IDH-mutant gliomas are characterized by the conversion of 2-oxoglutarate to (R)-2-hydroxyglutarate [(R)-2HG], an oncometabolite that disrupts cellular processes. Gunn et al. demonstrated that (R)-2HG inhibits KDM5 histone lysine demethylases, which plays a significant role in the transformation of IDH-mutant cancers, including acute myeloid leukemia (AML) and gliomas (ref: Gunn doi.org/10.1158/2159-8290.CD-22-0825/). This finding highlights the importance of KDM5 as a target for therapeutic intervention. Furthermore, Ferreyra Vega et al. conducted a longitudinal analysis of DNA methylation in IDH-mutant gliomas, revealing distinct methylation changes associated with tumor progression, which could serve as biomarkers for monitoring disease evolution (ref: Ferreyra Vega doi.org/10.1186/s40478-023-01520-1/). Kumar et al. explored the transcriptomic differences between lower-grade astrocytomas and glioblastomas, identifying PDGF gene expression and p53 alterations as critical factors influencing tumor behavior (ref: Kumar doi.org/10.1038/s41525-023-00351-2/). Together, these studies underscore the complex molecular landscape of IDH-mutant gliomas and the potential for targeted therapies based on specific genetic and epigenetic alterations. In addition to the molecular mechanisms, Shimizu et al. investigated the clinical implications of CDKN2A homozygous deletion in IDH-mutant astrocytomas. Their study utilized real-time polymerase chain reaction (qPCR) to assess CDKN2A status in 109 tumors, finding that patients with this deletion had significantly shorter survival rates (ref: Shimizu doi.org/10.1007/s10014-023-00450-z/). This highlights the prognostic value of CDKN2A in IDH-mutant gliomas and suggests that genetic profiling could guide treatment decisions. The integration of these molecular insights into clinical practice may improve patient outcomes by enabling more personalized therapeutic strategies.

Radiomics has emerged as a promising approach for enhancing the classification of gliomas, particularly in the context of molecular subtypes. Kihira et al. developed a multi-parametric radiomic model that improves the diagnostic performance of the T2-FLAIR mismatch sign, achieving a sensitivity of 62.5% and specificity of 70% for detecting 1p/19q co-deletion in IDH-1 mutant gliomas (ref: Kihira doi.org/10.3390/cancers15041037/). This model demonstrates the potential of integrating radiomic features with conventional imaging to provide more accurate diagnostic tools for clinicians. Similarly, Guo et al. trained a three-class radiomic model that classified IDH-mutant and wild-type gliomas, showing significant improvements in diagnostic performance, particularly for the IDHwt and IDHmut-noncodel subtypes (ref: Guo doi.org/10.1002/jmri.28630/). The study highlights the additive value of diffusion-weighted imaging (DWI) features in enhancing classification accuracy. Moreover, Guo et al. also assessed the diagnostic capabilities of various imaging techniques, including bi-exponential intravoxel incoherent motion imaging (IVIM) and three-dimensional pseudo-continuous arterial spin labeling (3D pCASL), in differentiating between lower-grade and high-grade gliomas while predicting IDH mutation status (ref: Guo doi.org/10.1016/j.ejrad.2023.110721/). Their findings suggest that these noninvasive imaging modalities can provide critical insights into tumor biology, potentially guiding treatment strategies. The integration of advanced imaging techniques with radiomics represents a significant advancement in the noninvasive assessment of gliomas, paving the way for improved diagnostic accuracy and personalized treatment approaches.

The genetic landscape of IDH-mutant gliomas is complex, with specific biomarkers playing crucial roles in tumor classification and prognosis. Park et al. conducted a multicenter study to evaluate whether qualitative and quantitative MRI parameters could predict CDKN2A/B homozygous deletion status in IDH-mutant astrocytomas. Their findings indicate that certain MRI characteristics are associated with the presence of this deletion, which is a significant prognostic marker (ref: Park doi.org/10.3348/kjr.2022.0732/). This study emphasizes the potential of imaging biomarkers to complement genetic testing in clinical practice. In a related study, Shimizu et al. confirmed that CDKN2A homozygous deletion correlates with poorer survival outcomes in IDH-mutant astrocytomas, reinforcing the importance of this genetic alteration in patient management (ref: Shimizu doi.org/10.1007/s10014-023-00450-z/). Kumar et al. further explored the biological implications of PDGF gene expression and p53 alterations in diffuse astrocytic gliomas, revealing that these genetic factors contribute to the distinct clinical behaviors observed in IDH-mutant versus wild-type tumors (ref: Kumar doi.org/10.1038/s41525-023-00351-2/). The contrasting progression patterns between IDH-mutant and wild-type gliomas underscore the necessity for tailored therapeutic approaches based on genetic profiling. Collectively, these studies highlight the critical role of genetic and imaging biomarkers in understanding the biology of IDH-mutant gliomas and their potential utility in guiding clinical decision-making.

The clinical implications of IDH mutations in gliomas are profound, particularly concerning prognosis and treatment strategies. Priambada et al. reviewed the immunohistochemical expression of key biomarkers, including IDH1 and ATRX, in Indonesian glioma patients, emphasizing the survival disparities between IDH-mutant and wild-type tumors (ref: Priambada doi.org/10.2147/IJGM.S397550/). Their findings suggest that understanding the molecular profile of gliomas is essential for accurate diagnosis and effective treatment planning. Additionally, Tuna et al. reported elevated levels of urinary 8-hydroxy-2'-deoxyguanosine in IDH1-wildtype glioblastoma patients, indicating a correlation between oxidative stress and tumor recurrence (ref: Tuna doi.org/10.1016/j.dnarep.2023.103463/). This highlights the potential for noninvasive biomarkers to monitor disease progression and treatment response. Kumar et al. also contributed to the understanding of the biological behavior of diffuse astrocytic gliomas by comparing transcriptomic profiles based on IDH mutation status, revealing that wild-type tumors often progress more rapidly to glioblastoma compared to their mutant counterparts (ref: Kumar doi.org/10.1038/s41525-023-00351-2/). This difference in progression rates underscores the need for tailored therapeutic approaches and close monitoring of IDH-mutant gliomas. Overall, these studies collectively underscore the importance of integrating molecular and clinical data to enhance prognostic accuracy and inform treatment decisions in patients with IDH-mutant gliomas.

Noninvasive diagnostic approaches are increasingly vital in the management of gliomas, particularly for assessing tumor grade and IDH mutation status. Guo et al. evaluated the diagnostic performance of diffusion-weighted imaging (DWI), bi-exponential intravoxel incoherent motion imaging (IVIM), and three-dimensional pseudo-continuous arterial spin labeling (3D pCASL) in differentiating lower-grade from high-grade gliomas (ref: Guo doi.org/10.1016/j.ejrad.2023.110721/). Their study demonstrated that these imaging modalities could effectively predict IDH mutation status, providing valuable insights into tumor biology without the need for invasive procedures. The use of DWI and IVIM, in particular, showed promise in enhancing diagnostic accuracy, which is crucial for guiding treatment decisions. Additionally, Tuna et al. reported that urinary levels of 8-hydroxy-2'-deoxyguanosine were significantly elevated in IDH1-wildtype glioblastoma patients, suggesting a link between oxidative stress and tumor recurrence (ref: Tuna doi.org/10.1016/j.dnarep.2023.103463/). This finding indicates that noninvasive biomarkers could play a critical role in monitoring treatment efficacy and disease progression. Fukuya et al. further supported the utility of noninvasive approaches by identifying tumor volume and calcifications as indicators for preoperative differentiation of grade II/III diffuse gliomas, highlighting the potential for imaging characteristics to inform clinical decision-making (ref: Fukuya doi.org/10.1007/s11060-023-04244-3/). Collectively, these studies emphasize the importance of noninvasive diagnostic techniques in the comprehensive assessment of gliomas, paving the way for improved patient management and outcomes.