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...
Main Authors: | , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2021-09-01
|
Series: | Molecular Oncology |
Subjects: | |
Online Access: | https://doi.org/10.1002/1878-0261.12921 |
id |
doaj-28d37e0d23014ce69edcf3d7dc5605f7 |
---|---|
record_format |
Article |
spelling |
doaj-28d37e0d23014ce69edcf3d7dc5605f72021-09-02T02:01:46ZengWileyMolecular Oncology1574-78911878-02612021-09-011592273228410.1002/1878-0261.12921Clinical utility of targeted next‐generation sequencing for the diagnosis of myeloid neoplasms with germline predispositionCristina Andrés‐Zayas0Julia Suárez‐González1Gabriela Rodríguez‐Macías2Nieves Dorado3Santiago Osorio4Patricia Font5Diego Carbonell6María Chicano7Paula Muñiz8Mariana Bastos9Mi Kwon10José Luis Díez‐Martín11Ismael Buño12Carolina Martínez‐Laperche13Genomics Unit Gregorio Marañón General University Hospital Gregorio Marañón Health Research Institute (IiSGM) Madrid SpainGenomics Unit Gregorio Marañón General University Hospital Gregorio Marañón Health Research Institute (IiSGM) Madrid SpainDepartment of Hematology Gregorio Marañón General University Hospital Madrid SpainGregorio Marañón Health Research Institute (IiSGM) Madrid SpainGregorio Marañón Health Research Institute (IiSGM) Madrid SpainGregorio Marañón Health Research Institute (IiSGM) Madrid SpainGregorio Marañón Health Research Institute (IiSGM) Madrid SpainGregorio Marañón Health Research Institute (IiSGM) Madrid SpainGregorio Marañón Health Research Institute (IiSGM) Madrid SpainGregorio Marañón Health Research Institute (IiSGM) Madrid SpainGregorio Marañón Health Research Institute (IiSGM) Madrid SpainGregorio Marañón Health Research Institute (IiSGM) Madrid SpainGenomics Unit Gregorio Marañón General University Hospital Gregorio Marañón Health Research Institute (IiSGM) Madrid SpainGregorio Marañón Health Research Institute (IiSGM) Madrid SpainMyeloid 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.https://doi.org/10.1002/1878-0261.12921family historygenetic counselinghereditary cancermyeloid neoplasms with germline predispositionnext‐generation sequencing |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Cristina Andrés‐Zayas Julia Suárez‐González Gabriela Rodríguez‐Macías Nieves Dorado Santiago Osorio Patricia Font Diego Carbonell María Chicano Paula Muñiz Mariana Bastos Mi Kwon José Luis Díez‐Martín Ismael Buño Carolina Martínez‐Laperche |
spellingShingle |
Cristina Andrés‐Zayas Julia Suárez‐González Gabriela Rodríguez‐Macías Nieves Dorado Santiago Osorio Patricia Font Diego Carbonell María Chicano Paula Muñiz Mariana Bastos Mi Kwon José Luis Díez‐Martín Ismael Buño Carolina Martínez‐Laperche Clinical utility of targeted next‐generation sequencing for the diagnosis of myeloid neoplasms with germline predisposition Molecular Oncology family history genetic counseling hereditary cancer myeloid neoplasms with germline predisposition next‐generation sequencing |
author_facet |
Cristina Andrés‐Zayas Julia Suárez‐González Gabriela Rodríguez‐Macías Nieves Dorado Santiago Osorio Patricia Font Diego Carbonell María Chicano Paula Muñiz Mariana Bastos Mi Kwon José Luis Díez‐Martín Ismael Buño Carolina Martínez‐Laperche |
author_sort |
Cristina Andrés‐Zayas |
title |
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_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_sort |
clinical utility of targeted next‐generation sequencing for the diagnosis of myeloid neoplasms with germline predisposition |
publisher |
Wiley |
series |
Molecular Oncology |
issn |
1574-7891 1878-0261 |
publishDate |
2021-09-01 |
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. |
topic |
family history genetic counseling hereditary cancer myeloid neoplasms with germline predisposition next‐generation sequencing |
url |
https://doi.org/10.1002/1878-0261.12921 |
work_keys_str_mv |
AT cristinaandreszayas clinicalutilityoftargetednextgenerationsequencingforthediagnosisofmyeloidneoplasmswithgermlinepredisposition AT juliasuarezgonzalez clinicalutilityoftargetednextgenerationsequencingforthediagnosisofmyeloidneoplasmswithgermlinepredisposition AT gabrielarodriguezmacias clinicalutilityoftargetednextgenerationsequencingforthediagnosisofmyeloidneoplasmswithgermlinepredisposition AT nievesdorado clinicalutilityoftargetednextgenerationsequencingforthediagnosisofmyeloidneoplasmswithgermlinepredisposition AT santiagoosorio clinicalutilityoftargetednextgenerationsequencingforthediagnosisofmyeloidneoplasmswithgermlinepredisposition AT patriciafont clinicalutilityoftargetednextgenerationsequencingforthediagnosisofmyeloidneoplasmswithgermlinepredisposition AT diegocarbonell clinicalutilityoftargetednextgenerationsequencingforthediagnosisofmyeloidneoplasmswithgermlinepredisposition AT mariachicano clinicalutilityoftargetednextgenerationsequencingforthediagnosisofmyeloidneoplasmswithgermlinepredisposition AT paulamuniz clinicalutilityoftargetednextgenerationsequencingforthediagnosisofmyeloidneoplasmswithgermlinepredisposition AT marianabastos clinicalutilityoftargetednextgenerationsequencingforthediagnosisofmyeloidneoplasmswithgermlinepredisposition AT mikwon clinicalutilityoftargetednextgenerationsequencingforthediagnosisofmyeloidneoplasmswithgermlinepredisposition AT joseluisdiezmartin clinicalutilityoftargetednextgenerationsequencingforthediagnosisofmyeloidneoplasmswithgermlinepredisposition AT ismaelbuno clinicalutilityoftargetednextgenerationsequencingforthediagnosisofmyeloidneoplasmswithgermlinepredisposition AT carolinamartinezlaperche clinicalutilityoftargetednextgenerationsequencingforthediagnosisofmyeloidneoplasmswithgermlinepredisposition |
_version_ |
1721181571853058048 |