Year-end Sale % OFF 
Abstract
Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing.
Highlights
Burkitt lymphoma (BL) is the most common B-cell lymphoma in children
Given that a recent study has identified differential expression of the E12 and E47 TCF3 isoforms in pluripotent human embryonic stem cells (ESCs) compared to differentiated cells we extended our analysis to published data from ESCs and induced pluripotent stem cells[49,50] (Supplementary Fig. 8)
In depth characterization of IG-MYC fusions on chromosome 8 (MYC) breakpoint sequences, the MYC mutations, and MYC transcripts allowed us to reassess the mechanisms leading to generation of the IG-MYC translocations and to identify a complex interplay of mutational, regulatory, transcriptional, and possibly post-transcriptional mechanisms leading to enhanced MYC activity
Summary
Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. 1234567890():,; Burkitt lymphoma (BL), including its leukemic counterpart Burkitt leukemia (B-AL), is a highly aggressive lymphoid neoplasm supposed to derive from germinal center B (GCB) cells[1] It is the most common B-cell lymphoma in children and occurs in adults[2,3]. Recent sequencing studies identified recurrent somatic mutations in ID3, TCF3, CCND3, and SMARCA4 in both, sporadic and endemic BL15–18. These studies mostly applied exome, transcriptome, or targeted sequencing strategies, neither taking into account the non-coding genome nor systematically integrating the various layers of nucleic-acid encoded information. By integration of the different datasets we provide insights into the complex genomic and transcriptomic changes underlying MYC dysregulation, the potential cell of origin of sBL, and the complementarity of mutational mechanisms deregulating key pathways in BL
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
