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Lookup NU author(s): Dr Christopher CareyORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
© 2022 Ferrata Storti Foundation. B cell non-Hodgkin lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common subtypes of B-NHL, such as diffuse large B-cell lymphoma, have been comprehensively interrogated at the genomic level, but rarer subtypes, such as mantle cell lymphoma, remain less extensively characterized. Furthermore, multiple B-NHL subtypes have thus far not been comprehensively compared using the same methodology to identify conserved or subtype-specific patterns of genomic alterations. Here, we employed a large targeted hybrid-capture sequencing approach encompassing 380 genes to interrogate the genomic landscapes of 685 B-NHL tumors at high depth, including diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, and Burkitt lymphoma. We identified conserved hallmarks of B-NHL that were deregulated in the majority of tumors from each subtype, including frequent genetic deregulation of the ubiquitin proteasome system. In addition, we identified subtype-specific patterns of genetic alterations, including clusters of co-occurring mutations and DNA copy number alterations. The cumulative burden of mutations within a single cluster were more discriminatory of B-NHL subtypes than individual mutations, implicating likely patterns of genetic cooperation that contribute to disease etiology. We therefore provide the first cross-sectional analysis of mutations and DNA copy number alterations across major B-NHL subtypes and a framework of co-occurring genetic alterations that deregulate genetic hallmarks and likely cooperate in lymphomagenesis.
Author(s): Ma MCJ, Tadros S, Bouska A, Heavican T, Yang H, Deng Q, Moore D, Akhter A, Hartert K, Jain N, Showell J, Ghosh S, Street L, Davidson M, Carey C, Tobin J, Perumal D, Vose JM, Lunning MA, Sohani AR, Chen BJ, Buckley S, Nastoupil LJ, Davis RE, Westin JR, Fowler NH, Parekh S, Gandhi M, Neelapu S, Stewart D, Bhalla K, Iqbal J, Greiner T, Rodig SJ, Mansoor A, Green MR
Publication type: Article
Publication status: Published
Journal: Haematologica
Year: 2022
Volume: 107
Issue: 3
Pages: 690-701
Print publication date: 01/03/2022
Online publication date: 01/04/2021
Acceptance date: 15/03/2021
Date deposited: 05/04/2022
ISSN (electronic): 1592-8721
Publisher: Ferrata Storti Foundation
URL: https://doi.org/10.3324/haematol.2020.274258
DOI: 10.3324/haematol.2020.274258
PubMed id: 33792219
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