NDLI: Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma

Content Provider	PubMed Central
Author	Abate, Francesco Ambrosio, Maria Raffaella Mundo, Lucia Laginestra, Maria Antonella Fuligni, Fabio Rossi, Maura Sakellarios, Zairis Sara, Gazaneo Falco, Giulia De Stefano, Lazzi Bellan, Cristiana Rocca, Bruno Jim Amato, Teresa Marasco, Elena Etebari, Maryam Ogwang, Martin Calbi, Valeria Isaac, Ndede Patel, Kirtika Chumba, David Piccaluga, Pier Paolo Pileri, Stefano Leoncini, Lorenzo Rabadan, Raul
Editor	Lieberman, Paul M.
Copyright Year	2015
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.
Related Links	http://dx.doi.org/10.1371/journal.ppat.1005158
Starting Page	1005158
File Format	PDF
ISSN	15537374
e-ISSN	15537374
Journal	PLoS Pathogens
Issue Number	10
Volume Number	11
Language	English
Publisher	Public Library of Science
Publisher Date	2015-10-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Immunology Genetics Molecular Biology Microbiology Parasitology Virology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Virology Molecular Biology Parasitology Immunology Microbiology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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