[PMID]: | 28465297 |
[Au] Autor: | Kaymaz Y; Oduor CI; Yu H; Otieno JA; Ong'echa JM; Moormann AM; Bailey JA |
[Ad] Endereço: | Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts. |
[Ti] Título: | Comprehensive Transcriptome and Mutational Profiling of Endemic Burkitt Lymphoma Reveals EBV Type-Specific Differences. |
[So] Source: | Mol Cancer Res;15(5):563-576, 2017 05. |
[Is] ISSN: | 1557-3125 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | 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 ( /ß1i, /ß2i, /ß5i, and /PA28ß) 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 , and 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. |
[Mh] Termos MeSH primário: |
Linfoma de Burkitt/genética Infecções por Vírus Epstein-Barr/genética Perfilação da Expressão Gênica/métodos Herpesvirus Humano 4/classificação Mutação
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[Mh] Termos MeSH secundário: |
Adolescente Linfoma de Burkitt/virologia Criança Pré-Escolar Doenças Endêmicas Feminino Redes Reguladoras de Genes Genoma Viral Herpesvirus Humano 4/genética Seres Humanos Quênia/epidemiologia Masculino Taxa de Mutação Análise de Sequência de RNA
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[Pt] Tipo de publicação: | COMPARATIVE STUDY; JOURNAL ARTICLE |
[Em] Mês de entrada: | 1802 |
[Cu] Atualização por classe: | 180221 |
[Lr] Data última revisão:
| 180221 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170504 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1158/1541-7786.MCR-16-0305 |
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