DNA methylation epitypes of Burkitt lymphoma with distinct molecular and clinical features

Nicole Thomas, Simon Fraser University, Burnaby, British Columbia, Canada.
Carlos A. García-Prieto, Josep Carreras Leukaemia Research Institute, Badalona, Spain.
Kostiantyn Dreval, BC Cancer Research Centre, Vancouver, Canada.
Laura K. Hilton, BC Cancer Agency, Vancouver, BC, Canada.
Jeremy S. Abramson, Massachusetts General Hospital, Boston, MA, United States.
Nancy L. Bartlett, Washington University in St. Louis, St. Louis, MO, United States.
Jeffrey Bethony, George Washington University Hospital, Washington, DC, United States.
Jay Bowen, Nationwide Children's, Columbus, OH.
Anthony C. Bryan, Nationwide Children's Hospital, Columbus, OH, United States.
Corey Casper, Banner Health, Seattle, WA, United States.
Maureen A. Dyer, Frederick National Laboratory for Cancer Research, Frederick, MD, United States.
Julie M. Gastier-Foster, Baylor College of Medicine, Houston, TX, United States.
Alina S. Gerrie, British Columbia Cancer Agency, Vancouver, Canada.
Timothy C. Greiner, University of Nebraska Medical Center, Omaha, NE, United States.
Nicholas B. Griner, National Cancer Institute, Rockville, United States.
Thomas G. Gross, National Cancer Institute, Rockville, MD, United States.
Nancy Harris, Harvard University.
John D. Irvin, Foundation for Burkitt Lymphoma Research, Marco Island, Florida, United States.
Elaine S. Jaffe, National Cancer Institute, Bethesda, MD, United States.
Fabio E. Leal, Instituto Nacional de Cancer, Rio de Janeiro, Brazil.
Sam M. Mbulaiteye, National Cancer Institute, Bethesda, MD, United States.
Charles G. Mullighan, St. Jude Children's Research Hospital, Memphis, TN, United States.
Andrew J. Mungall, BC Cancer, Vancouver, BC, Canada.
Karen L. Mungall, BC Cancer Agency, Vancouver, BC, Canada.
Constance Namirembe, Uganda Cancer Institute, Kampala, Uganda.
Ariela Noy, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Martin D. Ogwang, St. Mary's Hospital, Gulu, Uganda.
Jackson Orem, Uganda Cancer Institution, Uganda.
German Ott, Robert-Bosch-Krankenhaus and Dr.Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
Hilary Petrello, Nationwide Children's Hospital, Columbus, OH, United States.
Steven J. Reynolds, National Institute of Allergy and Infectious Diseases, Washington, DC, United States.
Steven H. Swerdlow, University of Pittsburgh, Pittsburgh, PA, United States.

Document Type

Journal Article

Publication Date

5-8-2025

Journal

Blood cancer discovery

DOI

10.1158/2643-3230.BCD-24-0240

Abstract

The genetic subtypes of Burkitt Lymphoma (BL) have been defined, whereas the role of epigenetics remains to be comprehensively characterized. We searched genomic DNA from 218 patients across four continents, for recurrent DNA methylation patterns and their associations with clinical and molecular features. We identified DNA methylation patterns that were not fully explained by EBV status or mutation status, leading to two epitypes, described here as HypoBL and HyperBL. Each is characterized by distinct genomic and clinical features including global methylation, mutation burden, aberrant somatic hypermutation, and survival outcomes. Methylation, gene expression and mutational differences between the epitypes support a model in which each arises from a distinct cell-of-origin. These results, pending validation in external cohorts, point to a refined risk assessment for BL patients who may experience inferior outcomes.

Department

Microbiology, Immunology, and Tropical Medicine

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