Background: Gliomas represent almost 30% of all primary brain tumors and account for 80% of malignant primary ones. In the last two decades, significant progress has been made in understanding gliomas’ molecular origin and development. These advancements have demonstrated a remarkable improvement in classification systems based on mutational markers, which contribute paramount information in addition to traditional histology-based classification. Methods: We performed a narrative review of the literature including each molecular marker described for adult diffuse gliomas used in the World Health Organization (WHO) central nervous system 5. Results: The 2021 WHO classification of diffuse gliomas encompasses many molecular aspects considered in the latest proposed hallmarks of cancer. The outcome of patients with diffuse gliomas relies on their molecular behavior and consequently, to determine clinical outcomes for these patients, molecular profiling should be mandatory. At least, the following molecular markers are necessary for the current most accurate classification of these tumors: (1) isocitrate dehydrogenase (IDH) IDH-1 mutation, (2) 1p/19q codeletion, (3) cyclin-dependent kinase inhibitor 2A/B deletion, (4) telomerase reverse transcriptase promoter mutation, (5) α-thalassemia/ mental retardation syndrome X-linked loss, (6) epidermal growth factor receptor amplification, and (7) tumor protein P53 mutation. These molecular markers have allowed the differentiation of multiple variations of the same disease, including the differentiation of distinct molecular Grade 4 gliomas. This could imply different clinical outcomes and possibly impact targeted therapies in the years to come. Conclusion: Physicians face different challenging scenarios according to the clinical features of patients with gliomas. In addition to the current advances in clinical decision-making, including radiological and surgical techniques, understanding the disease’s molecular pathogenesis is paramount to improving the benefits of its clinical treatments. This review aims to describe straightforwardly the most remarkable aspects of the molecular pathogenesis of diffuse gliomas.

Background/Objectives: Combined chromosome 7 gain and chromosome 10 loss (+7/−10) is the most frequent cytogenetic alteration and a defining diagnostic criterion for isocitrate dehydrogenase wild-type (IDHwt) glioblastoma. Despite the association with poor prognosis, its clinical and therapeutic significance remains unclear. We aim to systematically review its clinical significance, focusing on prevalence, prognostic value, and potential association with therapeutic resistance in adult patients. Methods: PubMed, Embase, CENTRAL, Scopus, EBSCOhost, and Web of Science were searched from inception to April 2025, using controlled vocabulary and free-text terms. Eligible studies included adult glioblastoma with molecular confirmation of combined chromosome 7 gain and chromosome 10 loss and reported survival or treatment response. Quality was assessed qualitatively, and findings were synthesized descriptively. Results: Of 3249 records, 5 observational studies (523 patients) were included. The signature was present in 60% to 70% of glioblastoma cases and frequently co-occurred with epidermal growth factor receptor amplification and telomerase reverse transcriptase promoter mutations. This alteration was consistently associated with shorter survival (mean, 8–70 weeks) compared with tumors lacking the alteration (19–170 weeks). In one study, the signature was more common in radioresistant tumors (9/20 vs. 1/10). Molecular evidence suggests that this alteration arises early in tumorigenesis. Conclusions: The +7/−10 cytogenetic alteration, common in glioblastoma, is frequently associated with aggressive clinical behavior. While exploratory data suggest a possible association with radiotherapy response, current evidence is insufficient to establish a predictive or therapeutic role. Its principal clinical value lies in diagnosis, molecular classification, and risk stratification. Incorporating cytogenetic testing for this alteration into routine glioblastoma workup may improve risk stratification and guide individualized management.

Background/Objectives: The reclassification of gliomas in the 5th edition of the World Health Organization’s Classification of Tumors of the Central Nervous System (WHOCNS5) integrates histological and molecular criteria to improve diagnostic accuracy and enable an individualized treatment approach. This study aims to analyze the feasibility of WHOCNS5 reclassification by examining its impact on diagnostic distribution, clinical features, and overall survival (OS) in adult patients from Colombia. Methods: We retrospectively analyzed 68 adults with diffuse gliomas (2015–2023) from two referral hospitals in Bogotá, Colombia. Molecular testing for IDH, 1p/19q, ATRX, TP53, EGFR, TERT, and CDKN2A/B enabled tumor reclassification according to WHOCNS5. Clinical, radiographic, and survival data were statistically analyzed. Results: 58.8% of patients were male, with a mean age of 56.6 ± 15.5 years. A total of 51.5% of the cases varied in the diagnosis after molecular reclassification. WHOCNS5 identified 66.2% glioblastomas vs 48.5% according to WHOCNS3, and 11.8% oligodendrogliomas vs 17.6 according to WHOCNS3. Using the WHOCNS3 criteria, OS differed significantly among tumor subtypes (p = 0.03), while reclassification under WHOCNS5 reduced these differences (p = 0.13), although IDH-mutant astrocytomas and oligodendrogliomas showed a survival advantage. In all subtypes, a younger age and gender predicted better OS (p < 0.001 and p = 0.02, respectively). Conclusions: Implementing the WHOCNS5 reclassification substantially altered glioma categorization and refined prognostic interpretation in over half of the cases. Trends toward improved outcomes in IDH-mutant tumors persist after reclassification.

Background/Objectives: The 2021 World Health Organization Classification of Tumors of the Central Nervous System (WHO CNS5) integrates histological and molecular criteria for adult diffuse gliomas, but comprehensive molecular testing may be difficult to implement in resource-limited settings. This study assessed the feasibility of a sequential, marker-based approach for diagnostic reassessment and described its association with clinical characteristics and overall survival (OS) in adults from Colombia. Methods: We retrospectively analyzed 68 adults with diffuse gliomas treated at two referral hospitals in Bogotá, Colombia, between 2015 and 2023. Molecular assessment used IHC, FISH, PCR, and Sanger sequencing according to the available tissue and diagnostic workflow. The study did not include comprehensive NGS or systematic assessment of combined whole-chromosome 7 gain/chromosome 10 loss (+7/−10). Results: The diagnosis changed after molecular reassessment in 51.5% of cases. The proportion classified as glioblastoma increased from 48.5% under the historical histologic classification to 66.2% under the WHO CNS5-based algorithm, whereas FISH-defined oligodendrogliomas decreased from 17.6% to 11.8%. OS differed among historical histologic groups (p = 0.03), but not among the WHO CNS5-based groups (p = 0.13). Female sex was associated with longer OS in unadjusted analysis (p = 0.02), while age was the only independent predictor in the multivariable analysis. Conclusions: Sequential molecular reassessment materially changed diagnostic categorization in this cohort and was feasible using locally available marker-based methods. However, the results are exploratory, limited by small molecular subgroups, incomplete molecular coverage, and the retrospective treatment context; they should not be interpreted as demonstrating improved treatment selection or survival after reclassification.