Open AccessClinical utility of targeted next‐generation sequencing for the diagnosis of myeloid neoplasms with germline predisposition
Author(s) -
AndrésZayas Cristina,
SuárezGonzález Julia,
RodríguezMacías Gabriela,
Dorado Nieves,
Osorio Santiago,
Font Patricia,
Carbonell Diego,
Chicano María,
Muñiz Paula,
Bastos Mariana,
Kwon Mi,
DíezMartín José Luis,
Buño Ismael,
MartínezLaperche Carolina
Publication year - 2021
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12921
Subject(s) - germline , germline mutation , genetics , disease , biology , genetic heterogeneity , myeloid , genetic predisposition , mutation , genetic testing , genetic counseling , gene , phenotype , medicine , cancer research
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.