UMMS Affiliation

Department of Pathology

Publication Date

2021-04-01

Document Type

Article Postprint

Disciplines

Cancer Biology | Genetics and Genomics | Hematology | Hemic and Lymphatic Diseases | Immune System Diseases | Neoplasms | Oncology | Pathology

Abstract

B-cell non-Hodgkin's 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 (DLBCL) have been comprehensively interrogated at the genomic level. But rarer subtypes such as mantle cell lymphoma (MCL) remain sparsely 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 DLBCL, MCL, follicular lymphoma (FL), and Burkitt lymphoma (BL). We identified conserved hallmarks of B-NHL that were deregulated in the majority of tumor from each subtype, including the frequent genetic deregulation of the ubiquitin proteasome system (UPS). 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.

Keywords

B-cell non-Hodgkin's lymphoma, B-NHL, genomics

Rights and Permissions

Copyright (c) 2021 Ferrata Storti Foundation. This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

DOI of Published Version

10.3324/haematol.2020.274258

Source

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. Subtype-specific and co-occurring genetic alterations in B-cell non-Hodgkin lymphoma. Haematologica. 2021 Apr 1. doi: 10.3324/haematol.2020.274258. Epub ahead of print. PMID: 33792219. Link to article on publisher's site

Journal/Book/Conference Title

Haematologica

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

33792219

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

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