Abstract
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.