Capture-based targeted sequencing using a T-cell control in myeloid malignancies and idiopathic cytopenias.
T-cell control
germline control
idiopathic cytopenia
myelodysplastic syndrome
next-generation sequencing
variant of unknown significance
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
11 Mar 2024
11 Mar 2024
Historique:
revised:
30
01
2024
received:
21
11
2023
accepted:
20
02
2024
medline:
11
3
2024
pubmed:
11
3
2024
entrez:
11
3
2024
Statut:
aheadofprint
Résumé
We report on a study of next-generation sequencing in 257 patients undergoing investigations for cytopenias. We sequenced bone marrow aspirates using a target enrichment panel comprising 82 genes and used T cells from paired blood as a control. One hundred and sixty patients had idiopathic cytopenias, 81 had myeloid malignancies and 16 had lymphoid malignancies or other diagnoses. Forty-seven of the 160 patients with idiopathic cytopenias had evidence of somatic pathogenic variants consistent with clonal cytopenias. Only 39 genes of the 82 tested were mutated in the 241 patients with either idiopathic cytopenias or myeloid neoplasms. We confirm that T cells can be used as a control to distinguish between germline and somatic variants. The use of paired analysis with a T-cell control significantly reduced the time molecular scientists spent reporting compared to unpaired analysis. We identified somatic variants of uncertain significance (VUS) in a higher proportion (24%) of patients with myeloid malignancies or clonal cytopenias compared to less than 2% of patients with non-clonal cytopenias. This suggests that somatic VUS are indicators of a clonal process. Lastly, we show that blood depleted of lymphocytes can be used in place of bone marrow as a source of material for sequencing.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
ID : A127
Informations de copyright
© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
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