Subtype
Diffuse Glioma
CI-CAN-00002519Explore in graph →
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Subtype
CI-CAN-00002519Explore in graph →
Variants & evidence
342 evidence items mapped to this entity or its descendants, grouped by molecular profile, then therapy. 50 items per page.
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| IDH1 R132H1 | ||||||||
| Pan-Mutant-IDH1 Inhibitor Bay-1436032 | GlioblastomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | — | submitted | EID2325In an experimental study, glioblastoma cells expressing IDH1 R132H were associated with sensitivity to (bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide), comparable to cells expressing wi… (full text at CIViC) PMID 21045145 · Seltzer et al., 2010 · Open in CIViC | civic |
| IDH1 R132S2 | ||||||||
| Bevacizumab | High-Grade Glioma, NOS | Predictive | B | Supports Sensitivity Response | 2 | submitted | EID2339In a clinical study of 63 recurrent glioma patients, patients treated with bevacizumab monotherapy (n=11) and harboring IDH1 codon 132 mutation were associated with improved progression free survival … (full text at CIViC) PMID 22199315 · Lv et al., 2011 · Open in CIViC | civic |
| Cetuximab | GlioblastomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | — | submitted | EID4033In a clinical study of 63 recurrent glioma patients, de novo glioblastoma patients treated with cetuximab monotherapy (n=27) and harboring IDH1 codon 132 mutation were associated with improved overal… (full text at CIViC) PMID 22199315 · Lv et al., 2011 · Open in CIViC | civic |
| IDH1 Mutation + IDH2 MutationIDH1IDH21 | ||||||||
| Vorasidenib | Glioma | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID11708In this study, 331 patients with IDH-mutant grade 2 gliomas were either given vorasidenib (n = 168) or a placebo (n = 163). A median PFS of 27.7 months was reported in the vorasidenib group, compared … (full text at CIViC) PMID 37272516 · Mellinghoff et al., 2023 · Open in CIViC | civic |
| IDH2 R1722 | ||||||||
| (prognostic) | GlioblastomaCURATED_BROADER | Prognostic | B | Supports Better Outcome | 5 | accepted | EID482In patients with a glioblastoma, those with mutations at R172 of IDH2 had better overall survival than wild-type patients. PMID 19228619 · Yan et al., 2009 · Open in CIViC | civic |
| 〃 | Anaplastic AstrocytomaALIAS | Prognostic | B | Supports Better Outcome | 5 | accepted | EID483In patients with anaplastic astrocytoma, those with mutations at R172 of IDH2 had better overall survival than wild-type patients. PMID 19228619 · Yan et al., 2009 · Open in CIViC | civic |
| IDH2 R172G + IDH2 R172K + IDH2 R172W1 | ||||||||
| Vorasidenib | Low Grade Glioma | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID11509This phase 3 clinical trial was conducted to assess the progression-free survival in patients with IDH-mutant gliomas treated with Vorasidenib, an oral brain-penetrant inhibitor, which showed prelimin… (full text at CIViC) PMID 37272516 · Mellinghoff et al., 2023 · Open in CIViC | civic |
| IDH2 R172M + IDH2 R172S1 | ||||||||
| Vorasidenib | Low Grade Glioma | Predictive | A | Supports Sensitivity Response | 2 | submitted | EID12235This phase 3 clinical trial was conducted to assess the progression-free survival in patients with IDH-mutant gliomas treated with Vorasidenib, an oral brain-penetrant inhibitor, which showed prelimin… (full text at CIViC) PMID 37272516 · Mellinghoff et al., 2023 · Open in CIViC | civic |
| IL33 Overexpression1 | ||||||||
| (prognostic) | High-Grade Glioma, NOS | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID8003IL33 expression was assessed by qRT-PCR, IHC, and western blot in 86 glioma (grade I-IV) tissue samples and 16 normal controls. IL33 expression was consistently shown to be elevated in glioma tissues … (full text at CIViC) PMID 27050560 · Zhang et al., 2017 · Open in CIViC | civic |
| NTRK2 Fusion4 | ||||||||
| (diagnostic) | Pilocytic Astrocytoma | Diagnostic | C | Supports Positive | 2 | accepted | EID8653A case report showing a two-year-old girl with an unusual pilocytic astrocytoma (PA) with both classic- and anaplastic- appearing tumors. A custom NGS panel identified a novel KANK1-NTRK2 fusion in bo… (full text at CIViC) PMID 29804288 · López et al., 2019 · Open in CIViC | civic |
| (oncogenic) | Brain GlioblastomaALIAS | Oncogenic | C | Supports Oncogenicity | 1 | accepted | EID10896From a retrospective review of 38,095 tumor samples from 33,997 patients that underwent fusion screening at Memorial Sloan Kettering Cancer Center, 87 tumors were found to be positive for an NTRK1, NT… (full text at CIViC) PMID 31375766 · Solomon et al., 2020 · Open in CIViC | civic |
| Larotrectinib | Anaplastic Ependymoma | Predictive | C | Supports Sensitivity Response | ||||
| BRAF Fusion12 | ||||||||
| (diagnostic) | Pilocytic Astrocytoma | Diagnostic | B | Supports Positive | 5 | accepted | EID7148Genetic alterations in pilocytic astrocytoma (PA) were evaluated. Whole-genome sequencing of normal (blood) and tumor samples (n=96) was performed along with corresponding RNA-Seq (n=73) and mate-pair… (full text at CIViC) PMID 23817572 · Jones et al., 2013 · Open in CIViC | civic |
| (prognostic) | Childhood Low Grade Glioma | Prognostic | B | Supports Better Outcome | 4 | accepted | EID7193KIAA1549-BRAF fusion was identified in 87 of 272 patients with PLGGs using Fluorescence In situ hybridization (FISH) analysis. This mutation was strongly associated with a greater progression-free sur… (full text at CIViC) PMID 29948154 · Yang et al., 2018 · Open in CIViC | civic |
| 〃 | Childhood Low Grade Glioma | Prognostic | B | Supports Better Outcome | 4 | |||
| NTRK1 Fusion1 | ||||||||
| (oncogenic) | High-Grade Glioma, NOS | Oncogenic | C | Supports Oncogenicity | 2 | submitted | EID12609In the STARTRK-NG Phase 1/2 trial of entrectinib in pediatric patients, with extracranial solid tumors or primary CNS tumors, aged <22 years with relapsed or refractory disease, tumors with fusions… (full text at CIViC) PMID 35395680 · Desai et al., 2022 · Open in CIViC | civic |
| KIT EXPRESSION1 | ||||||||
| Sunitinib | GlioblastomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID10180Phase II trial of sunitinib in 40 patients with first recurrence of primary glioblastoma. Median PFS 2.2 mo, median OS 9.2 mo, 5 stable disease >=6 months, no objective responses, so primary study end… (full text at CIViC) PMID 24311637 · Hutterer et al., 2014 · Open in CIViC | civic |
| KRAS Mutation1 | ||||||||
| (diagnostic) | Pilocytic Astrocytoma | Diagnostic | C | Supports Positive | 3 | submitted | EID7150Genetic alterations in 96 patients with pilocytic astrocytoma (PA) were evaluated. Two new alterations with double KRAS mutations (p.[Glu63Lys]+[Arg73Met] and p.[Leu19Phe]+[Gln22Lys] ) were observed. PMID 23817572 · Jones et al., 2013 · Open in CIViC | civic |
| LRP1B Deletion1 | ||||||||
| (prognostic) | GlioblastomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID1645A retrospective study of 178 glioblastoma patients found that LRP1B deletion (complete transcript, N=4 or focal transcript deletion of >150kb, N=13) was associated with a lower progress free survival … (full text at CIViC) PMID 26428308 · Tabouret et al., 2015 · Open in CIViC | civic |
| MDM2 Amplification1 | ||||||||
| Navtemadlin + RG7112Sequential | GlioblastomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 1 | submitted | EID9023Through the analysis of 10 patient-derived glioblastoma cells, AMG232 was found to have increased sensitivity in comparison to RG7112 with the average IC50 of 76nM vs. 720nM; thus indicating a 9.5 fol… (full text at CIViC) PMID 30022047 · Her et al., 2018 · Open in CIViC | civic |
| MET Amplification1 | ||||||||
| Crizotinib | GlioblastomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1565A 62 year old female was diagnosed with glioblastoma (GBM) WHO grade 4. Treatment included radiation, temozolomide and cediranib. MET amplification was found by FISH, and ALK and MET inhibitor crizoti… (full text at CIViC) PMID 22162573 · Chi et al., 2012 · Open in CIViC | civic |
| ST-EPN-ZFTA2 | ||||||||
| (prognostic) | Supratentorial Ependymoma ZFTA Fusion-Positive | Prognostic | B | Supports Better Outcome | 3 | accepted | EID11445An international multi-institutional study identified108 patients with a methylation profile of supratentorial ependymoma, ZFTA fusion-positive, by whole genome DNA methylation profiling. The study fo… (full text at CIViC) PMID 37287693 · Ng et al., 2023 · Open in CIViC | civic |
| 〃 | Supratentorial Ependymoma ZFTA Fusion-Positive | Prognostic | B | Supports Better Outcome | 3 | accepted | EID11447In a series of 54 cases of ependymoma diagnosed in children </= 3 years, methylation profiling of all tumours was undertaken as part of a prospective clinical trial (SJYC07 - maximal safe surgical res… (full text at CIViC) PMID 30976811 · Upadhyaya et al., 2019 · Open in CIViC | civic |
| MGMT Expression1 | ||||||||
| (prognostic) | GlioblastomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID7977In a trial of 68 glioblastoma patients treated with either temozolomide or semustine, MGMT expression was found to be inversely correlated with survival. Patients in the MGMT high expression group (n=… (full text at CIViC) PMID 24248532 · Wang et al., 2014 · Open in CIViC | civic |
| MGMT Promoter Methylation7 | ||||||||
| (prognostic) | GlioblastomaCURATED_BROADER | Prognostic | B | Supports Better Outcome | 5 | accepted | EID491In patients with glioblastoma, those with methylated MGMT promoters have better overall survival than those with unmethylated promoters. PMID 15758010 · Hegi et al., 2005 · Open in CIViC | civic |
| 〃 | GlioblastomaCURATED_BROADER | Prognostic | B | Supports Better Outcome | 4 | accepted | EID172MGMT promoter methylation was associated with increased overall and disease-free survival as well as tumor regression in patients with gliomas. PMID 11070098 · Esteller et al., 2000 · Open in CIViC | civic |
| 〃 | OligodendrogliomaCURATED_BROADER | Prognostic | B | Supports | ||||
| MGMT RS169062521 | ||||||||
| Temozolomide | GlioblastomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID822The T allele of the rs16906252 SNP was associated with MGMT methylation and low protein expression. Germline presence of the T allele increased the risk of glioblastoma development (adjusted odds rati… (full text at CIViC) PMID 25910840 · Rapkins et al., 2015 · Open in CIViC | civic |
| MGMT Underexpression4 | ||||||||
| Temozolomide | GlioblastomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID2899In this study, patients with low MGMT expression, compared with patients with high MGMT expression, had a significantly higher response rate (55% v 7%, respectively; P = .004) and improved PFS (median… (full text at CIViC) PMID 17442989 · Chinot et al., 2007 · Open in CIViC | civic |
| 〃 | High-Grade Glioma, NOS | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID2901This study showed that low MGMT mRNA expression was strongly predictive for prolonged time to progression, treatment response, and length of survival in univariate and multivariate models (p<0.0001). … (full text at CIViC) PMID 21365007 · Kreth et al., 2011 · Open in CIViC | civic |
| 〃 | GlioblastomaCURATED_BROADER | Predictive | ||||||
| MIR21 Overexpression2 | ||||||||
| (prognostic) | Glioma | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID8000High expression of miR-21 was shown to be associated with worse OS (p<0.001) and PFS (p<0.001) in a Kaplan-Meier analysis of TCGA glioma dataset (n=641). Multivariate Cox regression analysis also show… (full text at CIViC) PMID 32144351 · Jiang et al., 2020 · Open in CIViC | civic |
| 〃 | Anaplastic AstrocytomaALIAS | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID8001The expression of a set of miRNAs was evaluated by qRT-PCR in 124 astrocytoma (grade I-IV) samples and 60 adjacent normal tissue samples in order to determine miRNAs with altered expression in astrocy… (full text at CIViC) PMID 20219352 · Zhi et al., 2010 · Open in CIViC | civic |
| BEND2 Fusion1 | ||||||||
| (diagnostic) | Astroblastoma, MN1-Altered | Diagnostic | B | Supports Positive | 4 | accepted | EID8510The authors studied tumors carrying a diagnosis of CNS primitive neuroectodermal tumors (PNETs). They identified four novel DNA methylation-defined brain tumor groups. One group, designated high-grade… (full text at CIViC) PMID 26919435 · Sturm et al., 2016 · Open in CIViC | civic |
| BEND2 Fusion + CXXC5 FusionCXXC5BEND21 | ||||||||
| (diagnostic) | Astroblastoma, MN1-AlteredALIAS | Diagnostic | B | Supports Positive | 3 | submitted | EID12688In a clinicopathologic and molecular series of astroblastoma (n = 8; biomarker MN1 rearrangement; primary endpoint diagnostic detection), MN1 break-apart FISH identified rearrangements in all informat… (full text at CIViC) PMID 28990708 · Hirose et al., 2018 · Open in CIViC | civic |
Data updated 15 hours agoSource updated unknownsource: civic (CC0)
Evidence levels, directions and ratings are those assigned by CIViC curators. "Submitted" items have not completed curation review. This is not treatment guidance.
| 4 |
| accepted |
EID10360An MRI in a previously healthy 6-year-old boy now presenting with neurologic abnormalities and seizures revealed a mass obstructing the foramen of Monro and diffuse leptomeningeal dissemination. The p… (full text at CIViC) PMID 34651095 · Mangum et al., 2021 · Open in CIViC |
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| 〃 | GlioblastomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID10361An MRI of 26-year-old man presenting with motor weakness and language difficultly revealed a lesion in the left frontal lobe that extended across the corpus callosum. Histologic analysis of the biopsy… (full text at CIViC) PMID 34041811 · Shepherd et al., 2021 · Open in CIViC | civic |
EID7200Hawkins et al. (2011) retrospectively studied 70 consecutive patient with incompletely resected pediatric low-grade astrocytomas (PLGA). KIAA1549-BRAF fusion was identified in 60% of cases in this coh… (full text at CIViC) PMID 21610142 · Hawkins et al., 2011 · Open in CIViC |
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| (diagnostic) | Pilocytic Astrocytoma | Diagnostic | B | Supports Positive | 4 | accepted | EID7319This study identified a novel rearrangement event between the uncharacterized gene KIAA-1549 and BRAF in 66% (29 of 44) of pilocytic astrocytoma but not in 244 higher-grade astrocytomas that were eval… (full text at CIViC) PMID 18974108 · Jones et al., 2008 · Open in CIViC | civic |
| (oncogenic) | Pilocytic Astrocytoma | Oncogenic | D | Supports Oncogenicity | 3 | accepted | EID7337This study identified a novel rearrangement event between the uncharacterized gene KIAA-1549 and BRAF in 66% (29 of 44) of pilocytic astrocytomas. The fusion gene was shown to delete the N-terminal BR… (full text at CIViC) PMID 18974108 · Jones et al., 2008 · Open in CIViC | civic |
| PLX4720 + VemurafenibSubstitutes | Childhood Low Grade Glioma | Predictive | D | Supports Adverse Response | 4 | submitted | EID7204Activated BRAF protein kinase mutations are characteristic of pediatric astrocytomas with KIAA1549-BRAF fusion commonly observed in low-grade astrocytomas. Sievert et al. (2013) generated BRAF fusion … (full text at CIViC) PMID 23533272 · Sievert et al., 2013 · Open in CIViC | civic |
| Selumetinib | Childhood Pilocytic Astrocytoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID7486In a phase 2 trial, patients with pediatric low-grade glioma after at least one standard therapy were treated with MEK1/2 inhibitor selumetinib. In stratum 1, nine patients with WHO grade I pilocytic… (full text at CIViC) PMID 31151904 · Fangusaro et al., 2019 · Open in CIViC | civic |
| 〃 | Childhood Pilocytic Astrocytoma | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID8943In this preclinical experiment, a pediatric pilocytic astrocytoma cell line (DKFZ-BT66) harboring KIAA1549:BRAF fusion was generated from a two year old patient. Treatment with selumetinib resulted in… (full text at CIViC) PMID 28002790 · Selt et al., 2017 · Open in CIViC | civic |
| Sorafenib + VemurafenibSubstitutes | Childhood Pilocytic Astrocytoma | Predictive | D | Supports Resistance | 2 | accepted | EID7402A pilocytic astrocytoma (PA) cell line named DKFZ-BT66 was generated from a 2-year old patient with the disease. Expression of KIAA1549-BRAF fusion in this cell line was identified. Treatment with sor… (full text at CIViC) PMID 28002790 · Selt et al., 2017 · Open in CIViC | civic |
| Trametinib | Childhood Pilocytic Astrocytoma | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID8944In this preclinical experiment, a pediatric pilocytic astrocytoma cell line (DKFZ-BT66) harboring KIAA1549:BRAF fusion was generated from a two year old patient. Treatment with trametinib resulted in … (full text at CIViC) PMID 28002790 · Selt et al., 2017 · Open in CIViC | civic |
| Everolimus + TrametinibCombination | Childhood Low Grade Glioma | Predictive | D | Supports Sensitivity Response | 3 | rejected | EID7197This preclinical study proposed to use a combination therapy of an MEK inhibitor (e.g. trametinib) and an mTOR inhibitor (e.g. everolimus) for the treatment of pediatric low-grade gliomas (PLGGs) with… (full text at CIViC) PMID 29156677 · Jain et al., 2017 · Open in CIViC | civic |
| 〃 | Childhood Low Grade Glioma | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID7199This preclinical study proposed to use a combination therapy of an MEK inhibitor (e.g. trametinib) and an mTOR inhibitor (e.g. everolimus) for the treatment of pediatric low-grade gliomas (PLGGs) with… (full text at CIViC) PMID 29156677 · Jain et al., 2017 · Open in CIViC | civic |
| 4 |
| accepted |
EID490In a study of 152 anaplastic oligodendroglial tumors, 121 samples had MGMT promoter methylation. Those with promoter methylation had better progression-free and overall survival. PMID 19901104 · van den Bent et al., 2009 · Open in CIViC |
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| Carmustine | GlioblastomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID308MGMT promoter methylation has been shown to confer sensitivity to alkylating agents, such as carmustine, in glioblastoma cells. PMID 11070098 · Esteller et al., 2000 · Open in CIViC | civic |
| Lomustine + TemozolomideCombination | GlioblastomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 3 | submitted | EID7303In a small Phase 3 trial, patients with newly diagnosed glioblastoma with methylation of the MGMT promoter randomely assigned to lomustine plus temozolomide in addition to radiotherapy (n=66) or temoz… (full text at CIViC) PMID 30782343 · Herrlinger et al., 2019 · Open in CIViC | civic |
| O6-Benzylguanine | GlioblastomaCURATED_BROADER | Predictive | E | Supports Sensitivity Response | 4 | accepted | EID309In patients lacking MGMT promoter methylation, the use of an MGMT inhibitor, such as O(6)-benzylguanine, in combination with alkylating agents (Carmustine) may be useful in treating patients with init… (full text at CIViC) PMID 11070098 · Esteller et al., 2000 · Open in CIViC | civic |
| Temozolomide | GlioblastomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID307In a randomized clinical trial, patients with MGMT promoter methylation benefitted from temozolomide. This benefit was also methylation status dependent, as those without methylation did not see incre… (full text at CIViC) PMID 15758010 · Hegi et al., 2005 · Open in CIViC | civic |
| B |
| Supports Sensitivity Response |
| 3 |
| accepted |
EID2903In 41 glioblastomas treated with temozolomide (TMZ) therapy (MGMT-immunopositive: n = 22, negative: n = 19), both progression free survival and overall survival were significantly better in MGMT-immun… (full text at CIViC) PMID 21331613 · Watanabe et al., 2011 · Open in CIViC |
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| 〃 | OligodendrogliomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID2902In this study, loss of chromosome 1p and low MGMT protein expression were associated with objective response (P < .003 and P < .04, respectively). However, only 54% of the study group had evaluation o… (full text at CIViC) PMID 16541434 · Levin et al., 2006 · Open in CIViC | civic |