Man Chun John Ma, The University of Texas MD Anderson Cancer Center
Saber Tadros, The University of Texas MD Anderson Cancer Center
Alyssa Bouska, University of Nebraska Medical CenterFollow
Tayla Heavican, University of Nebraska Medical Center
Haopeng Yang, The University of Texas MD Anderson Cancer Center
Qing Deng, The University of Texas MD Anderson Cancer Center
Dalia Moore, University of Nebraska Medical Center
Ariz Akhter, University of Calgary
Keenan Hartert, University of Nebraska Medical Center
Neeraj Jain, The University of Texas MD Anderson Cancer Center
Jordan Showell, The University of Texas MD Anderson Cancer Center
Sreejoyee Ghosh, The University of Texas MD Anderson Cancer Center
Lesley Street, University of Calgary
Marta Davidson, University of Calgary
Christopher Carey, Newcastle University
Joshua Tobin, University of Queensland
Deepak Perumal, Icahn School of Medicine at Mount Sinai
Julie M. Vose, University of Nebraska Medical CenterFollow
Matthew A. Lunning, University of Nebraska Medical CenterFollow
Aliyah R. Sohani, Massachusetts General Hospital and Harvard Medical School
Benjamin J. Chen, University of Massachusetts Medical School
Shannon Buckley, University of Nebraska Medical CenterFollow
Loretta J. Nastoupil, The University of Texas MD Anderson Cancer Center
R. Eric Davis, The University of Texas MD Anderson Cancer Center
Jason R. Westin, The University of Texas MD Anderson Cancer Center
Nathan H. Fowler, The University of Texas MD Anderson Cancer Center
Samir Parekh, Icahn School of Medicine at Mount Sinai
Maher Gandhi, University of Queensland
Sattva Neelapu, The University of Texas MD Anderson Cancer Center
Douglas Stewart, University of Queensland
Kapil Bhalla, Brigham and Womens Hospital
Javeed Iqbal, University of Nebraska Medical CenterFollow
Timothy Greiner, University of Nebraska Medical CenterFollow
Scott J. Rodig, The University of Texas MD Anderson Cancer Center
Adnan Mansoor, University of Calgary
Michael R. Green, The University of Texas MD Anderson Cancer Center

Document Type

Article

Journal Title

Haematologica

Publication Date

2022

Volume

107

Abstract

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.

ISSN

1592-8721

Creative Commons License

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

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