scholarly journals Study of Histomolecular Classification of Glioma-Integrating Histology and Molecular Analysis in the Diagnosis of Brain Tumors

2018 ◽  
Vol 07 (02) ◽  
pp. 129-134
Author(s):  
Shameen Devi ◽  
Michelle De Padua ◽  
Iravathy Kalal
Keyword(s):  
Anaplastic Astrocytoma ◽  
Idh1 Mutation ◽  
Tumor Type ◽  
Diffuse Astrocytoma ◽  
Isocitrate Dehydrogenase 1 ◽  
Anaplastic Oligoastrocytoma ◽  
Diffuse Gliomas ◽  
Grade Ii ◽  
Classification Of Gliomas

Abstract Introduction The updated 2016 classification of gliomas incorporates well-established molecular parameters into the classification of diffuse gliomas, taking into account isocitrate dehydrogenase 1 (IDH1) mutation, α-thalassemia/mental retardation syndrome X-linked (ATRX) loss, and 1p/19q co-deletion. Aim and Objectives To study IDH1 and ATRX mutations in gliomas, 1p/19q co-deletion by fluorescent in situ hybridization (FISH) in oligodendroglioma, and to correlate IDH1, ATRX, and 1p/19q with tumor type and grade. Material and Methods Total 73 cases of gliomas were diagnosed on histology and graded as astrocytoma (grades 2–4), oligodendroglioma (grades 2–3), and oligoastrocytoma (grades 2–3) by two pathologists independently. IDH mutation and ATRX expression were analyzed using immunohistochemistry in all cases whereas 1p/19q co-deletion was studied using FISH in cases with oligodendroglioma and oligoastrocytoma morphology. Results Total 48 cases of astrocytoma, 9 cases of oligoastrocytoma, and 16 cases of oligodendroglioma were included. The maximum number of IDH1 mutation cases were seen in diffuse astrocytoma (7/10; 70%) as compared with anaplastic astrocytoma (5/15; 33.33%), glioblastoma multiforme (GBM) (3/23; 13.04%) grade II oligoastrocytoma (3/6; 50%), anaplastic oligoastrocytoma (2/3; 66.67%), and oligodendroglioma grade II (7/10; 70%). ATRX loss was seen in diffuse astrocytoma grade II (6/10; 60%), anaplastic astrocytoma (6/15; 40%), oligoastrocytoma grade II (2/6; 33.33%), and anaplastic oligoastrocytoma (1/3; 33.33%). 1p/19q co-deletion was seen in oligoastrocytoma (2/2; 100%), anaplastic oligoastrocytoma (1/2; 50%), oligodendroglioma (3/4; 75%), and anaplastic oligodendroglioma (1/3; 33.33%). Six of the seven cases with 1p/19q co-deletion also showed IDH1 mutation. One of seven 1p/19q co-deleted cases had loss of expression of ATRX. Conclusion Incorporation of IDH1 mutation, ATRX loss, and 1p/19q co-deletion molecular studies help in a more accurate diagnosis and classification of gliomas.

scholarly journals The Relationship Between IDH1 Mutation Status and Metabolic Imaging in Nonenhancing Supratentorial Diffuse Gliomas: A 11C-MET PET Study

2019 ◽  
Vol 18 ◽  
pp. 153601211989408
Author(s):  
Nijiati Kudulaiti ◽  
Huiwei Zhang ◽  
Tianming Qiu ◽  
Junfeng Lu ◽  
Abudumijiti Aibaidula ◽  
...  
Keyword(s):  
Standardized Uptake Value ◽  
Idh1 Mutation ◽  
Metabolic Imaging ◽  
Wild Type ◽  
Isocitrate Dehydrogenase 1 ◽  
Mutation Status ◽  
Positron Emission ◽  
Diffuse Gliomas ◽  
The Relationship ◽  
Met Pet

Purpose: We evaluated the relationship between isocitrate dehydrogenase 1 (IDH1) mutation status and metabolic imaging in patients with nonenhancing supratentorial diffuse gliomas using 11C-methionine positron emission tomography (11C-MET PET). Materials and Methods: Between June 2012 and November 2017, we enrolled 86 (38 women and 48 men; mean age, 41.9 ± 13.1 years [range, 8-67 years]) patients with newly diagnosed supratentorial diffuse gliomas. All patients underwent preoperative 11C-MET PET. Tumor samples were obtained and immunohistochemically analyzed for IDH1 mutation status. Results: The mutant and wild-type IDH1 diffuse gliomas had significantly different mean maximum standardized uptake value values (2.73 [95% confidence interval, CI: 2.32-3.16] vs 3.85 [95% CI: 3.22-4.51], respectively; P = .004) and mean tumor-to-background ratio (1.90 [95% CI: 1.65-2.16] vs 2.59 [95% CI: 2.17-3.04], respectively; P = .007). Conclusions: 11C-methionine PET can noninvasively evaluate the IDH1 mutation status of patients with nonenhancing supratentorial diffuse gliomas.

Isocitrate dehydrogenase mutations in diffuse gliomas: clinical and aetiological implications

2011 ◽  
Vol 64 (10) ◽  
pp. 835-844 ◽  
Author(s):  
R Gupta ◽  
R Webb-Myers ◽  
S Flanagan ◽  
M E Buckland
Keyword(s):  
Isocitrate Dehydrogenase ◽  
Mutation Detection ◽  
Diagnostic Value ◽  
Mutation Status ◽  
Idh Mutations ◽  
Diffuse Gliomas ◽  
Prognostic Implications ◽  
Classification Of Gliomas ◽  
Generation Sequencing

The discovery of isocitrate dehydrogenase (IDH) mutations in gliomas is one example of the large impact that next-generation sequencing is having on the understanding of tumour biology and human disease in general. IDH mutations are early and common events in the development of astrocytomas, oligodendrogliomas and oligoastrocytomas. IDH mutations are also found in some myeloid malignancies and soft tissue tumours, but are rare in other malignancies. IDH mutation detection can be incorporated into routine pathology practice via immunohistochemistry and/or standard sequencing techniques and has great diagnostic value. An emerging theme is that IDH mutation status in gliomas is of great prognostic relevance, and there are proposals to include IDH mutation status in the next iteration of the WHO classification of gliomas. The mechanisms of action(s) of mutant IDH are not fully understood, but the understanding is progressing rapidly, and may provide a mechanism to link diverse proneoplastic processes such as oxidative damage and epigenetic dysregulation. There are exciting prospects of novel therapies for glioma patients emerging from the elucidation of these mechanisms. Given the diagnostic and prognostic implications of IDH mutation, and the potential for new therapies, all gliomas should be assessed for IDH mutation status in the future.

scholarly journals Fractal analysis of 11C-methionine PET in patients with newly diagnosed glioma

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Yukito Maeda ◽  
Yuka Yamamoto ◽  
Takashi Norikane ◽  
Katsuya Mitamura ◽  
Tetsuhiro Hatakeyama ◽  
...  
Keyword(s):  
Fractal Dimension ◽  
Fractal Analysis ◽  
Anaplastic Astrocytoma ◽  
Idh1 Mutation ◽  
Lower Grade ◽  
Diffuse Astrocytoma ◽  
Newly Diagnosed ◽  
Mutation Status ◽  
Lower Grade Glioma ◽  
Met Pet

Abstract Background The present study tested the possible utility of fractal analysis from l-[methyl-11C]-methionine (MET) uptake in patients with newly diagnosed gliomas for differentiating glioma, especially in relation to isocitrate dehydrogenase 1 (IDH1) mutation status, and as compared with the conventional standardized uptake value (SUV) parameters. Methods Investigations of MET PET/CT were performed retrospectively in 47 patients with newly diagnosed glioma. Tumors were divided into three groups: lower grade glioma (IDH1-mutant diffuse astrocytoma and IDH1-mutant anaplastic astrocytoma), higher grade glioma (IDH1-wildtype diffuse astrocytoma and IDH1-wildtype anaplastic astrocytoma), and glioblastoma. The fractal dimension for tumor, maximum SUV (SUVmax) for tumor (T) and mean SUV for normal contralateral hemisphere (N) were calculated, and the tumor-to-normal (T/N) ratio was determined. Metabolic tumor volume (MTV) and total lesion MET uptake (TLMU) were also measured. Results There were significant differences in SUVmax (p = 0.006) and T/N ratio (p = 0.02) between lower grade glioma and glioblastoma. There were no significant differences among any of the three groups in MTV or TLMU. Significant differences were obtained in the fractal dimension between lower grade glioma and higher grade glioma (p = 0.006) and glioblastoma (p < 0.001). Conclusions The results of this preliminary study in a small patient population suggest that the fractal dimension using MET PET in patients with newly diagnosed gliomas is useful for differentiating glioma, especially in relation to IDH1 mutation status, which has not been possible with SUV parameters.

scholarly journals Combination of the Distance From Tumor Edge to Subventricular Zone and IDH Mutation Predicts Prognosis of Patients With Glioma

2021 ◽  
Vol 11 ◽  
Author(s):  
Shuixian Zhang ◽  
Fengchun Zhao ◽  
Tengyuan Zhou ◽  
Dan Liu ◽  
Xiaohong Yao ◽  
...  
Keyword(s):  
Subventricular Zone ◽  
Univariate Analysis ◽  
Idh1 Mutation ◽  
Wild Type ◽  
Isocitrate Dehydrogenase 1 ◽  
Who Grade ◽  
Grade Ii ◽  
Tumor Edge ◽  
Two Parameters

Both subventricular zone (SVZ) contact and isocitrate dehydrogenase 1 (IDH1) mutation have been reported to be related to the outcome of glioma, respectively. However, far too little attention has been paid to the role of tumor edge-SVZ distance in the outcome of glioma. We aim to assess the value of tumor-SVZ distance, as well as combined tumor-SVZ distance and IDH status, in predicting the outcome of gliomas (WHO grade II–IV). Here, the MR images and clinical data from 146 patients were included in the current study. The relationship between survival and the tumor-SVZ distance as well as survival and combination of tumor-SVZ distance and IDH status were determined via univariate and multivariate analyses. In univariate analysis of tumor-SVZ distance, the patients were divided into three types (SVZ involvement, tumor-SVZ distance from 0 to 10 mm, and tumor-SVZ distance &gt;10 mm). The results showed that the OS (p = 0.02) and PFS (p = 0.002) for the patients had a positive correlation with the tumor-SVZ distance. In addition, simple linear correlation found a significant relationship between the two parameters (OS and PFS) and tumor-SVZ distance in patients with non-SVZ-contacting glioma. Combination analysis of the tumor-SVZ distance and IDH status showed that IDH1 mutation and SVZ non-involvement enable favorable outcomes, whereas IDH1 wild type with SVZ involvement indicates a significantly worse prognosis in all patients. Moreover, in patients with non-SVZ-contacting glioma, IDH1 mutation concurrent with tumor-SVZ distance &gt;10 mm has better OS and PFS. IDH1 wild type and tumor-SVZ distance from 0 to 10 mm suggest poorer OS and PFS. Multivariate analysis showed WHO grade IV, SVZ involvement, tumor-SVZ distance from 0 to 10 mm, IDH1 mutation, gross total resection, and chemotherapy serve as independent predictors of OS. WHO grade IV, SVZ involvement, tumor-SVZ distance from 0 to 10 mm, IDH1 mutation, and chemotherapy serve as independent predictors of PFS of patients with glioma. In conclusion, tumor-SVZ distance and IDH1 mutation status are the determinants affecting patient outcome.

scholarly journals Molecular Classification of Diffuse Gliomas

2020 ◽  
Vol 47 (4) ◽  
pp. 464-473
Author(s):  
Navya Kalidindi ◽  
Rosemarylin Or ◽  
Sam Babak ◽  
Warren Mason
Keyword(s):  
Dna Methylation ◽  
Molecular Markers ◽  
World Health ◽  
Low Grade ◽  
Diffuse Glioma ◽  
Isocitrate Dehydrogenase 1 ◽  
Anaplastic Gliomas ◽  
Diffuse Gliomas ◽  
The Impact

ABSTRACT:Technological advances in the field of molecular genetics have improved the ability to classify brain tumors into subgroups with distinct clinical features and important therapeutic implications. The World Health Organization’s newest update on classification of gliomas (2016) incorporated isocitrate dehydrogenase 1 and 2 mutations, ATRX loss, 1p/19q codeletion status, and TP53 mutations to allow for improved classification of glioblastomas, low-grade and anaplastic gliomas. This paper reviews current advances in the understanding of diffuse glioma classification and the impact of molecular markers and DNA methylation studies on survival of patients with these tumors. We also discuss whether the classification and grading of diffuse gliomas should be based on histological findings, molecular markers, or DNA methylation subgroups in future iterations of the classification system.

scholarly journals Gene Expression Profiling in Human High-Grade Astrocytomas

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Zhongyu Liu ◽  
Zhiqiang Yao ◽  
Chao Li ◽  
Yicheng Lu ◽  
Chunfang Gao
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Anaplastic Astrocytoma ◽  
Low Grade ◽  
Diffuse Astrocytoma ◽  
Who Grade ◽  
Grade Ii ◽  
Who Grade Iii ◽  
Grade Iii

Diffuse astrocytoma of (WHO grade II) has a tendency to progress spontaneously to anaplastic astrocytoma (WHO grade III) and/or glioblastoma (WHO grade IV). However, the molecular basis of astrocytoma progression is still poorly understood. In current study, an essential initial step toward this goal is the establishment of the taxonomy of tumors on the basis of their gene expression profiles. We have used gene expression profiling, unsupervised (hierarchal cluster (HCL) and principal component analysis (PCA)) and supervised (prediction analysis for microarrays (PAM)) learning methods, to demonstrate the presence of three distinct gene expression signatures of astrocytomas (ACMs), which correspond to diffuse or low-grade astrocytoma (WHO grade II), Anaplastic astrocytoma (WHO grade III) and Glioblastoma multiforme (WHO grade IV). We also demonstrate a 171 gene-based classifier that characterize the distinction between these pathologic/molecular subsets of astrocytomas. These results further define molecular subtypes of astrocytomas and may potentially be used to define potential targets and further refine stratification approaches for therapy. In addition, this study demonstrates that combining gene expression analysis with detailed annotated pathway and gene ontology (GO) category resources was applied to highly enriched normal and tumor population; it can yield an understanding of the critical biological mechanism of astrocytomas.

scholarly journals HGG-45. PROTEOMIC ANALYSIS OF PEDIATRIC DIFFUSE ASTROCYTOMAS YIELDS PATHWAYS ASSOCIATED WITH BOTH PROGRESSION-FREE AND OVERALL SURVIVAL

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii352-iii352
Author(s):  
Blake Sells ◽  
Jessica Fleming ◽  
Richard Graham ◽  
Joseph McElroy ◽  
Jahar Haque ◽  
...  
Keyword(s):  
Diffuse Astrocytoma ◽  
Primary Tumors ◽  
Proteomic Data ◽  
New Therapeutic Approaches ◽  
Formalin Fixed Paraffin ◽  
Risk Of Progression ◽  
Formalin Fixed Paraffin Embedded ◽  
Diffuse Gliomas ◽  
Grade Ii

Abstract Brain tumors are now responsible for more deaths each year than any other childhood cancer. Current studies aim to discover key molecular drivers that can explain prognosis and serve as targets for new therapeutic approaches, reducing morbidity. In this study, we performed LC-MS/MS proteomics on a cohort of 28 primary diffuse astrocytoma formalin-fixed paraffin embedded samples (WHO Grades II-IV) from patients at Nationwide Children’s Hospital with a median follow-up time of 2.3 (0.6–20.2) years. Ingenuity Pathway Analysis was used to analyze the proteomic data after using both age and grade as covariates and only including proteins with p-values less than 0.05. The upregulation of a well-known oncogenic pathway, the Protein Kinase A signaling pathway, was significantly associated with greater risk of progression and death (P=5.5E-07 and P=4.6E-04). Integrin signaling, a pathway commonly suppressed in cancer, was similarly downregulated in those with greater risk of progression and death (P=3.3E-04 and P=1.7E-07). A global upstream analysis of the proteomic data also predicted activation of the oncogene MYCN in those who performed poorly, supporting previous studies. When comparing grade II (n=10) to grade III (n=8) and IV (n=10) primary tumors, the pathway most upregulated in higher histopathological grades was EIF2 Signaling (P=4.9E-49). This pathway has previously been associated with resistance in adult glioblastoma. These pathways, and the proteins detected within, may provide novel means by which to better understand and treat pediatric diffuse gliomas. Ongoing studies are in progress to understand how these pathways drive aggressiveness and differ from adult astrocytomas.

scholarly journals Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Junping Wang ◽  
Cheng Huo ◽  
Jinzhu Yin ◽  
Lixia Tian ◽  
Lili Ma ◽  
...  
Keyword(s):  
Disease Severity ◽  
Dna Methyltransferase ◽  
Diffuse Astrocytoma ◽  
Specific Sequence ◽  
Aberrant Expression ◽  
Astrocytoma Cell ◽  
Grade Ii ◽  
Astrocytoma Grade Iii ◽  
Astrocytoma Grade

The pro-oncogene ETS-1 (E26 transformation-specific sequence 1) is a key regulator of the proliferation and invasion of cancer cells. The present work examined the correlation of the aberrant expression of ETS-1 with histological or clinical classification of astrocytoma: grade I (pilocytic astrocytoma), grade II (diffuse astrocytoma), grade III (anaplastic astrocytoma), and grade IV (glioblastoma multiforme). MicroRNA, miR-338-5p, was predicted by an online tool (miRDB) to potentially target the 3’ untranslated region of ETS-1; this was confirmed by multi-assays, including western blot experiments or the point mutation of the targeting sites of miR-338-5p in ETS-1’s 3’untralation region (3’UTR). The expression of miR-338-5p was negatively associated with that of ETS-1 in astrocytoma, and deficiency of miR-338-5p would mediate aberrant expression of ETS-1 in astrocytoma. Mechanistically, hypermethylation of miR-338-5p by DNA methyltransferase 1 (DNMT1) resulted in repression of miR-338-5p expression and the aberrant expression of ETS-1. Knockdown or deactivation of DNMT1 decreased the methylation rate of the miR-338-5p promoter, increased the expression of miR-338-5p, and repressed the expression of ETS-1 in astrocytoma cell lines U251 and U87. These results indicate that hypermethylation of the miR-338-5p promoter by DNMT1 mediates the aberrant expression of ETS-1 related to disease severity of patients with astrocytoma.

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