Abstract
Relapse occurs in 10–40% of Burkitt lymphoma (BL) patients that have completed intensive chemotherapy regimens and is typically fatal. While treatment-naive BL has been characterized, the genomic landscape of BL at the time of relapse (rBL) has never been reported. Here, we present a genomic characterization of two rBL patients. The diagnostic samples had mutations common in BL, including MYC and CCND3. Additional mutations were detected at relapse, affecting important pathways such as NFκB (IKBKB) and MEK/ERK (NRAS) signaling, glutamine metabolism (SIRT4), and RNA processing (ZFP36L2). Genes implicated in drug resistance were also mutated at relapse (TP53, BAX, ALDH3A1, APAF1, FANCI). This concurrent genomic profiling of samples obtained at diagnosis and relapse has revealed mutations not previously reported in this disease. The patient-derived cell lines will be made available and, along with their detailed genetics, will be a valuable resource to examine the role of specific mutations in therapeutic resistance.
Acknowledgements
We acknowledge the support of the patients and their families who have consented to participate in lymphoma tissue banking within the LCBQ. We thank the Jewish General Hospital Foundation, the Cole Foundation, and the Fonds de Recherche du Québec en Santé for financially supporting the LCBQ. We also thank the Letai laboratory for teaching us how to perform the BH3 profiling protocol, Dr. Volker Blank’s laboratory (Lady Davis Institute) for the Namalwa and Raji cell lines, Dr. Raquel Aloyz’s laboratory (Lady Davis Institute) for the OCI-Ly8 cell line, and Sami Chaaban for critical review of the manuscript.
Ethics approval and consent to participate: This research was approved by the REB at the Jewish General Hospital (protocols 11-047, 12-052) and is in accordance with the declaration of Helsinki.
Consent for publication: Both patients consented to the LCBQ project (protocol 11-047), which includes the consent to publish the data generated from their samples.
Availability of data and materials: The datasets generated and/or analyzed during the current study will be made available upon article acceptance. Requests to have access to the cell lines should be made to Dr. Nathalie Johnson at [email protected].
Potential conflict of interest
Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1413186.