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BIOMARKER:

MGMT promoter methylation

i
Other names: MGMT, Methylated-DNA--protein-cysteine methyltransferase, 6-O-methylguanine-DNA methyltransferase, O-6-methylguanine-DNA-alkyltransferase
Entrez ID:
Related biomarkers:
5h
A systematic review of high impact CpG sites and regions for MGMT methylation in glioblastoma [A systematic review of MGMT methylation in GBM]. (PubMed, BMC Neurol)
The following systematic review details a comprehensive investigation of the current literature and highlights several potential key CpG sites that demonstrate significant association with OS, PFS, and MGMT expression. However, the relationship between extent of MGMT promoter methylation and survival may be non-linear and could be influenced by potential CpG hotspots, the extent of methylation at each CpG site, and MGMT enhancer methylation status. There were several limitations within the studies such as smaller sample sizes, variance between methylation testing methods, and differences in the various statistical methods to test for association to outcome. Further studies of high impact CpG sites in MGMT methylation is warranted.
Review • Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation • MGMT expression
11h
Treatment Strategies for Glioblastoma in the Elderly: What Should We Focus on Compared to Younger Patients. (PubMed, Cancers (Basel))
Furthermore, MGMT methylation seems to be associated with a longer PFS in elderly patients. Further investigations are required to confirm these findings, especially within prospective radiation therapy studies and molecular examinations.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation
21h
Predominance of MGMT promoter methylation among Pakistani glioblastoma patients. (PubMed, Mol Biol Rep)
This is the first comprehensive study highlighting a predominance of MGMT methylation in Pakistani GBM patients. Furthermore, our findings underscore the association of MGMT methylation with improved OS across diverse treatment modalities. Larger studies are imperative to validate our findings for better management of Pakistani GBM patients.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation
5d
Adjuvant re-irradiation vs. no early re-irradiation of resected recurrent glioblastoma: pooled comparative cohort analysis from two tertiary centers. (PubMed, J Neurooncol)
Factors such as MGMT promoter methylation status and treatment interval play crucial roles in determining patient outcomes after second surgery. Personalized treatment strategies should consider these factors to optimize the management of rGBM. Prospective research is needed to define the value of re-RT after second surgery and to inform decision making in this situation.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation • IDH wild-type
7d
Effects of Levetiracetam and Lacosamide on survival and seizure control in IDH-wild type glioblastoma during temozolomide plus radiation adjuvant therapy. (PubMed, Brain Spine)
In patients diagnosed with GBM IDH-WT undergoing chemoradiation therapy, the use of levetiracetam or lacosamide for controlling BTRE does not seem to modify survival. Lacosamide users exhibited a higher IRR of postoperative seizures compared to levetiracetam users, and MGMT promoter methylation appears to be a protective factor.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation • IDH wild-type
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temozolomide
8d
Integrative multi-omics characterization reveals sex differences in glioblastoma. (PubMed, Biol Sex Differ)
Collectively, our study provides unprecedented insights into the fundamental modulators of tumor progression and clinical outcomes between male and female GBM patients and facilitates sex-specific treatment interventions. Highlights Female GBM patients were characterized by increased MGMT promoter methylation and favorable clinical outcomes compared to male patients. Female GBMs exhibited higher levels of genomic instability, including aneuploidy and TMB. Each sex-specific GBM is characterized by unique pathway dysregulations and molecular subtypes. EGFR activation is prevalent in male patients, while female patients are marked by SPP1 hyperphosphorylation.
Journal • Tumor mutational burden
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EGFR (Epidermal growth factor receptor) • TMB (Tumor Mutational Burden) • MGMT (6-O-methylguanine-DNA methyltransferase) • SPP1 (Secreted Phosphoprotein 1)
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MGMT promoter methylation
9d
Management of glioblastoma in elderly patients: A review of the literature. (PubMed, Clin Transl Radiat Oncol)
The standard management protocol of newly diagnosed glioblastoma patients involves surgery followed by radiotherapy, chemotherapy in the form of temozolomide and further adjuvant temozolomide...For elderly patients who cannot tolerate chemotherapy, hypofractionated radiotherapy is an option. In contrast to the younger adult patients, it seems that a careful individualised approach is a key element in deciding the best treatment options for this group of patients.
Review • Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation
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temozolomide
11d
Prognosis of glioblastoma patients improves significantly over time interrogating historical controls. (PubMed, Eur J Cancer)
This increase of mOS over time in newly diagnosed GBM patients could be explained by better management of potentially associated non-neurological diseases, optimization of validated SOC, better management of treatments side effects, supportive care and participation in clinical trials.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation
14d
Ph I/II Study of NMS-03305293+TMZ in Adult Patients With Recurrent Glioblastoma (clinicaltrials.gov)
P1/2, N=150, Recruiting, Nerviano Medical Sciences | N=75 --> 150
Enrollment change
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EGFR (Epidermal growth factor receptor) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • MGMT (6-O-methylguanine-DNA methyltransferase) • TERT (Telomerase Reverse Transcriptase)
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EGFR mutation • EGFR amplification • MGMT promoter methylation • TERT mutation • IDH wild-type • TERT promoter mutation
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temozolomide • NMS-293
16d
NRG-BN007: Testing the Use of the Immunotherapy Drugs Ipilimumab and Nivolumab Plus Radiation Therapy Compared to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed MGMT Unmethylated Glioblastoma (clinicaltrials.gov)
P2/3, N=147, Active, not recruiting, National Cancer Institute (NCI) | N=485 --> 147 | Trial completion date: Aug 2024 --> Mar 2025 | Trial primary completion date: Aug 2024 --> Apr 2023
Enrollment change • Trial completion date • Trial primary completion date • Tumor mutational burden
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PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • MGMT (6-O-methylguanine-DNA methyltransferase)
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PD-L1 expression • MGMT promoter methylation • IDH1 R132H • IDH1 R132 • MGMT expression
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Opdivo (nivolumab) • Yervoy (ipilimumab) • temozolomide • ABP 206 (nivolumab biosimilar)
1m
Adult epithelioid glioblastoma exhibits an extremely poor prognosis and high frequency of SWI/SNF complex mutation: Insights from a retrospective study. (PubMed, Int J Cancer)
Adult eGBM carried a dismal prognosis compared to GBM with IDH and H3 wild-type (typical GBM) (OS: 13.89 vs 24.30 months; P = .003) and even typical GBM without MGMT promoter methylation (OS: 13.89 vs 22.08 months; P = .036). Based on these findings, it can be concluded that adult eGBM harbors a high frequency of the 7+/10- signature and alterations in the MAPK pathway, SWI/SNF complex and cyclin-related genes and portends an extremely poor prognosis.
Retrospective data • Journal
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BRAF (B-raf proto-oncogene) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MGMT (6-O-methylguanine-DNA methyltransferase) • TERT (Telomerase Reverse Transcriptase) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ARID1B (AT-Rich Interaction Domain 1B)
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BRAF V600E • BRAF V600 • CDKN2A deletion • MGMT promoter methylation • CDK4 amplification • TERT mutation • ARID1B mutation • TERT promoter mutation • BRAF amplification
1m
Computational pathology-based weakly supervised prediction model for MGMT promoter methylation status in glioblastoma. (PubMed, Front Neurol)
The model demonstrates effective prediction of MGMT promoter methylation status in glioblastoma and exhibits some degree of generalization capability. At the same time, our study also shows that adding Patches automatic screening module to the computational pathology research framework of glioma can significantly improve the model effect.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation
1m
MGMT promoter methylation prediction based on multiparametric MRI via vision graph neural network. (PubMed, J Med Imaging (Bellingham))
A graph representation of the medical images enabled good handling of complexity and irregularity. Our work provides an automatic secondary check pipeline to ensure the correctness of MGMT methylation status prediction.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation
2ms
Development of a rapid and comprehensive genomic profiling test supporting diagnosis and research for gliomas. (PubMed, Brain Tumor Pathol)
We applied our CGP for 23 consecutive cases of intracranial mass lesions, which demonstrated its efficacy in aiding diagnosis and prognostication. Our CGP offers a comprehensive and rapid molecular profiling for gliomas, which could potentially apply to clinical practices and research primarily in the field of brain tumors.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation
2ms
Treatment outcome of IDH1/2 wildtype CNS WHO grade 4 glioma histologically diagnosed as WHO grade II or III astrocytomas. (PubMed, J Neurooncol)
WHO grade 2 and 3 IDH1/2 wt astrocytomas, treated according to the same treatment protocols, have a similar OS. Age, extent of resection, and strong EGFR expression were the most important treatment related prognostic factors.
Journal
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EGFR (Epidermal growth factor receptor) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • MGMT (6-O-methylguanine-DNA methyltransferase) • TERT (Telomerase Reverse Transcriptase)
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EGFR amplification • EGFR expression • MGMT promoter methylation • TERT mutation • IDH wild-type
2ms
AI-driven estimation of O6 methylguanine-DNA-methyltransferase (MGMT) promoter methylation in glioblastoma patients: a systematic review with bias analysis. (PubMed, J Cancer Res Clin Oncol)
Our findings underscore the immense potential of AI-based machine learning (ML) and deep learning (DL) methods in non-invasively determining MGMT promoter methylation status. Importantly, the clinical significance of these AI-driven advancements lies in their capacity to transform GBM patient care by providing accurate and timely information for treatment decisions. However, the translation of these technical advancements into clinical practice presents challenges, including the need for large multi-institutional cohorts and the integration of diverse data types. Addressing these challenges will be critical in realizing the full potential of AI in improving the reliability and accessibility of MGMT estimation while lowering the risk of bias in clinical decision-making.
Review • Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation
2ms
Glioblastoma with high O6-methyl-guanine DNA methyltransferase expression are more immunologically active than tumors with low MGMT expression. (PubMed, Front Immunol)
The effectiveness of temozolomide (TMZ) treatment in GBM is linked to the methylation status of O6-methyl-guanine DNA methyltransferase (MGMT) promoter...These findings contribute to a better understanding of the immune response in MGMT-H tumors, emphasizing their potential for immunotherapy. Further studies are warranted to investigate on the mechanisms of MGMT expression and antitumor immunity.
Journal • IO biomarker • Epigenetic controller
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MGMT (6-O-methylguanine-DNA methyltransferase) • CD8 (cluster of differentiation 8)
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MGMT promoter methylation • MGMT expression
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temozolomide
2ms
Quality assessment of the MRI-radiomics studies for MGMT promoter methylation prediction in glioma: a systematic review and meta-analysis. (PubMed, Eur Radiol)
• Adherence to the indications of TRIPOD guidelines was generally low, as was RQS total score. • MGMT promoter methylation status prediction with MRI radiomic features provided heterogeneous diagnostic accuracy results across studies. • Studies that included grade IV glioma only and performed external validation had significantly lower diagnostic accuracy than others.
Retrospective data • Review • Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation
2ms
Identification of MGMT promoter methylation as a specific lipid metabolism biomarker, reveals the feasibility of atorvastatin application in glioblastoma. (PubMed, Metabolism)
MGMT promoter methylation status might be a well-performed biomarker of lipid metabolism in glioblastoma. The current study can be the basis of further mechanism studies and implementation of clinical trials, and the results provide preclinical evidence of atorvastatin administration in glioblastoma, especially for MGMT unmethylated tumors.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation
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temozolomide
2ms
De Ritis ratio in elderly glioblastoma patients treated with chemoradiation: A comprehensive analysis of serum biomarkers. (PubMed, Neurooncol Adv)
We aimed to comprehensively investigate the prognostic value of pretreatment laboratory parameters in elderly patients with glioblastoma treated with temozolomide (TMZ)-based chemoradiation...In multivariate analysis, KPS ≥ 70, MGMT promoter methylation, extent of resection greater than partial resection, De Ritis ratio < 1.2, and glucose level < 150 mg/dL were significant prognostic factors for improved OS. Along with well-known prognostic factors, pre-RT serum biomarkers, including the De Ritis ratio and glucose level, also had prognostic value in elderly patients with glioblastoma treated with TMZ-based chemoradiation.
Journal
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EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • MGMT (6-O-methylguanine-DNA methyltransferase) • TERT (Telomerase Reverse Transcriptase)
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TP53 mutation • EGFR mutation • EGFR amplification • MGMT promoter methylation • TERT mutation • IDH wild-type • TERT promoter mutation • TERT amplification
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temozolomide
2ms
MGMT in TMZ-based glioma therapy: Multifaceted insights and clinical trial perspectives. (PubMed, Biochim Biophys Acta Mol Cell Res)
Temozolomide (TMZ) is the most preferred and approved chemotherapeutic drug for either first- or second-line chemotherapy for glioma patients across the globe...Furthermore, MGMT promoter methylation, stability of MGMT protein, and related subsequent adaptive responses are also important contributors to strategic developments in glioma therapy. With applications to its identification as a prognostic biomarker, thus predicting response to advanced glioma therapy, this review aims to concentrate on the mechanistic role and regulation of MGMT gene expression at epigenetic, transcriptional, post-transcriptional, and post-translational levels functioning under the control of multiple signaling dynamics.
Review • Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation • MGMT expression
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temozolomide
2ms
dCas9/CRISPR-based methylation of O-6-methylguanine-DNA methyltransferase enhances chemosensitivity to temozolomide in malignant glioma. (PubMed, J Neurooncol)
dCas9/CRISPR is a viable method of epigenetic editing, using the DNMT3A catalytic domain. This study provides initial proof-of-principle for CRISPR technology applications in malignant glioma, laying groundwork for subsequent translational studies, with implications for future epigenetic editing-based clinical applications.
Journal
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DNMT3A (DNA methyltransferase 1) • MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation
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temozolomide
2ms
Development of A Radiomic Model for MGMT Promoter Methylation Detection in Glioblastoma Using Conventional MRI. (PubMed, Int J Mol Sci)
Our study confirms the presence of a subtle association between imaging characteristics and MGMT promoter methylation status. However, further verification of the strength of this association is needed, as the low diagnostic performance obtained in this validation cohort is not sufficiently robust to allow clinically meaningful predictions.
Retrospective data • Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation
3ms
Improved prognostic stratification of patients with isocitrate dehydrogenase-mutant astrocytoma. (PubMed, Acta Neuropathol)
Combination of these parameters allows for improved prediction of outcome. These data aid in designing upcoming trials using IDH inhibitors.
Journal
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MGMT (6-O-methylguanine-DNA methyltransferase)
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CDKN2A deletion • MGMT promoter methylation
3ms
Hypermethylation of MGMT Gene Promoter in Peripheral Blood Mononuclear Cells as a Noninvasive Biomarker for Colorectal Cancer Diagnosis. (PubMed, Adv Biomed Res)
ROC analyses indicated that the diagnostic power of the MGMT promoter methylation level for CRC was 0.754, with a sensitivity of 81.43% and a specificity of 75.71%, indicating a good biomarker for CRC diagnosis. Methylation evaluation of MGMT in PBMCs could be utilized as a diagnostic biomarker with high accuracy for prioritizing suspected CRC patients before colonoscopy.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation
3ms
Characteristics and Prognosis of Tumor-Related Epilepsy During Tumor Evolution in Patients With IDH Wild-Type Glioblastoma. (PubMed, Neurology)
The progression of tumor-related epilepsy with the evolution of glioblastoma, IDH-wild-type and the effects of surgery on seizure control argue for proper antiseizure medication and maximal safe resection. Tumor-related epilepsy is an independent predictor of a longer survival.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation • IDH wild-type
3ms
MRI characteristics of H3 G34-mutant diffuse hemispheric gliomas and possible differentiation from IDH-wild-type glioblastomas in adolescents and young adults. (PubMed, J Neurosurg Pediatr)
G34m-DHGs most frequently occur in the frontal, parietal, and temporal lobes in adolescent and young adults and are associated with radiological characteristics distinct from those of IDH-WT-GBMs. Successful identification can be achieved by using either VASARI features or radiomics signatures, which may contribute to prognostic evaluation and assist in clinical settings.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase) • ATRX (ATRX Chromatin Remodeler) • OLIG2 (Oligodendrocyte Transcription Factor 2)
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MGMT promoter methylation • IDH wild-type
3ms
Exploring MGMT methylation-driven structural connectivity changes in insular gliomas: a tractography and graph theoretical analysis. (PubMed, J Neurooncol)
Our findings highlight a significant, hemisphere-specific correlation between MGMT promoter methylation and structural connectivity in insular gliomas. This study provides new insights into the genetic influence on glioma pathology, which could inform targeted therapeutic strategies.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation
3ms
Patient-derived glioblastoma organoids reflect tumor heterogeneity and treatment sensitivity. (PubMed, Neurooncol Adv)
PGOs were subjected to temozolomide (TMZ) to assess viability...Overall, these findings demonstrate the robustness of PGOs in retaining the genetic and phenotypic heterogeneity in culture and the application of measuring clinically relevant drug responses. These data show that PGOs have the potential to be further developed into avatars for personalized adaptive treatment selection and actionable drug target discovery and as a platform to study GBM biology.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
|
MGMT promoter methylation
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temozolomide
3ms
MGMT promoter methylation in 1p19q-intact gliomas. (PubMed, J Neurooncol)
This ancillary analysis supports conclusions from the CATNON trial for adjuvant TMZ as standard-of-care for anaplastic astrocytomas (IDH-mutant and 1p19q-intact), irrespective of MGMT status. Determining the optimal strategy for diffuse gliomas that are IDH-wildtype will be particularly important. MGMT promoter methylation should be considered as a stratification factor in future clinical trials for these patients.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation • IDH wild-type
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temozolomide
4ms
Synthesis-based imaging-differentiation representation learning for multi-sequence 3D/4D MRI. (PubMed, Med Image Anal)
We conduct extensive experiments using three datasets including a toy dataset of 20,000 simulated subjects, a brain MRI dataset of 1251 subjects, and a breast MRI dataset of 2101 subjects, to demonstrate that (1) top-ranking sequences can be used to replace complete sequences with non-inferior performance; (2) combining MRI with our imaging-differentiation map leads to better performance in clinical tasks such as glioblastoma MGMT promoter methylation status prediction and breast cancer pathological complete response status prediction. Our code is available at https://github.com/fiy2W/mri_seq2seq.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
|
MGMT promoter methylation
4ms
Proteasome Inhibitors against Glioblastoma-Overview of Molecular Mechanisms of Cytotoxicity, Progress in Clinical Trials, and Perspective for Use in Personalized Medicine. (PubMed, Curr Oncol)
The accumulation of cell cycle inhibitors p21 and p27, and decreased levels of prosurvival molecules NFKB, survivin, and MGMT, underlie proteasome inhibitors' cytotoxicity when used alone or in combination with the anti-GBM cytostatic drug temozolomide (TMZ). The evidence gathered in preclinical studies substantiated the design of clinical trials that employed the two most promising proteasome inhibitors, bortezomib and marizomib...The data from this phase III study indicate that marizomib does not improve the PFS and OS of GBM patients; however, further analysis of the genetic and epigenetic background of each patient tumor may shed some light on the sensitivity of individual patients to proteasome inhibition. The mutational and epigenetic makeup of GBM cells, like genetic alterations to TP53 and PTEN, or MGMT promoter methylation levels may actually determine the response to proteasome inhibition.
Review • Journal
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TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • MGMT (6-O-methylguanine-DNA methyltransferase) • BIRC5 (Baculoviral IAP repeat containing 5)
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TP53 mutation • PTEN mutation • MGMT promoter methylation
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temozolomide • bortezomib • marizomib (NPI-0052)
4ms
Droplet digital PCR (ddPCR) using FFPE DNA to assess methylation status of MGMT gene among patients with IDH mutant astrocytoma and IDH wild-type glioblastoma. (PubMed, J Clin Pathol)
The sensitivity, specificity, positive predictive value and negative predictive value of the assay in detecting the methylation status was found to be 95%, 90%, 95% and 90%.The results show that MS ddPCR is a valuable tool to detect the methylation status of MGMT in FFPE with high sensitivity. This method is cost-effective and easy to perform and could be an attractive alternative to the routine method of MSP.
Journal • Epigenetic controller
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation • IDH wild-type
4ms
Clinical characteristics and prognostic factors of solitary and multiple adult gliomas: a retrospective study based on propensity score matching. (PubMed, Eur Rev Med Pharmacol Sci)
The prognosis for multiple gliomas is extremely poor, which is related to the fact that the most common pathological types are glioblastomas and the surgical procedure is challenging. Concurrent chemotherapy and radiotherapy are the strongest protective prognostic factors, and the differences in their molecular pathology expression compared to solitary gliomas remain for further investigation.
Retrospective data • Journal
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TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NF1 (Neurofibromin 1) • MGMT (6-O-methylguanine-DNA methyltransferase)
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TP53 mutation • IDH1 mutation • NF1 mutation • MGMT promoter methylation • IDH1 mutation + Chr del(1p) + Chr del(19q) • TP53 expression
4ms
A Revised Molecular Recursive Partitioning Analysis using T2-FLAIR-Based Surgical Extent in Patients With Glioblastoma: A Multi-Center Validation Study (RSNA 2023)
NE-GTR provided better outcome stratification than CE-GTR and refined the GBM-molRPA stratification. NE-GTR enhanced long-term survival in patients with IDH wild-type glioblastoma and positive MGMT promoter methylation status. *Clinical Relevance/Application: The study compared the impact of NE-GTR and CE-GTR on molecular-based recursive partitioning analysis (GBM-molRPA) in patients with newly developed glioblastoma.
Clinical
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation • IDH wild-type
5ms
Leptomeningeal Metastases in IDH-wildtype Glioblastomas Revisited: Comprehensive Analysis of Incidence, Risk Factors, and Prognosis Based on Postcontrast FLAIR Imaging (SNO 2023)
The incidence of LM is high in patients with IDH-wildtype glioblastoma. Aggressive clinical, imaging, and molecular factors are correlated with LM at initial diagnosis, whereas ventricular entry warrant imaging surveillance for LM at recurrence. The prognosis of LM is not discouraging as expected, and promote reconsideration of focused clinical trials.
Clinical
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation • IDH wild-type
5ms
Functional genomics and chemotherapy resistance screening identifies biomarkers and targetable mechanisms of CCNU resistance in gliomas (SNO 2023)
The bifunctional alkylator lomustine (CCNU) remains widely but heterogeneously used as one of the few effective treatments in glioblastoma (GBM) and IDH mutant gliomas...Shared targets were also identified in a CRISPR-activator screen performed on a CCNU sensitive cell line in the presence and absence of CCNU and converged on multiple mTOR pathway genes as top enriched targets and biomarkers of resistance in CCNU-resistant models. These druggable targets are currently being investigated for combination therapies with CCNU and potential to overcome resistance.
MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation
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lomustine
5ms
Clinicopathologic analysis of novel methylation clusters of IDH-wildtype diffuse gliomas (SNO 2023)
HGG_F separate into two groups dictated by brain location, and despite the presence of TERT promoter mutations, appear distinct from GBMs. Overall, our work represents an initial effort to understand the morphologic, genomic and clinical characteristics of these previously uncharacterized subtypes of gliomas.
Clinical • Tumor mutational burden
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TMB (Tumor Mutational Burden) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • POLE (DNA Polymerase Epsilon) • MGMT (6-O-methylguanine-DNA methyltransferase) • TERT (Telomerase Reverse Transcriptase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ATRX (ATRX Chromatin Remodeler)
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POLE mutation • CDKN2A mutation • MGMT promoter methylation • ATRX mutation • TERT mutation • IDH wild-type • TERT promoter mutation
5ms
Radiological, clinical, and molecular analyses unravel distinct subtypes of adult grade 4 butterfly gliomas affecting the prognosis (SNO 2023)
bG is not a sole subtype with just extensive invasion from the hemisphere. Our results highlight the pathophysiology of bG and may influence its management.
Clinical
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MGMT (6-O-methylguanine-DNA methyltransferase) • TERT (Telomerase Reverse Transcriptase) • H3-3A (H3.3 Histone A)
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BRAF mutation • IDH1 mutation • EGFR amplification • CDKN2A deletion • MGMT promoter methylation • TERT mutation • TERT promoter mutation