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Technical Validation and Clinical Utility of an NGS Targeted Panel to Improve Molecular Characterization of Pediatric Acute Leukemia

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 AmpliSe...

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Autores principales: Vicente-Garcés, Clara, Esperanza-Cebollada, Elena, Montesdeoca, Sara, Torrebadell, Montserrat, Rives, Susana, Dapena, José Luis, Català, Albert, Conde, Nuria, Camós, Mireia, Vega-García, Nerea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021638/
https://www.ncbi.nlm.nih.gov/pubmed/35463953
http://dx.doi.org/10.3389/fmolb.2022.854098
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author Vicente-Garcés, Clara
Esperanza-Cebollada, Elena
Montesdeoca, Sara
Torrebadell, Montserrat
Rives, Susana
Dapena, José Luis
Català, Albert
Conde, Nuria
Camós, Mireia
Vega-García, Nerea
author_facet Vicente-Garcés, Clara
Esperanza-Cebollada, Elena
Montesdeoca, Sara
Torrebadell, Montserrat
Rives, Susana
Dapena, José Luis
Català, Albert
Conde, Nuria
Camós, Mireia
Vega-García, Nerea
author_sort Vicente-Garcés, Clara
collection PubMed
description 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™ for Illumina® 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 1000×. 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.
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spelling pubmed-90216382022-04-22 Technical Validation and Clinical Utility of an NGS Targeted Panel to Improve Molecular Characterization of Pediatric Acute Leukemia Vicente-Garcés, Clara Esperanza-Cebollada, Elena Montesdeoca, Sara Torrebadell, Montserrat Rives, Susana Dapena, José Luis Català, Albert Conde, Nuria Camós, Mireia Vega-García, Nerea Front Mol Biosci Molecular Biosciences 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™ for Illumina® 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 1000×. 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. Frontiers Media S.A. 2022-04-07 /pmc/articles/PMC9021638/ /pubmed/35463953 http://dx.doi.org/10.3389/fmolb.2022.854098 Text en Copyright © 2022 Vicente-Garcés, Esperanza-Cebollada, Montesdeoca, Torrebadell, Rives, Dapena, Català, Conde, Camós and Vega-García. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Vicente-Garcés, Clara
Esperanza-Cebollada, Elena
Montesdeoca, Sara
Torrebadell, Montserrat
Rives, Susana
Dapena, José Luis
Català, Albert
Conde, Nuria
Camós, Mireia
Vega-García, Nerea
Technical Validation and Clinical Utility of an NGS Targeted Panel to Improve Molecular Characterization of Pediatric Acute Leukemia
title Technical Validation and Clinical Utility of an NGS Targeted Panel to Improve Molecular Characterization of Pediatric Acute Leukemia
title_full Technical Validation and Clinical Utility of an NGS Targeted Panel to Improve Molecular Characterization of Pediatric Acute Leukemia
title_fullStr Technical Validation and Clinical Utility of an NGS Targeted Panel to Improve Molecular Characterization of Pediatric Acute Leukemia
title_full_unstemmed Technical Validation and Clinical Utility of an NGS Targeted Panel to Improve Molecular Characterization of Pediatric Acute Leukemia
title_short Technical Validation and Clinical Utility of an NGS Targeted Panel to Improve Molecular Characterization of Pediatric Acute Leukemia
title_sort technical validation and clinical utility of an ngs targeted panel to improve molecular characterization of pediatric acute leukemia
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021638/
https://www.ncbi.nlm.nih.gov/pubmed/35463953
http://dx.doi.org/10.3389/fmolb.2022.854098
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