Glioblastoma, IDH-wildtype

107 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
FGFR3	FGFR3::TACC3	Constitutive activation of FGFR3 tyrosine kinase through fusion with TACC3, resulting in persistent MAPK and PI3K pathway signaling (PMID: 33168106).	Intrachromosomal tandem duplication at 4p16.3 (PMID: 33168106).	Recurrent (~3–5%) in IDH-wildtype glioblastoma (PMID: 33168106).	D, T	Yes (WHO CNS; NCCN)	FGFR3::TACC3 is a recurrent and characteristic fusion in IDH-wildtype glioblastoma and defines a molecular subset of tumors (PMID: 33168106). The fusion has diagnostic utility in confirming IDH-wildtype status in the appropriate histologic context (PMID: 29718398). Clinical responses to FGFR inhibitors have been reported, though therapeutic benefit in glioblastoma remains under investigation (PMID: 33168106).
NTRK1 / NTRK2 / NTRK3	ETV6::NTRK3, BCAN::NTRK1, TPM3::NTRK1, others (PMID: 29718398)	Constitutive TRK kinase activation caused by fusion-driven ligand-independent signaling (PMID: 32665022).	Variable inter- and intrachromosomal rearrangements (PMID: 29718398)	Rare (<5%), typically ≤2% of glioblastomas (PMID: 32665022).	D, T	Yes (NCCN; FDA tumor-agnostic approval)	NTRK fusions are rare but clinically actionable in glioblastoma. TRK inhibitors (e.g., larotrectinib, entrectinib) have demonstrated durable responses in NTRK fusion–positive tumors, including CNS neoplasms (PMID: 32665022). Prognostic significance in glioblastoma remains unclear due to low frequency.
MET	PTPRZ1::MET, ST7::MET, CAPZA2::MET, others (PMID: 29718398).	Fusion-mediated constitutive MET tyrosine kinase activation with downstream oncogenic signaling (PMID: 32761533).	Variable, often complex rearrangements (PMID: 29718398).	Rare (<5%), reported in ~2–3% of IDH-wildtype glioblastomas (PMID: 32761533).	D, T (emerging)	No	MET fusions, particularly PTPRZ1::MET, have been associated with aggressive clinical behavior and shorter progression-free survival in IDH-wildtype glioblastoma (PMID: 32761533). Therapeutic targeting of MET in this setting remains investigational.
ROS1	GOPC::ROS1, other rare partners (PMID: 31292243).	Constitutive ROS1 kinase activation resulting from fusion events (PMID: 31292243).	Variable chromosomal rearrangements (PMID: 31292243).	Rare (<5%), estimated <1% of adult glioblastomas (PMID: 31292243).	D, T (emerging)	No	ROS1 fusions are rare in glioblastoma but represent a potentially actionable alteration. Isolated case reports describe responses to ROS1 inhibitors such as entrectinib in ROS1-rearranged gliomas (PMID: 31292243).
EGFR	Structural rearrangements (e.g., EGFR::SEPT14, other EGFR fusions) (PMID: 29681515).	Aberrant EGFR signaling due to structural rearrangements or fusion events, promoting tumor growth and survival (PMID: 29681515).	Complex rearrangements involving chromosome 7p11.2 (PMID: 29681515).	Rare (<5%) for EGFR fusions; EGFR alterations overall are common in glioblastoma (PMID: 29681515).	D	Yes (WHO CNS)	EGFR structural rearrangements are part of the molecular spectrum of IDH-wildtype glioblastoma and contribute to diagnostic classification per WHO CNS criteria (PMID: 29681515). Targeted EGFR therapies have not demonstrated consistent clinical benefit in glioblastoma.
BRAF	Rare BRAF fusion events with various partners (PMID: 29681515).	Fusion-mediated activation of the MAPK signaling pathway (PMID: 29681515).	Variable chromosomal alterations (PMID: 29681515).	Rare (<5%) in adult glioblastoma (PMID: 29681515).	D	No	BRAF fusions are uncommon in adult glioblastoma and are more characteristic of pediatric low-grade gliomas. Their clinical significance in glioblastoma remains limited (PMID: 29681515).

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 7; chr7 [hg38]	EGFR, MET, CDK6	D, P	Yes (WHO CNS)	Gain of chromosome 7 is a hallmark cytogenetic abnormality of IDH-wildtype glioblastoma and, when combined with loss of chromosome 10, supports the diagnosis of glioblastoma in the appropriate histologic context (PMID: 29681515). Chromosome 7 gain often co-occurs with EGFR amplification and is associated with aggressive tumor behavior (PMID: 33168106).
10	Loss	Whole chromosome 10; chr10 [hg38]	PTEN	D, P	Yes (WHO CNS)	Loss of chromosome 10 is one of the most frequent alterations in IDH-wildtype glioblastoma and commonly accompanies chromosome 7 gain (PMID: 29681515). This alteration contributes to PTEN loss and PI3K pathway activation and is associated with poor prognosis (PMID: 33168106).
9	Loss / LOH	9p21.3; chr9:21,800,000–22,100,000 [hg38; ~0.3 Mb]	CDKN2A, CDKN2B	D, P	Yes (WHO CNS)	Homozygous deletion of CDKN2A/CDKN2B is a frequent event in IDH-wildtype glioblastoma and results in loss of cell cycle control (PMID: 29681515). CDKN2A homozygous deletion is recognized by WHO CNS as a molecular criterion supporting glioblastoma classification and is associated with adverse prognosis (PMID: 33168106).
12	Amp	12q14.1–q15; chr12:68,500,000–70,200,000 [hg38; ~1.7 Mb]	MDM2, CDK4	D, T	No	Amplification of MDM2 and/or CDK4 leads to dysregulation of the p53 and RB pathways and is recurrent in IDH-wildtype glioblastoma (PMID: 29681515). These amplifications may be mutually exclusive with CDKN2A deletion and are under investigation as potential therapeutic targets (PMID: 33168106).
13	Loss	13q14; chr13:48,000,000–50,000,000 [hg38; ~2 Mb]	RB1	P	No	Loss of chromosome 13q, including RB1, contributes to cell cycle deregulation in glioblastoma (PMID: 29681515). RB1 loss is associated with aggressive tumor behavior, though it is not independently diagnostic (PMID: 33168106).
19	Gain	19q12–q13; chr19 [hg38]	CCNE1, AKT2	P	No	Gain of chromosome 19 or 19q is observed in a subset of IDH-wildtype glioblastomas and may contribute to oncogenic signaling (PMID: 29681515). Unlike 1p/19q codeletion, isolated 19q gain has no defining diagnostic role in glioblastoma.
20	Gain	20q; chr20 [hg38]	AURKA	P	No	Gain of chromosome 20q has been reported as a recurrent secondary alteration in glioblastoma and may be associated with tumor progression (PMID: 33168106). Clinical significance remains limited.

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
Hyperdiploidy	Whole-genome duplication resulting in increased chromosomal content and global genomic instability	Recurrent (≈15–20%) in IDH-wildtype glioblastoma (PMID: 29681515)	P	No	Hyperdiploid tumors may have increased cell proliferation and genomic instability, contributing to aggressive behavior (PMID: 29681515). Not independently diagnostic. This is often a late event in tumor evolution, representing a transition from a lower-grade precursor to a fully manifest Glioblastoma.
Gain of odd-numbered chromosomes (1, 3, 5, 7, 11, 17)	Whole-chromosome gains leading to increased dosage of oncogenes (e.g., EGFR on 7, CCND1 on 11)	Common (>20%) (PMID: 29681515)	D, P	Yes (WHO CNS)	Gain of chromosome 7 is particularly important, often coupled with loss of chromosome 10, supporting IDH-wildtype glioblastoma diagnosis. Gains of other odd-numbered chromosomes are recurrent but secondary (PMID: 33168106).
1p/19q co-deletion	Simultaneous deletion of the short arm of chromosome 1 and long arm of chromosome 19	Rare (<5%) in IDH-wildtype glioblastoma (PMID: 29681515)	D	Yes (WHO CNS)	1p/19q co-deletion is a defining feature of oligodendroglioma, not IDH-wildtype glioblastoma. Its absence helps distinguish glioblastoma from oligodendroglioma (PMID: 29681515).
Complex karyotype without characteristic genetic findings	Multiple chromosomal gains, losses, and rearrangements without a single defining alteration	Common (>20%) (PMID: 29681515)	P	No	Reflects genomic instability typical of high-grade gliomas. Associated with tumor progression and poor prognosis but not independently diagnostic (PMID: 29681515).
Chromothripsis	Catastrophic chromosomal fragmentation and reassembly	Rare (~5%) (PMID: 29507423)	P	No	Can lead to focal amplifications of oncogenes (e.g., EGFR) or loss of tumor suppressors. Associated with aggressive tumor evolution (PMID: 29507423).
Microsatellite instability (MSI-high)	Defective mismatch repair leading to high mutation burden	Rare (<1%) (PMID: 29681515)	P, T	No	Most IDH-wildtype glioblastomas are microsatellite stable. MSI-high tumors are uncommon and may be considered for immunotherapy in rare cases (PMID: 29681515).
Homologous recombination deficiency (HRD)	Impaired DNA double-strand break repair via BRCA-related or other HR pathways	Rare (<5%) (PMID: 31293997)	P, T	No	HRD is uncommon in primary IDH-wildtype glioblastoma. When present, it may sensitize tumors to PARP inhibitors or platinum-based therapy (PMID: 31293997).
Mutational signature pattern – age-related	Predominantly COSMIC Signature 1 (spontaneous CpG deamination)	Common (>50%) (PMID: 29681515)	P	No	Age-related signature dominates the mutational landscape in IDH-wildtype glioblastoma, reflecting clock-like accumulation of mutations (PMID: 29681515).
Mutational signature pattern – therapy-induced hypermutation	Signature 11 (temozolomide-associated alkylation)	Recurrent in post-treatment tumors (≈5–10%) (PMID: 30104498)	P, T	No	Hypermutation can arise after temozolomide therapy, leading to resistance and altered therapeutic response. Relevant for treatment planning (PMID: 30104498).

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	C228T or C250T promoter SNV	Oncogene	Common (>60%) (PMID: 29681515, 33168106)	D, P	Yes (WHO CNS)	Defining molecular feature of IDH-wildtype glioblastoma. Associated with poor prognosis. Often co-occurs with EGFR amplification and PTEN loss. No FDA-approved therapy. (PMID: 29681515)
EGFR	In-frame insertion/deletion (exons 2–7), EGFRvIII variant	Oncogene	Common (>40%) (PMID: 29681515, 33168106)	D, P, T	Yes (WHO CNS; NCCN)	EGFRvIII variant leads to constitutive activation. Experimental EGFR-targeted therapies under clinical investigation. Often mutually exclusive with TP53 mutations. (PMID: 33168106)
PTEN	Frameshift, nonsense, splice site SNV/indel	Tumor Suppressor Gene	Recurrent (≈25–30%) (PMID: 29681515, 33168106)	P	Yes (WHO CNS)	Frequently co-mutated with EGFR amplification. Associated with poor prognosis. PI3K pathway inhibitors under clinical trials; no FDA-approved therapy (PMID: 33168106).
TP53	Missense or truncating SNV/indel	Tumor Suppressor Gene	Recurrent (≈25%) (PMID: 29681515, 33168106)	P	Yes (WHO CNS)	More common in secondary glioblastoma but present in a subset of IDH-wildtype. Often mutually exclusive with EGFR amplification. No FDA-approved therapy (PMID: 33168106).
NF1	Frameshift, nonsense, splice site SNV/indel	Tumor Suppressor Gene	Recurrent (≈15–20%) (PMID: 29681515)	P	No	Defines mesenchymal subset of IDH-wildtype GBM. Associated with poor prognosis. MEK inhibitors under investigation. (PMID: 33168106) NF1 mutations are often associated with high inflammatory signaling and may play a role in the tumor's microenvironment.
PIK3CA	Hotspot SNVs (E542K, E545K, H1047R)	Oncogene	Rare (<5%) (PMID: 29681515, 33168106)	P, T	No	Often co-occurs with PTEN loss. PI3K inhibitors available in clinical trials; no FDA-approved therapy specifically for GBM. (PMID: 33168106)
PIK3R1	Inactivating SNVs/indels	Tumor Suppressor Gene	Rare (<5%) (PMID: 29681515)	P	No	Frequently co-occurs with other PI3K pathway alterations. No FDA-approved therapy in GBM. (PMID: 33168106)
IDH1	R132H or other R132 hotspot SNV	Oncogene	Rare (<5%) in IDH-wildtype GBM (PMID: 29681515)	D	Yes (WHO CNS)	Absence defines IDH-wildtype GBM. FDA-approved IDH inhibitors exist for other tumors but not for GBM (PMID: 29681515).
RB1	Truncating, splice site SNV/indel	Tumor Suppressor Gene	Rare (<5%) (PMID: 29681515)	P	No	Often co-occurs with CDKN2A deletion. Associated with aggressive tumor behavior. No FDA-approved therapy (PMID: 33168106).
ATRX	Frameshift, nonsense, splice site SNV/indel	Tumor Suppressor Gene	Rare (<5%) (PMID: 29681515)	P	No	Mostly in IDH-mutant astrocytomas; rarely in IDH-wildtype GBM. Prognostic impact limited in IDH-wildtype (PMID: 29681515).

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	Hypermethylation of MGMT promoter CpG islands leads to silencing of DNA repair enzyme MGMT	Common (~40%) (PMID: 16595769, 18187677)	P, T	Yes (NCCN, WHO CNS)	Predictive biomarker for response to temozolomide. Associated with improved overall survival in IDH-wildtype GBM (PMID: 16595769, 18187677).
Global hypomethylation	Genome-wide loss of 5-methylcytosine, often in repetitive elements	Common (>50%) (PMID: 21984058)	P	No	Associated with genomic instability and tumor progression. Often co-occurs with TERT promoter mutations and EGFR amplification (PMID: 21984058).
CpG island methylator phenotype (G-CIMP negative)	Absence of IDH-associated G-CIMP hypermethylation	Common in IDH-wildtype GBM (~95%) (PMID: 21712401)	D, P	Yes (WHO CNS)	Helps distinguish IDH-wildtype from IDH-mutant GBM. Associated with poor prognosis compared to G-CIMP positive tumors (PMID: 21712401).
Histone H3K27me3 deregulation	Altered histone methylation marks via EZH2 or PRC2 dysregulation	Recurrent (~15–20%) (PMID: 31043788)	P	No	Linked to transcriptional silencing of tumor suppressor genes. Potential target for EZH2 inhibitors in clinical trials (PMID: 31043788).
Chromatin remodeling alterations (ATRX loss)	Inactivation of ATRX affects histone H3.3 deposition at telomeres.	Rare (<5%) (PMID: 29681515)	P	No	Leads to alternative lengthening of telomeres (ALT) phenotype. Mostly in IDH-mutant tumors; rarely in IDH-wildtype GBM (PMID: 29681515).

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

Put a link here or anywhere appropriate in this page (Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "http://www." portion.)

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 01/12/2026, https://ccga.io/index.php/CNS5:Glioblastoma, IDH-wildtype.