Glioma

Most gliomas are sporadic, but a small proportion arise in the setting of Mendelian disorders such as neurofibromatosis, tuberous sclerosis, and Li-Fraumeni syndrome. Genomic studies have also identified heritable risk alleles associated with increased glioma risk. Molecular alterations such as IDH mutation are common in glioma and are relevant to tumor biology, but the supplied grounding does not support a single unified cause for all gliomas.

Gliomas arise from neoplastic transformation of glial lineage cells and are biologically heterogeneous across histologic and molecular subtypes. The literature emphasizes molecular classification and alterations involving IDH, p53, BRAF, receptor tyrosine kinase signaling, DNA methylation, and gene-expression regulation. In IDH-mutant gliomas, mutant IDH has neomorphic activity that alters cancer metabolism, drives epigenetic change, and contributes to therapy resistance.

Risk is increased by certain inherited cancer syndromes, including neurofibromatosis, tuberous sclerosis, and Li-Fraumeni syndrome. Genome-wide association studies have identified heritable risk alleles in several genes associated with glioma susceptibility. Adult gliomas are reported more often in males than females, and gliomas occur across all ages.

Treatment depends on glioma subtype and molecular class. Circumscribed gliomas are generally managed with early complete resection, with chemotherapy if needed, while diffuse and other high-grade gliomas often require chemotherapy. For glioblastoma, the current standard of care is resection followed by radiotherapy plus temozolomide chemotherapy.