Analysis of genetic variants in myeloproliferative neoplasms using a 22-gene next-generation sequencing panel.
BMC Med Genomics
; 15(1): 10, 2022 01 15.
Article
em En
| MEDLINE
| ID: mdl-35033063
ABSTRACT
BACKGROUND:
The Philadelphia (Ph)-negative myeloproliferative neoplasms (MPNs), namely essential thrombocythaemia (ET), polycythaemia vera (PV) and primary myelofibrosis (PMF), are a group of chronic clonal haematopoietic disorders that have the propensity to advance into bone marrow failure or acute myeloid leukaemia; often resulting in fatality. Although driver mutations have been identified in these MPNs, subtype-specific markers of the disease have yet to be discovered. Next-generation sequencing (NGS) technology can potentially improve the clinical management of MPNs by allowing for the simultaneous screening of many disease-associated genes.METHODS:
The performance of a custom, in-house designed 22-gene NGS panel was technically validated using reference standards across two independent replicate runs. The panel was subsequently used to screen a total of 10 clinical MPN samples (ET n = 3, PV n = 3, PMF n = 4). The resulting NGS data was then analysed via a bioinformatics pipeline.RESULTS:
The custom NGS panel had a detection limit of 1% variant allele frequency (VAF). A total of 20 unique variants with VAFs above 5% (4 of which were putatively novel variants with potential biological significance) and one pathogenic variant with a VAF of between 1 and 5% were identified across all of the clinical MPN samples. All single nucleotide variants with VAFs ≥ 15% were confirmed via Sanger sequencing.CONCLUSIONS:
The high fidelity of the NGS analysis and the identification of known and novel variants in this study cohort support its potential clinical utility in the management of MPNs. However, further optimisation is needed to avoid false negatives in regions with low sequencing coverage, especially for the detection of driver mutations in MPL.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Policitemia Vera
/
Transtornos Mieloproliferativos
Tipo de estudo:
Diagnostic_studies
/
Guideline
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
BMC Med Genomics
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Malásia