Technical Validation and Clinical Utility of an NGS Targeted Panel to Improve Molecular Characterization of Pediatric Acute Leukemia
Por:
Vicente-Garces C, Esperanza-Cebollada E, Montesdeoca S, Torrebadell-Burriel M, Rives-Solà S, Dapena JL, Català-Temprano A, Conde N, Camós-Guijosa M and Vega-García N
Publicada:
7 abr 2022
Ahead of Print:
7 abr 2022
Resumen:
Development of next-generation sequencing (NGS) has provided useful genetic information to redefine diagnostic, prognostic, and therapeutic strategies for the management of acute leukemia (AL). However, the application in the clinical setting is still challenging. Our aim was to validate the AmpliSeq (TM) for Illumina (R) Childhood Cancer Panel, a pediatric pan-cancer targeted NGS panel that includes the most common genes associated with childhood cancer, and assess its utility in the daily routine of AL diagnostics. In terms of sequencing metrics, the assay reached all the expected values. We obtained a mean read depth greater than 1000x. The panel demonstrated a high sensitivity for DNA (98.5% for variants with 5% variant allele frequency (VAF)) and RNA (94.4%), 100% of specificity and reproducibility for DNA and 89% of reproducibility for RNA. Regarding clinical utility, 49% of mutations and 97% of the fusions identified were demonstrated to have clinical impact. Forty-one percent of mutations refined diagnosis, while 49% of them were considered targetable. Regarding RNA, fusion genes were more clinically impactful in terms of refining diagnostic (97%). Overall, the panel found clinically relevant results in the 43% of patients tested in this cohort. To sum up, we validated a reliable and reproducible method to refine pediatric AL diagnosis, prognosis, and treatment, and demonstrated the feasibility of incorporating a targeted NGS panel into pediatric hematology practice.
Filiaciones:
Vicente-Garces C:
Hematology Laboratory, Hospital Sant Joan de Déu Barcelona, Esplugues de Llobregat, Barcelona, Spain
Leukemia and Other Pediatric Hemopathies, Developmental Tumors Biology Group, Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
Esperanza-Cebollada E:
Hematology Laboratory, Hospital Sant Joan de Déu Barcelona, Esplugues de Llobregat, Barcelona, Spain
Leukemia and Other Pediatric Hemopathies, Developmental Tumors Biology Group, Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
Montesdeoca S:
Hematology Laboratory, Hospital Sant Joan de Déu Barcelona, Esplugues de Llobregat, Barcelona, Spain
Leukemia and Other Pediatric Hemopathies, Developmental Tumors Biology Group, Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
Torrebadell-Burriel M:
Hematology Laboratory, Hospital Sant Joan de Déu Barcelona, Esplugues de Llobregat, Barcelona, Spain
Leukemia and Other Pediatric Hemopathies, Developmental Tumors Biology Group, Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Rives-Solà S:
Leukemia and Other Pediatric Hemopathies, Developmental Tumors Biology Group, Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Pediatric Hematology and Oncology Department, Hospital Sant Joan de Déu Barcelona, University of Barcelona, Barcelona, Spain
Dapena JL:
Leukemia and Other Pediatric Hemopathies, Developmental Tumors Biology Group, Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
Pediatric Hematology and Oncology Department, Hospital Sant Joan de Déu Barcelona, University of Barcelona, Barcelona, Spain
Català-Temprano A:
Leukemia and Other Pediatric Hemopathies, Developmental Tumors Biology Group, Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Pediatric Hematology and Oncology Department, Hospital Sant Joan de Déu Barcelona, University of Barcelona, Barcelona, Spain
Conde N:
Leukemia and Other Pediatric Hemopathies, Developmental Tumors Biology Group, Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
Pediatric Hematology and Oncology Department, Hospital Sant Joan de Déu Barcelona, University of Barcelona, Barcelona, Spain
Camós-Guijosa M:
Hematology Laboratory, Hospital Sant Joan de Déu Barcelona, Esplugues de Llobregat, Barcelona, Spain
Leukemia and Other Pediatric Hemopathies, Developmental Tumors Biology Group, Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Vega-García N:
Hematology Laboratory, Hospital Sant Joan de Déu Barcelona, Esplugues de Llobregat, Barcelona, Spain
Leukemia and Other Pediatric Hemopathies, Developmental Tumors Biology Group, Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
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