Genomic alterations in pediatric tumors: clinical relevance and translational insights.

Abstract

Cancer is the leading cause of disease-related mortality in children. Next-generation sequencing (NGS) has emerged as a critical tool in precision oncology, enabling the identification of somatic genomic alterations that may inform diagnosis, prognosis, and therapy. This study evaluated the clinical utility of NGS in Israeli pediatric cancer patients. We conducted a retrospective analysis of pediatric patients with cancer who underwent NGS at Sheba Medical Center between 2016 and 2021. Bioinformatics pipelines were applied to detect and annotate genomic variants. Medical records were reviewed to correlate molecular findings with treatment modifications and clinical outcomes. A total of 97 patients were analyzed, revealing a heterogeneous spectrum of somatic alterations. Recurrent variants were observed in genes involved in DNA repair, cell cycle regulation, and signaling pathways. Several variants initially classified as of uncertain significance were subsequently reclassified as pathogenic in light of updated genomic knowledge. Comparative analysis demonstrated unique molecular features within the Israeli pediatric cancer population relative to international cohorts. Comprehensive genomic profiling provides clinically meaningful insights in pediatric oncology. NGS facilitates the identification of actionable variants, supports personalized therapeutic strategies, and underscores the importance of continued genomic research and collaborative efforts in improving outcomes for children with cancer. NGS identifies actionable mutations in pediatric cancers, with known mutation patterns characterized in large international cohorts. This study adds novel insights into the mutation landscape of pediatric cancer patients. Nearly 25% benefited from NGS-informed therapy, supporting routine genomic profiling at diagnosis.