Overlapping Gene Expression and Molecular Features in High-Grade B-Cell Lymphoma

Overlapping Gene Expression and Molecular Features in High-Grade B-Cell Lymphoma

Aggressive B-cell lymphoma encompasses Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and, as per the 2016 WHO classification, high-grade B-cell lymphoma (HGBL) not otherwise specified (NOS) and HGBL double/triple hit (DH/TH). However, the diagnostic distinction of HGBL from BL and DL...

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Bibliographic Details
Main Authors: Katharina D. Faißt, Cora C. Husemann, Karsten Kleo, Monika Twardziok, Michael Hummel
Format: Article
Language:English
Published: MDPI AG 2024-09-01
Series:Journal of Molecular Pathology
Subjects:
high-grade non-Hodgkin B-cell lymphoma
molecular profiling
gene expression
gene mutations
immunoglobulin gene rearrangements
Online Access:https://www.mdpi.com/2673-5261/5/4/28
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Summary:Aggressive B-cell lymphoma encompasses Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and, as per the 2016 WHO classification, high-grade B-cell lymphoma (HGBL) not otherwise specified (NOS) and HGBL double/triple hit (DH/TH). However, the diagnostic distinction of HGBL from BL and DLBCL is difficult by means of histology/immunostaining in a substantial number of patients. This study aimed to improve subtyping by the identification of molecular features of aggressive B-cell lymphomas, with a specific focus on HGBL. To this end, we performed a comprehensive gene expression and mutational pattern analysis as well as the detection of B-cell clonality of 34 cases diagnosed with BL (<i>n</i> = 4), DLBCL (<i>n</i> = 16), HGBL DH (<i>n</i> = 8), and HGBL NOS (<i>n</i> = 6). Three distinct molecular subgroups were identified based on gene expression, primarily influenced by MYC expression/translocation and cell proliferation. In HGBL, compared to BL, there was an upregulation of PRKAR2B and TERT. HGBL DH exhibited elevated expression of GAMT and SMIM14, while HGBL NOS showed increased expression of MIR155HG and LZTS1. Our gene mutation analysis revealed <i>MYC</i>, <i>ARID1A</i>, <i>BCL2</i>, <i>KMT2D</i>, and <i>PIM1</i> as the most affected genes in B-cell lymphoma, with <i>BCL2</i> and <i>CREBBP</i> predominant in HGBL DH, and <i>MYC</i> and <i>PIM1</i> in HGBL NOS. Clonality analysis of immunoglobulin heavy and light chain rearrangements did not show distinguishable V- or J-usage between the diagnostic subgroups.
ISSN:2673-5261

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