Tremendous efforts have been made to explore biomarkers for classification and grading on gliomas. The goal of this study was to identify more molecular features that are associated with clinical outcomes by comparing the genomic profiles of primary and recurrent gliomas and determine potential recurrence leading factors that are significantly enriched in relapse tumors. Hybrid capture based next generation sequencing (NGS) analysis was performed on 64 primary and 17 recurrent glioma biopsies. Copy number variation (CNV) was more frequent in recurrent tumors and CDKN2A/B loss was significantly enriched. In addition, overall mutations in cell cycle pathway are more common in relapse tumors. The patterns of gene sets, including IDH1/TERT and IDH1/TP53 exhibited significant difference between the groups. Survival analysis uncovered the worse disease-free survival (DFS) and overall survival (OS) associated with altered copy number and excessive activation of CELL CYCLE pathway. High Tumor Mutation Burden (TMB) was also a biomarker with great potential for poor prognosis. The assessment of genomic characteristics in primary versus recurrent gliomas aids the discovery of potential predictive biomarkers. The prognostic value of TMB in gliomas was raised for the first time.

Background: H3^K27M mutated diffuse midline gliomas (DMGs) are extremely aggressive and the leading cause of cancer‐related deaths in pediatric brain tumors with 5‐year survival <1%. Radiotherapy is the only established adjuvant treatment of H3^K27M DMGs; however, the radio‐resistance is commonly observed.Methods: We summarized current understandings of the molecular responses of H3^K27M DMGs to radiotherapy and provide crucial insights into current advances in radiosensitivity enhancement.Results: Ionizing radiation (IR) can mainly inhibit tumor cell growth by inducing DNA damage regulated by the cell cycle checkpoints and DNA damage repair (DDR) system. In H3K27M DMGs, the aberrant genetic and epigenetic changes, stemness genotype, and epithelial‐mesenchymal transition (EMT) disrupt the cell cycle checkpoints and DDR system by altering the associated regulatory signaling pathways, which leads to the development of radio‐resistance.Conclusions: The advances in mechanisms of radio‐resistance in H3^K27M DMGs promote the potential targets to enhance the sensitivity to radiotherapy.

Tobacco smoking is associated with increased risks of nearly 20 types of cancer. Although the association between smoking and gliomas, the most prevalent type of adult brain tumor, is still unconclusive, here, we found that the frequency of NF1 mutations was significantly increased in the glioma patients with smoking history compared to non-smoking patients (24% vs. 10%, P = 0.021). NF1 acts as a tumor suppressor gene is highly mutated in gliomas. The TCGA data analysis indicated that glioma patients carrying NF1 somatic mutations have worse overall survival (median survival time: smoking 19.9 months vs. non-smoking 36.8 month; P = 0.0018). In addition, we revealed that the NF1 and IDH1 mutations were mutually exclusive suggesting NF1 mutation has independent molecular mechanism involved in glioma biology.

Background: A critical aspect of glioma biology is their presentation as either single-lobe gliomas (SLGs) or multi-lobe gliomas (MLGs). Although MLGs are often presumed to represent more advanced disease stages, emerging evidence suggests that they may arise as distinct biological entities with unique genetic and molecular characteristics. Methods: In this multi-center retrospective study, we conducted a comprehensive genomic and molecular analysis of 174 glioma samples collected from 2018 to 2021, focusing on the mutational landscapes associated with SLGs and MLGs. Tumor samples were collected during operation and stored at –80 ° C. All DNA sequencing was performed using Illumina HiSeq. Tumor sites were defined based on pre-operative magnetic resonance imaging scans. R package “Maftools” was used for visualization of genomic mutations and statistical analyses. Materials and results: Our findings revealed that MLGs are associated with significantly shorter progression-free survival compared to SLGs. While canonical glioma-associated mutations, such as those in TERT, TP53, IDH, ATRX , and PTEN , were present in both groups, SLGs exhibited higher frequencies of mutations in ASXL1, CIC , and APC . This mutational enrichment was also conserved within the GBM subgroup, where single-lobe glioblastomas predominantly exhibited mutations in ASXL1, PIK3R1, EPHA2, IRS2, KDM5C, NOTCH4, TET2 , and TSC2 . Furthermore, pathway enrichment analysis revealed that SLGs showed enhanced activation of receptor tyrosine kinase–RAS (RTK-RAS), PI3K, and cell cycle signaling pathways, whereas MLGs demonstrated greater genomic instability and higher mutant allele frequencies. Conclusion: This study delineates the genetic and molecular distinctions between SLGs and MLGs, offering new insights into glioma heterogeneity and disease progression. These findings highlight the need to account for anatomical dispersion when interpreting glioma genomic profiles and could inform future stratified treatment approaches.