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Clinical utility of targeted next‐generation sequencing for the diagnosis of myeloid neoplasms with germline predisposition

Myeloid neoplasms (MN) with germline predisposition (MNGP) are likely to be more common than currently appreciated. Many of the genes involved in MNGP are also recurrently mutated in sporadic MN. Therefore, routine analysis of gene panels by next‐generation sequencing provides an effective approach...

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Autores principales: Andrés‐Zayas, Cristina, Suárez‐González, Julia, Rodríguez‐Macías, Gabriela, Dorado, Nieves, Osorio, Santiago, Font, Patricia, Carbonell, Diego, Chicano, María, Muñiz, Paula, Bastos, Mariana, Kwon, Mi, Díez‐Martín, José Luis, Buño, Ismael, Martínez‐Laperche, Carolina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410541/
https://www.ncbi.nlm.nih.gov/pubmed/33533142
http://dx.doi.org/10.1002/1878-0261.12921
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author Andrés‐Zayas, Cristina
Suárez‐González, Julia
Rodríguez‐Macías, Gabriela
Dorado, Nieves
Osorio, Santiago
Font, Patricia
Carbonell, Diego
Chicano, María
Muñiz, Paula
Bastos, Mariana
Kwon, Mi
Díez‐Martín, José Luis
Buño, Ismael
Martínez‐Laperche, Carolina
author_facet Andrés‐Zayas, Cristina
Suárez‐González, Julia
Rodríguez‐Macías, Gabriela
Dorado, Nieves
Osorio, Santiago
Font, Patricia
Carbonell, Diego
Chicano, María
Muñiz, Paula
Bastos, Mariana
Kwon, Mi
Díez‐Martín, José Luis
Buño, Ismael
Martínez‐Laperche, Carolina
author_sort Andrés‐Zayas, Cristina
collection PubMed
description Myeloid neoplasms (MN) with germline predisposition (MNGP) are likely to be more common than currently appreciated. Many of the genes involved in MNGP are also recurrently mutated in sporadic MN. Therefore, routine analysis of gene panels by next‐generation sequencing provides an effective approach to detect germline variants with clinical significance in patients with hematological malignancies. Gene panel sequencing was performed in 88 consecutive and five nonconsecutive patients with MN diagnosis. Disease‐causing germline mutations in CEBPα, ASXL1, TP53, MPL, GATA2, DDX41, and ETV6 genes were identified in nine patients. Six out of the nine patients with germline variants had a strong family history. These patients presented great heterogeneity in the age of diagnosis and phenotypic characteristics. In our study, there were families in which all the affected members presented the same subtype of disease, whereas members of other families presented various disease phenotypes. This intrafamiliar heterogeneity suggests that the acquisition of particular somatic variants may drive the evolution of the disease. This approach enabled high‐throughput detection of MNGP in patients with MN diagnosis, which is of great relevance for both the patients themselves and the asymptomatic mutation carriers within the family. It is crucial to make a proper diagnosis of these patients to provide them with the most suitable treatment, follow‐up, and genetic counseling.
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spelling pubmed-84105412021-09-03 Clinical utility of targeted next‐generation sequencing for the diagnosis of myeloid neoplasms with germline predisposition Andrés‐Zayas, Cristina Suárez‐González, Julia Rodríguez‐Macías, Gabriela Dorado, Nieves Osorio, Santiago Font, Patricia Carbonell, Diego Chicano, María Muñiz, Paula Bastos, Mariana Kwon, Mi Díez‐Martín, José Luis Buño, Ismael Martínez‐Laperche, Carolina Mol Oncol Research Articles Myeloid neoplasms (MN) with germline predisposition (MNGP) are likely to be more common than currently appreciated. Many of the genes involved in MNGP are also recurrently mutated in sporadic MN. Therefore, routine analysis of gene panels by next‐generation sequencing provides an effective approach to detect germline variants with clinical significance in patients with hematological malignancies. Gene panel sequencing was performed in 88 consecutive and five nonconsecutive patients with MN diagnosis. Disease‐causing germline mutations in CEBPα, ASXL1, TP53, MPL, GATA2, DDX41, and ETV6 genes were identified in nine patients. Six out of the nine patients with germline variants had a strong family history. These patients presented great heterogeneity in the age of diagnosis and phenotypic characteristics. In our study, there were families in which all the affected members presented the same subtype of disease, whereas members of other families presented various disease phenotypes. This intrafamiliar heterogeneity suggests that the acquisition of particular somatic variants may drive the evolution of the disease. This approach enabled high‐throughput detection of MNGP in patients with MN diagnosis, which is of great relevance for both the patients themselves and the asymptomatic mutation carriers within the family. It is crucial to make a proper diagnosis of these patients to provide them with the most suitable treatment, follow‐up, and genetic counseling. John Wiley and Sons Inc. 2021-07-16 2021-09 /pmc/articles/PMC8410541/ /pubmed/33533142 http://dx.doi.org/10.1002/1878-0261.12921 Text en © 2021 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Andrés‐Zayas, Cristina
Suárez‐González, Julia
Rodríguez‐Macías, Gabriela
Dorado, Nieves
Osorio, Santiago
Font, Patricia
Carbonell, Diego
Chicano, María
Muñiz, Paula
Bastos, Mariana
Kwon, Mi
Díez‐Martín, José Luis
Buño, Ismael
Martínez‐Laperche, Carolina
Clinical utility of targeted next‐generation sequencing for the diagnosis of myeloid neoplasms with germline predisposition
title Clinical utility of targeted next‐generation sequencing for the diagnosis of myeloid neoplasms with germline predisposition
title_full Clinical utility of targeted next‐generation sequencing for the diagnosis of myeloid neoplasms with germline predisposition
title_fullStr Clinical utility of targeted next‐generation sequencing for the diagnosis of myeloid neoplasms with germline predisposition
title_full_unstemmed Clinical utility of targeted next‐generation sequencing for the diagnosis of myeloid neoplasms with germline predisposition
title_short Clinical utility of targeted next‐generation sequencing for the diagnosis of myeloid neoplasms with germline predisposition
title_sort clinical utility of targeted next‐generation sequencing for the diagnosis of myeloid neoplasms with germline predisposition
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410541/
https://www.ncbi.nlm.nih.gov/pubmed/33533142
http://dx.doi.org/10.1002/1878-0261.12921
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