Molecular characterization of sorted malignant B cells from patients clinically identified with mantle cell lymphoma.

Autor: Hansen MH; Haematology-Pathology Research Laboratory, Research Unit for Haematology and Research Unit for Pathology, University of Southern Denmark and Odense University Hospital, Odense, Denmark., Cédile O; Haematology-Pathology Research Laboratory, Research Unit for Haematology and Research Unit for Pathology, University of Southern Denmark and Odense University Hospital, Odense, Denmark., Blum MK; Haematology-Pathology Research Laboratory, Research Unit for Haematology and Research Unit for Pathology, University of Southern Denmark and Odense University Hospital, Odense, Denmark., Hansen SV; Haematology-Pathology Research Laboratory, Research Unit for Haematology and Research Unit for Pathology, University of Southern Denmark and Odense University Hospital, Odense, Denmark., Ebbesen LH; Department of Hematology, Aarhus University Hospital, Denmark., Bentzen HHN; Department of Hematology, Aarhus University Hospital, Denmark., Thomassen M; Department of Clinical Genetics, Odense University Hospital, Denmark., Kruse TA; Department of Clinical Genetics, Odense University Hospital, Denmark., Kavan S; Department of Clinical Genetics, Odense University Hospital, Denmark., Kjeldsen E; Department of Hematology, Aarhus University Hospital, Denmark., Kristensen TK; Haematology-Pathology Research Laboratory, Research Unit for Haematology and Research Unit for Pathology, University of Southern Denmark and Odense University Hospital, Odense, Denmark., Haaber J; Haematology-Pathology Research Laboratory, Research Unit for Haematology and Research Unit for Pathology, University of Southern Denmark and Odense University Hospital, Odense, Denmark., Abildgaard N; Haematology-Pathology Research Laboratory, Research Unit for Haematology and Research Unit for Pathology, University of Southern Denmark and Odense University Hospital, Odense, Denmark., Nyvold CG; Haematology-Pathology Research Laboratory, Research Unit for Haematology and Research Unit for Pathology, University of Southern Denmark and Odense University Hospital, Odense, Denmark. Electronic address: charlotte.guldborg.nyvold@rsyd.dk.
Jazyk: angličtina
Zdroj: Experimental hematology [Exp Hematol] 2020 Apr; Vol. 84, pp. 7-18.e12. Date of Electronic Publication: 2020 Mar 12.
DOI: 10.1016/j.exphem.2020.03.001
Abstrakt: Mantle cell lymphoma (MCL) is a tumor with a poor prognosis. A few studies have examined the molecular landscape by next-generation sequencing and provided valuable insights into recurrent lesions driving this heterogeneous cancer. However, none has attempted to cross-link the individual genomic and transcriptomic profiles in sorted MCL cells to perform individual molecular characterizations of the lymphomas. Such approaches are relevant as MCL is heterogenous by nature, and thorough molecular diagnostics may potentially benefit the patient with more focused treatment options. In the work described here, we used sorted lymphoma cells from four patients at diagnosis and relapse by intersecting the coding DNA and mRNA. Even though only a few patients were included, this method enabled us to pinpoint a specific set of expressed somatic mutations, to present an overall expression profile different from the normal B cell counterparts, and to track molecular aberrations from diagnosis to relapse. Changes in single-nucleotide coding variants, subtle clonal changes in large-copy-number alterations, subclonal involvement, and changes in expression levels in the clinical course provided detailed information on each of the individual malignancies. In addition to mutations in known genes (e.g., TP53, CCND1, NOTCH1, ATM), we identified others, not linked to MCL, such as a nonsense mutation in SPEN and an MYD88 missense mutation in one patient, which along with copy number alterations exhibited a molecular resemblance to splenic marginal zone lymphoma. The detailed exonic and transcriptomic portraits of the individual MCL patients obtained by the methodology presented here could help in diagnostics, surveillance, and potentially more precise usage of therapeutic drugs by efficient screening of biomarkers.
(Copyright © 2020. Published by Elsevier Inc.)
Databáze: MEDLINE
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