each tumour was tested for co-deletion of chromosomes 1p and 19q and mutations of isocitrate dehydrogenase (IDH-1 and 2) genes...
March 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29156679/remote-intracranial-recurrence-of-idh-mutant-gliomas-is-associated-with-tp53-mutations-and-an-8q-gain
#12
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
#13
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/29016839/prognostic-relevance-of-genetic-alterations-in-diffuse-lower-grade-gliomas
#14
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)...
January 10, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/28866063/spinal-cord-astrocytoma-with-isocitrate-dehydrogenase-1-gene-mutation
#15
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...
December 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28851427/the-frequency-and-prognostic-effect-of-tert-promoter-mutation-in-diffuse-gliomas
#16
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
https://www.readbyqxmd.com/read/28801347/a-simple-algorithmic-approach-using-histology-and-immunohistochemistry-for-the-current-classification-of-adult-diffuse-glioma-in-a-resource-limited-set-up
#17
R T Rajeswarie, Shilpa Rao, Bevinahalli N Nandeesh, T Chickabasaviah Yasha, Vani Santosh
AIMS: The WHO 2016 classification of diffuse gliomas combines histological and molecular parameters for diagnosis. However, in view of cost constraints for molecular testing, an economical working formula is essential to reach a meaningful diagnosis in a resource-limited setting. The aim of this study was to establish a practical algorithmic approach using histology and immunohistochemistry (IHC) in the classification of diffuse gliomas in such a set-up. METHODS: Diffuse gliomas of WHO grade II and III diagnosed in our institute in the year 2016 were analysed for histological and IHC features, using the markers isocitrate dehydrogenase 1 (IDH1R132H) and α thalassemia/mental retardation syndrome X-linked gene (ATRX)...
August 11, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28674742/characterization-of-gliomas-from-morphology-to-molecules
#18
REVIEW
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)...
August 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28392842/dna-methylation-signatures-for-2016-who-classification-subtypes-of-diffuse-gliomas
#19
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/28124097/pan-mutant-idh1-inhibitor-bay-1436032-for-effective-treatment-of-idh1-mutant-astrocytoma-in-vivo
#20
Stefan Pusch, Sonja Krausert, Viktoria Fischer, Jörg Balss, Martina Ott, Daniel Schrimpf, David Capper, Felix Sahm, Jessica Eisel, Ann-Christin Beck, Manfred Jugold, Viktoria Eichwald, Stefan Kaulfuss, Olaf Panknin, Hartmut Rehwinkel, Katja Zimmermann, Roman C Hillig, Judith Guenther, Luisella Toschi, Roland Neuhaus, Andrea Haegebart, Holger Hess-Stumpp, Markus Bauser, Wolfgang Wick, Andreas Unterberg, Christel Herold-Mende, Michael Platten, Andreas von Deimling
Mutations in codon 132 of isocitrate dehydrogenase (IDH) 1 are frequent in diffuse glioma, acute myeloid leukemia, chondrosarcoma and intrahepatic cholangiocarcinoma. These mutations result in a neomorphic enzyme specificity which leads to a dramatic increase of intracellular D-2-hydroxyglutarate (2-HG) in tumor cells. Therefore, mutant IDH1 protein is a highly attractive target for inhibitory drugs. Here, we describe the development and properties of BAY 1436032, a pan-inhibitor of IDH1 protein with different codon 132 mutations...
April 2017: Acta Neuropathologica
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