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    Comprehensive Transcriptome and Mutational Profiling of Endemic Burkitt Lymphoma Reveals EBV Type-Specific Differences.

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    Authors
    Kaymaz, Yasin
    Oduor, Cliff I.
    Yu, Hongbo
    Otieno, Juliana A.
    Ong'echa, John Michael
    Moormann, Ann M.
    Bailey, Jeffrey A.
    UMass Chan Affiliations
    Division of Transfusion Medicine, Department of Medicine
    Department of Pathology
    Program in Molecular Medicine
    Program in Bioinformatics and Integrative Biology
    Document Type
    Journal Article
    Publication Date
    2017-05-01
    Keywords
    UMCCTS funding
    Bioinformatics
    Computational Biology
    Hemic and Lymphatic Diseases
    Immune System Diseases
    Molecular Biology
    Neoplasms
    Virus Diseases
    
    Metadata
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    Link to Full Text
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471630/
    Abstract
    Endemic Burkitt lymphoma (eBL) is the most common pediatric cancer in malaria-endemic equatorial Africa and nearly always contains Epstein-Barr virus (EBV), unlike sporadic Burkitt lymphoma (sBL) that occurs with a lower incidence in developed countries. Given these differences and the variable clinical presentation and outcomes, we sought to further understand pathogenesis by investigating transcriptomes using RNA sequencing (RNAseq) from multiple primary eBL tumors compared with sBL tumors. Within eBL tumors, minimal expression differences were found based on: anatomical presentation site, in-hospital survival rates, and EBV genome type, suggesting that eBL tumors are homogeneous without marked subtypes. The outstanding difference detected using surrogate variable analysis was the significantly decreased expression of key genes in the immunoproteasome complex (PSMB9/β1i, PSMB10/β2i, PSMB8/β5i, and PSME2/PA28β) in eBL tumors carrying type 2 EBV compared with type 1 EBV. Second, in comparison with previously published pediatric sBL specimens, the majority of the expression and pathway differences was related to the PTEN/PI3K/mTOR signaling pathway and was correlated most strongly with EBV status rather than geographic designation. Third, common mutations were observed significantly less frequently in eBL tumors harboring EBV type 1, with mutation frequencies similar between tumors with EBV type 2 and without EBV. In addition to the previously reported genes, a set of new genes mutated in BL, including TFAP4, MSH6, PRRC2C, BCL7A, FOXO1, PLCG2, PRKDC, RAD50, and RPRD2, were identified. Overall, these data establish that EBV, particularly EBV type 1, supports BL oncogenesis, alleviating the need for certain driver mutations in the human genome. IMPLICATIONS: Genomic and mutational analyses of Burkitt lymphoma tumors identify key differences based on viral content and clinical outcomes suggesting new avenues for the development of prognostic molecular biomarkers and therapeutic interventions.
    Source

    Mol Cancer Res. 2017 May;15(5):563-576. doi: 10.1158/1541-7786.MCR-16-0305.

    DOI
    10.1158/1541-7786.MCR-16-0305.
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/29129
    PubMed ID
    28465297
    ae974a485f413a2113503eed53cd6c53
    10.1158/1541-7786.MCR-16-0305.
    Scopus Count
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    UMass Chan Faculty and Researcher Publications
    Program in Bioinformatics and Integrative Biology Publications
    UMass Center for Clinical and Translational Science Supported Publications

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