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Next-generation Sequencing in Bone Marrow Failure Syndromes and Isolated Cytopenias: Experience of the Spanish Network on Bone Marrow Failure Syndromes

Inherited bone marrow failure syndromes (IBMFSs) are a group of congenital rare diseases characterized by bone marrow failure, congenital anomalies, high genetic heterogeneity, and predisposition to cancer. Appropriate treatment and cancer surveillance ideally depend on the identification of the mut...

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Autores principales: Gálvez, Eva, Vallespín, Elena, Arias-Salgado, Elena G., Sánchez-Valdepeñas, Carmen, Giménez, Yari, Navarro, Susana, Río, Paula, Bogliolo, Massimo, Pujol, Roser, Peiró, Montserrat, Nevado, Julián, Zubicaray, Josune, Sebastián, Elena, Catalá, Albert, Beléndez, Cristina, Díaz de Heredia, Cristina, Galera, Ana, Badell, Isabel, Madero, Luis, Perona, Rosario, Sastre, Leandro, Surrallés, Jordi, Bueren, Juan, Lapunzina, Pablo, Sevilla, Julián
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951136/
https://www.ncbi.nlm.nih.gov/pubmed/33718801
http://dx.doi.org/10.1097/HS9.0000000000000539
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author Gálvez, Eva
Vallespín, Elena
Arias-Salgado, Elena G.
Sánchez-Valdepeñas, Carmen
Giménez, Yari
Navarro, Susana
Río, Paula
Bogliolo, Massimo
Pujol, Roser
Peiró, Montserrat
Nevado, Julián
Zubicaray, Josune
Sebastián, Elena
Catalá, Albert
Beléndez, Cristina
Díaz de Heredia, Cristina
Galera, Ana
Badell, Isabel
Madero, Luis
Perona, Rosario
Sastre, Leandro
Surrallés, Jordi
Bueren, Juan
Lapunzina, Pablo
Sevilla, Julián
author_facet Gálvez, Eva
Vallespín, Elena
Arias-Salgado, Elena G.
Sánchez-Valdepeñas, Carmen
Giménez, Yari
Navarro, Susana
Río, Paula
Bogliolo, Massimo
Pujol, Roser
Peiró, Montserrat
Nevado, Julián
Zubicaray, Josune
Sebastián, Elena
Catalá, Albert
Beléndez, Cristina
Díaz de Heredia, Cristina
Galera, Ana
Badell, Isabel
Madero, Luis
Perona, Rosario
Sastre, Leandro
Surrallés, Jordi
Bueren, Juan
Lapunzina, Pablo
Sevilla, Julián
author_sort Gálvez, Eva
collection PubMed
description Inherited bone marrow failure syndromes (IBMFSs) are a group of congenital rare diseases characterized by bone marrow failure, congenital anomalies, high genetic heterogeneity, and predisposition to cancer. Appropriate treatment and cancer surveillance ideally depend on the identification of the mutated gene. A next-generation sequencing (NGS) panel of genes could be 1 initial genetic screening test to be carried out in a comprehensive study of IBMFSs, allowing molecular detection in affected patients. We designed 2 NGS panels of IBMFS genes: version 1 included 129 genes and version 2 involved 145 genes. The cohort included a total of 204 patients with suspected IBMFSs without molecular diagnosis. Capture-based targeted sequencing covered > 99% of the target regions of 145 genes, with more than 20 independent reads. No differences were seen between the 2 versions of the panel. The NGS tool allowed a total of 91 patients to be diagnosed, with an overall molecular diagnostic rate of 44%. Among the 167 patients with classified IBMFSs, 81 patients (48%) were diagnosed. Unclassified IBMFSs involved a total of 37 patients, of whom 9 patients (24%) were diagnosed. The preexisting diagnosis of 6 clinically classified patients (6%) was amended, implying a change of therapy for some of them. Our NGS IBMFS gene panel assay is a useful tool in the molecular diagnosis of IBMFSs and a reasonable option as the first tier genetic test in these disorders.
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spelling pubmed-79511362021-03-12 Next-generation Sequencing in Bone Marrow Failure Syndromes and Isolated Cytopenias: Experience of the Spanish Network on Bone Marrow Failure Syndromes Gálvez, Eva Vallespín, Elena Arias-Salgado, Elena G. Sánchez-Valdepeñas, Carmen Giménez, Yari Navarro, Susana Río, Paula Bogliolo, Massimo Pujol, Roser Peiró, Montserrat Nevado, Julián Zubicaray, Josune Sebastián, Elena Catalá, Albert Beléndez, Cristina Díaz de Heredia, Cristina Galera, Ana Badell, Isabel Madero, Luis Perona, Rosario Sastre, Leandro Surrallés, Jordi Bueren, Juan Lapunzina, Pablo Sevilla, Julián Hemasphere Article Inherited bone marrow failure syndromes (IBMFSs) are a group of congenital rare diseases characterized by bone marrow failure, congenital anomalies, high genetic heterogeneity, and predisposition to cancer. Appropriate treatment and cancer surveillance ideally depend on the identification of the mutated gene. A next-generation sequencing (NGS) panel of genes could be 1 initial genetic screening test to be carried out in a comprehensive study of IBMFSs, allowing molecular detection in affected patients. We designed 2 NGS panels of IBMFS genes: version 1 included 129 genes and version 2 involved 145 genes. The cohort included a total of 204 patients with suspected IBMFSs without molecular diagnosis. Capture-based targeted sequencing covered > 99% of the target regions of 145 genes, with more than 20 independent reads. No differences were seen between the 2 versions of the panel. The NGS tool allowed a total of 91 patients to be diagnosed, with an overall molecular diagnostic rate of 44%. Among the 167 patients with classified IBMFSs, 81 patients (48%) were diagnosed. Unclassified IBMFSs involved a total of 37 patients, of whom 9 patients (24%) were diagnosed. The preexisting diagnosis of 6 clinically classified patients (6%) was amended, implying a change of therapy for some of them. Our NGS IBMFS gene panel assay is a useful tool in the molecular diagnosis of IBMFSs and a reasonable option as the first tier genetic test in these disorders. Lippincott Williams & Wilkins 2021-03-09 /pmc/articles/PMC7951136/ /pubmed/33718801 http://dx.doi.org/10.1097/HS9.0000000000000539 Text en Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Article
Gálvez, Eva
Vallespín, Elena
Arias-Salgado, Elena G.
Sánchez-Valdepeñas, Carmen
Giménez, Yari
Navarro, Susana
Río, Paula
Bogliolo, Massimo
Pujol, Roser
Peiró, Montserrat
Nevado, Julián
Zubicaray, Josune
Sebastián, Elena
Catalá, Albert
Beléndez, Cristina
Díaz de Heredia, Cristina
Galera, Ana
Badell, Isabel
Madero, Luis
Perona, Rosario
Sastre, Leandro
Surrallés, Jordi
Bueren, Juan
Lapunzina, Pablo
Sevilla, Julián
Next-generation Sequencing in Bone Marrow Failure Syndromes and Isolated Cytopenias: Experience of the Spanish Network on Bone Marrow Failure Syndromes
title Next-generation Sequencing in Bone Marrow Failure Syndromes and Isolated Cytopenias: Experience of the Spanish Network on Bone Marrow Failure Syndromes
title_full Next-generation Sequencing in Bone Marrow Failure Syndromes and Isolated Cytopenias: Experience of the Spanish Network on Bone Marrow Failure Syndromes
title_fullStr Next-generation Sequencing in Bone Marrow Failure Syndromes and Isolated Cytopenias: Experience of the Spanish Network on Bone Marrow Failure Syndromes
title_full_unstemmed Next-generation Sequencing in Bone Marrow Failure Syndromes and Isolated Cytopenias: Experience of the Spanish Network on Bone Marrow Failure Syndromes
title_short Next-generation Sequencing in Bone Marrow Failure Syndromes and Isolated Cytopenias: Experience of the Spanish Network on Bone Marrow Failure Syndromes
title_sort next-generation sequencing in bone marrow failure syndromes and isolated cytopenias: experience of the spanish network on bone marrow failure syndromes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951136/
https://www.ncbi.nlm.nih.gov/pubmed/33718801
http://dx.doi.org/10.1097/HS9.0000000000000539
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