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Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma


Burkitt lymphoma is endemic in sub-Saharan Africa and affects primarily children of age 4–7 years. Historically, it was one of the first tumors associated with a virus (EBV) and bearing a translocation involving an oncogene, i.e. MYC. There are three distinct clinical variants of Burkitt lymphoma according to the World Health Organization: sporadic, endemic and immunodeficiency-related. Although there has been some recent work on the molecular characterization of sporadic Burkitt lymphomas, little is known about the pathogenesis of endemic cases. In this work, we analyzed 20 samples of RNASeq from Burkitt lymphoma collected in Lacor Hospital (Uganda, Africa) and validated in an extension panel of 73 samples from Uganda and Kenya. We identify the presence in the adjacent non-neoplastic tissue of other herpesviridae family members in 53% of the cases, namely cytomegalovirus (CMV) and Kaposi sarcoma herpesvirus (KSHV). We also demonstrate expression of EBV lytic genes in primary tumor samples and find an inverse association between EBV lytic expression and TCF3 activity. When studying the mutational profile of endemic Burkitt tumors, we find recurrent alterations in genes rarely mutated in sporadic Burkitt lymphomas, i.e. ARID1A, CCNF and RHOA, and lower numbers of mutations in genes previously reported to be commonly mutated in sporadic cases, i.e. MYC, ID3, TCF3, TP53. Together, these results illustrate a distinct genetic and viral profile of endemic Burkitt lymphoma, suggesting a dual mechanism of transformation (mutation versus virus driven in sBL and eBL respectively).


Vyšlo v časopise: Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma. PLoS Pathog 11(10): e32767. doi:10.1371/journal.ppat.1005158
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005158

Souhrn

Burkitt lymphoma is endemic in sub-Saharan Africa and affects primarily children of age 4–7 years. Historically, it was one of the first tumors associated with a virus (EBV) and bearing a translocation involving an oncogene, i.e. MYC. There are three distinct clinical variants of Burkitt lymphoma according to the World Health Organization: sporadic, endemic and immunodeficiency-related. Although there has been some recent work on the molecular characterization of sporadic Burkitt lymphomas, little is known about the pathogenesis of endemic cases. In this work, we analyzed 20 samples of RNASeq from Burkitt lymphoma collected in Lacor Hospital (Uganda, Africa) and validated in an extension panel of 73 samples from Uganda and Kenya. We identify the presence in the adjacent non-neoplastic tissue of other herpesviridae family members in 53% of the cases, namely cytomegalovirus (CMV) and Kaposi sarcoma herpesvirus (KSHV). We also demonstrate expression of EBV lytic genes in primary tumor samples and find an inverse association between EBV lytic expression and TCF3 activity. When studying the mutational profile of endemic Burkitt tumors, we find recurrent alterations in genes rarely mutated in sporadic Burkitt lymphomas, i.e. ARID1A, CCNF and RHOA, and lower numbers of mutations in genes previously reported to be commonly mutated in sporadic cases, i.e. MYC, ID3, TCF3, TP53. Together, these results illustrate a distinct genetic and viral profile of endemic Burkitt lymphoma, suggesting a dual mechanism of transformation (mutation versus virus driven in sBL and eBL respectively).


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