Show simple item record

dc.contributor.authorKaymaz, Yasin
dc.contributor.authorOduor, Cliff I.
dc.contributor.authorYu, Hongbo
dc.contributor.authorOtieno, Juliana A.
dc.contributor.authorOng'echa, John Michael
dc.contributor.authorMoormann, Ann M.
dc.contributor.authorBailey, Jeffrey A.
dc.date2022-08-11T08:08:22.000
dc.date.accessioned2022-08-23T15:52:24Z
dc.date.available2022-08-23T15:52:24Z
dc.date.issued2017-05-01
dc.date.submitted2017-06-30
dc.identifier.citation<p>Mol Cancer Res. 2017 May;15(5):563-576. doi: 10.1158/1541-7786.MCR-16-0305.</p>
dc.identifier.issn1557-3125
dc.identifier.doi10.1158/1541-7786.MCR-16-0305.
dc.identifier.pmid28465297
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29129
dc.description.abstractEndemic Burkitt lymphoma (eBL) is the most common pediatric cancer in malaria-endemic equatorial Africa and nearly always contains Epstein-Barr virus (EBV), unlike sporadic Burkitt lymphoma (sBL) that occurs with a lower incidence in developed countries. Given these differences and the variable clinical presentation and outcomes, we sought to further understand pathogenesis by investigating transcriptomes using RNA sequencing (RNAseq) from multiple primary eBL tumors compared with sBL tumors. Within eBL tumors, minimal expression differences were found based on: anatomical presentation site, in-hospital survival rates, and EBV genome type, suggesting that eBL tumors are homogeneous without marked subtypes. The outstanding difference detected using surrogate variable analysis was the significantly decreased expression of key genes in the immunoproteasome complex (PSMB9/β1i, PSMB10/β2i, PSMB8/β5i, and PSME2/PA28β) in eBL tumors carrying type 2 EBV compared with type 1 EBV. Second, in comparison with previously published pediatric sBL specimens, the majority of the expression and pathway differences was related to the PTEN/PI3K/mTOR signaling pathway and was correlated most strongly with EBV status rather than geographic designation. Third, common mutations were observed significantly less frequently in eBL tumors harboring EBV type 1, with mutation frequencies similar between tumors with EBV type 2 and without EBV. In addition to the previously reported genes, a set of new genes mutated in BL, including TFAP4, MSH6, PRRC2C, BCL7A, FOXO1, PLCG2, PRKDC, RAD50, and RPRD2, were identified. Overall, these data establish that EBV, particularly EBV type 1, supports BL oncogenesis, alleviating the need for certain driver mutations in the human genome. IMPLICATIONS: Genomic and mutational analyses of Burkitt lymphoma tumors identify key differences based on viral content and clinical outcomes suggesting new avenues for the development of prognostic molecular biomarkers and therapeutic interventions.
dc.language.isoen_US
dc.publisherAmerican Association for Cancer Research
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471630/
dc.subjectUMCCTS funding
dc.subjectBioinformatics
dc.subjectComputational Biology
dc.subjectHemic and Lymphatic Diseases
dc.subjectImmune System Diseases
dc.subjectMolecular Biology
dc.subjectNeoplasms
dc.subjectVirus Diseases
dc.titleComprehensive Transcriptome and Mutational Profiling of Endemic Burkitt Lymphoma Reveals EBV Type-Specific Differences.
dc.typeJournal Article
dc.source.journaltitleMolecular cancer research : MCR
dc.source.volume15
dc.source.issue5
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1354
dc.identifier.contextkey10382251
html.description.abstract<p>Endemic Burkitt lymphoma (eBL) is the most common pediatric cancer in malaria-endemic equatorial Africa and nearly always contains Epstein-Barr virus (EBV), unlike sporadic Burkitt lymphoma (sBL) that occurs with a lower incidence in developed countries. Given these differences and the variable clinical presentation and outcomes, we sought to further understand pathogenesis by investigating transcriptomes using RNA sequencing (RNAseq) from multiple primary eBL tumors compared with sBL tumors. Within eBL tumors, minimal expression differences were found based on: anatomical presentation site, in-hospital survival rates, and EBV genome type, suggesting that eBL tumors are homogeneous without marked subtypes. The outstanding difference detected using surrogate variable analysis was the significantly decreased expression of key genes in the immunoproteasome complex (PSMB9/β1i, PSMB10/β2i, PSMB8/β5i, and PSME2/PA28β) in eBL tumors carrying type 2 EBV compared with type 1 EBV. Second, in comparison with previously published pediatric sBL specimens, the majority of the expression and pathway differences was related to the PTEN/PI3K/mTOR signaling pathway and was correlated most strongly with EBV status rather than geographic designation. Third, common mutations were observed significantly less frequently in eBL tumors harboring EBV type 1, with mutation frequencies similar between tumors with EBV type 2 and without EBV. In addition to the previously reported genes, a set of new genes mutated in BL, including TFAP4, MSH6, PRRC2C, BCL7A, FOXO1, PLCG2, PRKDC, RAD50, and RPRD2, were identified. Overall, these data establish that EBV, particularly EBV type 1, supports BL oncogenesis, alleviating the need for certain driver mutations in the human genome.</p> <p>IMPLICATIONS: Genomic and mutational analyses of Burkitt lymphoma tumors identify key differences based on viral content and clinical outcomes suggesting new avenues for the development of prognostic molecular biomarkers and therapeutic interventions.</p>
dc.identifier.submissionpathfaculty_pubs/1354
dc.contributor.departmentDivision of Transfusion Medicine, Department of Medicine
dc.contributor.departmentDepartment of Pathology
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentProgram in Bioinformatics and Integrative Biology


This item appears in the following Collection(s)

Show simple item record