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 Recurrent (~ 6 - 13%) 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 (~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 (~ 1 - 4%) 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 (~ 1 - 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].
MLH1 Inactivating mutation / Methylation DNA repair (MMR) Rare (<5%) P, T No (WHO CNS5) MMR deficiency; drives high TMB and resistance to alkylating agents like TMZ[17].
MSH2 Loss-of-function mutation DNA repair (MMR) Rare (<5%) P, T No (WHO CNS5) Key MMR component; mutations lead to hypermutator status, often acquired in recurrent disease[17].
PMS2 Loss-of-function mutation DNA repair (MMR) Rare (<5%) P, T No (WHO CNS5) Functions with MLH1; deficiency contributes to mismatch repair secondary to TMZ treatment[17].
POLE Exonuclease domain mutations DNA Polymerase (Proofreading) Rare (<5%) P, T No (WHO CNS5) Leads to "ultramutated" phenotype; may predict exceptional response to immune checkpoint inhibitors[17].
BRAF V600E Missense mutation Oncogene Rare (<5%) D, P, T Yes (WHO CNS5 / NCCN) Common in epithelioid variant; diagnostic marker for epithelioid GBM and targetable with BRAF/MEK inhibitors[18][19].

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[20].

Genes and Main Pathways Involved

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
EGFR; amplification ± activating mutation (e.g., EGFRvIII) Receptor Tyrosine Kinase (RTK) / PI3K / MAPK Constitutive growth factor signaling → increased proliferation, survival, angiogenesis[8]
PDGFRA; amplification ± activating mutation RTK / PI3K Ligand-independent mitogenic signaling; proneural transcriptional association[1]
MET; amplification RTK / MAPK / PI3K Enhanced invasion, motility, and tumor progression[1]
PIK3CA; activating mutation PI3K / AKT / mTOR Increased survival signaling, metabolic activation, therapy resistance[8]
PIK3R1; inactivating mutation PI3K / AKT / mTOR Loss of regulatory inhibition → constitutive PI3K activation[8]
PTEN; deletion or inactivating mutation PI3K / AKT / mTOR Loss of AKT suppression → enhanced proliferation and survival[8]
NF1; inactivating mutation RAS / MAPK Sustained RAS pathway activation; mesenchymal phenotype association[1]
TP53; inactivating mutation p53 tumor suppressor pathway Impaired DNA damage response and apoptosis; genomic instability[8]
MDM2 / MDM4; amplification p53 pathway Functional suppression of p53 activity despite wildtype TP53[1]
CDKN2A/B; homozygous deletion RB cell cycle pathway Loss of G1/S checkpoint control via p16INK4a/p14ARF loss[8]
CDK4 / CDK6; amplification RB pathway RB hyperphosphorylation → uncontrolled cell cycle progression[1]
RB1; inactivating mutation or deletion RB pathway Loss of G1/S restriction point control[8]
TERT; promoter mutation Telomere maintenance Telomerase reactivation → cellular immortality[14]
MGMT; promoter methylation (epigenetic) DNA repair Reduced O6-alkylguanine repair → increased temozolomide sensitivity[12]

Genetic Diagnostic Testing Methods

Genetic Alteration / Biomarker Recommended Testing Method(s) Notes / Rationale
IDH1 R132H mutation Immunohistochemistry (IHC); confirm with targeted sequencing if negative in younger patients First-line exclusion test; IDH-wildtype status required for this entity. IHC detects the common R132H mutation; sequencing required to exclude non-canonical IDH1/IDH2 variants[16].
IDH1/IDH2 non-canonical mutations Targeted NGS panel or Sanger sequencing Necessary when IHC is negative but clinical context suggests possible IDH mutation (e.g., younger patient)[16].
TERT promoter mutation PCR-based assay; Sanger sequencing; NGS WHO diagnostic criterion in diffuse astrocytic tumor lacking histologic GBM features; supports classification as GBM, IDH-wildtype when combined with other molecular features[14].
EGFR amplification FISH; chromogenic ISH; copy-number analysis via NGS; SNP array One of the three WHO molecular criteria for GBM, IDH-wildtype in lower-grade appearing tumors; common driver amplification[8].
Combined whole chromosome 7 gain / chromosome 10 loss (+7/−10) SNP array; chromosomal microarray (CMA); copy-number profiling via NGS; methylation array CNV plot WHO diagnostic molecular signature; highly characteristic of IDH-wildtype GBM[1].
CDKN2A/B homozygous deletion FISH; chromosomal microarray; copy-number NGS Common RB pathway alteration; may have prognostic significance; detected as focal homozygous deletion[8].
PTEN loss (mutation or deletion) NGS for mutations; copy-number analysis; IHC (adjunct only) Common PI3K pathway alteration; IHC alone insufficient for definitive assessment[8].
TP53 mutation NGS panel; IHC (screening) Mutation common but not diagnostic; IHC used as screening surrogate; sequencing confirms alteration[1].
MGMT promoter methylation Methylation-specific PCR; pyrosequencing; quantitative methylation assay Predictive biomarker for temozolomide response; not diagnostic for entity classification but clinically actionable[12]
DNA methylation class (GBM, IDH-wildtype) Genome-wide methylation array classifier Useful in diagnostically ambiguous cases; provides integrated tumor classification and copy-number profile[20].
EGFRvIII structural variant RT-PCR; RNA-based NGS Detects specific EGFR rearrangement variant; biologic relevance; not required for diagnosis[1].
Broad molecular profiling panel Targeted DNA NGS panel ± RNA fusion panel Allows simultaneous detection of SNVs, indels, copy-number alterations, and selected fusions; increasingly standard in tertiary centers[1].

Familial Forms

Most cases of glioblastoma, IDH-wildtype are sporadic; however, rare familial cancer predisposition syndromes are associated with increased risk of high-grade glioma, including:

  • Li-Fraumeni syndrome (germline TP53 mutation)
  • Neurofibromatosis type 1 (germline NF1 mutation)
  • Turcot syndrome (APC or mismatch repair gene mutations)
  • Lynch syndrome (germline mismatch repair deficiency)
  • Neurofibromatosis type 2 (rare association)

Familial glioblastoma is uncommon (<5% of cases), and routine germline testing is not indicated unless there is suggestive personal or family history (early age at onset, multiple primary tumors, or known hereditary cancer syndrome)[18].

Additional Information

  • Most common malignant primary brain tumor in adults.
  • Defined by IDH-wildtype status with either classic histologic features (necrosis and/or microvascular proliferation) or specific molecular criteria (per WHO CNS5).
  • Predominantly affects older adults and arises in the cerebral hemispheres.
  • Radiographically presents as a heterogeneously enhancing mass with central necrosis and surrounding edema.
  • Highly infiltrative with inevitable local recurrence despite multimodal therapy.
  • Standard treatment: maximal safe resection followed by radiotherapy with concurrent and adjuvant temozolomide.
  • Median overall survival approximately 12–18 months; long-term survival is uncommon.
  • Most cases are sporadic; hereditary predisposition is rare.

Links

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References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 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 8.21 8.22 8.23 8.24 8.25 8.26 8.27 8.28 8.29 8.30 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 12.2 12.3 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. ↑ 14.0 14.1 14.2 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. ↑ 16.0 16.1 16.2 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. ↑ 17.0 17.1 17.2 17.3 Touat, Mehdi; Li, Yvonne Y.; Boynton, Adam N.; Spurr, Liam F.; Iorgulescu, J. Bryan; Bohrson, Craig L.; Cortes-Ciriano, Isidro; Birzu, Cristina; Geduldig, Jack E. (2020-04). "Mechanisms and therapeutic implications of hypermutation in gliomas". Nature. 580 (7804): 517–523. doi:10.1038/s41586-020-2209-9. ISSN 1476-4687. PMC 8235024. PMID 32322066. {{cite journal}}: Check date values in: |date= (help)
  18. ↑ 18.0 18.1 Louis, David N.; Perry, Arie; Wesseling, Pieter; Brat, Daniel J.; Cree, Ian A.; Figarella-Branger, Dominique; Hawkins, Cynthia; Ng, H. K.; Pfister, Stefan M. (2021-08-02). "The 2021 WHO Classification of Tumors of the Central Nervous System: a summary". Neuro-Oncology. 23 (8): 1231–1251. doi:10.1093/neuonc/noab106. ISSN 1523-5866. PMC 8328013. PMID 34185076.
  19. ↑ Nabors, Louis Burt; Hattangadi-Gluth, Jona; Horbinski, Craig; Portnow, Jana (2025-03-07). "NCCN CNS Tumor Guidelines Update for 2024". Neuro-Oncology. 27 (3): 595–596. doi:10.1093/neuonc/noae267. ISSN 1523-5866. PMC 11889715. PMID 39693230.
  20. ↑ 20.0 20.1 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.

Notes

Prior Author(s): *Citation of this Page: “Glioblastoma, IDH-wildtype”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 04/22/2026, https://ccga.io/index.php/CNS5:Glioblastoma, IDH-wildtype.

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