Currently, the use of microscopical examinations alone is insufficient for the histological classification and grading of gliomas. In recognition of the emerging role of molecular diagnostic approaches to glioma classification, the role of genetic profiles has been emphasized on, as in the distinct subtypes of glioma. Glioblastomas (WHO grade IV) may develop de novo (primary glioblastomas) or through progression from lower-grade astrocytomas (secondary glioblastomas) both glioblastomas show similar histological features. However, these subtypes of glioblastoma involve distinct disease entities that evolve through different genetic pathways and are likely to differ in prognosis and response to therapy. Oligodendroglioma is recognized as a particular subtype of gliomas that shows remarkable response to chemotherapy [procarbazine+CCNU+vincristine (PCV)], making their correct diagnosis important. However, the histological differentiation of oligodendrogliomas from diffuse astrocytoma could be highly subjective in cases without typical morphological features. Loss of heterozygosity (LOH) on chromosomes 1p and 19q is correlated with sensitivity to PCV chemotherapy with increased survival in anaplastic oligodendroglioma cases (WHO grade III). Similarly, combined LOH on 1p and 19q has been identified as a predictor of favorable overall survival in oligodendrogliomas. Additionally, the status of the O6-methylguanine-methyltransferase gene (O6-MGMT) is associated with resistance to temozolomide (TMZ). We have previously found methylation or expression mosaicism of O6-MGMT in gliomas, resulting in problems on tumor sampling and response to TMZ. An assessment of the O6-MGMT methylation mosaicism in heterogeneous glioma may provide a more accurate assessment for the response to TMZ. This article suggests that more biological and molecular approaches to brain tumor classification will provide improved means to treat these tumors.
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Neurosurg Rev
March 2025
Department of Neurosurgery, Allegheny Health Network Neuroscience Institute, Pittsburgh, PA, US.
Li-Fraumeni Syndrome (LFS) is a rare hereditary cancer syndrome characterized by an increased risk of early-onset and multiple tumors across various organ systems, predominantly linked to germline TP53 mutations. While commonly associated neoplasms include sarcomas, breast cancer, and adrenocortical carcinoma, the occurrence of high-grade gliomas (HGG), including glioblastoma multiforme (GBM), in LFS patients is less documented and typically presents at a younger age relative to sporadic cases. A systematic review following PRISMA guidelines was conducted, focusing on clinical studies and case reports that explore the association between HGG and LFS.
View Article and Find Full Text PDFJ Biomed Sci
March 2025
Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, No. 250, Wu Hsing Street, Taipei, 110, Taiwan.
Background: Glioblastoma multiforme (GBM) is an aggressive brain tumor with chemoresistant, immunosuppressive, and invasive properties. Despite standard therapies, including surgery, radiotherapy, and temozolomide (TMZ) chemotherapy, tumors inevitably recur in the peritumoral region. Targeting GBM-mediated immunosuppressive and invasive properties is a promising strategy to improve clinical outcomes.
View Article and Find Full Text PDFCancer Med
March 2025
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Background: Glioma, characterized by its cellular and molecular heterogeneity, presents formidable challenges in treatment strategy and prognostic assessment. The tumor microenvironment (TME) profoundly influences tumor behavior and treatment response, with tumor-associated neutrophils (TANs) playing a complex but understudied role. This study aimed to investigate the heterogeneity and role of TANs in glioma and to develop a prognostic model.
View Article and Find Full Text PDFJ Transl Med
March 2025
School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, Guangdong Province, China.
Background: Glioblastoma (GBM) patients frequently develop resistance to temozolomide (TMZ), the standard chemotherapy. While targeting cancer metabolism shows promise, the relationship between metabolic perturbation and drug resistance remains poorly understood.
Methods: We performed high-throughput CRISPR interference screens in GBM cells to identify genes modulating TMZ sensitivity.
Neuro Oncol
February 2025
Department of Radiation Oncology, University of California San Francisco, San Francisco, CA 94143, USA.
Background: Glioblastoma (GBM) carries a poor prognosis, and new therapeutic strategies are necessary to improve outcomes for patients with this disease. Alkylating chemotherapies including temozolomide (TMZ) and lomustine (CCNU) are critical for treating GBM, but resistance mechanisms, including hypomethylation of O6-methylguanine-DNA methyltransferase (MGMT) promoter, undermine treatment. CRISPRoff is a programmable epigenetic memory editor that can induce stable and heritable gene silencing after transient delivery, and we hypothesize that CRISPRoff could potentiate the activity of TMZ and CCNU through long term suppression of target genes.
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