Department of Pathology
Amino Acids, Peptides, and Proteins | Cancer Biology | Genetic Phenomena | Genomics | Hemic and Lymphatic Diseases | Neoplasms | Pathology
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 (DLBCL) have been comprehensively interrogated at the genomic level, but other less common subtypes such as mantle cell lymphoma (MCL) remain sparsely characterized. Furthermore, multiple B-NHL subtypes have thus far not been comprehensively compared 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 755 B-NHL tumors at high depth; primarily including DLBCL, MCL, follicular lymphoma (FL), and Burkitt lymphoma (BL). We identified conserved hallmarks of B-NHL that were deregulated across major subtypes, such as 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 that are pathognomonic. The cumulative burden of mutations within a single cluster were more significantly discriminatory of B-NHL subtypes than individual mutations, implicating likely patterns of genetic epistasis that contribute to disease etiology. We therefore provide a framework of co-occurring mutations that deregulate genetic hallmarks and likely cooperate in lymphomagenesis of B-NHL subtypes.
B-cell non-Hodgkin lymphoma, genetic alterations, pathology, ubiquitin proteasome system, lymphomagenesis, B-NHL
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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
DOI of Published Version
bioRxiv 674259; doi: https://doi.org/10.1101/674259. Link to preprint on bioRxiv service.
John Ma, Man Chun; Chen, Benjamin J.; and Green, Michael R., "Pathognomonic and epistatic genetic alterations in B-cell non-Hodgkin lymphoma" (2019). University of Massachusetts Medical School Faculty Publications. 1615.
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.