Search Results (558)

Malignant gliomas are the most common primary brain tumors, with dismal outcomes. Pet dogs have been proposed as a valuable model for studying gliomas. Here, we compare spontaneously occurring gliomas from adult and pediatric human and canine patients, focusing on the tumor microenvironment (TME) and the canonical pathways of human glioma dysregulation (RTK/RAS/PI(3)K, p53 and Rb). Transcriptomic, genomic, and methylation data from adult, pediatric, and canine samples were evaluated. Across cohorts, aberrant signaling in the three canonical pathways correlated with increasing tumor grade. Canine high-grade glioma (HGG) showed extensive pathway dysregulation, especially when incorporating differentially expressed genes such as TP53. PDGFRA was a key driver of glioma in purebred brachycephalic (“short-skulled”) dogs. IDH1 mutations and hypermethylation were concentrated in adult tumors. Both species exhibited increased neutrophils, M2 macrophages, and regulatory T cells, coupled with depletion of key antitumor effectors. PD-1 and PD-L1 immune checkpoint biology was similarly preserved. Canine glioma seems to occupy a “middle ground” between pediatric and adult. Methylation patterns mirrored pediatric glioma, yet immune infiltration and pathway activation resembled adult HGG. Complex heterogeneity between patients was a major similarity between species. Despite different driver mutations, dogs and humans converge on a similar malignant, immune-suppressed TME. Full article

Background: Brain tumours impose complex, spatially heterogeneous disturbances on neural circuits that extend far beyond the immediate lesion site. While gross anatomical displacement of the cortico-spinal tract (CST) has been extensively studied, the topological reorganization of the functionally informed structural connectome—and its dependence on tumour molecular phenotype—remains incompletely understood. Objectives: This study aimed to characterize upper-limb functionally informed network topology in brain tumour patients, identify histological and molecular patterns of structural reorganization at the cortical and subcortical level, and determine the impact on neurophysiological parameters. Methods: Forty-eight patients with supratentorial motor-eloquent tumours (MET’s) underwent diffusion-weighted imaging (DWI) as part of their preoperative motor mapping. Connectivity matrices based on streamline passing counts were extracted from 426 nodes of the HCPex atlas using DSI Studio^® upon seeding the structural connectome in the motor hotspot (best motor response) for the functional area of the upper limb identified using preoperative navigated transcranial magnetic stimulation (nTMS). Paired-sample t-tests compared tumour versus healthy hemispheres across network topology metrics. The impact of nTMS-derived excitability metrics—interhemispheric resting motor threshold ratio (iRMTr) and cortical silent period (CSP)—and tumour histological and molecular characteristics on the connectome was assessed. Results: The global network topology of the tumour hemisphere was preserved when compared to the healthy baseline hemisphere across all tumour types (p > 0.05). Subcortical analysis revealed significant hyper-connectivity in the tumour hemisphere, with elevated degree, strength, clustering coefficient, local efficiency, and eigenvector centrality (p < 0.05). Basal ganglia motor loop degree was increased in the tumour hemisphere (mean 7.37 versus 5.19; p = 0.0009). IDH-mutant tumours generated significantly more topologically organized compensatory networks than IDH-wildtype tumours (Clustering Coefficient 0.345 versus 0.273; p = 0.018). Of the cortical nodes on the side of the tumour, significant hyper-connectivity was seen in the supplementary motor area (p = 0.0011), premotor cortex (Area 6), with increased connection seen in 6 mp (medial premotor at p =0.0033) and 6 d (dorsal premotor at p = 0.025) and primary somatosensory cortex (p = 0.027). The presence of the tumour induced significant changes across all three domains: loss of CST volume (p < 0.001), prolongation of the cortical silent period indicative of intracortical inhibition (p < 0.0001), with significant prolongation in glioblastoma versus an oligodendroglioma. Conclusions: Brain tumours significantly impact the upper limb-centred structural connectome. While global network topology is preserved, tumours induce substantial subcortical and basal ganglia network reorganization by inducing compensatory hyper-connectivity. These findings suggest that structural connectomics offers a novel framework for non-invasive tumour characterization and surgical planning. Full article

Acute myeloid leukemia (AML) is predominantly a disease of older adults, with a median age at diagnosis of 68–72 years. Management in this population is complicated by adverse cytogenetic and molecular features, higher rates of secondary disease, and patient-specific factors such as comorbidity and frailty. This narrative review synthesizes the current evidence on risk stratification and treatment of AML in adults aged 60 years and older, with dedicated attention to patients aged 60–75 (“fit” older adults) and those older than 75, including octogenarians. The VIALE-A trial established venetoclax plus azacitidine as standard of care for patients ineligible for intensive chemotherapy (composite complete remission 66.4%; median overall survival 14.7 vs. 9.6 months with azacitidine alone). For fit adults aged 60–75, the choice between intensive chemotherapy and venetoclax-based regimens remains under active investigation, with emerging randomized data suggesting comparable outcomes and a possible advantage for venetoclax-based approaches in adverse-risk disease. Risk stratification has evolved beyond the 2022 European LeukemiaNet (ELN) classification, which was developed in intensively treated cohorts; the 2024 ELN genetic risk classification for less-intensive therapy now provides a framework specific to this population. TP53-mutated AML, including multi-hit disease, remains the dominant unmet need across all treatment modalities. Advances in reduced-intensity conditioning have expanded transplant eligibility into the seventh and eighth decades, and molecularly targeted approaches, including FLT3, IDH1/2, and menin inhibitors, are reshaping frontline and relapsed/refractory therapy. This review covers epidemiology, risk stratification, treatment stratified by age, fitness, and genetic subgroup, the role of transplantation and maintenance therapy, and the limitations of the current evidence base for this heterogeneous population. Full article

Background/Objectives: Oligodendroglioma-like morphology may generate diagnostic uncertainty in central nervous system tumors, although oligodendroglioma is defined by the integrated presence of IDH mutation and whole-arm 1p/19q codeletion. This study aimed to evaluate the diagnostic pitfalls of oligodendroglioma-like morphology by comparing initial microscopic impressions with final integrated diagnoses. Methods: We retrospectively reviewed 23 non-oligodendroglial central nervous system tumors showing focal or predominant oligodendroglioma-like morphology but not fulfilling the integrated diagnostic criteria for oligodendroglioma. Clinical, radiological, histopathological, immunohistochemical, molecular/cytogenetic, initial microscopic impression, final integrated diagnosis, and follow-up data were analyzed descriptively. Results: Initial microscopic impressions included low-grade glial tumor, high-grade glial tumor, dysembryoplastic neuroepithelial tumor, ependymoma, astroblastoma, oligodendroglioma, dysplasia, central neurocytoma, metastatic epithelial tumor, and pilocytic astrocytoma/low-grade glial tumor. Final integrated diagnoses were astrocytoma, IDH-mutant, CNS WHO grade 2–4 (n = 9); dysembryoplastic neuroepithelial tumor (n = 3); central neurocytoma (n = 3); metastatic renal cell carcinoma (n = 2); low-grade glioneuronal tumor (n = 2); and PLNTY, glioblastoma IDH-wildtype, supratentorial ependymoma, and pilocytic astrocytoma (n = 1 each). Conclusions: Oligodendroglioma-like morphology should be interpreted as a diagnostic pitfall pattern rather than a specific diagnosis. Structured integrated reappraisal using targeted immunohistochemical and molecular/cytogenetic testing helps refine differential diagnosis in routine neuropathology practice. Full article

Background/Objectives: Pediatric solid tumors (PST) are a biologically distinct group of malignancies whose developmental origins and molecular drivers differ substantially from those of adult cancers, with direct implications for therapeutic strategy and clinical outcome. This review synthesizes current evidence on molecular pathogenesis, tumor microenvironment biology, and the structural conditions that shape access to care across select PST. Methods: A narrative review of peer-reviewed literature was conducted primarily using PubMed, supplemented by Google Scholar, covering publications from 2000 to 2025. Tumor types were selected based on their prevalence in the pediatric population and the availability of evidence addressing both molecular features and health disparities. Body: Across eight tumor types (neuroblastoma, Ewing sarcoma, pediatric brain tumors, rhabdomyosarcoma, Wilms tumor, retinoblastoma, osteosarcoma, and chondrosarcoma), recurrent molecular alterations including MYCN amplification, EWS-FLI1 fusions, PAX-FOXO1 rearrangements and IDH 1/2 mutations emerge as central determinants of disease behavior and eligibility for treatment. The tumor microenvironment manifests as a shared mediator of immune exclusion and therapeutic resistance across tumor types, with, but not limited to, tumor-associated macrophages, myeloid-derived suppressor cells, and checkpoint molecule expression, identified as recurrent features influencing treatment response. Immunotherapeutic strategies have shown variable efficacy across PST, with the most consistent clinical benefit established in neuroblastoma. A critical and underappreciated pattern stands out across tumor types: children carrying the most aggressive molecular subtypes are disproportionately those with the least access to therapies those subtypes demand, emphasizing an overlap of biological and structural disadvantage that is also amplified in low- and middle-income countries, where late-stage presentation, treatment abandonment and limited access to molecular diagnostics compound the biological disadvantage. Conclusions: Within the eight PST reviewed, the most aggressive molecular subtypes and the greatest structural disadvantages converge in the same children; those carrying MYCN amplification, PAX-FOXO1 fusions, or EWS-FLI1 fusions are disproportionately those with the least access to the therapies their biology demands. Genomic and immunologic advances will only reach their full clinical potential when paired with inclusive trial data, diversified genomic databases, and most importantly, equitable access to biomarker-specialized therapies across all populations. Full article

(1) Background: Modifications to tumor classifications could fundamentally alter the foundation of research approaches. A concrete illustration of this issue is the actual WHO classification of tumors of the central nervous system, published in 2021. According to the WHO classification, GBM is an IDH wild-type tumor. However, some multi-omics databases retain the classification from the time the samples for the datasets were collected, prior to the WHO 2021 classification, including IDH mutant GBMs. We were interested in assessing the number of papers published in the biomedical literature from 2022 to 2025 that are based on these databases, to ensure the correct implementation of the WHO 2021 classification of GBM. (2) Methods: We systematically reviewed publications in the biomedical literature from 2022 to 2025 that utilized the two most widely used multi-omics databases in the glioma research field, the CGGA and TCGA databases, to assess the correct application of the classification of GBM. (3) Results: We identified 269 publications, but only 45 (14%) correctly included only IDH wild-type GBM; 83 (33%) also contained IDH mutant tumors; and 141 (53%) provided no information about the IDH status of their research material. (4) Conclusions: Using a systematic search strategy, we found that 1/3 of published papers used IDH mutant tumors, and 1/2 of the studies did not report the IDH status of the tumors. Full article

Background/Objectives: Isocitrate Dehydrogenase (IDH)1/2-mutant diffuse gliomas represent a biologically distinct subgroup of adult brain tumors in which eary metabolic reprogramming and accumulation of the oncometabolite D-2-hydroxyglutarate (D-2HG) drive epigenetic, immunologic, and clinical characteristics, including a high burden of glioma-associated epilepsy. This review summarizes the molecular and metabolic consequences of IDH mutations, their role in glioma-associated epilepsy, and the evolving impact of mutant IDH-targeted therapies in contemporary neuro-oncology. Methods: We conducted a narrative review of key molecular, translational, imaging, and clinical studies on IDH-mutant diffuse gliomas. The literature included the 2021 (World Health Organization) WHO Classification of Tumours of the Central Nervous System, studies investigating D-2HG biology and glioma-associated epilepsy, and prospective clinical trials and real-world evidence evaluating IDH-targeted therapies and contemporary antiseizure management. Particular emphasis was placed on vorasidenib, advanced metabolic imaging, and emerging liquid biopsy approaches. Results: IDH mutations are early driver events that promote D-2HG accumulation, resulting in widespread epigenetic reprogramming, metabolic dysregulation, and an immunosuppressive tumor microenvironment. D-2HG has also been implicated in the development of glioma-associated epilepsy, although the underlying mechanisms remain incompletely understood. Advances in integrated histomolecular diagnostics, magnetic resonance spectroscopy, amino acid positron emission tomography, and cerebrospinal fluid liquid biopsy have improved disease classification and treatment monitoring. Mutant IDH inhibitors, particularly vorasidenib, prolong progression-free survival, delay the need for subsequent treatment, and reduce intratumoral D-2HG concentrations, and have shown encouraging early signals of improved seizure control and preserved health-related quality of life in patients with grade 2 IDH-mutant gliomas, although this evidence remains preliminary and requires confirmation in larger prospective studies. Conclusions: IDH-mutant diffuse gliomas exemplify precision neuro-oncology, in which a single metabolic alteration informs diagnosis, disease monitoring, and targeted therapeutic approach. Additionally, ongoing studies are expected to further define the role of IDH inhibition across different disease stages and in combination with immunotherapy and standard treatments. Lastly, future clinical trials should systematically incorporate seizure outcomes, neurocognitive function, patient-reported outcomes, and immunologic endpoints to optimize both tumor control and quality of life. Full article

Gliomas are the most common malignant primary brain tumors. The 2021 WHO classification requires the integration of molecular biomarkers, including IDH mutation, MGMT promoter methylation, and 1p/19q codeletion, alongside histological criteria, yet their assessment still relies on invasive surgical biopsy. We present M²-YOLO (Multi-task Molecular YOLO), a unified deep learning framework that simultaneously performs glioma instance segmentation and non-invasive molecular biomarker prediction from preoperative multi-sequence MRI. The proposed approach was evaluated on the multi-site UTSW-Glioma dataset comprising 625 patients. M²-YOLO achieved Dice scores of 0.853 for edema and 0.697 for tumor core segmentation, together with AUC-ROC values of 0.849 for IDH mutation and 0.718 for 1p/19q codeletion prediction. MGMT prediction yielded an AUC of 0.520, consistent with the limited discriminative capacity of anatomical MRI for this biomarker. These results demonstrate the potential of a unified multi-task framework for combining tumor delineation and molecular characterization within a single non-invasive workflow, supporting future applications in precision neuro-oncology. Full article

Background/Objectives: Myeloproliferative neoplasms (MPNs) are chronic myeloid malignancies characterized by substantial genetic heterogeneity. Although routine molecular evaluation focuses on canonical driver alterations (BCR::ABL1, JAK2, CALR, and MPL), additional somatic mutations have important diagnostic and prognostic implications. Methods: We retrospectively analyzed 1209 consecutive patients who underwent peripheral blood next-generation sequencing (NGS) for suspected or established MPNs using a comprehensive 75-gene DNA/RNA panel. Results: Canonical driver alterations were identified in 141 patients, while 1068 were driver-negative. Retrospective analysis demonstrated that 251 patients (21%) harbored at least one additional pathogenic or likely pathogenic mutation that was not routinely reported. Among driver-positive patients, 57 of 141 (40%) carried clinically relevant co-mutations, including high-molecular-risk genes such as ASXL1, TP53, SRSF2, SF3B1, RUNX1, U2AF1, and IDH2. Furthermore, 194 of 1068 (18%) driver-negative patients harbored additional pathogenic mutations, several of which supported clonal hematopoiesis or alternative myeloid neoplasms. Peripheral blood and bone marrow molecular findings demonstrated high concordance (R² = 0.87). Conclusions: These findings indicate that comprehensive NGS performed at the time of initial evaluation provides clinically relevant genomic information beyond canonical driver mutations, improves disease classification and risk stratification, and may facilitate earlier diagnosis and personalized management of patients with suspected MPNs. Full article

Background/Objectives: Neurological impairment after glioma resection is a common postoperative event, but many deficits improve during recovery. The present study investigated whether transient and persistent postoperative neurological deficits differ in their association with overall survival (OS) and progression-free survival (PFS). Methods: We retrospectively reviewed data from patients who underwent initial surgical treatment for glioma in our institution. Neurological function was evaluated using documented clinical examinations performed before surgery, in the immediate postoperative period, and during routine follow-up 3–6 months after the procedure. Results: The study cohort comprised 496 patients, of whom 44.4% were women. The mean age at surgery was 60 years (95% CI, 58–61), and the average follow-up period was 21 months (95% CI, 19–23). According to the 2021 WHO classification, 80.0% of tumors were grade 4, 11.1% were grade 3, and 7.3% were grade 2. IDH mutations were absent in 81% of cases. Median survival for the entire cohort was 34 months (95% CI, 30–38). Preoperative neurological deficits, including hemiparesis, were not significantly associated with OS. Postoperative deficits that were resolved by the follow-up assessment showed no relationship with either OS or PFS, irrespective of IDH mutation status. In contrast, neurological deficits that persisted at follow-up were independently associated with shorter OS and PFS among patients with IDH-wild-type gliomas (p < 0.001), whereas no significant association was observed in the IDH-mutant subgroup. Similarly, when new neurological deficits were present at follow-up, poorer OS and PFS were predicted only in patients with IDH-wild-type tumors (p < 0.001). Conclusions: Temporary neurological deterioration following glioma surgery does not appear to adversely influence overall or progression-free survival, regardless of IDH status. However, persistent postoperative deficits, as well as newly acquired deficits that remain evident during follow-up, are strong indicators of an unfavorable prognosis in patients with IDH-wild-type gliomas. Full article

The prognostic relevance of IDH1 mutations remains unclear in acute myeloid leukemia (AML). This study, representing the first Turkish AML cohort characterized for IDH1 mutations, aimed to determine the frequency of IDH1, FLT3 and NPM1 mutations and to describe the associated clinical characteristics. We retrospectively analyzed clinical, cytogenetic, and molecular data for 57 AML patients. Bone marrow aspirates were evaluated cytogenetically using G-banding, and molecular mutations were assessed by PCR or NGS (MiSeq-Illumina). IDH1 mutations were detected in 7% of patients; FLT3 and NPM1 mutations were detected in 38.6% and 19.3% of patients, respectively. A significant positive correlation existed between IDH1 and NPM1 mutations (r = 0.388, p = 0.003). Overall mortality was 56.1% and remission was achieved in 43.9%. Older age (p = 0.029) and comorbidities (p = 0.009) were significantly linked to mortality. Mortality was 100% in the four IDH1-mutant patients and significantly higher in NPM1-mutant patients. Overall survival was shorter in IDH1-mutants, although the difference did not reach statistical significance (log-rank p = 0.057). Relapse occurred in 26.3%, rising to 50% in the IDH1-mutated subgroup. In this limited cohort, IDH1-mutant cases were associated with shorter overall survival and higher mortality; however, the small number of IDH1-mutant patients (n = 4) precludes definitive prognostic conclusions. Outcomes in NPM1-mutated patients were also less favorable than typically expected, possibly related to co-occurring IDH1 mutations. These descriptive findings characterize the molecular landscape of AML in an underrepresented Turkish population and may provide a foundation for larger, multicenter studies rather than confirming a prognostic role for these mutations. Full article

This study combined the damage effect of UV and the repair effect of He-Ne laser, employing UV-He-Ne laser (UV-LA) sequential mutagenesis to improve the protease-producing ability of Bacillus velezensis. Compared with UV mutagenesis, UV-LA treatment elevated the positive mutation rate from 12.50% to 16.67%, and the enzyme activity of the mutant strain increased from 20.81 U/mL to 34.04 U/mL. Following 20 passages, the degree of enzyme production decline of the UV-LA strain was reduced from 44% to 23% compared with that of the UV strain, showing better genetic stability. Subsequent investigation revealed that the physiological activity (L-LDH, ATP content) and the activities of various key metabolic enzymes (PFK, IDH, ATPase) in the UV-LA strain exceeded those in the UV strain. Genome sequencing results showed that the UV-LA strain had fewer mutations than the UV strain, and the mutation sites were more concentrated in the regulatory region. Proteomic analysis identified 108 differentially expressed proteins (56 upregulated and 52 downregulated) between the UV strain and UV-LA strain, primarily associated with bacterial energy metabolism, translation, and secretion systems. Research indicates that UV-LA treatment may leverage the laser’s light effects to reduce UV damage, thereby achieving regulation of metabolic and secretory processes. This study is expected to develop a novel and efficient mutagenesis method for microbial breeding and to offer new ideas for expanding the application of UV mutagenesis technology. Full article

In the companion article in this issue of Current Oncology, ‘Management of AML in Older Patients: An Updated Canadian Consensus’, the authors have presented the third iteration of Canadian consensus guidelines on AML treatment in the elderly. While many aspects of AML treatment in the elderly have become better defined, some old questions remain and new questions and controversies have arisen. Here, we address three topics on which there is, at this time, no universal consensus. The first is the development and features of new risk-stratification systems specifically aimed at older, less-intensively treated patients. Several different systems now exist in parallel, potentially causing confusion amongst clinicians. The second topic is good-prognosis AML subtypes (IDH1- and NPM1-mutated AML). In the Canadian context, IDH1-mutated AML is of particular interest due to the new availability of ivosidenib in Canada. The third topic is adverse-risk AML subtypes (FLT3- and TP53-mutated AML). FLT3-mutated AML remains problematic, although it is anticipated that new drug approvals and measurable residual disease-based treatment approaches may alleviate this, at least in part. And in particular, TP53-mutated AML remains a major problem. Ongoing clinical trial enrollment is essential. Full article

Background/Objectives: Chondrosarcoma is a clinically heterogeneous malignancy, and the prognostic role of its genetic features remains incompletely defined. While isocitrate dehydrogenase (IDH) mutations are well characterized, the significance of less common alterations—particularly telomerase reverse transcriptase (TERT) promoter mutations—remains unclear. This study aimed to define the genomic profile of chondrosarcoma and evaluate the prognostic relevance of TERT mutations, alone and in combination with IDH mutations. Methods: We retrospectively analyzed 91 patients with chondrosarcoma, including 54 patients with available next-generation sequencing data for genomic analyses. Tumors were assessed for mutations in IDH, TERT, TP53, and groups of genes involved in key cellular functions (e.g., cell cycle control, chromatin regulation). Associations with tumor characteristics were evaluated, recurrence outcomes were assessed using logistic regression, and overall survival was analyzed using Kaplan–Meier and Cox models adjusted for tumor subtype, grade, and size. Results: IDH mutations were present in 52% of tumors; other alterations included TP53 (16%), TERT (7.7%), chromatin-related genes (14%), and cell cycle genes (8.8%). TERT mutations were enriched in dedifferentiated tumors (p = 0.017) and occurred exclusively in grade 3 disease (“p < 0.001”). TERT-mutant tumors were associated with worse overall survival upon unadjusted analysis (HR 7.02, p = 0.024), but not after adjustment (HR 3.81, p = 0.160). All TERT mutations co-occurred with IDH mutations, and this subgroup had particularly poor survival (HR 7.76, p = 0.022), albeit limited by small numbers. Conclusions: These findings suggest that specific mutations, alone or in combination, may influence clinical outcomes by reflecting more aggressive tumor biology. TERT mutations, particularly with concurrent IDH mutations, may identify high-risk patients and complement established prognostic factors. Further validation is needed. Full article

Background/Objectives: Noninvasive determination of glioma molecular profiles is clinically crucial for assessing therapeutic efficacy and predicting disease outcomes. This study aimed to evaluate the potential of morphological magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), magnetic resonance spectroscopy (MRS), and dynamic contrast-enhanced perfusion-weighted imaging (DCE-PWI) in predicting TP53 gene status and X-linked alpha-thalassemia intellectual disability syndrome (ATRX) gene status in isocitrate dehydrogenase (IDH)-mutant gliomas. Methods: A retrospective analysis was performed on 106 IDH-mutant glioma patients using morphological MRI, DWI, MRS, and DCE-PWI data. Statistical comparisons of imaging parameters across molecular status groups were conducted, and logistic regression models were developed to predict molecular status, with diagnostic performance evaluated by receiver operating characteristic (ROC) curve analysis. Five-fold stratified cross-validation with 1000 bootstrap resamples was employed to assess model generalizability Results: Among 106 IDH-mutant gliomas, the TP53-mutant group showed a greater proportion of tumors with >33% enhancement (p = 0.018), higher Cho/Cr (p < 0.001), and higher Cho/NAA (p = 0.005) than the TP53-wildtype group. Multivariable analysis demonstrated that the Cho/Cr ratio was an independent predictor of TP53 mutation in IDH-mutant gliomas (odds ratio [OR] = 2.037, p = 0.021), with the model achieving an apparent AUC of 0.741. DCE-PWI parameters showed no significant differences across molecular subgroups. Ve was significantly elevated in ATRX-mutant tumors (median 57.16 vs. 30.63, p = 0.029). Ktrans, Kep, Vp, and iAUC showed no significant differences between groups (all p > 0.05). Furthermore, multivariable analysis showed that ADC values (OR = 1.005, p = 0.017) and the Cho/NAA ratio (OR = 3.073, p = 0.023) emerged as independent predictors of ATRX mutation, with the model achieving an apparent AUC of 0.863. Five-fold cross-validation demonstrated that the Cho/Cr model for TP53 prediction achieved a mean AUC of 0.717 ± 0.043 (Bootstrap 95% CI: 0.616–0.814), and the ADC + ChoNAA model for ATRX prediction achieved 0.865 ± 0.124 (95% CI: 0.780–0.953). All predictors remained significant across all five folds. Pooled confusion matrices yielded sensitivities of 0.623 and 0.757, specificities of 0.696 and 0.909, and accuracies of 0.654 and 0.840, respectively. Conclusions: Multimodal MRI techniques (morphological MRI, DWI, MRS, and DCE-PWI) can help predict TP53 and ATRX status without surgery. Higher Cho/Cr and Cho/NAA ratios were independently associated with TP53 mutation, whereas lower ADC and higher Cho/NAA independently predicted ATRX mutation. These findings suggest that a focused imaging protocol may be sufficient for preoperative molecular profiling in this tumor type. Full article