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Idh mutant glioma

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
José E Velázquez Vega, Daniel J Brat
Recent advances in molecular pathology have reshaped the practice of brain tumor diagnostics. The classification of gliomas has been restructured with the discovery of isocitrate dehydrogenase (IDH) 1/2 mutations in the vast majority of lower grade infiltrating gliomas and secondary glioblastomas (GBM), with IDH-mutant astrocytomas further characterized by TP53 and ATRX mutations. Whole-arm 1p/19q codeletion in conjunction with IDH mutations now define oligodendrogliomas, which are also enriched for CIC, FUBP1, PI3K, NOTCH1, and TERT-p mutations...
March 8, 2018: Advances in Anatomic Pathology
Anteneh M Feyissa, Gregory A Worrell, William O Tatum, Deependra Mahato, Benjamin H Brinkmann, Steven S Rosenfeld, Karim ReFaey, Perry S Bechtle, Alfredo Quinones-Hinojosa
OBJECTIVE: To examine the relationship between high-frequency oscillations (HFOs) and the presence of preoperative seizures, World Health Organization tumor grade, and isocitrate dehydrogenase 1 (IDH1) mutational status in gliomas. METHODS: We retrospectively studied intraoperative electrocorticography recorded in 16 patients with brain tumor (12 presenting with seizures) who underwent awake craniotomy and surgical resection between September 2016 and June 2017...
February 28, 2018: Neurology
M Unterrrainer, I Winkelmann, B Suchorska, A Giese, V Wenter, F W Kreth, J Herms, P Bartenstein, J C Tonn, N L Albert
PURPOSE: For the clinical evaluation of O-(2-18 F-fluoroethyl)-L-tyrosine (18 F-FET) PET images, the use of standard summation images obtained 20-40 min after injection is recommended. However, early summation images obtained 5-15 min after injection have been reported to allow better differentiation between low-grade glioma (LGG) and high-grade glioma (HGG) by capturing the early18 F-FET uptake peak specific for HGG. We compared early and standard summation images with regard to delineation of the PET-derived biological tumour volume (BTV) in correlation with the molecular genetic profile according the updated 2016 WHO classification...
February 27, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Christine Marosi
No abstract text is available yet for this article.
February 21, 2018: EBioMedicine
Serah Choi, Yao Yu, Matthew R Grimmer, Michael Wahl, Susan M Chang, Joseph F Costello
Low-grade gliomas cause considerable morbidity and most will recur after initial therapy. At recurrence, low-grade gliomas can undergo transformation to high-grade gliomas (grade III or grade IV), which are associated with worse prognosis. Temozolomide (TMZ) provides survival benefit in patients with glioblastomas (GBMs) but its value in patients with low-grade gliomas is less clear. A subset of TMZ-treated, IDH-mutant, low-grade astrocytomas recur as more malignant tumors with thousands of de novo, coding mutations bearing a signature of TMZ-induced hypermutation...
February 14, 2018: Neuro-oncology
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
Hanumantha Rao Madala, Surendra R Punganuru, Viswanath Arutla, Subhasis Misra, T J Thomas, Kalkunte S Srivenugopal
Isocitrate dehydrogenases 1 and 2 (IDH1,2), the key Krebs cycle enzymes that generate NADPH reducing equivalents, undergo heterozygous mutations in >70% of low- to mid-grade gliomas and ~20% of acute myeloid leukemias (AMLs) and gain an unusual new activity of reducing the α-ketoglutarate (α-KG) to D-2 hydroxyglutarate (D-2HG) in a NADPH-consuming reaction. The oncometabolite D-2HG, which accumulates >35 mM, is widely accepted to drive a progressive oncogenesis besides exacerbating the already increased oxidative stress in these cancers...
February 11, 2018: Cancers
Min Zhou, Yue Zhou, Huijun Liao, Benjamin C Rowland, Xiangquan Kong, Nils D Arvold, David A Reardon, Patrick Y Wen, Alexander P Lin, Raymond Y Huang
Background: Isocitrate dehydrogenase (IDH) mutations result in abnormal accumulation of 2-hydroxyglutarate (2HG) in gliomas that can be detected by MRS. We examined the diagnostic accuracy of 2HG single-voxel spectroscopy (SVS) and chemical shift imaging (CSI) in both newly-diagnosed and post-treatment settings. Methods: Long-TE (97 ms) SVS and CSI were acquired in 85 subjects, including a discovery cohort of 39 patients who had postoperative residual or recurrent glioma with confirmed IDH-mutation status and 6 normal volunteers, a prospective preoperative validation cohort of 24 patients with newly-diagnosed brain mass, and a prospective recurrent-lesion validation cohort of 16 previously-treated IDH-mutant glioma patients with suspected tumor recurrence...
February 9, 2018: Neuro-oncology
Z Wang, X Liu, Z Wang, Z Bao, W Zhang, C Zhang, T Jiang
BACKGROUND: Isocitrate dehydrogenase (IDH) mutation is the initiating event that defines major clinical and prognostic classes of gliomas, but the potential mechanisms have not been well interpreted yet. The main objective of the current study was to better understand the underlying biology of IDH mutant gliomas as captured by gene expression profiles. METHODS: RNA sequencing data of WHO grade II-IV gliomas from the Chinese Glioma Genome Atlas (CGGA, N=325) were used to assess differentially expressed genes between IDH mutant and wild type gliomas and to construct a gene expression-based classifier to detect IDH mutant samples with high sensitivity and specificity...
February 12, 2018: Current Molecular Medicine
Jun Muto, Edouard Dezamis, Odile Rigaux-Viode, Sophie Peeters, Alexandre Roux, Marc Zanello, Charles Mellerio, Xavier Sauvageon, Pascale Varlet, Catherine Oppenheim, Johan Pallud
OBJECTIVE: We assessed the impact of surgery on postoperative cognitive function and ability to work in adult patients harboring a diffuse low-grade glioma involving eloquent brain regions and having a functional-based maximal surgical resection using intraoperative corticosubcortical mapping under awake conditions. METHODS: We prospectively included 39 consecutive diffuse IDH-mutant low-grade glioma patients without preoperative and adjuvant oncological treatment and assessed preoperative (mean 24...
February 9, 2018: World Neurosurgery
H H Jiang, G Li, J M Wang, X L Li, Y Cui, S Lin
Objective: To explore the prognostic impact of 2016 World Health Organization (WHO) classification of central nervous system (CNS) tumors on patients with low grade gliomas (LGG). Methods: A total of 482 patients diagnosed with LGG in Beijing Tiantan Hospital affiliated to Capital Medical University from January 2009 to May 2016 were pathologically reclassified and retrospectively reviewed. In the survival analysis, Kaplan-Meier Plot was used to univariate analysis and Cox proportional hazards model was used to multivariate analysis...
January 30, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Akshitkumar M Mistry, Cindy L Vnencak-Jones, Bret C Mobley
The presence of the single-nucleotide polymorphism (SNP) rs11554137:C>T in the IDH1 gene is associated with a significantly lower survival in acute myeloid leukemia patients. The impact of its presence in glioblastoma on patient survival is unclear. We retrospectively reviewed 171 adult (> 18 years of age) patients treated at a single, tertiary academic center for supratentorial glioblastoma (WHO grade IV) between 2013 and 2017. We conducted Kaplan-Meier overall and progression free survival analyses based on the IDH1 and IDH2 gene status of patients' glioblastoma (IDH wild type, mutant, and IDH1 rs11554137:C>T SNP)...
February 8, 2018: Journal of Neuro-oncology
Pierre Bady, Sebastian Kurscheid, Mauro Delorenzi, Thierry Gorlia, Martin J van den Bent, Khê Hoang-Xuan, Élodie Vauléon, Anja Gijtenbeek, Roelien Enting, Brian Thiessen, Olivier Chinot, Frédéric Dhermain, Alba A Brandes, Jaap C Reijneveld, Christine Marosi, Martin J B Taphoorn, Wolfgang Wick, Andreas von Deimling, Pim French, Roger Stupp, Brigitta G Baumert, Monika E Hegi
The optimal treatment for patients with low-grade glioma (LGG) WHO grade II remains controversial. Overall survival ranges from 2 to over 15 years depending on molecular and clinical factors. Hence, risk-adjusted treatments are required for optimizing outcome and quality of life. We aim at identifying mechanisms and associated molecular markers predictive for benefit from radiotherapy (RT) or temozolomide (TMZ) in LGG patients treated in the randomized phase III trial EORTC 22033. As candidate biomarkers for these genotoxic treatments, we considered the DNA methylome of 410 DNA damage response (DDR) genes...
January 24, 2018: Acta Neuropathologica
Jung Ho Im, Je Beom Hong, Se Hoon Kim, Junjeong Choi, Jong Hee Chang, Jaeho Cho, Chang-Ok Suh
We assessed the appropriateness of current radiotherapy volume for WHO grade III gliomas. The records of 73 patients with WHO grade III gliomas who received postoperative radiotherapy between 2001 and 2013 were retrospectively reviewed. Based on the 2016 WHO classification, 25/73 (34.2%) patients had anaplastic oligodendroglioma (AO), IDH-mutant and 1p/19q-codeleted; 11/73 (15.1%) patients had anaplastic astrocytoma, IDH-mutant; and 37/73 (50.7%) patients had anaplastic astrocytoma, IDH-wildtype. The extent of resection (EOR) was total in 43 patients (58...
January 15, 2018: Scientific Reports
Girolamo Crisi, Silvano Filice, Maria Michiara, Pellegrino Crafa, Silvia Lana
OBJECTIVE: The objective of this study was to assess the effective performance of short echo time magnetic resonance spectroscopy (short TE MRS) for 2HG detection as biomarker of isocitrate dehydrogenase (IDH) status in all grade glioma (GL). METHODS: A total of 82 GL patients were prospectively investigated by short TEMRS at 3.0 T as part of a multimodal magnetic resonance imaging study protocol. Spectral analysis was performed using linear combination model. Tumor specimens were diagnosed as IDH mutant or wild type according to the 2016 World Health Organization (WHO) classification of brain tumors...
December 28, 2017: Journal of Computer Assisted Tomography
Javier E Villanueva-Meyer, Matthew D Wood, Byung Se Choi, Marc C Mabray, Nicholas A Butowski, Tarik Tihan, Soonmee Cha
OBJECTIVE: Grade II diffuse gliomas (DGs) with isocitrate dehydrogenase (IDH) mutations are associated with better prognosis than their IDH wild-type counterparts. We sought to determine the MRI characteristics associated with IDH mutational status and ascertain whether MRI considered in combination with IDH mutational status can better predict the clinical outcomes of grade II DGs. MATERIALS AND METHODS: Preoperative MRI examinations were retrospectively studied for qualitative tumor characteristics, including location, extent, cortical involvement, margin sharpness, cystic component, mineralization or hemorrhage, and contrast enhancement...
December 20, 2017: AJR. American Journal of Roentgenology
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...
December 14, 2017: Pathology, Research and Practice
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
Huy Gia Vuong, Ahmed M A Altibi, Uyen N P Duong, Hanh T T Ngo, Thong Quang Pham, Aden Ka-Yin Chan, Chul-Kee Park, Kar-Ming Fung, Lewis Hassell
The clinical significance of telomerase reverse transcriptase (TERT) promoter mutation in glioma remains unclear. The aim of our meta-analysis is to investigate the prognostic impact TERT promoter mutation in glioma patients and its interaction with other molecular markers, particularly Isocitrate Dehydrogenase (IDH) mutation from aggregate level data. Relevant articles were searched in four electronic databases including PubMed, Scopus, Web of Science and Virtual Health Library. Pooled HRs were calculated using random effect model weighted by inverse variance method...
December 2017: Critical Reviews in Oncology/hematology
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