Molecular pathology and clinical implications of diffuse glioma

The prognosis for diffusely infiltrating gliomas at World Health Organization (WHO) grade 2-4 remains dismal due to their heterogeneity. The rapid development of genome-wide molecular-profiling-associated studies has greatly promoted the accuracy of glioma classification. Thus, the latest version of the WHO classification of the central nervous system tumors published in 2021 has incorporated more molecular biomarkers together with histological features for the diagnosis of gliomas. Advanced usage of molecular pathology in clinical diagnostic practice provides also new opportunities for the therapy of patients with glioma, including surgery, radiotherapy and chemotherapy, targeted therapy, immunotherapy, and more precision clinical trials. Herein, we highlight the updates in the classification of gliomas according to the latest WHO guidelines and summarize the clinically relevant molecular markers by focusing on their applications in clinical practice. We also review the advances in molecular features of gliomas, which can facilitate the development of glioma therapies, thereby discussing the challenges and future directions of molecular pathology toward precision medicine for patients with glioma.