Genetic subgroups inform on pathobiology in adult and pediatric Burkitt lymphoma

Nicole Thomas, Kostiantyn Dreval, Daniela S. Gerhard, Laura K. Hilton, Jeremy S. Abramson, Richard F. Ambinder, Stefan Barta, Nancy L. Bartlett, Jeffrey Bethony, Kishor Bhatia, Jay Bowen, Anthony C. Bryan, Ethel Cesarman, Corey Casper, Amy Chadburn, Manuela Cruz, Dirk P. Dittmer, Maureen A. Dyer, Pedro Farinha, Julie M. Gastier-FosterAlina S. Gerrie, Bruno M. Grande, Timothy Greiner, Nicholas B. Griner, Thomas G. Gross, Nancy L. Harris, John D. Irvin, Elaine S. Jaffe, David Henry, Rebecca Huppi, Fabio E. Leal, Michael S. Lee, Jean Paul Martin, Marie Reine Martin, Sam M. Mbulaiteye, Ronald Mitsuyasu, Vivian Morris, Charles G. Mullighan, Andrew J. Mungall, Karen Mungall, Innocent Mutyaba, Mostafa Nokta, Constance Namirembe, Ariela Noy, Martin D. Ogwang, Abraham Omoding, Jackson Orem, German Ott, Hilary Petrello, Stefania Pittaluga, James D. Phelan, Juan Carlos Ramos, Lee Ratner, Steven J. Reynolds, Paul G. Rubinstein, Gerhard Sissolak, Graham Slack, Shaghayegh Soudi, Steven H. Swerdlow, Alexandra Traverse-Glehen, Wyndham H. Wilson, Jasper Wong, Robert Yarchoan, Jean C. ZenKlusen, Marco A. Marra, Louis M. Staudt, David W. Scott, Ryan D. Morin

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Burkitt lymphoma (BL) accounts for most pediatric non-Hodgkin lymphomas, being less common but significantly more lethal when diagnosed in adults. Much of the knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult BL (aBL) and other adult lymphomas not fully explored. We sought to more thoroughly identify the somatic changes that underlie lymphomagenesis in aBL and any molecular features that associate with clinical disparities within and between pBL and aBL. Through comprehensive whole-genome sequencing of 230 BL and 295 diffuse large B-cell lymphoma (DLBCL) tumors, we identified additional significantly mutated genes, including more genetic features that associate with tumor Epstein-Barr virus status, and unraveled new distinct subgroupings within BL and DLBCL with 3 predominantly comprising BLs: DGG-BL (DDX3X, GNA13, and GNAI2), IC-BL (ID3 and CCND3), and Q53-BL (quiet TP53). Each BL subgroup is characterized by combinations of common driver and noncoding mutations caused by aberrant somatic hypermutation. The largest subgroups of BL cases, IC-BL and DGG-BL, are further characterized by distinct biological and gene expression differences. IC-BL and DGG-BL and their prototypical genetic features (ID3 and TP53) had significant associations with patient outcomes that were different among aBL and pBL cohorts. These findings highlight shared pathogenesis between aBL and pBL, and establish genetic subtypes within BL that serve to delineate tumors with distinct molecular features, providing a new framework for epidemiologic, diagnostic, and therapeutic strategies.

Original languageEnglish
Pages (from-to)904-916
Number of pages13
Issue number8
StatePublished - Feb 23 2023


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