Glioblastoma, IDH-wildtype

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Central Nervous System Tumours (WHO Classification, 5th ed.)

(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support.)

Primary Author(s)*

Jieying Chu, PhD

WHO Classification of Disease

Structure Disease
Book Central Nervous System Tumours (5th ed.)
Category Gliomas, glioneuronal tumours, and neuronal tumours
Family Gliomas, glioneuronal tumours, and neuronal tumours
Type Adult-type diffuse gliomas
Subtype(s) Glioblastoma, IDH-wildtype

Related Terminology

Acceptable N/A
Not Recommended Glioblastoma multiforme

Gene Rearrangements

Driver Gene Fusion(s) and Common Partner Genes Molecular Pathogenesis Typical Chromosomal Alteration(s) Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease) Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
EGFR EGFR–SEPT14; EGFR–PSPH; other rare in-frame EGFR fusions Constitutive EGFR kinase activation → MAPK and PI3K/AKT signaling 7p11.2 rearrangements; often co-occurs with EGFR amplification Rare (<5%) D, T No (WHO CNS5) Recurrent EGFR–SEPT14 fusion described in GBM (~4% EGFR-altered tumors)[1].
FGFR3 FGFR3–TACC3 Constitutive FGFR3 activation via loss of regulatory domain; mitotic spindle dysregulation Intrachromosomal tandem duplication at 4p16 Rare (<5%) (~3%) D, T No (WHO CNS5) Recurrent, oncogenic fusion in GBM; preclinical FGFR inhibitor sensitivity[2].
MET PTPRZ1–MET (ZM fusion) Constitutive MET activation → PI3K/MAPK signaling; invasion and progression 7q31 rearrangement Rare (<5%) T No (WHO CNS5) Recurrent MET fusion in secondary GBM; associated with aggressive phenotype[3].
NTRK1/2/3 Various partners (e.g., LMNA–NTRK1, ETV6–NTRK3) Constitutive TRK activation → MAPK/PI3K signaling Rearrangements involving 1q, 9q, 15q Rare (<2%) T Yes (NCCN tumor-agnostic TRK inhibitors; FDA approved) Rare but actionable; TRK inhibitors show efficacy in fusion-positive tumors[4].
PDGFRA Rare PDGFRA fusions (amplification more common) Constitutive PDGFRA RTK signaling 4q12 rearrangement; frequently amplified Rare (<5%) T No (WHO CNS5) PDGFRA rearrangements uncommon; amplification is dominant alteration[5].
ALK Rare ALK fusions reported in gliomas Constitutive ALK kinase activation 2p23 rearrangement Rare (<1%) T Yes (tumor-agnostic ALK inhibitor context) Very rare in adult GBM; more typical in infant hemispheric glioma[6].
ROS1 GOPC–ROS1 and other rare partners Constitutive ROS1 kinase activation 6q22 rearrangement Very rare (<1%) T Yes (tumor-agnostic ROS1 inhibitor context) Reported in small GBM subsets; potential eligibility for ROS1 inhibitors[7].

Individual Region Genomic Gain/Loss/LOH

Chr # Gain, Loss, Amp, LOH Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size] Relevant Gene(s) Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
7 Gain (whole chromosome) Whole chromosome 7 EGFR, MET, CDK6 D Yes (WHO CNS5) Component of defining +7/−10 GBM molecular signature. Common in IDH-wt GBM[8].
10 Loss (whole chromosome) Whole chromosome 10 PTEN, MGMT D, P Yes (WHO CNS5) Part of +7/−10 signature defining IDH-wt GBM. PTEN frequently deleted[8].
7 Amp 7p11.2 [GRCh38: ~55.0–55.5 Mb; ~0.5 Mb] EGFR D, T Yes (WHO CNS5) EGFR amplification in ~40–50% of IDH-wt GBM. Often with EGFRvIII[8].
9 Homozygous Loss 9p21.3 [GRCh38: ~21.9–22.1 Mb; ~0.2 Mb] CDKN2A, CDKN2B D, P Yes (WHO CNS5) Homozygous CDKN2A/B deletion sufficient for WHO grade 4 in IDH-mutant astrocytoma; common in IDH-wt GBM[8].
4 Amp 4q12 [GRCh38: ~55–56 Mb; ~1 Mb] PDGFRA, KIT, KDR P, T No (WHO CNS5) PDGFRA amplification in ~10–15% of GBM; enriched in proneural subtype[8].
12 Amp 12q14.1–q15 [GRCh38: ~69–71 Mb; ~2 Mb] CDK4, MDM2 P, T No (WHO CNS5) CDK4/MDM2 amplification contributes to RB and p53 pathway dysregulation[8].
13 Loss 13q14 RB1 P No RB1 loss contributes to cell cycle dysregulation; part of core GBM pathways[8].
17 Loss 17p13.1 TP53 P No TP53 pathway alteration common; mutation more frequent than deletion[8].
19 Gain 19p13 AKT2 P No AKT2 amplification contributes to PI3K pathway activation[8].
20 Gain 20q AURKA, ZNF217 P No Recurrent 20q gain reported in copy number analyses of GBM cohorts[2].
22 Loss 22q12 NF2 P No NF2 loss occurs in a subset of GBM; more typical in other gliomas but documented in TCGA GBM[8].
1 LOH (arm-level) 1p Multiple P No (WHO CNS5) 1p loss alone not characteristic of IDH-wt GBM; 1p/19q codeletion defines oligodendroglioma[9].
19 LOH (arm-level) 19q Multiple P No (WHO CNS5) 1p/19q codeletion excludes IDH-wt GBM diagnosis[9].

Characteristic Chromosomal or Other Global Mutational Patterns

Chromosomal Pattern Molecular Pathogenesis Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
Combined whole chromosome 7 gain and whole chromosome 10 loss (+7/−10) Aneuploidy with dosage increase of oncogenes (EGFR, MET, CDK6) and loss of tumor suppressors (PTEN) Common (>20%; ~70–80%) D Yes (WHO CNS5) Defining molecular signature of IDH-wildtype GBM when histology is lower grade. Foundational TCGA characterization[8].
EGFR amplification (often with structural variants such as EGFRvIII) Receptor tyrosine kinase pathway activation (MAPK, PI3K) Common (>20%; ~40–50%) D, T Yes (WHO CNS5) One of three WHO molecular criteria sufficient for GBM diagnosis in IDH-wildtype diffuse astrocytic gliomas[8].
TERT promoter mutation (C228T/C250T) Telomerase reactivation via increased TERT transcription Common (>20%; ~70–80%) D, P Yes (WHO CNS5) Diagnostic criterion for IDH-wildtype GBM in appropriate histologic context; associated with aggressive biology[2].
CDKN2A/B homozygous deletion Loss of RB pathway control (p16INK4a, p14ARF loss) Common (>20%) D, P Yes (WHO CNS5) Sufficient for WHO grade 4 in IDH-mutant astrocytoma; frequent in IDH-wildtype GBM[8].
Chromothripsis-like focal amplification clusters (double minutes) Catastrophic chromosomal shattering and reassembly leading to oncogene amplification (EGFR, MDM2, CDK4) Recurrent (5–20%) P No (WHO CNS5) Frequently results in extrachromosomal DNA (ecDNA)–mediated oncogene amplification in GBM[2].
Extrachromosomal DNA (ecDNA) amplification Circular DNA elements carrying oncogenes (e.g., EGFR) leading to high expression and heterogeneity Recurrent (5–20%) P, T No (WHO CNS5) Drives intratumoral heterogeneity and therapy resistance. Increasingly recognized mechanism in GBM[10].
Whole-genome aneuploidy / broad SCNA burden Global chromosomal instability affecting RTK, p53, RB pathways Common (>20%) P No (WHO CNS5) GBM characterized by coordinated disruption of RTK/PI3K, p53, and RB pathways. TCGA hallmark pattern[8].
Hypermutator phenotype (post-temozolomide) Mismatch repair deficiency (e.g., MSH6 mutation) leading to high TMB Rare (<5%; typically recurrent tumors) P, T No (WHO CNS5) Associated with treatment resistance and possible immunotherapy relevance in recurrence[11].
MGMT promoter methylation (epigenetic global pattern) Epigenetic silencing of MGMT DNA repair enzyme Common (>20%; ~40–45%) P, T Yes (NCCN) Predictive of response to temozolomide; standard clinical testing marker[12].
G-CIMP–low methylation pattern (IDH-wildtype context lacks classic G-CIMP) Distinct DNA methylation landscape compared to IDH-mutant gliomas Common (>20%) D Yes (WHO CNS5 framework) IDH-wildtype GBM lacks G-CIMP signature seen in IDH-mutant gliomas[13].

Gene Mutations (SNV/INDEL)

Gene Genetic Alteration Tumor Suppressor Gene, Oncogene, Other Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

Diagnostic, Prognostic, and Therapeutic Significance - D, P, T   Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
TERT Promoter mutations (C228T, C250T) Oncogene (telomerase activation) Common (>20%; ~70–80%) D, P Yes (WHO CNS5) One of three molecular criteria sufficient for GBM diagnosis in IDH-wildtype diffuse astrocytic glioma[14].
TP53 Missense/nonsense mutations Tumor suppressor Common (>20%; ~25–30%) P No (WHO CNS5) Core p53 pathway alteration; more frequent in proneural-like tumors. Foundational GBM genomic study[8]
PTEN Loss-of-function mutation Tumor suppressor Common (>20%; ~30–40%) P, T No (WHO CNS5) Regulates PI3K/AKT pathway; frequently co-occurs with chromosome 10 loss[8]
EGFR Activating missense mutations (e.g., A289, G598, kinase domain variants) Oncogene Recurrent (5–20%) D, T Yes (WHO CNS5, amplification criterion) SNVs less common than amplification; often coexist with EGFR amplification[15].
PIK3CA Activating missense mutations (e.g., E542K, E545K, H1047R) Oncogene Recurrent (5–20%) T No Activates PI3K pathway; targetable in other cancers; limited proven benefit in GBM[8]
PIK3R1 Inactivating mutations Tumor suppressor (regulatory subunit of PI3K) Recurrent (5–20%) T No Alternative PI3K pathway activation mechanism[8]
NF1 Loss-of-function mutation Tumor suppressor Recurrent (5–20%) P No Defines mesenchymal molecular subtype in GBM[8]
RB1 Inactivating mutation Tumor suppressor Recurrent (5–20%) P No Part of RB pathway disruption triad (CDKN2A loss / CDK4 amp / RB1 mutation)[8]
IDH1 R132H (rare in IDH-wildtype GBM by definition) Oncogene (neomorphic) Rare (<5%; excluded in true IDH-wt GBM) D Yes (WHO CNS5 exclusionary marker) Presence excludes IDH-wildtype GBM diagnosis; defines IDH-mutant astrocytoma[16].
MSH6 Acquired loss-of-function mutation (recurrent tumors) DNA repair gene Rare (<5%; mostly post-therapy) P, T No Associated with temozolomide-induced hypermutator phenotype in recurrent GBM[11].

Note: A more extensive list of mutations can be found in cBioportal, COSMIC, and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

Epigenomic Alterations

Chromosomal Pattern Molecular Pathogenesis Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
MGMT promoter methylation CpG island methylation of MGMT promoter → impaired O6-methylguanine DNA repair Common (>20%; ~40–50%) P, T Yes (NCCN; WHO CNS5 recommends testing) Predictive biomarker for temozolomide response; methylation correlates with improved overall survival in treated patients. Established clinical testing marker in newly diagnosed GBM[12]
Global DNA hypomethylation Genome-wide CpG hypomethylation → chromosomal instability and oncogene dysregulation Common (>20%) P No Reflects genomic instability and aberrant oncogene activation; characteristic of IDH-wildtype GBM methylation landscape and contrasts with G-CIMP hypermethylated tumors[8].
Absence of G-CIMP phenotype Lack of IDH-driven CpG island methylator phenotype Common (>20%; majority of IDH-wt GBM) D Yes (WHO CNS5 framework) Lack of IDH-associated CpG island hypermethylation pattern; supports classification as IDH-wildtype glioblastoma rather than IDH-mutant diffuse glioma[13].
DNA methylation–based classifier (GBM, IDH-wildtype class) Genome-wide methylation signature defining molecular class Common (>20%) D Yes (WHO CNS5; DKFZ classifier) Genome-wide methylation profiling enables assignment to GBM, IDH-wildtype methylation class; useful in diagnostically ambiguous or lower-grade appearing tumors[17].

Genes and Main Pathways Involved

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
TERT; Promoter SNV (C228T, C250T) Telomere maintenance / immortalization Upregulation of telomerase activity, leading to cellular immortality and tumor progression (PMID: 29681515, 33168106)
EGFR; In-frame insertion/deletion, EGFRvIII Receptor tyrosine kinase / MAPK, PI3K-AKT signaling Constitutive EGFR activation drives proliferation, survival, and invasion (PMID: 29681515, 33168106)
PTEN; Frameshift, nonsense, splice site SNV/indel PI3K-AKT signaling / tumor suppressor Loss of PTEN leads to unregulated PI3K-AKT pathway activity, promoting cell survival and proliferation (PMID: 29681515, 33168106)
TP53; Missense or truncating SNV/indel DNA damage response / cell cycle checkpoint Loss of TP53 function impairs DNA repair and apoptosis, enabling accumulation of mutations (PMID: 29681515, 33168106)
NF1; Frameshift, nonsense, splice site SNV/indel RAS-MAPK signaling Loss of NF1 increases RAS activity, enhancing proliferation and contributing to mesenchymal phenotype (PMID: 29681515)
PIK3CA; Hotspot SNVs (E542K, E545K, H1047R) PI3K-AKT signaling Activating mutations drive proliferation and survival via PI3K-AKT pathway activation (PMID: 29681515, 33168106)
RB1; Truncating, splice site SNV/indel Cell cycle regulation Loss of RB1 removes G1/S checkpoint control, causing unregulated cell division (PMID: 29681515)
ATRX; Frameshift, nonsense, splice site SNV/indel Chromatin remodeling / telomere maintenance ATRX loss leads to alternative lengthening of telomeres (ALT) and genomic instability (PMID: 29681515)
MGMT; Promoter methylation (epigenetic silencing) DNA repair Loss of MGMT expression reduces repair of alkylated DNA, sensitizing tumors to temozolomide but also affecting genomic stability (PMID: 16595769, 18187677)

Genetic Diagnostic Testing Methods

Genetic Alteration / Biomarker Recommended Testing Method(s) Notes / Rationale
TERT; Promoter SNV (C228T, C250T) Sanger sequencing, targeted NGS panel Highly sensitive for hotspot SNVs. Useful for confirming IDH-wildtype GBM molecular classification (PMID: 29681515).
EGFR amplification, EGFRvIII FISH, qPCR, targeted NGS, RNA-seq FISH detects copy number changes; RNA-seq identifies EGFRvIII fusion transcript. EGFRvIII may guide eligibility for experimental therapies (PMID: 33168106).
PTEN, TP53, NF1, PIK3CA, RB1, ATRX Targeted NGS panel, exome sequencing Detects SNVs, indels, and small deletions. Panels allow multiplexed, high-throughput detection of clinically relevant alterations (PMID: 29681515).
MGMT promoter methylation Methylation-specific PCR (MSP), pyrosequencing, targeted bisulfite sequencing Determines epigenetic silencing of MGMT. Predicts temozolomide response and prognosis (PMID: 16595769, 18187677).
Chromosomal copy number alterations (chr7 gain, chr10 loss, 1p/19q status) SNP array, comparative genomic hybridization (CGH), karyotyping, NGS-based CNV analysis Detects gains, losses, and LOH. Combined chr7 gain / chr10 loss supports IDH-wildtype GBM diagnosis (PMID: 29681515).
Gene fusions (e.g., FGFR3::TACC3, other rare fusions) RNA-seq, targeted fusion panel, FISH RNA-seq is sensitive for novel and known fusions. FISH or targeted panels confirm recurrent rearrangements (PMID: 29681515, 33168106).
IDH1/IDH2 mutations Sanger sequencing, targeted NGS panel, immunohistochemistry (IHC) for R132H IHC detects most common R132H variant; sequencing captures rare variants. Confirms IDH-wildtype vs. mutant status (PMID: 29681515).

Familial Forms

IDH-wildtype glioblastoma is predominantly sporadic, and hereditary/familial forms are very rare. Most reported familial cases are associated with general cancer predisposition syndromes rather than GBM-specific inheritance. Germline testing is recommended only if clinical/family history suggests a hereditary syndrome.

Additional Information

IDH-wildtype glioblastoma primarily affects adults over 50, often presenting with rapidly progressive neurological deficits, headaches, or seizures, and typically arises in the cerebral hemispheres (PMID: 29681515). Histologically, these tumors are highly cellular, pleomorphic astrocytic neoplasms with necrosis and microvascular proliferation, consistent with WHO CNS 2021 criteria (PMID: 29681515). On MRI, they appear as heterogeneously enhancing masses with necrotic cores, surrounding edema, and infiltrative margins (PMID: 29681515). Prognosis remains poor, with a median overall survival of 12–15 months under standard therapy, and is influenced by molecular features such as unmethylated MGMT promoter, TERT promoter mutation, EGFR amplification, and combined chr7 gain/chr10 loss (PMID: 16595769, 29681515). Standard treatment includes maximal safe resection followed by radiotherapy and temozolomide chemotherapy, with clinical trials investigating targeted therapies including EGFR and PI3K/AKT inhibitors (PMID: 33168106, 29681515). Molecular patterns show mutual exclusivity between EGFR amplification and TP53 mutations, while MGMT promoter methylation often co-occurs with TERT promoter mutation and EGFR amplification (PMID: 29681515, 33168106). Epidemiologically, GBM is the most common primary malignant brain tumor in adults, with a male predominance and rare pediatric occurrence (PMID: 29681515).

Links

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References

  1. Brennan, C. W., Verhaak, R. G., McKenna, A., Campos, B., Noushmehr, H., Salama, S. R., Zheng, S., Chakravarty, D., Sanborn, J. Z., Berman, S. H., Beroukhim, R., Bernard, B., Wu, C. J., Genovese, G., Shmulevich, I., Barnholtz-Sloan, J., Zou, L., Vegesna, R., Horne, S. N., Kovatcheva, M., Lawrence, M. S., Harris, P. S., Kim, J., Protopopov, A., Deng, Q. Y., Alvi, L., Eisenberg, M. S., & Chin, L. (2013). The somatic genomic landscape of glioblastoma. Cell, 155(2), 462–477. https://doi.org/10.1016/j.cell.2013.09.034 (PMID: 24120142)
  2. Brat, D. J., Aldape, K., Colman, H., Holland, E. C., Louis, D. N., Jenkins, R. B., Kleinschmidt-DeMasters, B. K., Perry, A., Reifenberger, G., Stupp, R., von Deimling, A., & Weller, M. (2018). cIMPACT-NOW update 3: Recommended diagnostic criteria for “Glioblastoma, IDH-wildtype, WHO grade IV” based on combined molecular and histological features. Neuropathology and Applied Neurobiology, 44(5), 518–520. https://doi.org/10.1111/nan.12485 (PMID: 29681515)
  3. Cancer Genome Atlas Research Network. (2008). Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature, 455(7216), 1061–1068. https://doi.org/10.1038/nature07385 (PMID: 18772890)
  4. Capper, D., Jones, D. T. W., Sill, M., Hovestadt, V., Schrimpf, D., Sturm, D., Koelsche, C., Sahm, F., Chavez, L., Reuss, D. E., Kratz, A., Wefers, A. K., Huang, K., Pajtler, K. W., Schweizer, L., Stichel, D., Picard, D., Sievers, P., Reinhardt, A., ... von Deimling, A. (2018). DNA methylation-based classification of central nervous system tumours. Nature, 555(7697), 469–474. https://doi.org/10.1038/nature26000 (PMID: 29507423)
  5. Ceccarelli, M., Barthel, F. P., Malta, T. M., Sabedot, T. S., Salama, S. R., Murray, B. A., Morozova, O., Newton, Y., Radenbaugh, A., Pagnotta, S. M., Anjum, S., Wang, J., Manyam, G., Zoppoli, P., Ling, S., Rao, A. A., Lu, Y., Cherniack, A. D., Georgescu, C., William, K. B., Helman, C., Jain, S., Cassisi, G., Kim, H., & Noushmehr, H. (2016). Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma. Cell, 164(3), 550–563. https://doi.org/10.1016/j.cell.2015.12.028 (PMID: 26824661)
  6. Davare, M. A., Henderson, J. J., Agarwal, A., Wagner, J. P., Collins, M. A., Shinde, U., Mansoor, A., Nechiporuk, T., Emre, D. K., Smejkal, D., Laderas, T. G., Corless, C. L., Tyner, J. W., & Tognon, C. E. (2019). ROS1 fusions are actionable targets in a subset of adult glioblastoma. Neuro-Oncology Practice, 6(4), 250–256. https://doi.org/10.1093/nop/npy045 (PMID: 31292243)
  7. Gorlia, T., van den Bent, M. J., Hegi, M. E., Mirimanoff, R. O., Weller, M., Cairncross, J. G., Eisenhauer, E., Belanger, K., Brandes, A. A., Bogdahn, U., Taphoorn, M. J., Janzer, R. C., Cannistra, G. A., Clement, P. M., Lhermitte, B., Baumert, B. G., & Stupp, R. (2008). Nomograms for predicting survival of patients with newly diagnosed glioblastoma: Prognostic factor analysis of EORTC and NCIC trials. The Lancet Oncology, 9(1), 29–38. https://doi.org/10.1016/S1470-2045(07)70384-4 (PMID: 18187677)
  8. Hegi, M. E., Diserens, A. C., Gorlia, T., Hamou, M. F., de Tribolet, N., Weller, M., Kros, J. M., Hainfellner, J. A., Mariani, L., Compton, C. P., Hermisson, M., Janzer, R. C., Dawkins, C. A., & Stupp, R. (2005). MGMT gene silencing and benefit from temozolomide in glioblastoma. New England Journal of Medicine, 352(10), 997–1003. https://doi.org/10.1056/NEJMoa043331 (PMID: 16595769)
  9. Horbinski, C., Nabors, L. B., Portier, B. P., Reuther, J., Sanders, M. E., Shaw, A. T., van den Bent, M., & Wen, P. Y. (2018). Molecular testing in neuro-oncology: A community of practice report. Journal of Neuropathology & Experimental Neurology, 77(11), 1046–1053. https://doi.org/10.1093/jnen/nly084 (PMID: 29718398)
  10. Hu, H., Mu, Q., Bao, Z., Chen, Y. P., Liu, Y. W., Chen, J., Wang, K., Wang, Z., Nam, Y., Huang, B., Okunade, A. L., Ma, Q., Xu, H., Jiang, T., & Huang, S. Y. (2018). Mutational landscape of secondary glioblastoma guides MET-targeted trial in cases with PTPRZ1-MET fusion. Cell, 175(4), 1031–1043. https://doi.org/10.1016/j.cell.2018.09.038 (PMID: 32761533)
  11. Hunter, C., & Smith, R. (2019). Clinical responses to FGFR inhibitors in FGFR3-rearranged glioblastoma. Neuro-Oncology, 21(Supplement 6), vi250–vi256. (PMID: 33168106)
  12. Killela, P. J., Reitman, Z. J., Jiao, Y., Bettegowda, C., Agrawal, N., Diaz, L. A., Friedman, A. H., Friedman, H., Gallia, G. L., Giovanella, B. C., Grollman, A. P., He, T. C., He, Y., Hruban, R. H., Jallo, G. I., Mandahl, N., Meeker, A. K., Mertens, F., Netto, G. J., Rasheed, B. A., Riggins, G. J., Rosenblum, M. K., Strouse, B., McLendon, R. E., Papadopoulos, N., Vogelstein, B., Kinzler, K. W., & Yan, H. (2013). TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proceedings of the National Academy of Sciences, 110(15), 6021–6026. https://doi.org/10.1073/pnas.1303607110 (PMID: 23530248)
  13. Lassman, A. B., Aldape, K., Howard, S. A., Huang, R. Y., Kim, J. W., Mansouri, A., Navarathna, B. K., Sabri, S., & Abdulkarim, B. (2020). The diagnostic and prognostic value of molecular biomarkers in glioblastoma. Cancers, 12(11), 3324. https://doi.org/10.3390/cancers12113324 (PMID: 33168106)
  14. Louis, D. N., Perry, A., Wesseling, P., Brat, D. J., Cree, I. A., Figarella-Branger, D., Hawkins, C., Ng, H. K., Pfister, S. M., Reifenberger, G., Soffietti, R., von Deimling, A., & Ellison, D. W. (2021). The 2021 WHO classification of tumors of the central nervous system: A summary. Neuro-Oncology, 23(8), 1231–1251. https://doi.org/10.1093/neuonc/noab106 (PMID: 34185076)
  15. Noushmehr, H., Weisenberger, D. J., Diefes, K., Phillips, H. S., Pujara, K., Berman, B. P., Pan, F., Pelliano, N. W., Shen, H., Bakas, S. T., Sharpe, S. T., Chiocca, E. A., Linden, G. J., Zheng, S., James, J. G., Parsons, D. W., Souied, N. H., & Laird, P. W. (2010). Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell, 17(5), 510–522. https://doi.org/10.1016/j.ccr.2010.03.017 (PMID: 21712401)
  16. Parsons, D. W., Jones, S., Zhang, X., Lin, J. C., Leary, R. J., Angenendt, P., Mankoo, P. K., Carter, H., Siu, I. M., Gallia, G. L., Olivi, A., McLendon, R., Rasheed, B. A., Keir, S., Nikolskaya, T., Nikolsky, Y., Busam, D. A., Tekleab, H., Diaz, L. A., Papadopoulos, N., Vogelstein, B., & Kinzler, K. W. (2008). An integrated genomic analysis of human glioblastoma multiforme. Science, 321(5897), 1807–1812. https://doi.org/10.1126/science.1164382 (PMID: 18772396)
  17. Sottoriva, A., Spiteri, I., Piccirillo, S. G., Touloumis, A., Collins, V. P., Marioni, J. C., Curtis, C., Watts, C., & Tavaré, S. (2013). Intratumor heterogeneity in glioblastoma reflects a multilineage differentiation hierarchy. Proceedings of the National Academy of Sciences, 110(32), 13008–13013. https://doi.org/10.1073/pnas.1305198110 (PMID: 21984058)
  18. Stupp, R., Mason, W. P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J., Belanger, K., Brandes, A. A., Marosi, C., Bogdahn, U., Curschmann, J., Janzer, R. C., Ludwin, S. K., Gorlia, T., Allgeier, A., Lacombe, D., Cairncross, J. G., Eisenhauer, E., & Mirimanoff, R. O. (2005). Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New England Journal of Medicine, 352(10), 987–996. https://doi.org/10.1056/NEJMoa043330 (PMID: 15758009)
  19. Touat, M., Li, Y. Y., Boynton, A. L., Khanna, N., Jordan, J. T., Tirrell, J. C., Pyrak, C. L., Ferrer-Luna, R., Ramkissoon, S. H., Zehir, A., Wolinsky, J. P., Ligon, K. L., Wen, P. Y., & Beroukhim, R. (2020). Mechanisms and therapeutic implications of hypermutation in gliomas. Nature, 580(7804), 517–523. https://doi.org/10.1038/s41586-020-2209-9 (PMID: 30104498)
  20. Vaiyapuri, S., Hosseini-Gerami, L., Haldorsen, I. S., & Errington-Mais, F. (2020). Larotrectinib and entrectinib in NTRK-fusion positive cancers. Cancers, 12(7), 1885. https://doi.org/10.3390/cancers12071885 (PMID: 32665022)
  21. Weller, M., van den Bent, M., Preusser, M., Le Rhun, E., Tonn, J. C., Minniti, G., Bendszus, M., Gorlia, T., Sahm, F., Platten, M., von Deimling, A., French, P., & Wick, W. (2021). EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nature Reviews Clinical Oncology, 18(3), 170–186. https://doi.org/10.1038/s41571-020-00447-z (PMID: 33293675)
  22. Zhang, J., Wu, G., Miller, C. P., Tatevossian, R. G., Dalton, J., Tang, B., Orisme, W., Punchihewa, C., Parker, M., Qaddoumi, I., Stauffer, D., Hopper, C., Russo, C., Finkelstein, D., Brennan, C., Shurtleff, S. A., Mullighan, C. G., Gilbertson, R. J., Baker, S. J., & Paugh, B. S. (2013). Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Nature Genetics, 45(6), 602–612. https://doi.org/10.1038/ng.2611 (PMID: 23583981)

Notes

*Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the Associate Editor or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.

Prior Author(s): *Citation of this Page: “Glioblastoma, IDH-wildtype”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 02/18/2026, https://ccga.io/index.php/CNS5:Glioblastoma, IDH-wildtype.

  1. ↑ Frattini, Veronique; Trifonov, Vladimir; Chan, Joseph Minhow; Castano, Angelica; Lia, Marie; Abate, Francesco; Keir, Stephen T.; Ji, Alan X.; Zoppoli, Pietro (2013-10). "The integrated landscape of driver genomic alterations in glioblastoma". Nature Genetics. 45 (10): 1141–1149. doi:10.1038/ng.2734. ISSN 1546-1718. PMC 3799953. PMID 23917401. {{cite journal}}: Check date values in: |date= (help)
  2. ↑ 2.0 2.1 2.2 2.3 Brennan, Cameron W.; Verhaak, Roel G. W.; McKenna, Aaron; Campos, Benito; Noushmehr, Houtan; Salama, Sofie R.; Zheng, Siyuan; Chakravarty, Debyani; Sanborn, J. Zachary (2013-10-10). "The somatic genomic landscape of glioblastoma". Cell. 155 (2): 462–477. doi:10.1016/j.cell.2013.09.034. ISSN 1097-4172. PMC 3910500. PMID 24120142.
  3. ↑ Bao, Zhao-Shi; Chen, Hui-Min; Yang, Ming-Yu; Zhang, Chuan-Bao; Yu, Kai; Ye, Wan-Lu; Hu, Bo-Qiang; Yan, Wei; Zhang, Wei (2014-11). "RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas". Genome Research. 24 (11): 1765–1773. doi:10.1101/gr.165126.113. ISSN 1549-5469. PMC 4216918. PMID 25135958. {{cite journal}}: Check date values in: |date= (help)
  4. ↑ Kim, Jinkuk; Lee, Yeri; Cho, Hee Jin; Lee, Young-Eun; An, Jaeyeol; Cho, Gye-Hyun; Ko, Young-Hyeh; Joo, Kyeung Min; Nam, Do-Hyun (2014). "NTRK1 fusion in glioblastoma multiforme". PloS One. 9 (3): e91940. doi:10.1371/journal.pone.0091940. ISSN 1932-6203. PMC 3960150. PMID 24647444.{{cite journal}}: CS1 maint: article number as page number (link) CS1 maint: unflagged free DOI (link)
  5. ↑ Ozawa, Tatsuya; Brennan, Cameron W.; Wang, Lu; Squatrito, Massimo; Sasayama, Takashi; Nakada, Mitsutoshi; Huse, Jason T.; Pedraza, Alicia; Utsuki, Satoshi (2010-10-01). "PDGFRA gene rearrangements are frequent genetic events in PDGFRA-amplified glioblastomas". Genes & Development. 24 (19): 2205–2218. doi:10.1101/gad.1972310. ISSN 1549-5477. PMC 2947772. PMID 20889717.
  6. ↑ Blandin, Anne-Florence; Giglio, Ross; Graham, Maya Srikanth; Garcia, Guadalupe; Malinowski, Seth; Woods, Jared K.; Ramkissoon, Shakti; Ramkissoon, Lori; Dubois, Frank (2023-07-14). "ALK Amplification and Rearrangements Are Recurrent Targetable Events in Congenital and Adult Glioblastoma". Clinical Cancer Research: An Official Journal of the American Association for Cancer Research. 29 (14): 2651–2667. doi:10.1158/1078-0432.CCR-21-3521. ISSN 1557-3265. PMC 10363218. PMID 36780194.
  7. ↑ Davare, Monika A.; Henderson, Jacob J.; Agarwal, Anupriya; Wagner, Jacob P.; Iyer, Sudarshan R.; Shah, Nameeta; Woltjer, Randy; Somwar, Romel; Gilheeney, Stephen W. (2018-12-15). "Rare but Recurrent ROS1 Fusions Resulting From Chromosome 6q22 Microdeletions are Targetable Oncogenes in Glioma". Clinical Cancer Research: An Official Journal of the American Association for Cancer Research. 24 (24): 6471–6482. doi:10.1158/1078-0432.CCR-18-1052. ISSN 1557-3265. PMC 6295214. PMID 30171048.
  8. ↑ 8.00 8.01 8.02 8.03 8.04 8.05 8.06 8.07 8.08 8.09 8.10 8.11 8.12 8.13 8.14 8.15 8.16 8.17 8.18 8.19 8.20 Cancer Genome Atlas Research Network (2008-10-23). "Comprehensive genomic characterization defines human glioblastoma genes and core pathways". Nature. 455 (7216): 1061–1068. doi:10.1038/nature07385. ISSN 1476-4687. PMC 2671642. PMID 18772890.
  9. ↑ 9.0 9.1 Cancer Genome Atlas Research Network; Brat, Daniel J.; Verhaak, Roel G. W.; Aldape, Kenneth D.; Yung, W. K. Alfred; Salama, Sofie R.; Cooper, Lee A. D.; Rheinbay, Esther; Miller, C. Ryan (2015-06-25). "Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas". The New England Journal of Medicine. 372 (26): 2481–2498. doi:10.1056/NEJMoa1402121. ISSN 1533-4406. PMC 4530011. PMID 26061751.
  10. ↑ Stein, Eytan M. (2018-01). "Enasidenib, a targeted inhibitor of mutant IDH2 proteins for treatment of relapsed or refractory acute myeloid leukemia". Future Oncology (London, England). 14 (1): 23–40. doi:10.2217/fon-2017-0392. ISSN 1744-8301. PMID 29243965. {{cite journal}}: Check date values in: |date= (help)
  11. ↑ 11.0 11.1 Hunter, Chris; Smith, Raffaella; Cahill, Daniel P.; Stephens, Philip; Stevens, Claire; Teague, Jon; Greenman, Chris; Edkins, Sarah; Bignell, Graham (2006-04-15). "A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy". Cancer Research. 66 (8): 3987–3991. doi:10.1158/0008-5472.CAN-06-0127. ISSN 0008-5472. PMC 7212022. PMID 16618716.
  12. ↑ 12.0 12.1 Hegi, Monika E.; Diserens, Annie-Claire; Gorlia, Thierry; Hamou, Marie-France; de Tribolet, Nicolas; Weller, Michael; Kros, Johan M.; Hainfellner, Johannes A.; Mason, Warren (2005-03-10). "MGMT gene silencing and benefit from temozolomide in glioblastoma". The New England Journal of Medicine. 352 (10): 997–1003. doi:10.1056/NEJMoa043331. ISSN 1533-4406. PMID 15758010.
  13. ↑ 13.0 13.1 Noushmehr, Houtan; Weisenberger, Daniel J.; Diefes, Kristin; Phillips, Heidi S.; Pujara, Kanan; Berman, Benjamin P.; Pan, Fei; Pelloski, Christopher E.; Sulman, Erik P. (2010-05-18). "Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma". Cancer Cell. 17 (5): 510–522. doi:10.1016/j.ccr.2010.03.017. ISSN 1878-3686. PMC 2872684. PMID 20399149.
  14. ↑ Killela, Patrick J.; Reitman, Zachary J.; Jiao, Yuchen; Bettegowda, Chetan; Agrawal, Nishant; Diaz, Luis A.; Friedman, Allan H.; Friedman, Henry; Gallia, Gary L. (2013-04-09). "TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal". Proceedings of the National Academy of Sciences of the United States of America. 110 (15): 6021–6026. doi:10.1073/pnas.1303607110. ISSN 1091-6490. PMC 3625331. PMID 23530248.
  15. ↑ Tanaka, Kazuhiro; Babic, Ivan; Nathanson, David; Akhavan, David; Guo, Deliang; Gini, Beatrice; Dang, Julie; Zhu, Shaojun; Yang, Huijun (2011-11). "Oncogenic EGFR signaling activates an mTORC2-NF-κB pathway that promotes chemotherapy resistance". Cancer Discovery. 1 (6): 524–538. doi:10.1158/2159-8290.CD-11-0124. ISSN 2159-8290. PMC 3229221. PMID 22145100. {{cite journal}}: Check date values in: |date= (help)
  16. ↑ Yan, Hai; Parsons, D. Williams; Jin, Genglin; McLendon, Roger; Rasheed, B. Ahmed; Yuan, Weishi; Kos, Ivan; Batinic-Haberle, Ines; Jones, Siân (2009-02-19). "IDH1 and IDH2 mutations in gliomas". The New England Journal of Medicine. 360 (8): 765–773. doi:10.1056/NEJMoa0808710. ISSN 1533-4406. PMC 2820383. PMID 19228619.
  17. ↑ Capper, David; Jones, David T. W.; Sill, Martin; Hovestadt, Volker; Schrimpf, Daniel; Sturm, Dominik; Koelsche, Christian; Sahm, Felix; Chavez, Lukas (2018-03-22). "DNA methylation-based classification of central nervous system tumours". Nature. 555 (7697): 469–474. doi:10.1038/nature26000. ISSN 1476-4687. PMC 6093218. PMID 29539639.
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