Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma. - PubMed - NCBI
PLoS Pathog. 2015 Oct 15;11(10):e1005158. doi: 10.1371/journal.ppat.1005158. eCollection 2015.
Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma.
Abate F1,
Ambrosio MR2,
Mundo L2,
Laginestra MA3,
Fuligni F3,
Rossi M3,
Zairis S4,
Gazaneo S2,
De Falco G5,
Lazzi S2,
Bellan C2,
Rocca BJ2,
Amato T2,
Marasco E3,
Etebari M3,
Ogwang M6,
Calbi V6,
Ndede I7,
Patel K7,
Chumba D7,
Piccaluga PP3,
Pileri S8,
Leoncini L9,
Rabadan R1.
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.
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