Diagnostic and predictive molecular biomarkers in brain tumors across the lifespan: an age-stratified consensus statement

Molecular profiling has significantly advanced neuro-oncology, enabling the integration of biomarkers into the diagnosis and management of brain tumors. Precision medicine is emerging as a promising strategy; however, the marked heterogeneity of central nervous system tumors results in a low prevalence of actionable targets, limiting clinical applicability. Despite these challenges, ongoing progress in genetics and molecular biology offers new opportunities for targeted therapies. The incidence and clinical relevance of biomarkers vary across tumor types and age groups, reflecting the biological complexity of brain neoplasms throughout life. A multidisciplinary expert panel conducted a systematic review of the literature and developed a consensus statement addressing key predictive biomarkers across pediatric, adolescent and young adult (AYA), adult, and elderly populations. Evidence was evaluated for diagnostic, prognostic, and therapeutic relevance. Clinical benefit from targeted therapies has been demonstrated for a limited number of alterations, including BRAF p.V600E, NTRK fusions, EGFR, H3 K27M, and IDH1/2 mutations, while several additional biomarkers remain under investigation. The consensus provides an age-stratified overview of these molecular alterations and discusses challenges such as variability in testing approaches, interpretation of variants of uncertain significance, and limited access to comprehensive molecular diagnostics. Based on current evidence and expert opinion, the statement highlights the need for age-adapted testing strategies, multidisciplinary molecular tumor boards, and increased clinical trial availability for patients with rare or emerging biomarkers. These recommendations aim to support the implementation of precision medicine and improve outcomes across all age groups.