This section shows a general overview of information for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.
- The whole genome landscape of Burkitt lymphoma subtypes.
- Paper ID
- Duke University, United States.
PMID: 31558468 (view at PubMed or Europe PMC)
- Burkitt lymphoma (BL) is an aggressive, MYC-driven lymphoma comprising three distinct clinical subtypes, including sporadic BLs that occur worldwide, endemic BLs that occur predominantly in sub-Saharan Africa, and immunodeficiency-associated BLs that occur primarily in the setting of HIV. In this study, we comprehensively delineated the genomic basis of BL through whole genome sequencing of 101 tumors representing all 3 subtypes of BL to identify 72 driver genes. These data were additionally informed by CRISPR screens in BL cell lines to functionally annotate the role of oncogenic drivers. Nearly every driver gene was found to have both coding and non-coding mutations highlighting the importance of whole genome sequencing for identifying driver events. Our data implicate coding and non-coding mutations in <i>IGLL5</i>, <i>BACH2</i>, <i>SIN3A</i> and <i>DNMT1</i> EBV infection was associated with higher mutation load, with EBV type 1 showing a higher mutational burden than type 2 EBV. While sporadic and immunodeficiency-associated BLs had similar genetic profiles, endemic BLs manifested more frequent mutations in <i>BCL7A</i> and <i>BCL6</i>, and fewer genetic alterations in <i>DNMT1, SNTB2, CTCF.</i> Silencing mutations in <i>ID3</i> were a common feature of all three subtypes of BL. <i>In vitro</i>, mass spectrometry-based proteomics demonstrated that the ID3 protein binds primarily to TCF3 and TCF4. <i>In vivo</i> knockout of <i>ID3</i> potentiated the effects of <i>MYC</i>, leading to rapid tumorigenesis and tumor phenotypes consistent with those observed in the human disease.
- Paper Status
- Genes Analysed
- Mutated Samples
- Total No. of Samples