Genomic alterations in pediatric tumors: clinical relevance and translational insights.
In a retrospective cohort of 97 pediatric cancer patients at an Israeli center, NGS identified heterogeneous and potentially actionable somatic alterations, enabled later pathogenic reclassification of some uncertain variants, and was reported to inform therapy with benefit in nearly 25% of patients.
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In a retrospective cohort of 97 pediatric cancer patients at an Israeli center, NGS identified heterogeneous and potentially actionable somatic alterations, enabled later pathogenic reclassification of some uncertain variants, and was reported to inform therapy with benefit in nearly 25% of patients.
Research significance
The record supports that genomic profiling can identify alterations used to guide treatment in some pediatric patients; it is reasonable—but not demonstrated here—to hypothesize that routine profiling at diagnosis could improve treatment selection or outcomes, because specific therapies, definitions of benefit, and comparative outcome data are not provided.
Source abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. IMPACT: 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.