Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma

Francesco Abate, Maria Raffaella Ambrosio, Lucia Mundo, Maria Antonella Laginestra, Fabio Fuligni, Maura Rossi, Sakellarios Zairis, Sara Gazaneo, Giulia De Falco, Stefano Lazzi, Cristiana Bellan, Bruno Jim Rocca, Teresa Amato, Elena Marasco, Maryam Etebari, Martin Ogwang, Valeria Calbi, Isaac Ndede, Kirtika Patel, David ChumbaPier Paolo Piccaluga, Stefano Pileri, Lorenzo Leoncini, Raul Rabadan

Research output: Contribution to journalArticlepeer-review

Abstract

Endemic Burkitt lymphoma (eBL) is primarily found in children in equatorial regions and represents the first historical example of a virus-associated human malignancy. Although Epstein-Barr virus (EBV) infection and MYC translocations are hallmarks of the disease, it is unclear whether other factors may contribute to its development. We performed RNA-Seq on 20 eBL cases from Uganda and showed that the mutational and viral landscape of eBL is more complex than previously reported. First, we found the presence of other herpesviridae family members in 8 cases (40%), in particular human herpesvirus 5 and human herpesvirus 8 and confirmed their presence by immunohistochemistry in the adjacent non-neoplastic tissue. Second, we identified a distinct latency program in EBV involving lytic genes in association with TCF3 activity. Third, by comparing the eBL mutational landscape with published data on sporadic Burkitt lymphoma (sBL), we detected lower frequencies of mutations in MYC, ID3, TCF3 and TP53, and a higher frequency of mutation in ARID1A in eBL samples. Recurrent mutations in two genes not previously associated with eBL were identified in 20% of tumors: RHOA and cyclin F (CCNF). We also observed that polyviral samples showed lower numbers of somatic mutations in common altered genes in comparison to sBL specimens, suggesting dual mechanisms of transformation, mutation versus virus driven in sBL and eBL respectively.

Original languageEnglish
Article numbere1005158
JournalPLoS Pathogens
Volume11
Issue number10
DOIs
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

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