A group of scientists partly funded by the Terry Fox Research Institute has discovered a better way to classify Burkitt’s lymphoma (BL), a rare type of lymphoma that mainly affects children and can be deadly if not caught in time.
Published in Blood (March 2019), the new classification shifts the focus away from geography and towards exposure to the Epstein-Barr Virus (EBV), a virus linked to several illnesses including infectious mononucleosis and BL.
“This is a paradigm shift in how we think of BL,” said Bruno Grande, a PhD candidate at Simon Fraser University in BC and the paper’s co-first author. “For decades, we have classified Burkitt’s lymphoma geographically, separating cases in the developing world (known as endemic BL) from cases elsewhere (known as sporadic BL), but one of the key findings of this paper is that EBV status is way more important than geography for understanding the nature of BL.”
To reach this conclusion, the team constructed the largest and most comprehensive cohort of BL patients yet, made up of patients from both Africa and North America. They then used whole genome and transcriptome sequencing to determine how molecular and genetic features varied amongst patients. They found that patients who were EBV-positive shared a similar profile of mutations leading to BL, regardless of where they were diagnosed.
“This essentially means that a patient in Uganda that has EBV-positive BL is more similar to an EBV-positive BL patient in Tennessee than to their EBV-negative neighbour,” Grande explained.
Identifying these similarities is not only important for classifying the disease more precisely, but could change how the disease is treated in the near future.
“Our study sheds light on the mechanisms that EBV uses to allow tumour cells to grow into BL, namely by disrupting apoptosis (programmed cell death),” Grande said. “This has revealed potential targets that could be attacked through combination therapies, which we believe could lead to less-toxic treatments for EBV-positive BL patients and better survival rates.”
Genome-wide discovery of somatic coding and non-coding mutations in pediatric endemic and sporadic Burkitt lymphoma
Bruno M. Grande, Daniela S. Gerhard, Aixiang Jiang, Nicholas B. Griner, Jeremy S. Abramson, Thomas B. Alexander, Hilary Allen, Leona W. Ayers, Jeffrey M. Bethony, Kishor Bhatia, Jay Bowen, Corey Casper, John Kim Choi, Luka Culibrk, Tanja M. Davidsen, Maureen A. Dyer, Julie M. Gastier-Foster, Patee Gesuwan, Timothy C. Greiner, Thomas G. Gross, Benjamin Hanf, Nancy Lee Harris, Yiwen He, John D. Irvin, Elaine S. Jaffe, Steven J.M. Jones, Patrick Kerchan, Nicole Knoetze, Fabio E. Leal, Tara M. Lichtenberg, Yussanne Ma, Jean Paul Martin, Marie-Reine Martin, Sam M. Mbulaiteye, Charles G. Mullighan, Andrew J. Mungall, Constance Namirembe, Karen Novik, Ariela Noy, Martin D. Ogwang, Abraham Omoding, Jackson Orem, Steven J. Reynolds, Christopher K. Rushton, John T. Sandlund, Roland Schmitz, Cynthia Taylor, Wyndham H. Wilson, George W. Wright, Eric Y. Zhao, Marco A. Marra, Ryan D. Morin, Louis M. Staudt
This work was supported in part by funding from TFRI to the Terry Fox New Investigator Award in Exploring Clonal Evolution in non-Hodgkin Lymphomas using Serial Tumour Sampling and Liquid Biopsies to Ryan Morin.