Genetic Markers and Mutations in Primary Spinal Cord Tumors and Their Impact on Clinical Management

Background: Primary spinal cord tumors are rare neoplasms representing 2–4% of central nervous system tumors. Despite their low incidence, their impact on neurological function is profound. Historically, tumor classification and management have relied primarily on histopathology. However, advances in molecular diagnostics have highlighted the critical role of genetic alterations in tumor behavior, prognosis, and treatment response. Methods: This narrative review summarizes current evidence on genetic mutations in primary intramedullary spinal cord tumors, focusing on their prognostic value and implications for clinical management. Emphasis is placed on integration of genetic features into diagnostic criteria and clinical practice. Results: Distinct molecular profiles define many spinal cord tumor subtypes. In ependymomas, MYCN amplification confers aggressive biology and poor prognosis, while HOXB13 expression is a diagnostic marker for myxopapillary ependymomas. H3 K27M mutations in astrocytomas predict poor survival but demonstrate grade-dependent outcomes, while TERT promoter mutations influence prognosis in combination with other genetic events. BRAF V600E mutations, although infrequent, provide opportunities for targeted therapy in gangliogliomas and astrocytomas. In spinal glioblastomas, data regarding influence of specific mutations on prognosis remain limited. Syndromic tumors, including NF2-associated ependymomas and VHL-associated hemangioblastomas, highlight the importance of genetic counseling and surveillance. Conclusions: Integration of molecular diagnostics into spinal cord tumor management represents a paradigm shift from morphology-based to biology-driven practice. Genetic alterations inform prognosis, refine risk stratification, and increasingly guide therapeutic decision-making, including the use of targeted therapies and adjuvant radiation. Despite progress, challenges remain due to the rarity of these tumors, small sample sizes, and limited access to molecular testing. Future directions include adoption of molecularly stratified clinical trials. Ultimately, molecular precision promises to enhance survival and quality of life for patients with these rare but impactful tumors.