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dc.contributor.authorJohn Ma, Man Chun
dc.contributor.authorChen, Benjamin J.
dc.contributor.authorGreen, Michael R.
dc.date2022-08-11T08:08:23.000
dc.date.accessioned2022-08-23T15:53:36Z
dc.date.available2022-08-23T15:53:36Z
dc.date.issued2019-06-19
dc.date.submitted2019-06-20
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.doi10.1101/674259
dc.identifier.urihttp://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.abstractB-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.isoen_US
dc.rightsThe copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectB-cell non-Hodgkin lymphoma
dc.subjectgenetic alterations
dc.subjectpathology
dc.subjectubiquitin proteasome system
dc.subjectlymphomagenesis
dc.subjectB-NHL
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectCancer Biology
dc.subjectGenetic Phenomena
dc.subjectGenomics
dc.subjectHemic and Lymphatic Diseases
dc.subjectNeoplasms
dc.subjectPathology
dc.titlePathognomonic and epistatic genetic alterations in B-cell non-Hodgkin lymphoma [preprint]
dc.typePreprint
dc.source.journaltitlebioRxiv
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2627&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1615
dc.identifier.contextkey14778189
refterms.dateFOA2022-08-23T15:53:36Z
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.submissionpathfaculty_pubs/1615
dc.contributor.departmentDepartment of Pathology


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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.
Except where otherwise noted, this item's license is described as 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.