Pathognomonic and epistatic genetic alterations in B-cell non-Hodgkin lymphoma [preprint]
dc.contributor.author | John Ma, Man Chun | |
dc.contributor.author | Chen, Benjamin J. | |
dc.contributor.author | Green, Michael R. | |
dc.date | 2022-08-11T08:08:23.000 | |
dc.date.accessioned | 2022-08-23T15:53:36Z | |
dc.date.available | 2022-08-23T15:53:36Z | |
dc.date.issued | 2019-06-19 | |
dc.date.submitted | 2019-06-20 | |
dc.identifier.citation | <p>bioRxiv 674259; doi: https://doi.org/10.1101/674259. <a href="https://doi.org/10.1101/674259" target="_blank">Link to preprint on bioRxiv service.</a></p> | |
dc.identifier.doi | 10.1101/674259 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/29385 | |
dc.description | <p>Full author list omitted for brevity. For the full list of authors, see article.</p> | |
dc.description.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 (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. | |
dc.language.iso | en_US | |
dc.rights | The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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. | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | B-cell non-Hodgkin lymphoma | |
dc.subject | genetic alterations | |
dc.subject | pathology | |
dc.subject | ubiquitin proteasome system | |
dc.subject | lymphomagenesis | |
dc.subject | B-NHL | |
dc.subject | Amino Acids, Peptides, and Proteins | |
dc.subject | Cancer Biology | |
dc.subject | Genetic Phenomena | |
dc.subject | Genomics | |
dc.subject | Hemic and Lymphatic Diseases | |
dc.subject | Neoplasms | |
dc.subject | Pathology | |
dc.title | Pathognomonic and epistatic genetic alterations in B-cell non-Hodgkin lymphoma [preprint] | |
dc.type | Preprint | |
dc.source.journaltitle | bioRxiv | |
dc.identifier.legacyfulltext | https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2627&context=faculty_pubs&unstamped=1 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/faculty_pubs/1615 | |
dc.identifier.contextkey | 14778189 | |
refterms.dateFOA | 2022-08-23T15:53:36Z | |
html.description.abstract | <p>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.</p> | |
dc.identifier.submissionpath | faculty_pubs/1615 | |
dc.contributor.department | Department of Pathology |