Capture-based targeted sequencing using a T-cell control in myeloid malignancies and idiopathic cytopenias

Grzegorz Pietka, Corinne De Lord, Gwynn Matthias, Betty Cheung, Sangeeta Atwal, Michelle Furtado, Jonathan Cullis, Liz Grey-Davies, Srinivasan Narayanan, Andrew McGregor, Mari Kilner, Jenny Bosworth, Mary Frances McMullin, Thomas Coats, Agapi Parcharidou, Jamie Cavenagh, Jenny Byrne, Sunil Iyengar, Kabir Mohammed, Nicholas CrossMike Hubank, Sara Ribeiro, Jamshid Khorashad, Dorte Wren, Simon O'Connor, David Taussig

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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.

Original languageEnglish
JournalBritish Journal of Haematology
Early online date11 Mar 2024
Publication statusEarly online date - 11 Mar 2024

Bibliographical note

© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.


  • Hematology


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