Real-World Performance of Integrative Clinical Genomics in Pediatric Precision Oncology

Jazyk angličtina Země Spojené státy americké Médium print-electronic

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid39442669
Odkazy

PubMed 39442669
DOI 10.1016/j.labinv.2024.102161
PII: S0023-6837(24)01839-7
Knihovny.cz E-zdroje

Despite significant improvement in the survival of pediatric patients with cancer, treatment outcomes for high-risk, relapsed, and refractory cancers remain unsatisfactory. Moreover, prolonged survival is frequently associated with long-term adverse effects due to intensive multimodal treatments. Accelerating the progress of pediatric oncology requires both therapeutic advances and strategies to mitigate the long-term cytotoxic side effects, potentially through targeting specific molecular drivers of pediatric malignancies. In this report, we present the results of integrative genomic and transcriptomic profiling of 230 patients with malignant solid tumors (the "primary cohort") and 18 patients with recurrent or otherwise difficult-to-treat nonmalignant conditions (the "secondary cohort"). The integrative workflow for the primary cohort enabled the identification of clinically significant single nucleotide variants, small insertions/deletions, and fusion genes, which were found in 55% and 28% of patients, respectively. For 38% of patients, molecularly informed treatment recommendations were made. In the secondary cohort, known or potentially driving alteration was detected in 89% of cases, including a suspected novel causal gene for patients with inclusion body infantile digital fibromatosis. Furthermore, 47% of findings also brought therapeutic implications for subsequent management. Across both cohorts, changes or refinements to the original histopathological diagnoses were achieved in 4% of cases. Our study demonstrates the efficacy of integrating advanced genomic and transcriptomic analyses to identify therapeutic targets, refine diagnoses, and optimize treatment strategies for challenging pediatric and young adult malignancies and underscores the need for broad implementation of precision oncology in clinical settings.

Center for Precision Medicine University Hospital Brno Brno Czech Republic; Department of Pediatric Oncology University Hospital Brno and Faculty of Medicine Masaryk University Brno Czech Republic

Central European Institute of Technology Masaryk University Brno Czech Republic

Central European Institute of Technology Masaryk University Brno Czech Republic; Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic

Central European Institute of Technology Masaryk University Brno Czech Republic; Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic; Center for Precision Medicine University Hospital Brno Brno Czech Republic; Department of Pathology University Hospital Brno and Faculty of Medicine Masaryk University Brno Czech Republic

Central European Institute of Technology Masaryk University Brno Czech Republic; Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic; Department of Biochemistry Faculty of Science Masaryk University Brno Czech Republic

Central European Institute of Technology Masaryk University Brno Czech Republic; Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic; Department of Biochemistry Faculty of Science Masaryk University Brno Czech Republic; Center for Precision Medicine University Hospital Brno Brno Czech Republic

Central European Institute of Technology Masaryk University Brno Czech Republic; Department of Internal Medicine Hematology and Oncology University Hospital Brno and Faculty of Medicine Masaryk University Brno Czech Republic

Department of Internal Medicine Hematology and Oncology University Hospital Brno and Faculty of Medicine Masaryk University Brno Czech Republic

Department of Pathology University Hospital Brno and Faculty of Medicine Masaryk University Brno Czech Republic

Department of Pediatric Oncology University Hospital Brno and Faculty of Medicine Masaryk University Brno Czech Republic

Department of Pediatrics and Adolescent Medicine Comprehensive Center for Pediatrics and Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Pharmacology Faculty of Medicine Masaryk University Brno Czech Republic; Department of Pharmacy University Hospital Brno Brno Czech Republic

Division of Neuropathology and Neurochemistry Department of Neurology Medical University of Vienna Vienna Austria

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