Subtype
Adult-Type Diffuse Glioma
CI-CAN-00009389Explore in graph →
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Subtype
CI-CAN-00009389Explore in graph →
Variants & evidence
200 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 |
|---|---|---|---|---|---|---|---|---|
| MYB Rearrangement2 | ||||||||
| (diagnostic) | Diffuse AstrocytomaALIAS | Diagnostic | B | Supports Positive | 3 | accepted | EID11778The study compiled the clinicopathologic and molecular features of 46 gliomas with a MYB or MYBL1 alteration diagnosed at a single center. The tumors showed low-grade histopathologic features and were… (full text at CIViC) PMID 31595312 · Chiang et al., 2019 · Open in CIViC | civic |
| 〃 | Diffuse AstrocytomaALIAS | Diagnostic | C | Supports Positive | 2 | accepted | EID11790A research study performed in 2010 involved 57 pediatric low-grade gliomas (LGGs) and a comparison group of 59 pediatric high-grade gliomas (HGGs). Among the LGG group, there were 34 cases of pilocyti… (full text at CIViC) PMID 21046410 · Tatevossian et al., 2010 · Open in CIViC | civic |
| NF1 D1644H + NF1 Q1189*1 | ||||||||
| Selumetinib | Diffuse AstrocytomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 1 | submitted | EID12342A 14.6-year-old male [ID: 6] with a family history of neurofibromatosis type 1 (NF1) affecting both parents and a sibling. The patient was asymptomatic at diagnosis, and a biopsy of the left frontal g… (full text at CIViC) PMID 35945463 · Lucas et al., 2022 · Open in CIViC | civic |
| NF1 Mutation1 | ||||||||
| (predisposing) | Pilocytic Astrocytoma | Predisposing | C | Supports Predisposition | 2 | rejected | EID12272This study reported 47 neurofibromatosis type 1 (NF1) patients with biallelic inactivation of NF1 genes were detected in all glial tumors. Targeted capture-based next-generation sequencing (479 cancer… (full text at CIViC) PMID 35945463 · Lucas et al., 2022 · Open in CIViC | civic |
| PA-NF1 + NF1 Mutation4 | ||||||||
| (diagnostic) | Pilocytic Astrocytoma | Diagnostic | B | Supports Positive | 4 | rejected | EID12267This study reported 47 neurofibromatosis type 1 (NF1) patients with biallelic inactivation of NF1 genes were detected in all glial tumors. Targeted capture-based next-generation sequencing (479 cancer… (full text at CIViC) PMID 35945463 · Lucas et al., 2022 · Open in CIViC | civic |
| 〃 | Anaplastic AstrocytomaALIAS | Diagnostic | B | Supports Positive | 4 | submitted | EID12268This study reported 47 neurofibromatosis type 1 (NF1) patients with biallelic inactivation of NF1 genes were detected in all glial tumors. Targeted capture-based next-generation sequencing (479 cancer… (full text at CIViC) PMID 35945463 · Lucas et al., 2022 · Open in CIViC | civic |
| Selumetinib | Anaplastic AstrocytomaALIAS | Predictive | ||||||
| NF1 p.R1276*1 | ||||||||
| (predisposing) | Pilocytic Astrocytoma | Predisposing | C | Supports Predisposition | 3 | rejected | EID12286This study reported 47 neurofibromatosis type 1 (NF1) patients with biallelic inactivation of NF1 genes were detected in all glial tumors. Targeted capture-based next-generation sequencing (479 cancer… (full text at CIViC) PMID 35945463 · Lucas et al., 2022 · Open in CIViC | civic |
| NF1 G629R + NF1 Splice Site (c.205-1G>C)2 | ||||||||
| Carboplatin + Selumetinib + Trametinib + VincristineSubstitutes | Pilocytic Astrocytoma | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID12271This study reported 47 neurofibromatosis type 1 (NF1) patients with biallelic inactivation of NF1 genes were detected in all glial tumors. Targeted capture-based next-generation sequencing (479 cancer… (full text at CIViC) PMID 35945463 · Lucas et al., 2022 · Open in CIViC | civic |
| 〃 | Pilocytic Astrocytoma | Predictive | C | Supports Sensitivity Response | 2 | rejected | EID12359This study reported 47 neurofibromatosis type 1 (NF1) patients with biallelic inactivation of NF1 genes were detected in all glial tumors. Targeted capture-based next-generation sequencing (479 cancer… (full text at CIViC) PMID 35945463 · Lucas et al., 2022 · Open in CIViC | civic |
| NTRK1 Fusion1 | ||||||||
| (oncogenic) | GlioblastomaCURATED_BROADER | Oncogenic | D | Supports Oncogenicity | 4 | submitted | EID10930RNAseq data of 162 glioblastoma patients identified NTRK1 fusions with both NFASC and BCABN. By analyzing exome and RNA data, the NFASC-NTRK1 fusion was found to retain NTRK1's kinase and transmembran… (full text at CIViC) PMID 24647444 · Kim et al., 2014 · Open in CIViC | civic |
| PIK3CA Mutation1 | ||||||||
| Buparlisib | GlioblastomaCURATED_BROADER | Predictive | B | Does Not Support Sensitivity Response | 3 | submitted | EID7072In this multicenter, open-label, multi-arm, phase 2 trial, 65 patients with PI3K pathway aberrations (defined by PTEN and pAKT IHC-Status in 95%, genomic testing in 5%) were treated with the PI3K inhi… (full text at CIViC) PMID 30715997 · Wen et al., 2019 · Open in CIViC | civic |
| PIK3R1 Mutation1 | ||||||||
| Buparlisib | GlioblastomaCURATED_BROADER | Predictive | B | Does Not Support Sensitivity Response | 3 | submitted | EID7073In this multicenter, open-label, multi-arm, phase 2 trial, 65 patients with PI3K pathway aberrations (defined by PTEN and pAKT IHC-Status in 95%, genomic testing in 5%) were treated with the PI3K inhi… (full text at CIViC) PMID 30715997 · Wen et al., 2019 · Open in CIViC | civic |
| PLK1 OVEREXPRESSION1 | ||||||||
| (prognostic) | GlioblastomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 2 | submitted | EID8005Kaplan-Meier analysis of PLK1 gene expression showed that elevated expression is significantly associated with shorter disease-free survival in GBM (p=9.1e-11). PMID 32180229 · Li et al., 2020 · Open in CIViC | civic |
| PMS2 K706FS*191 | ||||||||
| Nivolumab | GlioblastomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID1214Two siblings (6 and 3.5 years) from nonconsanguineous parents were diagnosed with glioblastoma multiforme. Both tumors harbored TP53 mutations and lack of MGMT promoter hypermethylation as poor progno… (full text at CIViC) PMID 27001570 · Bouffet et al., 2016 · Open in CIViC | civic |
| POLE Mutation1 | ||||||||
| Pembrolizumab | GlioblastomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1861Case report of a patient with glioblastoma multiforme and POLE germline mutation. The patient was treated with pembrolizumab and lymphocyte infiltration was noted after resection of a spinal metastasi… (full text at CIViC) PMID 27683556 · Johanns et al., 2016 · Open in CIViC | civic |
| PTEN Expression3 | ||||||||
| Dacomitinib | GlioblastomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID775In this preclinical study, the EGFR inhibitor dacomitinib had an effect on cell viability, self-renewal and proliferation in EGFR amplified GBM cells in-vitro and in-vivo (with or without the EGFRvIII… (full text at CIViC) PMID 25939761 · Zahonero et al., 2015 · Open in CIViC | civic |
| Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor | GlioblastomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID77449 patients (26 pretreatment tissues available for analysis) with recurrent glioblastomas who were treated with EGFR TKIs were analyzed in this study. Results were confirmed in an independent cohort o… (full text at CIViC) PMID 16282176 · Mellinghoff et al., 2005 · Open in CIViC | civic |
| Erlotinib + | ||||||||
| PTEN Mutation3 | ||||||||
| (diagnostic) | GlioblastomaCURATED_BROADER | Diagnostic | C | Supports Positive | 2 | accepted | EID1931Rasheed et al. identified that PTEN mutations occur with significantly greater frequency in adults with high-grade gliomas (42 adult glioblastoma multiforme and 13 adult anaplastic astrocytoma) compar… (full text at CIViC) PMID 9331072 · Rasheed et al., 1997 · Open in CIViC | civic |
| Buparlisib | GlioblastomaCURATED_BROADER | Predictive | B | Does Not Support Sensitivity Response | 3 | submitted | EID7074In this multicenter, open-label, multi-arm, phase 2 trial, 65 patients with PI3K pathway aberrations (defined by PTEN and pAKT IHC-Status in 95%, genomic testing in 5%) were treated with the PI3K inhi… (full text at CIViC) PMID 30715997 · Wen et al., 2019 · Open in CIViC | civic |
| Nivolumab + PembrolizumabSubstitutes | Glioblastoma | |||||||
| PTEN R173C2 | ||||||||
| (diagnostic) | GlioblastomaCURATED_BROADER | Diagnostic | C | Supports N/A | 3 | rejected | EID1932Bostrom et al identified R173C in the tumor sample of 1 subject (out of 36 glioblastomas tested). By PCR mRNA expression of PTEN was assayed for tumor samples harboring PTEN variants. PTEN expression… (full text at CIViC) PMID 9426052 · Boström et al., 1998 · Open in CIViC | civic |
| 〃 | GlioblastomaCURATED_BROADER | Diagnostic | C | Supports N/A | 2 | submitted | EID1933Fults et al identified 1 R173C mutation in a glioblastoma (of 45 tested). The tumor also displayed either all or partial LOH of 10q, there was no further resolution of the LOH size or mutational testi… (full text at CIViC) PMID 9499454 · Fults et al., 1998 · Open in CIViC | civic |
| PTEN R233*1 | ||||||||
| (prognostic) | GlioblastomaCURATED_BROADER | Prognostic | B | Does Not Support Poor Outcome | 3 | accepted | EID343PTEN nonsense mutations, including R233*, have been shown to be inactivating and loss-of-function, but do not have prognostic value in glioblastoma multiforme patients. PMID 22479427 · Carico et al., 2012 · Open in CIViC | civic |
| PTPN11 Mutation1 | ||||||||
| (diagnostic) | Pilocytic Astrocytoma | Diagnostic | C | Supports Positive | 3 | submitted | EID7153Genetic alterations in pilocytic astrocytoma (PA) were evaluated. Two alterations were found in the PTPN11 (aka SHP-2) gene, encoding a RAS-MAPK-related adaptor protein and phosphatase. Both alteratio… (full text at CIViC) PMID 23817572 · Jones et al., 2013 · Open in CIViC | civic |
| NTRK2 Fusion2 | ||||||||
| (oncogenic) | Pilocytic Astrocytoma | Oncogenic | C | Supports Oncogenicity | 1 | accepted | EID11449Whole genome sequencing of 96 pilocytic astrocytomas by the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project identified QKI::NTRK2 (e6::e16) fusions in 2 cases (5 yo & 12 yo males)… (full text at CIViC) PMID 23817572 · Jones et al., 2013 · Open in CIViC | civic |
| 〃 | Anaplastic AstrocytomaALIAS | Oncogenic | D | Supports Oncogenicity | 3 | accepted | EID11450Authors demonstrated that a flag-tagged QKI::NTRK2 (e6::e16) fusion was able to transform Ink4a−/−/Arf−/− astrocytes, and these cells induced astrocytomas when injected intracranially into mice. QKI… (full text at CIViC) PMID 27402815 · Ni et al., 2017 · Open in CIViC | civic |
| RB1 Loss-of-function1 | ||||||||
| Palbociclib | GlioblastomaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | accepted | EID1595A panel of 21 glioblastoma cell lines harboring various mutations was treated with palbociclib. 16 of the cell lines with intact Rb showed decreased proliferation (bromodeoxyuridine incorporation, Brd… (full text at CIViC) PMID 20354191 · Michaud et al., 2010 · Open in CIViC | civic |
| ROS1 Overexpression1 | ||||||||
| Gefitinib | GlioblastomaCURATED_BROADER | Predictive | D | Supports Resistance | 1 | submitted | EID1970Gefitinib resistant clones were subject to RNAseq and the expression of several genes was found to be upregulated. These genes are mainly tyrosine kinase receptors and include ROS1, DDR1 and PDGFRA. T… (full text at CIViC) PMID 25978031 · Aljohani et al., 2015 · Open in CIViC | civic |
| EGFR Fusion2 | ||||||||
| (oncogenic) | GlioblastomaCURATED_BROADER | Oncogenic | D | Supports Oncogenicity | 1 | submitted | EID10934SEC61G::EGFR fusion identified in 4 out of 164 (2.4%) glioblastoma tumors (TCGA GBM working group, patient samples with pathobiology data). Fusion transcripts were confirmed by RNA-seq and were freque… (full text at CIViC) PMID 24120142 · Brennan et al., 2013 · Open in CIViC | civic |
| 〃 | GlioblastomaCURATED_BROADER | Oncogenic | D | Supports Oncogenicity | 1 | submitted | EID10935TCGA pan-cancer data analysis of 9,624 tumors across 33 tumor types identified 25,664 fusions. Significantly associated gene fusion and increased expression level (by RNAseq compared to samples withou… (full text at CIViC) PMID 29617662 · Gao et al., 2018 · Open in CIViC | civic |
| SLC12A2 OVEREXPRESSION1 | ||||||||
| Antisecretory Factor-enriched Egg Yolk Powder Supplement + TemozolomideCombination | GlioblastomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID12689Antisecretory factor (AF) induction by the SPC diet or Salovum in GBM xenografts (GBM43, GBM6) reduced NKCC1-mediated chloride influx, chloride permeability, and blocked regulatory volume increase in … (full text at CIViC) PMID 29431617 · Ilkhanizadeh et al., 2018 · Open in CIViC | civic |
| TERT C228T2 | ||||||||
| (prognostic) | GlioblastomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 2 | submitted | EID6934Evaluation of 25 Korean patients with primary glioblastomas, individuals with TERT promoter mutations (N=16) had worse overall survival (median 81.7 weeks [95% confidence interval (CI), 61.71–101.85])… (full text at CIViC) PMID 29344264 · Jeong et al., 2017 · Open in CIViC | civic |
| 〃 | GlioblastomaCURATED_BROADER | Prognostic | D | Supports Poor Outcome | 2 | submitted | EID6935Surgical samples from 25 Korean patients with primary glioblastomas were disassociated for cell culture and evaluated for TERT promoter mutations (N=16 mutant, N=9 wildtype). All patients harbored the… (full text at CIViC) PMID 29344264 · Jeong et al., 2017 · Open in CIViC | civic |
| TERT C250T1 | ||||||||
| (oncogenic) | GlioblastomaCURATED_BROADER | Oncogenic | B | Supports Oncogenicity | 4 | submitted | EID10331TERT promoter mutations are activating and commonly found at two hotspots within the TERT promoter region which occur 124 and 146 base pairs (hg19) upstream of the translation start site. These hotspo… (full text at CIViC) PMID 23955565 · Nonoguchi et al., 2013 · Open in CIViC | civic |
| TERT Promoter Mutation2 | ||||||||
| (prognostic) | GlioblastomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID516In 187 patients with glioblastoma, those with TERT promoter mutations had worse cummulative survival than wild-type patients. The most common mutation was C228T (73% of mutants) followed by C250T (27%… (full text at CIViC) PMID 23955565 · Nonoguchi et al., 2013 · Open in CIViC | civic |
| 〃 | GlioblastomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID6933In 50 patients with primary glioblastomas, patients without TERT promoter mutations (N=13, median 27 mo) survived longer than those harboring mutations (N=37, 14 mo; P = 0.01 by the log rank test; HR … (full text at CIViC) PMID 23530248 · Killela et al., 2013 · Open in CIViC | civic |
| TP53 M237I2 | ||||||||
| Unspecified therapy | GlioblastomaCURATED_BROADER | Predictive | C | Supports N/A | 5 | submitted | EID8064mutants in diverse tumor types activate different p53 target genes, but some may give rise to the same GoF phenotype. 12,13 For example, M237I, in glioblastoma, and R282W, in lung cancer, trigger chem… (full text at CIViC) PMID 29260852 · Silva et al., 2018 · Open in CIViC | civic |
| Temozolomide | GlioblastomaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID7979The glioblastoma T98G cell line possesses a TP53 M237I variant. This cell line initially exhibited resistance to temozolomide treatment, but a five-fold increase in chemosensitivity (IC50 112.15 ug/ml… (full text at CIViC) PMID 24248532 · Wang et al., 2014 · Open in CIViC | civic |
| TP53 Mutation2 | ||||||||
| (prognostic) | GlioblastomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID7976In a trial of 68 glioblastoma patients treated with either temozolomide or semustine, 24 patients were found to have TP53 mutations at codons 175, 248, or 273. Patients with TP53 mutation were found t… (full text at CIViC) PMID 24248532 · Wang et al., 2014 · Open in CIViC | civic |
| Temozolomide | GlioblastomaCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID7978In a trial of 68 glioblastoma patients treated with either temozolomide or semustine, 24 patients were found to have TP53 mutations at codons 175, 248, or 273. Kaplan-Meier analysis of the 35 patients… (full text at CIViC) PMID 24248532 · Wang et al., 2014 · Open in CIViC | civic |
| TP53 P72R1 | ||||||||
| (prognostic) | OligodendrogliomaCURATED_BROADER | Prognostic | B | Does Not Support Poor Outcome | 2 | submitted | EID6932In the evaluation of 275 oligodendroglial tumors, the specific genotype at amino acid 72 of TP53 (Arg/Arg, Arg/Pro, or Pro/Pro) was not associated grade of malignancy (low- vs. high-grade, P = 0.650) … (full text at CIViC) PMID 17854663 · Idbaih et al., 2007 · Open in CIViC | civic |
| TP53 R273H1 | ||||||||
| Temozolomide | GlioblastomaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID7980The glioblastoma U138 cell line possesses a TP53 R273H variant. This cell line initially exhibited resistance to temozolomide treatment, but a four-fold increase in chemosensitivity (IC50 127.79 ug/ml… (full text at CIViC) PMID 24248532 · Wang et al., 2014 · Open in CIViC | civic |
| NTRK1 Fusion1 | ||||||||
| Larotrectinib | Gliosarcoma | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID11746A 9-month-old boy with no family history of cancer presented with increased head circumference, and MRI demonstrated a solid lesion in the left frontal lobe. A subtotal surgical resection was performe… (full text at CIViC) PMID 35034013 · Mançano et al., 2022 · Open in CIViC | civic |
| VEGFA Overexpression1 | ||||||||
| Bevacizumab | GlioblastomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID7013We found that high VEGF expression (mean positive area > 5,000 pixels/×400 field) was associated with increased likelihood of achieving radiographic response (P = .024; Table 2). PMID 18182667 · Sathornsumetee et al., 2008 · Open in CIViC | civic |
| VEGFA Overexpression of VEGF1211 | ||||||||
| Bevacizumab | GlioblastomaCURATED_BROADER | Predictive | B | Supports Resistance | 4 | submitted | EID9490In a clinical study including 12 patients already treated with bevacizumab, high levels of plasma VEGF-121 decrease the OS and the PFS (p = 0.0246 and p = 0.0295) compared to low level of expression. PMID 29747600 · Martini et al., 2018 · Open in CIViC | civic |
| NTRK2 Fusion1 | ||||||||
| (diagnostic) | Pilocytic Astrocytoma | Diagnostic | C | Supports Positive | 3 | submitted | EID7151Genetic alterations in pilocytic astrocytoma (PA) were evaluated. Two new NTRK2 fusion events were identified in this study. These two NTRK2 fusion events, namely QKI-NTRK2 (2 of 96 samples) and NACC2… (full text at CIViC) PMID 23817572 · Jones et al., 2013 · Open in CIViC | civic |
| WDR12 OVEREXPRESSION1 | ||||||||
| (prognostic) | GlioblastomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID8004Expression of WDR12 was found to be significantly higher in tumour than normal tissue from TCGA LGG and GBM datasets. Kaplan-Meier analysis showed high WDR12 expression to be significantly associated … (full text at CIViC) PMID 32180229 · Li et al., 2020 · Open in CIViC | civic |
Data updated 10 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.
| C |
| Supports Sensitivity Response |
| 3 |
| submitted |
EID12270This study reported 47 neurofibromatosis type 1 (NF1) patients with biallelic inactivation of NF1 genes were detected in all glial tumors. Targeted capture-based next-generation sequencing (479 cancer… (full text at CIViC) PMID 35945463 · Lucas et al., 2022 · Open in CIViC |
| civic |
| Trametinib | Pilocytic Astrocytoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID12269This study reported 47 neurofibromatosis type 1 (NF1) patients with biallelic inactivation of NF1 genes were detected in all glial tumors. Targeted capture-based next-generation sequencing (479 cancer… (full text at CIViC) PMID 35945463 · Lucas et al., 2022 · Open in CIViC | civic |
| GlioblastomaCURATED_BROADER |
| Predictive |
| B |
| Supports Sensitivity Response |
| 3 |
| accepted |
EID1129Expression of EGFRvIII and PTEN was evaluated in 26 patients with glioblastomas treated with erlotinib or gefitinib and no EGFR or Her2/neu kinase domain mutations. 7 patients responded to treatment w… (full text at CIViC) PMID 16282176 · Mellinghoff et al., 2005 · Open in CIViC |
| civic |
| Predictive |
| B |
| Supports Resistance |
| 4 |
| submitted |
EID8176In this retrospective study of 66 GBM patients treated with PD-1 inhibitors (nivolumab or pembrolizumab) at recurrence, mutations in PTEN were frequently found among non-responders. Of 45 IDH1 wild-ty… (full text at CIViC) PMID 30742119 · Zhao et al., 2019 · Open in CIViC |
| civic |