Nicole Thomas, Simon Fraser University, Burnaby, Canada.
Kostiantyn Dreval, Simon Fraser University, Burnaby, Canada.
Daniela S. Gerhard, National Cancer Institute, Bethesda, United States.
Laura K. Hilton, BC Cancer, Vancouver, Canada.
Jeremy S. Abramson, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, United States.
Stefan K. Barta, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Nancy L. Bartlett, Washington University School of Medicine, St. Louis, Missouri, United States.
Jeffrey Bethony, George Washington University, Washington, District of Columbia, United States.
Kishor Bhatia, Lantern Pharma, Ellicott city, Maryland, United States.
Jay Bowen, Nationwide Children's Hospital, Columbus, Ohio, United States.
Anthony C. Bryan, Nationwide Children's Hospital, Columbus, Ohio, United States.
Ethel Cesarman, Weill Cornell Medicine, New York, New York, United States.
Corey Casper, AAHI, Seattle, Washington, United States.
Manuela Cruz, Simon Fraser University, Burnaby, British Columbia, Canada.
Maureen Dyer, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, United States.
Pedro Farinha, British Columbia Cancer, Vancouver, Canada.
Julie Gastier-Foster, Texas Children's Hospital / Baylor College of Medicine, Houston, Texas, United States.
Alina S. Gerrie, University of British Columbia and BC Cancer, Vancouver, Canada.
Bruno Grande, Sage Bionetworks, Seattle, Washington, United States.
Timothy C. Greiner, University of Nebraska Medical Center, Omaha, Nebraska, United States.
Nicholas Griner, Charles River Laboratories, Ayer, Massachusetts, United States.
Thomas G. Gross, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States.
Nancy Lee Harris, Massachusetts General Hospital, Boston, Massachusetts, United States.
John D. Irvin, foundation for burkitt lymphoma research, marco island, United States.
Elaine S. Jaffe, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States.
David Henry, Pennsylvania Hospital, Phila, United States.
Rebecca Liddell Huppi, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States.
Fabio E. Leal, Instituto Nacional de Câncer José de Alencar, Rio de Janeiro, Brazil.
Michael Lee, University of North Carolina, Chapel Hill, North Carolina, United States.
Jean Paul Martin, Foundation for Burkitt Lymphoma Research, GENEVA, Switzerland.
Marie-Reine Martin, Foundation for Burkitt Lymphoma Research, Geneva, Switzerland.
Sam M. Mbulaiteye, National Cancer Institute, Bethesda, Maryland, United States.

Document Type

Journal Article

Publication Date







Burkitt lymphoma (BL) accounts for the majority of pediatric non-Hodgkin lymphomas being less common but significantly more lethal when diagnosed in adults. Much of our knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult (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 (SMGs) including more genetic features that associate with tumor EBV status, and unraveled new distinct subgroupings within BL and DLBCL with three predominantly comprising BLs: DGG-BL (DDX3X, GNA13 and GNAI2), IC-BL (ID3, CCND3), and Q53-BL (quiet TP53). Each BL subgroup is characterized by combinations of common driver and non-coding mutations caused by aberrant somatic hypermutation (aSHM). 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 epidemiological, diagnostic, and therapeutic strategies.


Microbiology, Immunology, and Tropical Medicine