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Comprehensive Custom NGS Panel Validation for the Improvement of the Stratification of B-Acute Lymphoblastic Leukemia Patients

Background: B-acute lymphoblastic leukemia (B-ALL) is a hematological neoplasm of the stem lymphoid cell of the B lineage, characterized by the presence of genetic alterations closely related to the course of the disease. The number of alterations identified in these patients grows as studies of the...

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Autores principales: Montaño, Adrián, Hernández-Sánchez, Jesús, Forero-Castro, Maribel, Matorra-Miguel, María, Lumbreras, Eva, Miguel, Cristina, Santos, Sandra, Ramírez-Maldonado, Valentina, Fuster, José Luís, de Las Heras, Natalia, García-de Coca, Alfonso, Sierra, Magdalena, Dávila, Julio, de la Fuente, Ignacio, Olivier, Carmen, Olazabal, Juan, Martínez, Joaquín, Vega-García, Nerea, González, Teresa, Hernández-Rivas, Jesús María, Benito, Rocío
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565730/
https://www.ncbi.nlm.nih.gov/pubmed/32967112
http://dx.doi.org/10.3390/jpm10030137
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author Montaño, Adrián
Hernández-Sánchez, Jesús
Forero-Castro, Maribel
Matorra-Miguel, María
Lumbreras, Eva
Miguel, Cristina
Santos, Sandra
Ramírez-Maldonado, Valentina
Fuster, José Luís
de Las Heras, Natalia
García-de Coca, Alfonso
Sierra, Magdalena
Dávila, Julio
de la Fuente, Ignacio
Olivier, Carmen
Olazabal, Juan
Martínez, Joaquín
Vega-García, Nerea
González, Teresa
Hernández-Rivas, Jesús María
Benito, Rocío
author_facet Montaño, Adrián
Hernández-Sánchez, Jesús
Forero-Castro, Maribel
Matorra-Miguel, María
Lumbreras, Eva
Miguel, Cristina
Santos, Sandra
Ramírez-Maldonado, Valentina
Fuster, José Luís
de Las Heras, Natalia
García-de Coca, Alfonso
Sierra, Magdalena
Dávila, Julio
de la Fuente, Ignacio
Olivier, Carmen
Olazabal, Juan
Martínez, Joaquín
Vega-García, Nerea
González, Teresa
Hernández-Rivas, Jesús María
Benito, Rocío
author_sort Montaño, Adrián
collection PubMed
description Background: B-acute lymphoblastic leukemia (B-ALL) is a hematological neoplasm of the stem lymphoid cell of the B lineage, characterized by the presence of genetic alterations closely related to the course of the disease. The number of alterations identified in these patients grows as studies of the disease progress, but in clinical practice, the conventional techniques frequently used are only capable of detecting the most common alterations. However, techniques, such as next-generation sequencing (NGS), are being implemented to detect a wide spectrum of new alterations that also include point mutations. Methods: In this study, we designed and validated a comprehensive custom NGS panel to detect the main genetic alterations present in the disease in a single step. For this purpose, 75 B-ALL diagnosis samples from patients previously characterized by standard-of-care diagnostic techniques were sequenced. Results: The use of the custom NGS panel allowed the correct detection of the main genetic alterations present in B-ALL patients, including the presence of an aneuploid clone in 14 of the samples and some of the recurrent fusion genes in 35 of the samples. The panel was also able to successfully detect a number of secondary alterations, such as single nucleotide variants (SNVs) and copy number variations (CNVs) in 66 and 46 of the samples analyzed, respectively, allowing for further refinement of the stratification of patients. The custom NGS panel could also detect alterations with a high level of sensitivity and reproducibility when the findings obtained by NGS were compared with those obtained from other conventional techniques. Conclusions: The use of this custom NGS panel allows us to quickly and efficiently detect the main genetic alterations present in B-ALL patients in a single assay (SNVs and insertions/deletions (INDELs), recurrent fusion genes, CNVs, aneuploidies, and single nucleotide polymorphisms (SNPs) associated with pharmacogenetics). The application of this panel would thus allow us to speed up and simplify the molecular diagnosis of patients, helping patient stratification and management.
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spelling pubmed-75657302020-10-26 Comprehensive Custom NGS Panel Validation for the Improvement of the Stratification of B-Acute Lymphoblastic Leukemia Patients Montaño, Adrián Hernández-Sánchez, Jesús Forero-Castro, Maribel Matorra-Miguel, María Lumbreras, Eva Miguel, Cristina Santos, Sandra Ramírez-Maldonado, Valentina Fuster, José Luís de Las Heras, Natalia García-de Coca, Alfonso Sierra, Magdalena Dávila, Julio de la Fuente, Ignacio Olivier, Carmen Olazabal, Juan Martínez, Joaquín Vega-García, Nerea González, Teresa Hernández-Rivas, Jesús María Benito, Rocío J Pers Med Article Background: B-acute lymphoblastic leukemia (B-ALL) is a hematological neoplasm of the stem lymphoid cell of the B lineage, characterized by the presence of genetic alterations closely related to the course of the disease. The number of alterations identified in these patients grows as studies of the disease progress, but in clinical practice, the conventional techniques frequently used are only capable of detecting the most common alterations. However, techniques, such as next-generation sequencing (NGS), are being implemented to detect a wide spectrum of new alterations that also include point mutations. Methods: In this study, we designed and validated a comprehensive custom NGS panel to detect the main genetic alterations present in the disease in a single step. For this purpose, 75 B-ALL diagnosis samples from patients previously characterized by standard-of-care diagnostic techniques were sequenced. Results: The use of the custom NGS panel allowed the correct detection of the main genetic alterations present in B-ALL patients, including the presence of an aneuploid clone in 14 of the samples and some of the recurrent fusion genes in 35 of the samples. The panel was also able to successfully detect a number of secondary alterations, such as single nucleotide variants (SNVs) and copy number variations (CNVs) in 66 and 46 of the samples analyzed, respectively, allowing for further refinement of the stratification of patients. The custom NGS panel could also detect alterations with a high level of sensitivity and reproducibility when the findings obtained by NGS were compared with those obtained from other conventional techniques. Conclusions: The use of this custom NGS panel allows us to quickly and efficiently detect the main genetic alterations present in B-ALL patients in a single assay (SNVs and insertions/deletions (INDELs), recurrent fusion genes, CNVs, aneuploidies, and single nucleotide polymorphisms (SNPs) associated with pharmacogenetics). The application of this panel would thus allow us to speed up and simplify the molecular diagnosis of patients, helping patient stratification and management. MDPI 2020-09-21 /pmc/articles/PMC7565730/ /pubmed/32967112 http://dx.doi.org/10.3390/jpm10030137 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Montaño, Adrián
Hernández-Sánchez, Jesús
Forero-Castro, Maribel
Matorra-Miguel, María
Lumbreras, Eva
Miguel, Cristina
Santos, Sandra
Ramírez-Maldonado, Valentina
Fuster, José Luís
de Las Heras, Natalia
García-de Coca, Alfonso
Sierra, Magdalena
Dávila, Julio
de la Fuente, Ignacio
Olivier, Carmen
Olazabal, Juan
Martínez, Joaquín
Vega-García, Nerea
González, Teresa
Hernández-Rivas, Jesús María
Benito, Rocío
Comprehensive Custom NGS Panel Validation for the Improvement of the Stratification of B-Acute Lymphoblastic Leukemia Patients
title Comprehensive Custom NGS Panel Validation for the Improvement of the Stratification of B-Acute Lymphoblastic Leukemia Patients
title_full Comprehensive Custom NGS Panel Validation for the Improvement of the Stratification of B-Acute Lymphoblastic Leukemia Patients
title_fullStr Comprehensive Custom NGS Panel Validation for the Improvement of the Stratification of B-Acute Lymphoblastic Leukemia Patients
title_full_unstemmed Comprehensive Custom NGS Panel Validation for the Improvement of the Stratification of B-Acute Lymphoblastic Leukemia Patients
title_short Comprehensive Custom NGS Panel Validation for the Improvement of the Stratification of B-Acute Lymphoblastic Leukemia Patients
title_sort comprehensive custom ngs panel validation for the improvement of the stratification of b-acute lymphoblastic leukemia patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565730/
https://www.ncbi.nlm.nih.gov/pubmed/32967112
http://dx.doi.org/10.3390/jpm10030137
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