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

•DNA–RNA sequencing correlation provides high-resolution lymphoma characterization.•Sorted MCL cells and B cells were used for optimal tumor exome and transcriptome analysis.•Intersected genome and transcriptome sequencing minimizes false-positive mutations.•Mutated genes in MCL patients are involve...

Full description

Saved in:
Bibliographic Details
Published in:Experimental hematology 2020-04, Vol.84, p.7-18.e12
Main Authors: Hansen, Marcus Høy, Cédile, Oriane, Blum, Mia Koldby, Hansen, Simone Valentin, Ebbesen, Lene Hyldahl, Bentzen, Hans Herluf Nørgaard, Thomassen, Mads, Kruse, Torben A., Kavan, Stephanie, Kjeldsen, Eigil, Kristensen, Thomas Kielsgaard, Haaber, Jacob, Abildgaard, Niels, Nyvold, Charlotte Guldborg
Format: Article
Language:English
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•DNA–RNA sequencing correlation provides high-resolution lymphoma characterization.•Sorted MCL cells and B cells were used for optimal tumor exome and transcriptome analysis.•Intersected genome and transcriptome sequencing minimizes false-positive mutations.•Mutated genes in MCL patients are involved in the Notch signaling pathway or cross-talk.•Copy number and molecular profiles guide lymphoma subtype characterization. [Display omitted] 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.
ISSN:0301-472X
1873-2399
DOI:10.1016/j.exphem.2020.03.001