scholarly journals IDH mutation, 1p19q codeletion and ATRX loss in WHO grade II gliomas

Oncotarget ◽  
2015 ◽  
Vol 6 (30) ◽  
pp. 30295-30305 ◽  
Author(s):  
Heather E. Leeper ◽  
Alissa A. Caron ◽  
Paul A. Decker ◽  
Robert B. Jenkins ◽  
Daniel H. Lachance ◽  
...  
Keyword(s):  
Idh Mutation ◽  
Who Grade ◽  
1P19q Codeletion ◽  
Grade Ii ◽  
Who Grade Ii Gliomas

Absence of IDH mutation identifies a novel radiologic and molecular subtype of WHO grade II gliomas with dismal prognosis

2010 ◽  
Vol 120 (6) ◽  
pp. 719-729 ◽  
Author(s):  
Philippe Metellus ◽  
Bema Coulibaly ◽  
Carole Colin ◽  
Andre Maues de Paula ◽  
Alexandre Vasiljevic ◽  
...  
Keyword(s):  
Molecular Subtype ◽  
Idh Mutation ◽  
Who Grade ◽  
Dismal Prognosis ◽  
Grade Ii ◽  
Who Grade Ii Gliomas

Distinct IDH1/IDH2 mutation profiles in purely insular versus paralimbic WHO Grade II gliomas

2013 ◽  
Vol 118 (4) ◽  
pp. 866-872 ◽  
Author(s):  
Catherine Gozé ◽  
Lamisse Mansour ◽  
Valérie Rigau ◽  
Hugues Duffau
Keyword(s):  
Molecular Profile ◽  
Consecutive Series ◽  
Who Grade ◽  
1P19q Codeletion ◽  
Tumor Group ◽  
Significant Difference ◽  
Temporal Structures ◽  
Grade Ii ◽  
Who Grade Ii Gliomas ◽  
Grade Ii Glioma

Object The molecular profile of diffuse WHO Grade II gliomas involving the insular lobe, with a possible impact on outcome, is controversial. The authors undertook this study to investigate a possible difference of molecular patterns between purely insular Grade II gliomas and paralimbic Grade II gliomas that involve both the insular lobe and the frontal and/or temporal structures. Methods From a consecutive series of 47 patients who underwent resection of a Grade II glioma invading the insula, 2 subgroups were identified. The first subgroup included 11 patients with a purely insular tumor. The second subgroup included 36 patients with a paralimbic Grade II glioma also involving the frontal and/or temporal lobe. The authors searched systematically for TP53 mutations, 1p19q codeletion, and IDH1/IDH2 mutations. Results There was no significant difference between the 2 subgroups with respect to 1p19q codeletion or TP53 mutations rates. Conversely, IDH1/IDH2 mutations were found in all 11 (100%) of the insular Grade II gliomas but only 20 (55%) of 36 paralimbic Grade II gliomas (p = 0.008). Ten (28%) of the 36 patients in the paralimbic tumor group experienced a malignant transformation, and 6 of them died; whereas neither transformation nor death occurred in the insular tumor group (trend toward significance, p = 0.088). Conclusions These findings demonstrate for the first time distinct IDH1/IDH2 and consequently distinct “triplenegative” patterns in purely insular versus paralimbic Grade II gliomas. Such findings could explain discrepancies reported in the literature, because insular and paralimbic gliomas have not been separated in previous reports. These results may enable physicians to refine the management of Grade II gliomas involving the insula according to the presence or lack of invasion of the frontal and/or temporal areas.

scholarly journals IDH1 Non-Canonical Mutations and Survival in Patients with Glioma

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 342 ◽  
Author(s):  
Enrico Franceschi ◽  
Dario De Biase ◽  
Vincenzo Di Nunno ◽  
Annalisa Pession ◽  
Alicia Tosoni ◽  
...  
Keyword(s):  
Idh1 Mutation ◽  
Who Grade ◽  
Tissue Samples ◽  
1P19q Codeletion ◽  
Idh1 R132h ◽  
Rare Mutations ◽  
Grade Ii ◽  
Idh1 Mutations ◽  
R132h Mutation ◽  
Generation Sequencing

Background: Non-canonical mutations of the isocitrate dehydrogenase (IDH) genes have been described in about 20–25% and 5–12% of patients with WHO grade II and III gliomas, respectively. To date, the prognostic value of these rare mutations is still a topic of debate. Methods: We selected patients with WHO grade II and III gliomas and IDH1 mutations with available tissue samples for next-generation sequencing. The clinical outcomes and baseline behaviors of patients with canonical IDH1 R132H and non-canonical IDH1 mutations were compared. Results: We evaluated 433 patients harboring IDH1 mutations. Three hundred and ninety patients (90.1%) had a canonical IDH1 R132H mutation while 43 patients (9.9%) had a non-canonical IDH1 mutation. Compared to those with the IDH1 canonical mutation, patients with non-canonical mutations were younger (p < 0.001) and less frequently presented the 1p19q codeletion (p = 0.017). Multivariate analysis confirmed that the extension of surgery (p = 0.003), the presence of the 1p19q codeletion (p = 0.001), and the presence of a non-canonical mutation (p = 0.041) were variables correlated with improved overall survival. Conclusion: the presence of non-canonical IDH1 mutations could be associated with improved survival among patients with IDH1 mutated grade II–III glioma.

Surgery for Diffuse WHO Grade II Gliomas: Volumetric Analysis of a Multicenter Retrospective Cohort From the German Study Group for Intraoperative Magnetic Resonance Imaging

Neurosurgery ◽  
2019 ◽  
Vol 86 (1) ◽  
pp. E64-E74 ◽  
Author(s):  
Moritz Scherer ◽  
Hajrulla Ahmeti ◽  
Constantin Roder ◽  
Florian Gessler ◽  
Christine Jungk ◽  
...  
Keyword(s):  
Regression Models ◽  
Cox Regression ◽  
Study Group ◽  
Incomplete Resection ◽  
Who Grade ◽  
German Study ◽  
Significant Survival ◽  
Idh Mutations ◽  
Grade Ii ◽  
Who Grade Ii Gliomas

Abstract BACKGROUND In diffuse WHO grade II gliomas (LGG), the extent of resection (EOR) required to achieve significant survival benefits remains elusive. OBJECTIVE To evaluate the association of residual volume (RV) and EOR with progression-free survival (PFS) or overall survival (OS) in LGG in a retrospective, multicenter series by the German study group of intraoperative MRI (GeSGIM). METHODS Consecutive cases were retrospectively assessed from 5 centers. Tumors were volumetrically quantified before and after surgery, and clinical data were analyzed, including IDH mutations and neurologic deficits. Kaplan–Meier estimates, accelerated failure time models (AFT), and multivariate Cox regression models were calculated to identify determinants of survival. RESULTS A total of 140 cases were analyzed. Gross total resection (GTR) was associated with significantly longer PFS compared to any incomplete resection (P = .009). A significant survival disadvantage was evident even for small (&gt;0-5 ml) residuals and increased for moderate (&gt;5-20 ml) and large remnants (&gt;20 ml) P = .001). Accordingly, PFS increased continuously for 20% incremental steps of EOR (P &lt; .001). AFT models supported the notion of a continuous association of RV and EOR with PFS. Multivariate Cox regression models confirmed RV (P = .01) and EOR (P = .005) as continuous prognosticators of PFS. Univariate analysis showed significant associations of RV and EOR with OS. CONCLUSION Our data support the hypothesis of a continuous relationship of RV and EOR with survival for LGG with superiority seen for GTR. Hence, GTR should be achieved whenever safely feasible, and resections should be maximized whenever tumor has to be left behind to spare function.

scholarly journals IDH mutation status is associated with distinct vascular gene expression signatures in lower-grade gliomas

2018 ◽  
Vol 20 (11) ◽  
pp. 1505-1516 ◽  
Author(s):  
Lei Zhang ◽  
Liqun He ◽  
Roberta Lugano ◽  
Kenney Roodakker ◽  
Michael Bergqvist ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Lower Grade ◽  
Idh Mutation ◽  
Wild Type ◽  
Who Grade ◽  
Mutation Status ◽  
Grade Ii ◽  
Grade Ii Glioma

Abstract Background Vascular gene expression patterns in lower-grade gliomas (LGGs; diffuse World Health Organization [WHO] grades II–III gliomas) have not been thoroughly investigated. The aim of this study was to molecularly characterize LGG vessels and determine if tumor isocitrate dehydrogenase (IDH) mutation status affects vascular phenotype. Methods Gene expression was analyzed using an in-house dataset derived from microdissected vessels and total tumor samples from human glioma in combination with expression data from 289 LGG samples available in the database of The Cancer Genome Atlas. Vascular protein expression was examined by immunohistochemistry in human brain tumor tissue microarrays (TMAs) representing WHO grades II–IV gliomas and nonmalignant brain samples. Regulation of gene expression was examined in primary endothelial cells in vitro. Results Gene expression analysis of WHO grade II glioma indicated an intermediate stage of vascular abnormality, less severe than that of glioblastoma vessels but distinct from normal vessels. Enhanced expression of laminin subunit alpha 4 (LAMA4) and angiopoietin 2 (ANGPT2) in WHO grade II glioma was confirmed by staining of human TMAs. IDH wild-type LGGs displayed a specific angiogenic gene expression signature, including upregulation of ANGPT2 and serpin family H (SERPINH1), connected to enhanced endothelial cell migration and matrix remodeling. Transcription factor analysis indicated increased transforming growth factor beta (TGFβ) and hypoxia signaling in IDH wild-type LGGs. A subset of genes specifically induced in IDH wild-type LGG vessels was upregulated by stimulation of endothelial cells with TGFβ2, vascular endothelial growth factor, or cobalt chloride in vitro. Conclusion IDH wild-type LGG vessels are molecularly distinct from the vasculature of IDH-mutated LGGs. TGFβ and hypoxia-related signaling pathways may be potential targets for anti-angiogenic therapy of IDH wild-type LGG.

scholarly journals ACTR-20. EFFICACY OF INITIAL TEMOZOLOMIDE FOR HIGH-RISK LOW GRADE GLIOMAS IN A PHASE II AINO (ITALIAN ASSOCIATION FOR NEURO-ONCOLOGY) STUDY: A POST-HOC ANALYSIS WITHIN MOLECULAR SUBGROUPS OF WHO 2016

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi16-vi17
Author(s):  
Roberta Rudà ◽  
Alessia Pellerino ◽  
Andrea Pace ◽  
Carmine Maria Carapella ◽  
Cristina Dealis ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Response Rate ◽  
Long Term Results ◽  
Molecular Subgroups ◽  
Who Grade ◽  
Post Hoc Analysis ◽  
Grade Ii ◽  
Post Hoc ◽  
Who Grade Ii Gliomas

Abstract BACKGROUND The optimal management of high risk WHO grade II gliomas after surgery is still debated. The efficacy of initial temozolomide to delay radiotherapy and risk of cognitive defects could vary across the molecular subgroups of WHO 2016, but information on this issue are lacking. PATIENTS AND METHODS A post-hoc analysis has been performed on a cohort of high risk WHO grade II gliomas, who received initial temozolomide alone in phase II multicenter study, with the objective of re-evaluating the long-term results across the different molecular subgroups of the WHO 2016 classification. The primary endpoint of the study, carried out between 2007 and 2010, was response rate according to RANO, being seizure response, PFS and OS secondary endpoints. RESULTS Response rate (partial and minor responses) among oligodendrogliomas IDH-mutant and 1p/19q codeleted (76%) was significantly higher than that among diffuse astrocytomas either mutant (55%) or wild-type (36%). A reduction of seizure frequency >50% was observed in 87% patients and a seizure freedom in 72%. The probability of seizure reduction >50% was significantly associated with the presence of an IDH mutation. Median PFS, PFS at 5 and 10 years, median OS and OS at 5 and 10 years were all significantly longer in oligodendrogliomas IDH-mutant and 1p/19q codeleted. Of patients who did not recur or delay radiotherapy at recurrence for a median follow-up of 8.2 years, 67% and 59%, respectively, were oligodendrogliomas IDH-mutant and 1p/19q codeleted. CONCLUSIONS The post-hoc analysis of this phase II trial suggests that the beneficial effects of initial temozolomide prevail in oligodendrogliomas IDH-mutant and 1p/19q codeleted: thus, these tumors, when incompletely resected or progressive after surgery, especially when suffering from pharmacoresistant seizures, could receive temozolomide as initial treatment with radiotherapy and chemotherapy at recurrence. The trial was registered with EU Clinical Trials Register, EudraCT n. 2007/000386-38.

scholarly journals IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II–III diffuse gliomas

2015 ◽  
Vol 129 (4) ◽  
pp. 585-596 ◽  
Author(s):  
Adriana Olar ◽  
Khalida M. Wani ◽  
Kristin D. Alfaro-Munoz ◽  
Lindsey E. Heathcock ◽  
Hinke F. van Thuijl ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mitotic Index ◽  
Idh Mutation ◽  
Who Grade ◽  
Mutation Status ◽  
Diffuse Gliomas ◽  
Grade Ii

scholarly journals Prognostic significance of imaging contrast enhancement for WHO grade II gliomas

2009 ◽  
Vol 11 (2) ◽  
pp. 176-182 ◽  
Author(s):  
Johan Pallud ◽  
Laurent Capelle ◽  
Luc Taillandier ◽  
Denys Fontaine ◽  
Emmanuel Mandonnet ◽  
...  
Keyword(s):  
Contrast Enhancement ◽  
Prognostic Significance ◽  
Who Grade ◽  
Grade Ii ◽  
Who Grade Ii Gliomas
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