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Objective To evaluate the predictive value of T2-fluid attenuated inversion recovery (FLAIR) signal suppression rate for the short arm of chromosome 1 and long arm of chromosome 19 (1p/19q) molecular features in lower-grade gliomas (LGG), and to construct and verify the predictive model based on magnetic resonance imaging (MRI) tumor features and T2-FLAIR signal suppression rate. Methods Clincal and imaging data of the patients with pathologically confirmed supratentorial LGG (WHO grade 2~3) in our medical center from 2017 to 2021 were collected and retrospectively analyzed. According to the results of postoperative molecular pathology, they were divided into 1p/19q-codeleted (1p/19q-Codel) and 1p/19q-noncodeleted (1p/19q-Noncodel) groups. MRI tumor features were blindly assessed by 2 neuroradiologists. Five circular regions of interest were respectively delineated in the tumor area and the normal-appearing white matter in contralateral semioval center using the hot-spot method in order to calculate the T2-FLAIR signal suppression rate. The differences of clinical features, MRI tumor features and T2-FLAIR signal suppression rate were analyzed between the 2 groups. Univariate and multivariate logistic regression analyses were used to screen independent predictors and constructa predictive model and nomogram. Receiver operating characteristic (ROC) curve, calibration curve and Hosmer-Lemeshow test were applied to assess the model performance, and the model was internally validated by bootstrap method. Results A total of 146 supratentorial LGG patients were enrolled, including 68 being assigned into the 1p/19q-Codel group and 78 into the 1p/19q-Noncodel group. The T2-FLAIR signal suppression rate was 0.43 (0.28, 0.62) in the 1p/19q-Noncodel group, which was significantly higher than that in the 1p/19q-Codel group [0.29 (0.24, 0.35), P0.374 (P0.374 in predicting 1p/19q-Noncodel was 0.720, the sensitivity was 60.26% and the specificity was 83.82%. DeLong test indicated that T2-FLAIR signal suppression rate >0.374 was more effective than T2-FLAIR mismatch sign in predicting 1p/19q molecular features (P0.374 combined with cortex infiltration and calcification had good performance, with an AUC value of 0.808, and the AUC value verified internally by bootstrap method was 0.807. At the same time, the calibration and goodness of fit of the model were good. Conclusion T2-FLAIR signal suppression rate can be used as a quantitative imaging marker to predict 1p/19q-Noncodel LGG. The predictive model with T2-FLAIR signal suppression rate >0.374 combined with cortex infiltration and calcification can effectively predict 1p/19q molecular features.

Oligodendrogliomas are defined at the molecular level by the presence of an IDH mutation and codeletion of chromosomal arms 1p and 19q. In the past, case reports and small studies described gliomas with sarcomatous features arising from oligodendrogliomas, so called oligosarcomas. Here, we report a series of 24 IDH-mutant oligosarcomas from 23 patients forming a distinct methylation class. The tumors were recurrences from prior oligodendrogliomas or developed de novo. Precursor tumors of 12 oligosarcomas were histologically and molecularly indistinguishable from conventional oligodendrogliomas. Oligosarcoma tumor cells were embedded in a dense network of reticulin fibers, frequently showing p53 accumulation, positivity for SMA and CALD1, loss of OLIG2 and gain of H3K27 trimethylation (H3K27me3) as compared to primary lesions. In 5 oligosarcomas no 1p/19q codeletion was detectable, although it was present in the primary lesions. Copy number neutral LOH was determined as underlying mechanism. Oligosarcomas harbored an increased chromosomal copy number variation load with frequent CDKN2A/B deletions. Proteomic profiling demonstrated oligosarcomas to be highly distinct from conventional CNS WHO grade 3 oligodendrogliomas with consistent evidence for a smooth muscle differentiation. Expression of several tumor suppressors was reduced with NF1 being lost frequently. In contrast, oncogenic YAP1 was aberrantly overexpressed in oligosarcomas. Panel sequencing revealed mutations in NF1 and TP53 along with IDH1/2 and TERT promoter mutations. Survival of patients was significantly poorer for oligosarcomas as first recurrence than for grade 3 oligodendrogliomas as first recurrence. These results establish oligosarcomas as a distinct group of IDH-mutant gliomas differing from conventional oligodendrogliomas on the histologic, epigenetic, proteomic, molecular and clinical level. The diagnosis can be based on the combined presence of (a) sarcomatous histology, (b) IDH-mutation and (c) TERT promoter mutation and/or 1p/19q codeletion, or, in unresolved cases, on its characteristic DNA methylation profile.

Summary: Molecular biomarkers are becoming increasingly important in the classification of intracranial gliomas. While tissue sampling remains the gold standard, there is growing interest in the use of deep learning (DL) techniques to predict these markers. This narrative review with a systematic approach identifies and synthesises the current published data on DL techniques using conventional MRI sequences for predicting isocitrate dehydrogenase (IDH) and 1p/19q‐codeletion status in World Health Organisation grade 2–4 gliomas. Three databases were searched for relevant studies. In all, 13 studies met the inclusion criteria after exclusions. Key results, limitations and discrepancies between studies were synthesised. High accuracy has been reported in some studies, but the existing literature has several limitations, including generally small cohort sizes, a paucity of studies with independent testing cohorts and a lack of studies assessing IDH and 1p/19q together. While DL shows promise as a non‐invasive means of predicting glioma genotype, addressing these limitations in future research will be important for facilitating clinical translation. [ABSTRACT FROM AUTHOR]

Objective: We aimed to summarize the clinicopathological characteristics and prognostic features of various molecular subtypes of diffuse gliomas (DGs) in the Chinese population. Methods: In total, 1,418 patients diagnosed with DG between 2011 and 2017 were classified into 5 molecular subtypes according to the 2016 WHO classification of central nervous system tumors. The IDH mutation status was determined by immunohistochemistry and/or DNA sequencing, and 1p/19q codeletion was detected with fluorescence in situ hybridization. The median clinical follow-up time was 1,076 days. T-tests and chi-square tests were used to compare clinicopathological characteristics. Kaplan-Meier and Cox regression methods were used to evaluate prognostic factors. Results: Our cohort included 15.5% lower-grade gliomas, IDH-mutant and 1p/19q-codeleted (LGG-IDHm-1p/19q); 18.1% lower-grade gliomas, IDH-mutant (LGG-IDHm); 13.1% lower-grade gliomas, IDH-wildtype (LGG-IDHwt); 36.1% glioblastoma, IDH-wildtype (GBM-IDHwt); and 17.2% glioblastoma, IDH-mutant (GBM-IDHm). Approximately 63.3% of the enrolled primary gliomas, and the median overall survival times for LGG-IDHm, LGG-IDHwt, GBM-IDHwt, and GBM-IDHm subtypes were 75.97, 34.47, 11.57, and 15.17 months, respectively. The 5-year survival rate of LGG-IDHm-1p/19q was 76.54%. We observed a significant association between high resection rate and favorable survival outcomes across all subtypes of primary tumors. We also observed a significant role of chemotherapy in prolonging overall survival for GBM-IDHwt and GBM-IDHm, and in prolonging post-relapse survival for the 2 recurrent GBM subtypes. Conclusions: By controlling for molecular subtypes, we found that resection rate and chemotherapy were 2 prognostic factors associated with survival outcomes in a Chinese cohort with DG.

Abstract Background Molecular markers for classification of gliomas include isocitrate dehydrogenase (IDH) mutations and codeletion of chromosomal arms 1p and 19q (1p/19q). While mutations in IDH enzymes result in the well‐characterized production of oncometabolite 2‐hydroxyglutarate, dysregulation of other metabolites in IDH tumors is less characterized. Similarly, the effects of 1p/19q codeletion on cellular metabolism are also unclear. Aim This study aimed to quantify changes in tumor metabolites in human glioma tissue as a function of both IDH mutation and 1p/19q codeletion. Methods and Results Deidentified human glioma tissue and associated clinical data were obtained from the Emory University Winship Cancer Institute tissue biobank from 14 patients (WHO grades II, III, and IV; seven female and seven male). Proton (1H) high‐resolution magic angle spinning (HR‐MAS) nuclear magnetic resonance (NMR) spectroscopy data were acquired using a 600 MHz Bruker AVANCE III NMR spectrometer. Metabolite concentrations were calculated using LCModel. Differences in metabolite concentrations as a function of IDH mutation, 1p/19q codeletion, and survival status were determined using Mann–Whitney U tests. Concentrations of alanine, glutamine, and glutamate were significantly lower in glioma tissue with IDH mutations compared to tissue with IDH wildtype. Additionally, glutamate concentration was significantly lower in glioma tissue with 1p/19q codeletion compared to intact 1p/19q. Exploratory analysis revealed alanine concentration varied significantly as a function of survival status. Conclusions Given the emerging landscape of glioma treatments that target metabolic dysregulation, an improved understanding of altered metabolism in molecular sub‐types of gliomas, including those with IDH mutation and 1p/19q codeletion, is an important consideration for treatment stratification and personalized medicine.

Oligodendrogliomas are a type of rare and incurable gliomas whose metabolic profiles have yet to be fully examined. The present study examined the spatial differences in metabolic landscapes underlying oligodendrogliomas and should provide unique insights into the metabolic characteristics of these uncommon tumors. Single-cell RNA-sequencing expression profiles from 4044 oligodendroglioma cells derived from tumors resected from four locations frontal, temporal, parietal, and frontotemporoinsular) and in which 1p/19q co-deletion and IDH1 or IDH2 mutations were confirmed were computationally analyzed through a robust workflow to elucidate relative differences in metabolic pathway activities among the different locations. Dimensionality reduction using metabolic expression profiles exhibited clustering corresponding to each location subgroup. From the 80 metabolic pathways examined, over 70 pathways had significantly different activity scores between location subgroups. Further analysis of metabolic heterogeneity suggests that mitochondrial oxidative phosphorylation accounts for considerable metabolic variation within the same locations. Steroid and fatty acid metabolism pathways were also found to be major contributors to heterogeneity. Oligodendrogliomas display distinct spatial metabolic differences in addition to intra-location metabolic heterogeneity. [ABSTRACT FROM AUTHOR]

BackgroundMolecular markers of WHO grade II/III glioma are known to have important prognostic and predictive implications and may be associated with unique imaging phenotypes. The purpose of this study is to determine whether three clinically relevant molecular markers identified in gliomas-IDH, 1p/19q, and MGMT status-show distinct quantitative MRI characteristics on FLAIR imaging.MethodsSixty-one patients with grade II/III gliomas who had molecular data and MRI available prior to radiation were included. Quantitative MRI features were extracted that measured tissue heterogeneity (homogeneity and pixel correlation) and FLAIR border distinctiveness (edge contrast; EC). T-tests were conducted to determine whether patients with different genotypes differ across the features. Logistic regression with LASSO regularization was used to determine the optimal combination of MRI and clinical features for predicting molecular subtypes.ResultsPatients with IDH wildtype tumors showed greater signal heterogeneity (p = 0.001) and lower EC (p = 0.008) within the FLAIR region compared to IDH mutant tumors. Among patients with IDH mutant tumors, 1p/19q co-deleted tumors had greater signal heterogeneity (p = 0.002) and lower EC (p = 0.005) compared to 1p/19q intact tumors. MGMT methylated tumors showed lower EC (p = 0.03) compared to the unmethylated group. The combination of FLAIR border distinctness, heterogeneity, and pixel correlation optimally classified tumors by IDH status.ConclusionQuantitative imaging characteristics of FLAIR heterogeneity and border pattern in grade II/III gliomas may provide unique information for determining molecular status at time of initial diagnostic imaging, which may then guide subsequent surgical and medical management.

Abstract A case of a true dual-genotype IDH-mutant oligoastrocytoma with two different cell types within a single mass in a young woman is presented. Imaging findings of the left frontal infiltrating glioma predicted the two neoplastic components that were identified upon resection. Tissue examination demonstrated areas of tumor with contrasting histologic and molecular features, including specific IDH1, ATRX, TP53, TERT and CIC mutational profiles, consistent with oligodendroglioma and astrocytoma, respectively. The clinical and radiological course over 17 months from first diagnosis included three surgical resections with slow progression of the astrocytic component, and ultimately chemotherapy and radiation treatments were commenced. Reports of the clinical courses for these rare cases of dual-genotype oligoastrocytomas will inform therapy choices, to optimize benefit while minimizing side effects. The steadily increasing number of cases suggests that the neoplasm might be reconsidered as an official entity by the WHO.

Background: Tumor-associated macrophages (TAM)s are critical regulators of glioma progression. As yet, however, TAMs in isocitrate dehydrogenase (IDH) mutated lower-grade gliomas (LGGs) have not been thoroughly investigated. The aim of this study was to determine whether 1p/19q co-deletion status affects the TAM phenotype or its prevalence in IDH mutated LGGs. Methods: TAMs in IDH mutated LGGs were analyzed using transcriptome data from 230 samples in the TCGA database in combination with transcriptome data from single-cell RNA sequencing of IDH-mutated LGGs. Proteins potentially involved in TAM regulation were examined by immuno-staining in primary LGG samples harboring IDH mutations. Essential signaling pathways regulating TAM phenotypes were investigated in a glioma mouse model using small molecule inhibitors. Results: Most of the TAMs in IDH-mutated LGGs expressed the M1 activation markers CD86 and TNF, whereas a subset of individual TAMs co-expressed both M1 and M2-related markers. Bioinformatics analysis in combination with immuno-staining of IDH-mutated patient samples revealed higher amounts of TAMs expressing M2-related markers in 1p/19q non-codeletion IDH-mutated LGGs compared to 1p/19q codeletion LGGs. The levels of transforming growth factor beta 1 (TGFβ1) and macrophage colony-stimulating factor (M-CSF) were significantly higher in 1p/19q non-codeletion LGGs than in 1p/19q codeletion LGGs. M-CSF and TGFβ1 signal inhibition decreased tumor growth and modulated the TAM phenotype in a glioma mouse model. Conclusions: Our data indicate that 1p/19q co-deletion status relates to distinct TAM infiltration in gliomas, which is likely mediated by M-CSF and TGFβ1 signaling. M-CSF and TGFβ1 signaling may play a pivotal role in regulating the TAM phenotype in glioma. [ABSTRACT FROM AUTHOR]

Background: Glioma, the most common brain tumor, is a heterogeneous group of glia-derived tumors, the majority of which have characteristics of diffuse infiltration and immunosuppression. The LGALS protein family is a large class of sugar-binding proteins. Among them, LGALS3 has been reported to promote tumor development and progression in some cancers. However, the clinical significance and biological functions of LGALS3 in glioma remain virtually unknown. The purpose of our research is to detect LGALS3 expression and its prognostic value in glioma and reveal the relationship between its expression and the clinico/molecular-pathological features of patients and immune cell infiltration.Methods: LGALS3 protein expression was examined by immunohistochemistry. The mRNA expression data of LGALS3 was downloaded and analyzed from TCGA and Rembrandt datasets. The association between LGALS3 and glioma clinically relevant diagnostic/molecular markers (IDH, 1p19q, ATRX, MGMT, and TERT) was examined using the Chi-Squared (χ2) test. The correlation between LGALS3 expression and the infiltration of multiple intra-tumoral immune cell types, including B cells (CD20), T cells (CD4 and CD8), macrophages (CD68), and M2 tumor-associated macrophages (CD163), was evaluated by Spearman correlation analysis. Kaplan-Meier analysis and the Cox regression analysis were applied to evaluate the prognostic value of LGALS3 in glioma. The log-rank test was used to evaluate Kaplan-Meier results for significance.Results: Out of all 304 glioma cases, LGALS3 protein was expressed in 125 glioma cases (41.1%, 125/304), with 69.2% (9/13) in WHO I, 9.8% (8/82) in WHO II, 34.2% (26/76) in WHO III, and 61.7% (82/133) in WHO IV. The expression of LGALS3 was correlated with patient age, WHO grade, PHH3 (mitosis), Ki67 index, IDH, 1p/19q codeletion, and TERT promoter status. LGALS3 was an independent poor prognostic marker in diffusely infiltrating gliomas and was positively correlated with immune cell infiltration, particularly CD163+ tumor-associated macrophages in the TCGA dataset, Rembrandt dataset, and our SYSUCC cohort (R = 0.419, 0.627, and 0.724).Conclusion: LGALS3 was highly expressed in pilocytic astrocytoma, GBM, and IDH wild-type LGG. It served as a poor prognostic marker in diffusely infiltrating gliomas. Based on its prognostic significance and strong correlation with CD163+ TAMs, it may act as an important therapeutic target for human glioma.

Adolescent and young adult gliomas are recently being studied as a distinct group and molecular alterations of oligodendroglioma in this group are not well defined. Few studies conducted on adolescent oligodendroglioma so far have found low frequencies of IDH mutations and 1p/19q co-deletion, which are the hallmark genetic alterations seen in adult oligodendroglioma. In this case report, we demonstrate presence of rare IDH2 mutation and 1p/19q co-deletion in an adolescent oligodendroglioma. [ABSTRACT FROM AUTHOR]

A case of a true dual-genotype IDH-mutant oligoastrocytoma with two different cell types within a single mass in a young woman is presented. Imaging findings of the left frontal infiltrating glioma predicted the two neoplastic components that were identified upon resection. Tissue examination demonstrated areas of tumor with contrasting histologic and molecular features, including specific IDH1, ATRX, TP53, TERT and CIC mutational profiles, consistent with oligodendroglioma and astrocytoma, respectively. The clinical and radiological course over 17 months from first diagnosis included three surgical resections with slow progression of the astrocytic component, and ultimately chemotherapy and radiation treatments were commenced. Reports of the clinical courses for these rare cases of dual-genotype oligoastrocytomas will inform therapy choices, to optimize benefit while minimizing side effects. The steadily increasing number of cases suggests that the neoplasm might be reconsidered as an official entity by the WHO. [ABSTRACT FROM AUTHOR]

Introduction: Recent discoveries in the molecular makeup of gliomas, the relationship of certain molecular drivers, and the patient's response to therapy and overall prognosis have resulted in a paradigm shift and redefined our understanding of glioma and revealed potential vulnerabilities within this recalcitrant and lethal disease.Areas covered: We summarize the current classification of malignant glioma in the context of the historical background, current data-driven treatment strategies, and recent discoveries of the mechanisms of pathogenesis of this disease which recapitulates the developing brain. We describe the relationship to common genetic alterations found in glioma, and possible avenues to exploit these newly revealed mechanisms.Expert opinion: Improved understanding of the molecular underpinnings of this disease has been directly translated into treatment decisions and an improved ability to counsel patients regarding their prognosis. We are beginning to see the first glimmer of a return on the investment in regard to immunotherapy in malignant glioma, with further anticipated successful exploitations of the unique pathophysiology of glioma. [ABSTRACT FROM AUTHOR]

The World Health Organization has updated their classification system for the diagnosis of gliomas, combining histological features with molecular data including isocitrate dehydrogenase 1 and codeletion of chromosomal arms 1p and 19q. 1p/19q codeletion analysis is commonly performed by fluorescence in situ hybridization (FISH). In this study, we developed a 57-gene targeted next-generation sequencing (NGS) panel including 1p/19q codeletion detection mainly to assess diagnosis and potential treatment response in melanoma, gastrointestinal stromal tumor, and glioma patients. Loss of heterozygosity analysis was performed using the NGS method on 37 formalin-fixed paraffin-embedded glioma tissues that showed 1p and/or 19q loss determined by FISH. Conventional methods were applied for the validation of some glioma-related gene mutations. In 81.1% (30 of 37) and 94.6% (35 of 37) of cases, 1p and 19q were found to be in agreement whereas concordance for 1p/19q codeletion and no 1p/19q codeletion was found in 94.7% (18 of 19) and 94.4% (17 of 18) of cases, respectively. Overall, comparing NGS results with those of conventional methods showed high concordance. In conclusion, the NGS panel allows reliable analysis of 1p/19q codeletion and mutation at the same time., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

ObjectiveTo investigate the clinical characteristics and prognostic value of TERTp and 1p/19q phenotype in DDP+TMZ concurrent chemoradiotherapy for newly diagnosed GBM with unmethylated MGMT promoter. MethodsA retrospective analysis was made in 73 newly diagnosed GBM with unmethylated MGMT promoter. All patients received DDP+TMZ. The aim of this study was to analyze the clinical characteristics, adverse reactions, PFS and OS of patients with different TERTp and 1p/19q groups. ResultsAccording to TERTp, there were 30 cases of TERTp wt and 43 cases of TERTp mut. According to 1p/19q, 62 cases were non-deletion and 11 cases were deletion. There was no significant difference in clinical parameters between two groups（P＞0.05）. Up to 31st January 2019, 44 patients had recurrence, 17 with TERTp wt and 27 with TERTp mut. The median PFS was 12.0 and 10.0 months, respectively. The 1-year PFS rate was 33.6% and 27.2%. 22 patients died, 9 with TERTp wt and 13 with TERTp mut. The median OS was 20.0 and 19.0 months. The 1-year OS rate was 77.9% and 73.2%. There were 38 recurrences in 1p/19q non-deletion and 6 recurrences in deletion. The median PFS was 10.0 and 22.0 months respectively. The 1-year PFS rate was 20.4% and 60.0%. There were 19 deaths with 1p/19q non-deletion, 3 deaths in deletion, and the median OS was 18.0 and 23.0 months. The 1-year OS rates were 60.3% and 88.9%. There was a better trend in the efficacy for 1p/19q non-deletion than that of deletion. But the difference was not significant. ConclusionThe efficacy of TERTp wt is slightly higher than that of TERTp mut. The efficacy of 1p/19q deletion group is higher than that of non-deletion, but the difference is not statistically significant. 1p/19q may have potential prognostic value in newly diagnosed GBM with unmethylated MGMT promoter receiving DDP +TMZ concurrent chemoradiotherapy, which deserves further study. [ABSTRACT FROM AUTHOR]

Purpose: Changes in MGMT promoter methylation, IDH1 and IDH2 mutation, and 1p/19q co-deletion status in gliomas between first and subsequent resections and their associated clinical factors are poorly described. In this study, we assayed these biomarkers in the clinical setting. Patients and methods: We used multiplex ligation-dependent probe amplification to measure MGMT promoter methylation, IDH mutation status, and 1p/19q co-deletion in 45 paired tumor samples from patients undergoing resection and subsequent re-resections for gliomas. Results: Molecular changes were present in 20 patients (44%). At least one molecular characteristic changed over time in 89% of patients with primary grade III tumors. Gliomas with IDH wild-type and/or non-co-deleted were stable, but IDH1/2 mutation and/or co-deletion were sometimes lost at the time of recurrence. In a multivariate analysis, adjuvant radiotherapy alone was independently associated (P=0.02) with changes in molecular profile. Conclusion: Molecular biomarkers change in gliomas during the course of the disease, most often MGMT methylation status. These changes in genetic profiles are related to adjuvant treatment with radiotherapy alone, which might be important for individualized treatment planning over the disease course. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies have suggested an association between relative leukocyte telomere length (rLTL) and glioma risk. This association may be influenced by several factors, including allergies, BMI, and smoking. Previous studies have shown that individuals with asthma and allergy have shortened relative telomere length, and decreased risk of glioma. Though, the details and the interplay between rLTL, asthma and allergies, and glioma molecular phenotype is largely unknown.Methods: rLTL was measured by qPCR in a Swedish population-based glioma case-control cohort (421 cases and 671 controls). rLTL was related to glioma risk and health parameters associated with asthma and allergy, as well as molecular events in glioma including IDH1 mutation, 1p/19q co-deletion, and EGFR amplification.Results: Longer rLTL was associated with increased risk of glioma (OR = 1.16; 95% CI 1.02-1.31). Similar to previous reports, there was an inverse association between allergy and glioma risk. Specific, allergy symptoms including watery eyes was most strongly associated with glioma risk. High body mass index (BMI) a year prior diagnosis was significantly protective against glioma in our population. Adjusting for allergy, asthma, BMI, and smoking did not markedly change the association between longer rLTL and glioma risk. rLTL among cases was not associated with IDH1 mutation, 1p/19q co-deletion, or EGFR amplification, after adjusting for age at diagnosis and sex.Conclusions: In this Swedish glioma case-control cohort, we identified that long rLTL increases the risk of glioma, an association not confounded by allergy, BMI, or smoking. This highlights the complex interplay of the immune system, rLTL and cancer risk. [ABSTRACT FROM AUTHOR]

Identifying the early genetic drivers can help diagnose glioma tumours in their early stages, before becoming malignant. However, there is emerging evidence that disturbance of epigenetic mechanisms also contributes to cell’s malignant transformation and cancer progression. Long non-coding RNAs are one of key epigenetic modulators of signalling pathways, since gene expression regulation is one of their canonical mechanisms. The aim of our study was to search new gliomagenesis-specific candidate lncRNAs involved in epigenetic regulation.

Introduction: Chromosomes 1p/19q co-deletion is a robust molecular marker for the diagnosis of oligodendroglial tumors, and has been included in the 2016 WHO modified classification. Although treatment for oligodendroglioma is controversial, upfront chemotherapy is regarded as one of the treatment option for low-grade tumor. We have treated all the 1p/19q co-deleted oligodendrogliomas, both grades II and III, with upfront chemotherapy without conventional radiotherapy for 20 years. The clinical experience from this trial may be suggestive for understanding of the biological features of oligodendroglioma with 1p/19q co-deletion toward precision medicine.Methods: This is a long-term retrospective data of the non-selected patients with 1p/19q co-deleted oligodendrogliomas uniformly treated with up-front chemotherapy. Seventy consecutive patients (48 with grade II and 22 with grade III tumors) were included.Results: The median follow-up period was 13 years. The 5-, 10-, and 15-year progression-free survival (PFS) rates were 85.7%, 54.8%, and 31.5%, respectively, and the median PFS was 146 months. In most cases, tumor recurrence was remained local and could be controlled by salvage surgery and/or chemotherapy. The 5-, 10-, and 15-year overall survival (OS) rates were 96.8%, 88.7%, and 80.0%, respectively, and the median OS was not reached. These survival data compared favorably with previous large clinical studies employing radiotherapy. Tumor grades based on World Health Organization classification, extent of surgery, and age affected neither PFS nor OS. Most patients were able to return to their premorbid social life.Conclusions: The long-term results drawn from 20-years of single institution experience show that the patients with 1p/19q co-deleted oligodendrogliomas can be successfully treated with up-front chemotherapy alone without compromising OS. [ABSTRACT FROM AUTHOR]

Purpose: According to the 2016 WHO classification lower-grade gliomas consist of three groups: IDH-mutated and 1p/19q co-deleted, IDH-mutated and IDH-wildtype tumors. The aim of this study was to evaluate the impact of surgical therapy for lower-grade gliomas with a particular focus on the molecular subgroups.Methods: This is a bi-centric retrospective analysis including 299 patients, who underwent treatment for lower-grade glioma between 1990 and 2016. All tumors were re-classified according to the 2016 WHO classification. Data concerning baseline and tumor characteristics, overall survival, different treatment modalities and functional outcome were analyzed.Results: A total of 112 (37.5%) patients with IDH-mutation and 1p/19q co-deletetion, 86 (28.8%) patients with IDH-mutation and 101 (33.8%) patients with IDH-wildtype tumors were identified. The median overall survival (mOS) differed significantly between the groups (p < 0.001). Surgical resection was performed in 226 patients and showed significantly improved mOS compared to the biopsy group (p = 0.001). Gross total resection (GTR) was associated with better survival (p = 0.007) in the whole cohort as well as in the IDH-mutated and IDH-wildtype groups compared to partial resection or biopsy. IDH-wildtype patients presented a significant survival benefit after combined radio-chemotherapy compared to radio- or chemotherapy alone (p = 0.02). Good clinical status (NANO) was associated with longer OS (p = 0.001).Conclusion: The impact of surgical treatment on the outcome of lower-grade gliomas depends to a great extent on the molecular subtype of the tumors. Patients with more aggressive tumors (IDH-wildtype) seem to profit from more intensive treatment like GTR, multiple resections and combined radio-/chemotherapy. [ABSTRACT FROM AUTHOR]

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.Study Type: Retrospective case control.Subjects: In all, there were 54 patients with a histopathological diagnosis of diffuse glioma (grade II). All were tested for IDH and 1p/19q.Field Strength/sequence: 3.0T, including T2 FLAIR sequence, axial T1 -weighted, and T2 -weighted sequence.Assessment: MRTA on a representative tumor region of interest (ROI) was made on preoperative T2 FLAIR images around the area that had the largest diameter of solid tumor using Omni Kinetics software.Statistical Tests: Differences between IDH-mutant and 1p/19q-codeleted and IDH-mutant and 1p/19q-intact gliomas were analyzed by the Mann-Whitney rank sum test. Receiver operating characteristic curves (ROC) were created to assess MRTA diagnostic performance. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated with a cutoff value according to the Youden Index.Results: Comparisons demonstrated significant differences in kurtosis (P = 0.007), energy (0.008), entropy (0.008), mean deviation (MD) (<0.001), and high gray-level run emphasis (HGLRE) (0.002), cluster shade (0.025), and sum average (0.002). First-order features comprising entropy (area under the curve [AUC] = 0.718, sensitivity = 97.1%) and energy (0.719, 94.1%) had the highest sensitivity but lower specificity (both 45%). Second-order features such as HGLRE (AUC = 0.750, sensitivity = 73.5%, specificity = 80.0%) and sum average (0.751, 70.6%, 80.0%) had relatively higher specificity, and all had AUC >0.7. MD had the highest diagnostic performance, with AUC = 0.878, sensitivity = 94.1%, specificity = 75.0%, PPV = 86.5%, and NPV = 88.2%.Data Conclusion: MRTA on T2 FLAIR images may be helpful in identifying oligodendroglioma, IDH-mutant, and 1p/19q-codeleted.Level Of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017. [ABSTRACT FROM AUTHOR]

Hintergrund: Traditionell wurden Gliome basierend auf ihren histopathologischen Eigenschaften klassifiziert. Mit Einführung der revidierten WHO(„World Health Organization“)-Klassifikation der Tumoren des Zentralnervensystems von 2016 wurden molekulare Eigenschaften in die Diagnose integriert.Ziel der Arbeit: Kernaspekte der WHO-Klassifikation von 2016 und Implikationen für die klinische Versorgung von Gliompatienten werden zusammengefasst. Zudem wird ein Überblick über experimentelle Therapiekonzepte gegeben.Ergebnisse: Oligodendrogliome werden seit 2016 durch das gleichzeitige Vorliegen einer Isozitratdehydrogenase(IDH)-1- oder -2-Mutation und einer Kodeletion der Chromosomenarme 1p und 19q definiert. Astrozytäre Tumoren werden in solche mit IDH-Wildtyp und mutierter IDH unterteilt. Astrozytome mit IDH-Wildtyp umfassen auch etwa 90 % der Glioblastome, die häufigsten und prognostisch ungünstigsten primären malignen Hirntumoren. Das Ausmaß der Resektion ist ein wichtiger prognostischer Faktor bei Patienten mit diffus wachsenden Gliomen. Postoperativ wird in der Regel kombiniert mit Strahlentherapie und alkylierender Chemotherapie behandelt. Die Hypermethylierung des Promoters des DNA-Reparaturgens O6-Methylguanin-DNA-Methyltransferase (MGMT) ist bei astrozytären Tumoren mit IDH-Wildtyp prädiktiv für das Ansprechen auf das Alkylans Temozolomid. Viele der sich aktuell in klinischer Testung befindlichen Therapieansätze zielen auf die Förderung einer gegen Tumorzellen gerichteten Immunantwort ab. Bislang existiert aber noch kein zugelassenes immuntherapeutisches Behandlungskonzept für Gliome.Diskussion: Etablierte Therapien von Gliomen sind Chirurgie, Strahlen- und Chemotherapie. Die Integration molekularer Aspekte in die Klassifikation von Gliomen bildet die Grundlage für personalisierte Therapieansätze. [ABSTRACT FROM AUTHOR]

In this study we aimed to identify the anatomic features of 1p/19q co-deletion and investigate the predictive values of tumor location and radiological characteristics for the survival of anaplastic oligodendroglial (AO) glioma patients. Voxel-based lesion-symptom mapping (VLSM) analysis was applied to define the brain regions associated with occurrence of 1p/19q co-deletion in a cohort of 206 AO tumor patients (discovery set) treated between May 2009 and September 2013. Retrospectively, the acquired clusters and radiological features were subjected to Kaplan–Meier survival analysis using data from the Chinese Glioma Genome Atlas (validation set) to evaluate their prognostic role in AO patients. The institutional review board approved this study. The right frontal lobe and right anterior insular lobe were specifically associated with high occurrence of 1p/19q co-deletion. For AO tumors not involving these areas, the absence of contrast enhancement predicted longer progression-free (p = 0.018) and overall survival (p = 0.020); moreover, in patients with contrast enhancement, edema could stratify the survival outcome (p = 0.013 for progression-free survival, p = 0.016 for overall survival). For AO tumors located in the VLSM-identified regions, edema was also able to stratify the survival outcome of patients without contrast enhancement (p = 0.025 for progression-free survival, p = 0.028 for overall survival). The 1p/19q co-deletion showed predilection for specific brain regions. According to the tumor involvement of VLSM-identified regions associated with 1p/19q co-deletion, radiological features were predictive for AO patient survival outcomes. [ABSTRACT FROM AUTHOR]

This paper reviews a case of metastatic 1p/19q codeleted oligodendrioglioma causing diffuse osteosclerosis and pain. Primary central nervous system (CNS) tumors rarely metastasize outside the CNS, and metastatic oligodendroglioma is rarer still. The patient in this study had relief of pain after being treated with temozolomide. We discuss this rare presentation and potential treatment options, and review the literature in regards to metastatic oligodendrogliomas.

Purpose of Review: This review summarizes the use of molecular diagnostics in glioma and its effect on the development of novel therapeutics and management decisions. Recent Findings: Genomic and proteomic profiling of brain tumors has provided significant expansion of our understanding of oncogenesis, characterization, and prognostication of brain tumors. Molecular markers such as MGMT, EGFR, IDH, 1p19q, ATRX, TERT, FGFR-TACC, and BRAF are now being used to classify brain tumors as well as influence management decisions. Several of these markers are also being used as therapeutic targets. Summary: We review the use of several molecular diagnostics in gliomas and discuss their impact on drug development and clinical trial design. In the future, molecular characterization based on a specific genomic, proteomic as well as transcriptomes for bioformatics analysis will provide clinicians the ability to rationally select drugs with actionable targets for each patient. [ABSTRACT FROM AUTHOR]

Background: Molecular markers for classification of gliomas include isocitrate dehydrogenase (IDH) mutations and codeletion of chromosomal arms 1p and 19q (1p/19q). While mutations in IDH enzymes result in the well-characterized production of oncometabolite 2-hydroxyglutarate, dysregulation of other metabolites in IDH tumors is less characterized. Similarly, the effects of 1p/19q codeletion on cellular metabolism are also unclear., Aim: This study aimed to quantify changes in tumor metabolites in human glioma tissue as a function of both IDH mutation and 1p/19q codeletion., Methods and Results: Deidentified human glioma tissue and associated clinical data were obtained from the Emory University Winship Cancer Institute tissue biobank from 14 patients (WHO grades II, III, and IV; seven female and seven male). Proton ( 1 H) high-resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy data were acquired using a 600 MHz Bruker AVANCE III NMR spectrometer. Metabolite concentrations were calculated using LCModel. Differences in metabolite concentrations as a function of IDH mutation, 1p/19q codeletion, and survival status were determined using Mann-Whitney U tests. Concentrations of alanine, glutamine, and glutamate were significantly lower in glioma tissue with IDH mutations compared to tissue with IDH wildtype. Additionally, glutamate concentration was significantly lower in glioma tissue with 1p/19q codeletion compared to intact 1p/19q. Exploratory analysis revealed alanine concentration varied significantly as a function of survival status., Conclusions: Given the emerging landscape of glioma treatments that target metabolic dysregulation, an improved understanding of altered metabolism in molecular sub-types of gliomas, including those with IDH mutation and 1p/19q codeletion, is an important consideration for treatment stratification and personalized medicine., (© 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

This paper reviews a case of metastatic 1p/19q codeleted oligodendrioglioma causing diffuse osteosclerosis and pain. Primary central nervous system (CNS) tumors rarely metastasize outside the CNS, and metastatic oligodendroglioma is rarer still. The patient in this study had relief of pain after being treated with temozolomide. We discuss this rare presentation and potential treatment options, and review the literature in regards to metastatic oligodendrogliomas. [ABSTRACT FROM AUTHOR]

Background: Canonical oligodendroglial tumors (ODGs) are characterized genetically by chromosomes 1p/19q codeletion.Aims: This study was essentially aimed at the detection of frequency of 1p/19q codeletion in the different histological spectrum of ODG tumors in a large cohort of Indian patients.Materials and Methods: All the ODG tumors evaluated for 1p/19q by fluorescence in-situ hybridization (FISH) during 2009-2015 were correlated with histology, immunohistochemical expression for p53 protein and clinical features.Results: A total of 676 cases included both pediatric (n = 18) and adult (n = 658) patients. Histologically, 346 pure ODGs [oligodendroglioma (OD) and anaplastic oligodendroglioma (AOD)] and 330 mixed ODGs [oligoastrocytomas (OA), anaplastic oligoastrocytomas (AOA) and glioblastoma with oligodendroglioma component (GBM-O)] were included. 1p/19q co-deletion was noted in 69% (60/87), 55.9% (145/259), 18.2% (18/99), 10.5% (18/172), and in 5.1% (3/59) cases of OD, AOD, OA, AOA, and GBM-O, respectively. In the pediatric age-group, 1p/19q codeletion was seen in 25% (2/8) of pure ODGs and in 10% (1/10) of mixed ODGs. In adults, it was observed in 60% (203/338) cases of pure ODGs and in 11.9% (38/320) cases of mixed ODGs. In adults, pure ODG histology (P = 0.00), frontal location (P = 0.004), calcification [in pure ODGs] (P = 0.03), and lack of p53 protein overexpression (P = 0.00) showed significant statistical correlation with 1p/19q codeletion.Conclusions: This study is unique in being one of the largest on ODGs for 1p/19q co-deletion including both pediatric and adult age groups of Indian patients. The results showed co-deletion in 60% of adult ODGs and 25% of pediatric pure ODGs. This reemphasizes the occurrence of 1p/19q codeletion, even though rare, in the pediatric age group. [ABSTRACT FROM AUTHOR]

Background:Meningiomas are one of the most common tumours to affect the central nervous system. Genetic mutations are important in meningeal tumourigenesis, progression and prognosis. In this study, we aimed to examine the effect of 1p/19q deletion on the diagnosis and prognosis of meningioma subtypes using the fluorescencein situhybridization (FISH) method. Methods:Twenty-four patients with meningioma were retrospectively studied. Tumour samples were obtained from 10 typical, 11 atypical and three anaplastic malignant meningiomas. The most representative tumour sections were screened for 1p/19q deletion using the FISH method. Results:Of the 24 patients, eight were women (33.3%) and 16 (66.7%) were men. The mean age was 56.6 years. The higher-grade meningioma was usually seen in males and had a higher rate of deletion on 1p (p = 0.001). There was a statistically significant difference between the grades and the rate of deletion on 19q (p = 0.042) and between the grades and the rates of polysomy, monosomy and amplification on 19q (p = 0.002;p = 0.001;p = 0.002, respectively). There was no statistical difference between 1p/19q codeletion and the grades of meningioma (p > 0.05). We detected higher level of Ki-67 in the condition of codeletion but did not find a statistical difference (p = 0.0553). Conclusion:Deletion on 1p, as well as deletion, polysomy, monosomy and amplification on 19q, are detected more frequently in high grade meningiomas. This amplification is most likely due to the amplification of oncogenes. [ABSTRACT FROM AUTHOR]

The prognosis of patients with WHO grade III gliomas is highly dependent on their genomic status such as the isocitrate dehydrogenase (IDH) 1/2 mutation and1p/19q co-deletion. However, difficulties have been associated with determining which tumors have certain genomic profiles by preoperative radiographical modalities, and the role of surgical resection in achieving better outcomes remains unclear. This retrospective study included 124 consecutive patients with newly diagnosed grade III gliomas. The genomic status of IDH1/2 and 1p/19q was analyzed in these patients. Tumors were then divided into 3 subgroups based on their genomic status; the IDH 1/2 mutation with the 1p/19q co-deletion (1p/19q co-del), the IDH 1/2 mutation without the 1p/19q co-deletion (non-1p/19q co-del), and the IDH 1/2 wild type (IDH wt). Survival times were compared between patients who underwent gross total resection and those who did not (GTR versus non-GTR). The relationships between genomic statuses and MR imaging characteristics such as ring-like or nodular enhancements by gadolinium, and very low intensity on T1-weighted images with blurry enhancements (T1VL) were also examined. Among all patients with grade III gliomas, GTR patients had longer median survival and progression-free times than those of non-GTR patients (undefined versus 87 months, p = 0.097, and 124 versus 34 months, p = 0.059, respectively). No significant differences were observed in survival between GTR and non-GTR patients in the 1p/19q co-del group (p = 0.14), or between GTR and non-GTR patients in the IDH wt group (26 and 27 months, p = 0.29). On the other hand, in non-1p/19q co-del group, survival was significantly longer in GTR patients than in non-GTR patients (undefined versus 77 months, p = 0.005). Radiographically, T1VL was detected in most tumors in the non-1p/19q co-del group (78.2 %), but only 6 (21.4 %) and 17 (41.5 %) tumors in the 1p/19q co-del and IDH wt groups, respectively. A correlation was not found between other genomic subgroups and MR imaging findings. Strict surgical removal is important to improve the prognosis of patients with grade III gliomas, especially for tumors with the IDH 1/2 mutation without the 1p/19q co-deletion. The MR finding of T1VL can be used to select candidates for more radical resection. [ABSTRACT FROM AUTHOR]

Introduction: Glioma classification and grading has been historically based in morphologic appearance of tumor cells: astrocytomas, oligodendrogliomas, oligoastrocytomas and ependymomas. Recent molecular advances have transformed the field of neuro-oncology, as some molecular markers harbor diagnostic, prognostic and therapeutic implications. Areas covered: In this paper we will review the major molecular changes associated with gliomas and their implications in diagnosis, prognosis, and opportunities in therapeutics. Expert commentary: Based on current understanding, adult diffuse infiltrating gliomas can be molecularly divided into three to five major subgroups with different clinical outcomes. Pediatric gliomas harbor mutations for H3F3A, ATRX and DAXX but not IDH. Circumscribed low-grade gliomas tend to have BRAF alterations. Clinical behavior of ependymomas correlates more with location than WHO grading. Posterior fossa ependymomas tend to behave worse than their cerebral or spinal cord counterparts. However, with the posterior fossa ependymomas, two distinct subtypes have emerged molecularly. [ABSTRACT FROM PUBLISHER]

The diffuse gliomas are primary central nervous system tumors that arise most frequently in the cerebral hemispheres of adults. They are currently classified as astrocytomas, oligodendrogliomas or oligoastrocytomas and range in grade from II to IV. Glioblastoma (GBM), grade IV, is the highest grade and most common form. The diagnosis of diffuse gliomas has historically been based primarily on histopathologic features, yet these tumors have a wide range of biological behaviors that are only partially explained by morphology. Biomarkers have now become an established component of the neuropathologic diagnosis of gliomas, since molecular alterations aid in classification, prognostication and prediction of therapeutic response. Isocitrate dehydrogenase (IDH) mutations are frequent in grades II and III infiltrating gliomas of adults, as well as secondary GBMs, and are a major discriminate of biologic class. IDH mutant infiltrating astrocytomas (grades II and III), as well as secondary GBMs, are characterized by TP53 and ATRX mutations. Oligodendrogliomas are also IDH mutant, but instead are characterized by 1p/19q co-deletion and mutations of CIC, FUBP1 , Notch1 and the TERT promoter. Primary GBMs typically lack IDH mutations and demonstrate EGFR, PTEN, TP53, PDGFRA, NF1 and CDKN2A/B alterations and TERT promoter mutations. Pediatric gliomas differ in their spectrum of disease from those in adults; high grade gliomas occurring in children frequently have mutations in H3F3A , ATRX and DAXX , but not IDH. Circumscribed, low grade gliomas, such as pilocytic astrocytoma, pleomorphic xanthoastrocytoma and ganglioglioma, need to be distinguished from diffuse gliomas in the pediatric population. These gliomas often harbor mutations or activating gene rearrangements in BRAF . [ABSTRACT FROM AUTHOR]

The aim of this study was to assess whether combining multimodal magnetic resonance imaging (MRI) with the determination of the 1p/19q codeletion status could improve the ability to predict anaplastic transformation in low-grade oligodendrogliomas. Twenty patients with grade II oligodendrogliomas were followed-up using multimodal MR [proton MR spectroscopy (MRS), perfusion, and conventional MR imaging]. All patients diagnoses were histologically proven, and 1p/19q codeletion status was analyzed for all patients. Median follow-up was 30.5 ± 11.4 months. Anaplastic transformation was observed in six patients. The only MRI feature that was associated with anaplastic transformation was an elevation of the choline/creatine ratio >2.4 which was observed in 4 out of 6 patients with anaplastic transformation versus 1 out of 14 patients without anaplastic transformation. In patients without 1p/19q codeletion, an elevation of the choline/creatine ratio >2.4 was associated with the occurrence of anaplastic transformation in all cases (4 out of 4 patients), with a mean time of 12 months. In contrast, in patients with a 1p/19q codeletion, no anaplastic transformation was observed in the patient who had an elevation of >2.4 of the choline/creatine ratio and two patients demonstrated an anaplastic transformation without any elevation of this ratio.Prospective validation in a larger series is needed, yet the present study suggests that combining data from in vivo proton MRS and genetic analysis could be a promising strategy to predict time to anaplastic transformation at the individual level in patients with low-grade oligodendrogliomas and may help deciding when chemotherapy and/or radiotherapy should be initiated in these tumors. [ABSTRACT FROM AUTHOR]

Diffuse gliomas are up till now graded based upon morphology. Recent findings indicate that isocitrate dehydrogenase (IDH) mutation status defines biologically distinct groups of tumors. The role of tumor grade and mitotic index in patient outcome has not been evaluated following stratification by IDH mutation status. To address this, we interrogated 558 WHO grade II-III diffuse gliomas for IDH1/2 mutations and investigated the prognostic impact of WHO grade within IDH-mutant and IDH-wild type tumor subsets independently. The prognostic impact of grade was modest in IDH-mutant [hazard ratio (HR) = 1.21, 95 % confidence interval (CI) = 0.91-1.61] compared to IDH-wild type tumors (HR = 1.74, 95 % CI = 0.95-3.16). Using a dichotomized mitotic index cut-off of 4/1000 tumor cells, we found that while mitotic index was significantly associated with outcome in IDH-wild type tumors (log-rank p < 0.0001, HR = 4.41, 95 % CI = 2.55-7.63), it was not associated with outcome in IDH-mutant tumors (log-rank p = 0.5157, HR = 1.10, 95 % CI = 0.80-1.51), and could demonstrate a statistical interaction ( p < 0.0001) between IDH mutation and mitotic index (i.e., suggesting that the effect of mitotic index on patient outcome is dependent on IDH mutation status). Patient age, an established prognostic factor in diffuse glioma, was significantly associated with outcome only in the IDH-wild type subset, and consistent with prior data, 1p/19q co-deletion conferred improved outcome in the IDH-mutant cohort. These findings suggest that stratification of grade II-III gliomas into subsets defined by the presence or absence of IDH mutation leads to subgroups with distinct prognostic characteristics. Further evaluation of grading criteria and prognostic markers is warranted within IDH-mutant versus IDH-wild type diffuse grade II-III gliomas as independent entities. [ABSTRACT FROM AUTHOR]

The treatment of patients with brain tumors has long been the domain of neurosurgery and radiotherapy but chemotherapy is now well established as an additional treatment option for many tumor entities in neuro-oncology. This is particularly true for patients with newly diagnosed and relapsing glioblastoma and anaplastic glioma as well as the treatment of medulloblastoma and primary lymphoma of the central nervous system (CNS). In addition to purely histopathological features, treatment decisions including those for chemotherapy are now based increasingly more on molecular tumor profiling. Within the group of gliomas these markers include the methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter and the 1p/19q status, which reflects the loss of genetic material on chromosome arms 1p and 19q. The presence of a 1p/19q codeletion is associated with a better prognosis and increased sensitivity to alkylating chemotherapy in patients with anaplastic gliomas. [ABSTRACT FROM AUTHOR]

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Diffuse gliomas are represented in the 2007 WHO classification as astrocytomas, oligoastrocytomas and oligodendrogliomas of grades II and III and glioblastomas WHO grade IV. Molecular data on these tumors have a major impact on prognosis and therapy of the patients. Consequently, the inclusion of molecular parameters in the WHO definition of brain tumors is being planned and has been forwarded as the 'ISN-Haarlem' consensus. We, here, analyze markers of special interest including ATRX, IDH and 1p/19q codeletion in a series of 405 adult patients. Among the WHO 2007 classified tumors were 152 astrocytomas, 61 oligodendrogliomas, 63 oligoastrocytomas and 129 glioblastomas. Following the concepts of the 'ISN-Haarlem', we rediagnosed the series to obtain 'integrated' diagnoses with 155 tumors being astrocytomas, 100 oligodendrogliomas and 150 glioblastomas. In a subset of 100 diffuse gliomas from the NOA-04 trial with long-term follow-up data available, the 'integrated' diagnosis had a significantly greater prognostic power for overall and progression-free survival compared to WHO 2007. Based on the 'integrated' diagnoses, loss of ATRX expression was close to being mutually exclusive to 1p/19q codeletion, with only 2 of 167 ATRX-negative tumors exhibiting 1p/19q codeletion. All but 4 of 141 patients with loss of ATRX expression and diffuse glioma carried either IDH1 or IDH2 mutations. Interestingly, the majority of glioblastoma patients with loss of ATRX expression but no IDH mutations exhibited an H3F3A mutation. Further, all patients with 1p/19 codeletion carried a mutation in IDH1 or IDH2. We present an algorithm based on stepwise analysis with initial immunohistochemistry for ATRX and IDH1-R132H followed by 1p/19q analysis followed by IDH sequencing which reduces the number of molecular analyses and which has a far better association with patient outcome than WHO 2007. [ABSTRACT FROM AUTHOR]