Pathogenesis and Immunity in Endemic Burkitt Lymphoma

This genomic landscape of Burkitt lymphoma represents a multimodal sequencing of tumors and control tissues and individuals to better understand the etiology, and molecular pathogenesis of Burkitt lymphoma including the roles of the associated Plasmodium falciparum malaria and EBV infections. Comprehensive sequencing set includes genomic, transcriptomic, and epigenomic datasets in concert with variable clinical phenotypes and outcome information such as anatomical presentation site, in-hospital survival rates, and EBV genome type. This deposit includes additional small RNA-seq data from endemic BL (eBL) tumors and RNA-sequencing data from sorted NK cell subsets from the peripheral blood of eBL patients. The additional small RNA-seq data are from tumor specimens from 17 eBL cases, of the previously deposited polyA RNA-seq data from 28 eBL cases (phs1282.V1). The additional RNAseq data from Fluorescence-activated cell sorting (FACS) of NK cell subsets, isolated from the peripheral blood of 7 eBL cases. The additional RNAseq data are from eBL tumor samples of 5 eBL cases, BL cell lines established from these tumor samples and also NSG mouse tumors created by implanting the established BL cell lines into NSG mice. The dataset also includes RNAseq data of the NSG mouse tumors after treatment with Rituximab (RIT) and Phosphate buffered saline (PBS). The fifth batch of data includes mRNA-seq from different passages of a single eBL cell line that have variable EBV phenotypes (low passage with lytic EBV and high passage with latent EBV). This batch also includes lytic and latent lymphoblastoid cell line (LCL) clones from a single blood donor generated through infection with the strain of EBV isolated from the aforementioned eBL cell line. For initial transcriptome analysis see: Kaymaz et al. "Comprehensive Transcriptome and Mutational Profiling of Endemic Burkitt Lymphoma Reveals EBV Type-specific Difference." Molecular Cancer Research, 2017, PMID: 28465297. For initial microRNA analysis see: Oduor et al. "Human and Epstein-Barr Virus miRNA Profiling as Predictive Biomarkers for Endemic Burkitt Lymphoma." Frontiers in Microbiology 8, 2017, PMID: 28400759. For initial NK subsets RNA expression analysis see: Forconi et al. "A new hope for CD56negCD16pos NK cells as unconventional cytotoxic mediators: an adaptation to chronic diseases." Frontiers in Cellular and Infection Microbiology, 2020, PMID: 32373555.For initial eBL cell line and mouse avatar RNA expression analysis see: Saikumar et al. "Endemic Burkitt lymphoma avatar mouse models for exploring inter-patient tumor variation and testing targeted therapies." Life Science Alliance, 2023, PMID: 36878637. For general overview of cohort study see: Buckle et al. "Factors influencing survival among Kenyan children diagnosed with endemic Burkitt lymphoma between 2003 and 2011: A historical cohort study." Int J Cancer. 15:1231, 2016, PMID: 27136063.]]>
Fine needle aspirates and venous blood were prospectively obtained between 2009 and 2012 at time of diagnosis and prior to commencing chemotherapy at Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH), a regional referral hospital for pediatric cancer in western Kenya. Tumor aspirates were smeared and stained with Giemsa/May-Grunwald for morphologic diagnosis by microscopy. Morphology was assessed by two independent pathologists to verify the diagnosis. Peripheral Blood Mononuclear Cells (PBMCs) were isolated from the blood immediately after collection and PBMCs were cryopreserved for future studies. Written informed consent was obtained from a parent or legal guardian of the child before enrollment. Ethical approval was obtained from the Institutional Review Board at the University of Massachusetts Medical School and the Scientific and Ethics Review Unit at the Kenya Medical Research Institute. Approval for this study was also granted by the JOOTRH, Kenya Ministry of Health Ethical Review Committee.]]>
Endemic Burkitt lymphoma (eBL) is the most prevalent pediatric cancer in sub-Saharan Africa. Its etiology has been linked to early-age infection with Epstein-Barr Virus (EBV) and residing in Plasmodium falciparum malaria holoendemic regions where children are commonly co-infected with this parasite. The etiologic mechanisms involving both human genetic mutations and the influence of EBV and malaria on B cell transformation are not fully understood. However, given that eBL can be cured with combination chemotherapy, treating children diagnosed with eBL is feasible even in resource-constrained settings. The overall goal of our BL consortium is to understand the basic biology resulting in B cell tumorigenesis in order to prevent and cure this pediatric cancer.]]>