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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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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. |
format | Online Article Text |
id | pubmed-9021638 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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